bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological Defects Created by Gamma Rays in a Carbon Nanotube Bilayer
Authors: Grushevskaya Halina , Timoshchenko Andrey , Lipnevich Ihor
Published: January 2023

Graphene sheets are a highly radiation-resistant material for prospective nuclear applications and nanoscale defect engineering. However, the precise mechanism of graphene radiation hardness has remained elusive. In this paper, we study the origin and nature of defects induced by gamma radiation in a graphene rolled-up plane. In order to reduce the environmental influence on graphene and reveal the small effects of gamma rays, we have synthesized a novel graphene-based nanocomposite material containing a bilayer of highly aligned carbon nanotube assemblies that have been decorated by organometallic compounds and suspended on nanoporous Al2O3 membranes. The bilayer samples were irradiated by gamma rays from a 137Cs source with a fluence rate of the order of 105 m−2s−1. The interaction between the samples and gamma quanta results in the appearance of three characteristic photon escape peaks in the radiation spectra. We explain the mechanism of interaction between the graphene sheets and gamma radiation using a pseudo-Majorana fermion graphene model, which is a quasi-relativistic N=3-flavor graphene model with a Majorana-like mass term. This model admits the existence of giant charge carrier currents that are sufficient to neutralize the impact of ionizing radiation. Experimental evidence is provided for the prediction that the 661.7-keV gamma quanta transfer enough energy to the electron subsystem of graphene to bring about the deconfinement of the bound pseudo-Majorana modes and involve C atoms in a vortical motion of the electron density flows in the graphene plane. We explain the radiation hardness of graphene by the topological non-triviality of the pseudo-Majorana fermion configurations comprising the graphene charge carriers.
Internal Explosion Performance of RDX@Nano-B Composite Explosives
Authors: Xi Peng , Sun Shiyan , Shang Yu , Wang Xiaofeng , Dong Jun , Feng Xuesong
Published: January 2023

Boron powder is an additive for metalized explosives with great application potential. To improve the energy release ability of boron powder, the composites of RDX and nano-boron (RDX@Nano-B) were prepared by the spray-drying process, and the metalized explosives based on it were designed (named PBX-B1). The detonation heat and explosion pressure of boron-containing explosives PBX-B1 under vacuum and air conditions were measured and analyzed by an internal explosion test. On the other hand, the equilibrium pressure and energy release of the PBX-B1 explosive system after detonation were analyzed and compared with that of an explosive formulation of the same composition (named PBX-B2). Results showed that the detonation heat of PBX-B1 was 7456 J/g in a vacuum environment, which was 34.8% higher than that of RDX (5530 J/g). However, in the air environment, the detonation heat of PBX-B1 increased by 19.2% compared with that in the vacuum environment, and the explosive gas products mainly included N2, NOx, CO, H2O, CH4, HCN, and CO2. The peak pressure and equilibrium pressures of PBX-B1 were 11.2 and 0.42 MPa, which were increased by 155% and 75% compared with the vacuum environment, respectively. It is worth noting that, compared with that of PBX-B2, the released energy in the aerobic combustion stage and equilibrium pressure of PBX-B1 were increased by 49.8% and 10.5%. This study demonstrated the strategy of improving the energy release of boron-containing metalized explosives through the design of an explosive microstructure, which provides important clues for the design of higher-energy metalized explosives.
Tunable Photoresponse in a Two-Dimensional Superconducting Heterostructure
Authors: Ji Zijie , Zhang Ruan , Zhu Shuangxing , Gu Feifan , Jin Yunmin , Xie Binghe , Wu Jiaxin , Cai Xinghan
Published: January 2023

The photo-induced superconducting phase transition is widely used in probing the physical properties of correlated electronic systems and to realize broadband photodetection with extremely high responsivity. However, such photoresponse is usually insensitive to electrostatic doping due to the high carrier density of the superconductor, restricting its applications in tunable optoelectronic devices. In this work, we demonstrate the gate voltage modulation to the photoresponsivity in a two-dimensional NbSe2-graphene heterojunction. The superconducting critical current of the NbSe2 relies on the gate-dependent hot carrier generation in graphene via the Joule heating effect, leading to the observed shift of both the magnitude and peak position of the photoresponsivity spectra as the gate voltage changes. This heating effect is further confirmed by the temperature and laser-power-dependent characterization of the photoresponse. In addition, we investigate the spatially-resolved photocurrent, finding that the superconductivity is inhomogeneous across the junction area. Our results provide a new platform for designing tunable superconducting photodetector and indicate that the photoresponse could be a powerful tool in studying the local electronic properties and phase transitions in low-dimensional superconducting systems.
Acknowledgment to the Reviewers of Nanomanufacturing in 2022
Authors:   Nanomanufacturing Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Influence of Sink Size on 15N and 13C Allocation during Different Phenological Phases of Spring Wheat Cultivars
Authors: Götz Klaus-Peter , Erekul Osman
Published: January 2023

The scientific objective of this study was to answer the question of whether sink limitation is also true for high quality wheat varieties. We examined the incorporation of 15N and 13C during phenological phases into vegetative parts and grains of Elite wheat Triso (E) and Quality wheat Naxos (A) when the spike is halved. Three splits of fertilizer were applied at EC 11, EC 30, EC 59, whereby 10% at EC 30 and EC 59 was 15N, and plants were also labelled with 13CO2. The application of only the third split as 15N, combined with spike-halving, resulted in a significantly higher 15N-content (+11%) of 0.486 mg 15N/g DM, compared to the control (0.437 mg15N/g DM). Labelling whole plants with 13CO2 at EC 59 resulted in a significantly higher 13C-content—40%—(0.223 mg 13C/g DM) of the grains of the control for Triso at the fully-ripe stage (EC 89), compared to Naxos (0.160 mg 13C/g DM). This superiority was reduced to 34%, and was also demonstrated by spike-halving (0.226 mg 13C/g DM, 0.169 mg 13C/g DM). Remobilization of 15N for control and spike-halving treatments were 68.2% and 61.1%, respectively. This clearly demonstrates that the reduction of the sink size by spike-halving leads to a 7% reduction in the remobilization of 15N from vegetative to reproductive tissues.
Measuring Food Service Satisfaction amongst Residents Living in Nursing Homes—A New and Valid Person-Centered Approach
Authors: Pankhurst Morgan , Yaxley Alison , Miller Michelle
Published: January 2023

Resident satisfaction with food services contributes to health and wellbeing. Measuring resident satisfaction is important; however, the small number of existing food service satisfaction questionnaires (FSSQs) are outdated, lack rigorous psychometric testing and do not reflect the shift to person-centered care. This study aimed to develop a valid and reliable FSSQ. Content validity was established by conducting interviews with residents, a systematic literature review and consultation with an expert panel. Data from 387 residents were used to establish construct validity (Principal Components Analysis), internal consistency (Cronbach’s alpha) and temporal stability (Gwet’s AC). The result was a three factor, 25-item scale with good/excellent internal consistency: Factor One (13 items–good food/service, α = 0.896), Factor Two (seven items–resident choice/food availability α = 0.648) and Factor Three (five items–resident participation/staff assistance, α = 0.729). Temporal stability was good/very good (Gwet’s AC 0.6242–0.9799 (p < 0.001). This is the first FSSQ available to nursing homes that meets the COSMIN® standards for excellence and incorporates person-centered care. The questionnaire is simple to use and interpret, providing food service managers with an accurate and reliable measure of resident satisfaction and assisting them in providing a meal and dining experience that supports the health and wellbeing of residents.
Sleep Duration, Body Mass Index, and Dietary Behaviour among KSU Students
Authors: Alafif Nora , Alruwaili Nawaf W.
Published: January 2023

Background: Adolescents who receive an adequate amount of sleep benefit from a positive health status. Previous studies have documented several health consequences connected with obesity as well as short sleep duration among adolescents. Poor sleep quality with obesity and uncontrolled diet can lead to chronic diseases in the future. This study aimed to examine the link between eating habits, sleep duration, and body mass index (BMI) among King Saud University (KSU) students. Methods: The study was cross-sectional and conducted from February to May 2021 on 311 recruited students (male and female) of KSU premises. Pittsburgh Sleep Quality Index questionnaire was used to describe sleep duration linked with a dietary pattern that included fruit and vegetable intake. The questionnaire consists of two sections of 15 and 10 questions each. The questionnaire was created using the Google Forms tool and distributed through social media platforms like Twitter and WhatsApp. The obtained data was transferred into excel to perform the statistical analysis. Results: The mean total of students who participated in this study was 21.45 ± 23.11. Female students (72.3%) were actively involved in this study. About 30.2% of students were found to be overweight and obese. Around 67.8% of students had insufficient sleep, 32.2% had adequate sleep, and over 70% of students fell asleep within 30 min of going to bed. A total of 71.7% of students showed good sleep quality, whereas 28.3% reported poor sleep quality. BMI was categorized into four groups: 17.7% of individuals were underweight, 52.1% were of normal weight threshold, 20.6% were overweight, and 9.6% were obese. On a regular basis, 12.5% of students consume vegetables and 6.4% fruits daily. The results of this study show that only 8% of students eat breakfast, whereas 62.1% eat lunch, and 29.9% eat dinner. Conclusion: This study concludes that short sleep duration was associated with obesity among KSU students. This association was also found between sleep duration and dietary factors, specifically in the consumption of fruits and vegetables in terms of eating behaviour.
Assessment of the Clinical Condition and Way of Patients’ Nutrition before and after Laparoscopic Sleeve Gastrectomy
Authors: Jastrzębska-Mierzyńska Marta , Ostrowska Lucyna , Witczak-Sawczuk Katarzyna , Razak Hady Hady
Published: January 2023

One of the most commonly performed bariatric procedures is the laparoscopic sleeve gastrectomy (LSG). It is highly effective in reducing body weight, but it carries the risk of developing nutritional deficiencies and their consequences. The aim of the study was to determine the clinical condition of obese patients after LSG in terms of nutritional status, metabolic disorders, and way of nutrition. Thirty participants (15 women and 15 men) took part in the study. A statistically significant reduction in the total body fat mass (women by 37.5% p < 0.05, men by 37.06% p < 0.05) and total fat free mass (women by 10% p < 0,05, men by 12.5% p < 0.05) was demonstrated 6 months after LSG. Moreover, insufficient protein intake has been shown in over 73% of women and 40% of men. Before and 6 months after LSG, insufficient intake of calcium, magnesium, potassium, folate, vitamin D, and iron was observed. Six months after the LSG, significant decreases of fasting glucose (p < 0.05), insulin (p < 0.05), TG (p < 0.05), and AST (p < 0.05) concentrations, were observed in both groups. Optimization of nutrition in order to prevent nutritional deficiencies and their complications is a key element of the therapy of obese patients treated surgically.
Nutritional Interventions for Patients with Severe Obesity Seeking Bariatric Surgery
Authors: Ben-Porat Tair , Sherf-Dagan Shiri
Published: January 2023

Bariatric surgery (BS) is usually considered when other weight-loss treatments have failed, and remains an effective long-term treatment for severe obesity and its related medical complications [...]
Rectus Femoris Muscle and Phase Angle as Prognostic Factor for 12-Month Mortality in a Longitudinal Cohort of Patients with Cancer (AnyVida Trial)
Authors: García-García Cristina , Vegas-Aguilar Isabel María , Rioja-Vázquez Rosalía , Cornejo-Pareja Isabel , Tinahones Francisco J. , García-Almeida José Manuel
Published: January 2023

Background: Cancer-related malnutrition is still unrecognized and undertreated in clinical practice. The morphofunctional assessment of disease-related malnutrition (DRM) is a new approach that focuses on evaluating changes in body composition and function. The aim of this study is to evaluate the prognostic value of classic and emerging assessment of malnutrition at 12-months survival in cancer patients. Methods. We conducted a prospective study on cancer outpatients. Bioelectrical impedance with phase angle (PhA), nutritional ultrasound by rectus femoris cross-sectional area (RFCSA), hand grip strength, and “Timed Up and Go Test” (TUG) were evaluated as predictors of mortality. Results. Fifty-seven patients were included. The non-survivors had lower PhA values than the survivors (4.7° vs. 5.4°; p < 0.001), and we had the same results with RFCSA 2.98 cm2/m2 vs. 4.27 cm2/m2 (p = 0.03). Cut-off points were identified using the ROC (receiver operating characteristic) curves for PhA (≤5.6° cancer patients, ≤5.9° men, ≤5.3° women), RFCSA (≤4.47 cm2/m2 cancer patients, ≤4.47° men, ≤2.73° women) and rectus femoris-Y-axis (RF-Y-axis; ≤1.3 cm cancer patients, ≤1.06 men, ≤1 women). In multivariate logistic regression analysis, we found that high PhA was significantly associated with a lower mortality hazard ratio (HR: 0.42 95% CI: 0.21–0.84, p = 0.014). Likewise, high RFCSA was associated with a decrease in mortality risk in the crude model (HR: 0.61 95% CI: 0.39–0.96, p = 0.031). This trend was also maintained in the adjusted models by the confounding variables. Conclusions. Low PhA and RFCSA values are significant independent predictors of mortality in cancer patients. These cut-off points are clinical data that can be used for nutritional assessment and the prediction of clinical outcomes.
Is Generation Z Ready to Engage in Entomophagy? A Segmentation Analysis Study
Authors: Kamenidou Irene (Eirini) , Mamalis Spyridon , Gkitsas Stergios , Mylona Ifigeneia , Stavrianea Aikaterini
Published: January 2023

This study examines the behavior and attitudes of adult Generation Z cohort members in relation to entomophagy. Specifically, it explores their familiarity with insect consumption, prior experience, and willingness to consume certain insect-based foods and drinks. Lastly, the Z cohort is segmented based on their behavior and attitudes. Through online quantitative research, a valid sample of 742 questionnaires was collected. Data analysis included descriptive statistics, reliability analysis, factor, hierarchical cluster, and K-means cluster analysis, as well as chi-square tests. Results revealed that 41.4% are familiar with what insect consumption is, and no one had previously engaged in entomophagy. The insect-based food that the Z cohort is most willing to try is bakery products containing insect flour. The 88.5% of the Z cohort is not willing to replace meat protein with insect protein, and 20.4% are interested in obtaining more information about entomophagy. Moreover, 6.3% of the Z cohort is “willing” to participate in sensory tests, but when contact information was requested, only one factual name with phone number was provided. Segmentation of the Z cohort’s behavior was performed based on eight variables and four segments were identified: the “Future potential insect consumers” (29.1%), the “Rejecters” (26.7%), the “Disgusted, prefer to starve” (22.2%), and the “Inconsistent” (22.0%). Overall, the Z cohort is not food neophobic, but is unwilling to engage in entomophagy. Communication strategies are suggested to increase awareness and provide information about entomophagy and its benefits.
A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study
Authors: Rigamonti Antonello E. , Frigerio Gianfranco , Caroli Diana , De Col Alessandra , Cella Silvano G. , Sartorio Alessandro , Fustinoni Silvia
Published: January 2023

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)—in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.
The Role of Maternal Vitamin D Deficiency in Offspring Obesity: A Narrative Review
Authors: Wu Yifan , Zeng Yuan , Zhang Qian , Xiao Xinhua
Published: January 2023

Currently, vitamin D (VD) deficiency during pregnancy is widespread globally, causing unfavorable pregnancy outcomes for both mothers and infants for a longer time than expected, based on the Developmental Origins of Health and Disease (DOHaD) theory. As VD plays a key role in maintaining normal glucose and lipid metabolism, maternal VD deficiency may lead to obesity and other obesity-related diseases among offspring later in life. This review mainly focuses on the effect of maternal VD deficiency on offspring lipid metabolism, reviewing previous clinical and animal studies to determine the effects of maternal VD deficit on offspring obesity and potential mechanisms involved in the progression of offspring obesity. Emerging clinical evidence shows that a low VD level may lead to abnormal growth (either growth restriction or largeness for gestational age) and lipid and glucose metabolism disorders in offspring. Here, we also outline the link between maternal VD deficiency and life-long offspring effects, including the disorder of adipogenesis, the secretion of adipocytokines (including leptin, resistin, and adiponectin), activated systemic inflammation, increased oxidative reactions in adipose tissue, insulin resistance, and abnormal intestinal gut microbiota. Thus, there is an urgent need to take active steps to address maternal VD deficiency to relieve the global burden of obesity.
Improvement of Spatial Memory and Cognitive Function in Mice via the Intervention of Milk Fat Globule Membrane
Authors: Zhou Yongjie , Zou Xiaoxiao , Feng Ruifang , Zhan Xin , Hong Hui , Luo Yongkang , Tan Yuqing
Published: January 2023

With the improvement of living standards, dietary interventions have become an appropriate approach to enhance memory and cognitive performance. The present study investigated the potential mechanisms of spatial memory and cognitive function improvement with the milk fat globule membrane (MFGM) intervention in mice. The Morris water maze experiment revealed that the trajectories of mice in group M were more disordered. Also, the immunohistochemical results demonstrated a significantly higher number of neurons in group M compared with group C, especially in the hippocampal dentate gyrus (DG) area. It is suggested that MFGM enhanced mice’s spatial memory and cognition from macroscopic behavior and microscopic cytology, respectively. Meanwhile, 47 differentially expressed proteins (DEPs) were identified, including 20 upregulated and 27 downregulated proteins. Upregulated (Sorbs 2, Rab 39, and Cacna 1e) and downregulated (Hp and Lrg 1) DEPs may improve spatial memory and cognition in mice by promoting synapse formation and increasing neurotransmitter receptors. KEGG enrichment analysis of the DEPs identified seven signaling pathways that were significantly enriched (p < 0.05). One of these pathways was neuroactive ligand-receptor interactions, which are strongly associated with improved spatial memory and cognitive performance. These findings give some new insights and references to the potential mechanisms of spatial memory and cognitive enhancement by MFGM.
Acknowledgment to the Reviewers of Organics in 2022
Authors:   Organics Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Endogenous Retroviruses as Modulators of Innate Immunity
Authors: Russ Eric , Iordanskiy Sergey
Published: January 2023

Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations that rendered them non-infectious; thereby, the genome could co-opt them into constructive roles with important biological functions. In the past two decades, with the help of advances in sequencing technology, ERVs are increasingly considered to be important components of the innate immune response. While typically silenced, expression of HERVs can be induced in response to traumatic, toxic, or infection-related stress, leading to a buildup of viral transcripts and under certain circumstances, proteins, including functionally active reverse transcriptase and viral envelopes. The biological activity of HERVs in the context of the innate immune response can be based on the functional effect of four major viral components: (1) HERV LTRs, (2) HERV-derived RNAs, (3) HERV-derived RNA:DNA duplexes and cDNA, and (4) HERV-derived proteins and ribonucleoprotein complexes. In this review, we will discuss the implications of HERVs in all four contexts in relation to innate immunity and their association with various pathological disease states.
Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases
Authors: Komal Sumra , Han Sheng-Na , Cui Liu-Gen , Zhai Miao-Miao , Zhou Yue-Jiao , Wang Pei , Shakeel Muhammad , Zhang Li-Rong
Published: January 2023

Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide, especially in developing countries. The increased prevalence rate and mortality due to CVDs, despite the development of several approaches for prevention and treatment, are alarming trends in global health. Chronic inflammation and macrophage infiltration are key regulators of the initiation and progression of CVDs. Recent data suggest that epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and RNA modifications, regulate cell development, DNA damage repair, apoptosis, immunity, calcium signaling, and aging in cardiomyocytes; and are involved in macrophage polarization and contribute significantly to cardiac disease development. Cardiac macrophages not only trigger damaging inflammatory responses during atherosclerotic plaque formation, myocardial injury, and heart failure but are also involved in tissue repair, remodeling, and regeneration. In this review, we summarize the key epigenetic modifications that influence macrophage polarization and contribute to the pathophysiology of CVDs, and highlight their potential for the development of advanced epigenetic therapies.
Efficacy of Topical Essential Oils in Musculoskeletal Disorders: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Bakó Eszter , Fehérvári Péter , Garami András , Dembrovszky Fanni , Gunther Emese Eszter , Hegyi Péter , Csupor Dezső , Böszörményi Andrea
Published: January 2023

Essential oils (EOs) are widely used topically in musculoskeletal disorders (MSDs); however, their clinical efficacy is controversial. Our aim was to find evidence that topical EOs are beneficial as an add-on treatment in MSDs. We performed a systematic review and meta-analysis to summarize the evidence on the available data of randomized controlled trials (RCTs). The protocol of this work was registered on PROSPERO. We used Web of Science, EMBASE, PubMed, Central Cochrane Library and Scopus electronic databases for systematic search. Eight RCTs were included in the quantitative analysis. In conclusion, EO therapy had a favorable effect on pain intensity (primary outcome) compared to placebo. The greatest pain-relieving effect of EO therapy was calculated immediately after the intervention (MD of pain intensity = −0.87; p = 0.014). EO therapy had a slightly better analgesic effect than placebo one week after the intervention (MD of pain intensity = −0.58; p = 0.077) and at the four-week follow-up as well (MD of pain intensity = −0.52; p = 0.049). EO therapy had a beneficial effect on stiffness (a secondary outcome) compared to the no intervention group (MD = −0.77; p = 0.061). This systematic review and meta-analysis showed that topical EOs are beneficial as an add-on treatment in reducing pain and stiffness in the investigated MSDs.
Endocannabinoid System: Chemical Characteristics and Biological Activity
Authors: Rezende Bismarck , Alencar Allan Kardec Nogueira , de Bem Graziele Freitas , Fontes-Dantas Fabrícia Lima , Montes Guilherme Carneiro
Published: January 2023

The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and the associated enzymatic apparatus responsible for maintaining energy homeostasis and cognitive processes. Several physiological effects of cannabinoids are exerted through interactions with various receptors, such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, and GPR19). Anandamide (AEA) and 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding to both CB1 and CB2 receptors. eCB plays a critical role in chronic pain and mood disorders and has been extensively studied because of its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities for eCB and are relevant to the treatment of several neurological diseases. This review provides a description of eCB components and discusses how phytocannabinoids and other exogenous compounds may regulate the eCB balance. Furthermore, we show the hypo- or hyperfunctionality of eCB in the body and how eCB is related to chronic pain and mood disorders, even with integrative and complementary health practices (ICHP) harmonizing the eCB.
Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant Klebsiella pneumoniae
Authors: Byrnes Declan , Masterson Claire H. , Brady Jack , Alagesan Senthilkumar , Gonzalez Hector E. , McCarthy Sean D. , Fandiño Juan , O’Toole Daniel P. , Laffey John G.
Published: January 2023

Background: Pulmonary sepsis is a leading cause of hospital mortality, and sepses arising from antimicrobial-resistant (AMR) bacterial strains are particularly difficult to treat. Here we investigated the potential of mesenchymal stromal cells (MSCs) to combat established Klebsiella pneumoniae pneumosepsis and further evaluated MSC preconditioning and pre-activation methods. Methods: The potential for naïve and preconditioned MSCs to enhance wound healing, reduce inflammation, preserve metabolic activity, and enhance bacterial killing was assessed in vitro. Rats were subjected to intratracheal K. pneumoniae followed by the intravenous administration of MSCs. Physiological indices, blood, bronchoalveolar lavage (BAL), and tissues were obtained 72 h later. Results: In vitro assays confirmed that preconditioning enhances MSC function, accelerating pulmonary epithelial wound closure, reducing inflammation, attenuating cell death, and increasing bacterial killing. Cytomix-pre-activated MSCs are superior to naïve and hypoxia-exposed MSCs in attenuating Klebsiella pneumosepsis, improving lung compliance and oxygenation, reducing bacteria, and attenuating histologic injuries in lungs. BAL inflammatory cytokines were reduced, correlating with decreases in polymorphonuclear (PMN) cells. MSCs increased PMN apoptosis and the CD4:CD8 ratio in BAL. Systemically, granulocytes, classical monocytes, and the CD4:CD8 ratio were reduced, and nonclassical monocytes were increased. Conclusions: Preconditioning with cytokines, but not hypoxia, enhances the therapeutic potential of MSCs in clinically relevant models of K. pneumoniae-induced pneumosepsis.
Physicochemical Properties and Transdermal Absorption of a Flurbiprofen and Lidocaine Complex in the Non-Crystalline Form
Authors: Xu Qihui , Furuishi Takayuki , Fukuzawa Kaori , Yonemochi Etsuo
Published: January 2023

Amorphous drug formulations exploiting drug–drug interactions have been extensively studied. This study aims to develop a transdermal system containing an amorphous complex of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen (FLU) and lidocaine (LDC) for alleviating chronic pain. The high-viscosity complex between FLU and LDC (Complex) was obtained by heating in ethanol. For the complex, attenuated total reflection-Fourier transform infrared spectroscopy showed a shift in the carboxy-group-derived peak of FLU, and differential scanning calorimetry indicated the endothermic peaks associated with the melting of FLU and LDC disappeared. 13C dipolar decoupling and 15N cross-polarization magic-angle spinning nuclear magnetic resonance measurement suggested the interaction between the carboxyl group of FLU and the secondary amine of LDC. The interaction between the aromatic rings of FLU and LDC contributed to the molecular complex formation. The solubility of FLU from the complex was about 100 times greater than FLU alone. The skin permeation flux of FLU from the complex through the hairless mouse skin was 3.8 times higher than FLU alone in hypromellose gel. Thus, adding LDC to the formulation can be an effective method for enhancing the skin permeation of NSAIDs, which can prove useful for treating chronic pain and inflammatory diseases.
The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering
Authors: Feng Ziyi , Su Xin , Wang Ting , Sun Xiaoting , Yang Huazhe , Guo Shu
Published: January 2023

Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, and “growth factors”. However, the traditional construction approach is not flexible and is unable to adapt to the specific shape of the defect, causing the cells inside the bone to be unable to receive adequate nourishment. Therefore, a simple but effective solution using the “bottom-up” method is proposed. Microspheres are structures with diameters ranging from 1 to 1000 µm that can be used as supports for cell growth, either in the form of a scaffold or in the form of a drug delivery system. Herein, we address a variety of strategies for the production of microspheres, the classification of raw materials, and drug loading, as well as analyze new strategies for the use of microspheres in bone tissue engineering. We also consider new perspectives and possible directions for future development.
Optimisation of AAV-NDI1 Significantly Enhances Its Therapeutic Value for Correcting Retinal Mitochondrial Dysfunction
Authors: Chadderton Naomi , Palfi Arpad , Maloney Daniel M. , Carrigan Matthew , Finnegan Laura K. , Hanlon Killian S. , Shortall Ciara , O’Reilly Mary , Humphries Peter , Cassidy Lorraine , Kenna Paul F. , Millington-Ward Sophia , Farrar G. Jane
Published: January 2023

AAV gene therapy for ocular disease has become a reality with the market authorisation of LuxturnaTM for RPE65-linked inherited retinal degenerations and many AAV gene therapies currently undergoing phase III clinical trials. Many ocular disorders have a mitochondrial involvement from primary mitochondrial disorders such as Leber hereditary optic neuropathy (LHON), predominantly due to mutations in genes encoding subunits of complex I, to Mendelian and multifactorial ocular conditions such as dominant optic atrophy, glaucoma and age-related macular degeneration. In this study, we have optimised the nuclear yeast gene, NADH-quinone oxidoreductase (NDI1), which encodes a single subunit complex I equivalent, creating a candidate gene therapy to improve mitochondrial function, independent of the genetic mutation driving disease. Optimisation of NDI1 (ophNdi1) substantially increased expression in vivo, protected RGCs and increased visual function, as assessed by optokinetic and photonegative response, in a rotenone-induced murine model. In addition, ophNdi1 increased cellular oxidative phosphorylation and ATP production and protected cells from rotenone insult to a significantly greater extent than wild type NDI1. Significantly, ophNdi1 treatment of complex I deficient patient-derived fibroblasts increased oxygen consumption and ATP production rates, demonstrating the potential of ophNdi1 as a candidate therapy for ocular disorders where mitochondrial deficits comprise an important feature.
An Approach to Evaluate the Effective Cytoplasmic Concentration of Bioactive Agents Interacting with a Selected Intracellular Target Protein
Authors: Khramtsov Yuri V. , Ulasov Alexey V. , Rosenkranz Andrey A. , Slastnikova Tatiana A. , Lupanova Tatiana N. , Georgiev Georgii P. , Sobolev Alexander S.
Published: January 2023

To compare the effectiveness of various bioactive agents reversibly acting within a cell on a target intracellular macromolecule, it is necessary to assess effective cytoplasmic concentrations of the delivered bioactive agents. In this work, based on a simple equilibrium model and the cellular thermal shift assay (CETSA), an approach is proposed to assess effective concentrations of both a delivered bioactive agent and a target protein. This approach was tested by evaluating the average concentrations of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated-protein 1 (Keap1) proteins in the cytoplasm for five different cell lines (Hepa1, MEF, RAW264.7, 3LL, and AML12) and comparing the results with known literature data. The proposed approach makes it possible to analyze both binary interactions and ternary competition systems; thus, it can have a wide application for the analysis of protein–protein or molecule–protein interactions in the cell. The concentrations of Nrf2 and Keap1 in the cell can be useful not only in analyzing the conditions for the activation of the Nrf2 system, but also for comparing the effectiveness of various drug delivery systems, where the delivered molecule is able to interact with Keap1.
Small Extracellular Vesicles as a New Class of Medicines
Authors: Lee Inkyu , Choi Yoonjeong , Shin Dong-U , Kwon Minjeong , Kim Seohyun , Jung Hanul , Nam Gi-Hoon , Kwon Minsu
Published: January 2023

Extracellular vesicles (EVs) are nanovesicles that are naturally released from cells in a lipid bilayer-bound form. A subset population with a size of 200 nm, small EVs (sEVs), is enticing in many ways. Initially perceived as mere waste receptacles, sEVs have revealed other biological functions, such as cell-to-cell signal transduction and communication. Besides their notable biological functions, sEVs have profound advantages as future drug modalities: (i) excellent biocompatibility, (ii) high stability, and (iii) the potential to carry undruggable macromolecules as cargo. Indeed, many biopharmaceutical companies are utilizing sEVs, not only as diagnostic biomarkers but as therapeutic drugs. However, as all inchoate fields are challenging, there are limitations and hindrances in the clinical translation of sEV therapeutics. In this review, we summarize different types of sEV therapeutics, future improvements, and current strategies in large-scale production.
Microwave-Assisted Functionalization of Multi-Walled Carbon Nanotubes for Biosensor and Drug Delivery Applications
Authors: Thakur Chanchal Kiran , Karthikeyan Chandrabose , Abou-Dahech Mariam Sami , Altabakha Moawia Mohd A. M. , Al Shahwan Moayad Jamal Saeed , Ashby Charles R. , Tiwari Amit K. , Babu R. Jayachandra , Moorthy Narayana Subbiah Hari Narayana
Published: January 2023

Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. The present review focuses on the synthetic and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs, using amino acids and other molecular frameworks containing amino groups, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers.
Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects
Authors: Rybchenko Vladislav S. , Aliev Teimur K. , Panina Anna A. , Kirpichnikov Mikhail P. , Dolgikh Dmitry A.
Published: January 2023

Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. The present review surveys the actual antibody–cytokine fusion protein (immunocytokine) formats, their targets, mechanisms of action, and anti-tumor and other biological effects. Special attention is paid to the formats designed to prevent the off-target cytokine–receptor interactions, potentially inducing side effects. Here, we describe preclinical and clinical data and the efficacy of the antibody-mediated cytokine delivery approach, either as a single therapy or in combination with other agents.
Mechanism for Stabilizing an Amorphous Drug Using Amino Acids within Co-Amorphous Blends
Authors: Guinet Yannick , Paccou Laurent , Hédoux Alain
Published: January 2023

Designing co-amorphous formulations is now recognized as a relevant strategy for improving the bioavailability of low-molecular-weight drugs. In order to determine the most suitable low-molecular-weight excipients for stabilizing the drug in the amorphous state, screening methods were developed mostly using amino acids as co-formers. The present study focused on the analysis of the thermal stability of co-amorphous blends prepared by cryo-milling indomethacin with several amino acids in order to understand the stabilization mechanism of the drug in the amorphous state. Combining low- and mid-frequency Raman investigations has provided information on the relation between the physical properties of the blends and those of the H-bond network of the amorphous drug. This study revealed the surprising capabilities of L-arginine to stiffen the H-bond network in amorphous indomethacin and to drastically improve the stability of its amorphous state. As a consequence, this study suggests that amino acids can be considered as stiffeners of the H-bond network of indomethacin, thereby improving the stability of the amorphous state.
Polarization-Sensitive Nonlinear Optical Interaction of Ultrashort Laser Pulses with HPHT Diamond
Authors: Krasin George K. , Gulina Yulia S. , Kuzmin Evgeny V. , Martovitskii Victor P. , Kudryashov Sergey I.
Published: January 2023

The filamentation of focused 300 fs laser pulses with variable polarization azimuth in bulk of synthetic HPHT diamond demonstrates the possibility of polarization-dependent bandgap control for crystal dielectric photoexcitation. This directly affects the value of the filamentation threshold power, which exhibits the distinct dependence on the polarization azimuth angle. The nonlinear photoluminescence yield, when focusing ultrashort laser pulses with variable polarization in bulk of the synthetic diamond, indicates different polarization-dependent regimes in the dynamics of electron-hole plasma formation, arising due to different processes of photoexcitation and recombination of free carriers during the filamentation process. Thus, at the onset of the filamentation process, at relatively low intensities, the photoluminescence yield rate depends on polarization azimuth controlling bandgap, while at high intensities the resulting dense absorbing plasma exhibits isotropy with respect to laser radiation polarization, and photoluminescence yield weakly depends on polarization azimuth.
Evaluating Introgression Sorghum Germplasm Selected at the Population Level While Exploring Genomic Resources as a Screening Method
Authors: Winans Noah D. , Klein Robert R. , Fonseca Jales Mendes Oliveira , Klein Patricia E. , Rooney William L.
Published: January 2023

To exploit the novel genetic diversity residing in tropical sorghum germplasm, an expansive backcross nested-association mapping (BC-NAM) resource was developed in which novel genetic diversity was introgressed into elite inbreds. A major limitation of exploiting this type of genetic resource in hybrid improvement programs is the required evaluation in hybrid combination of the vast number of BC-NAM populations and lines. To address this, the utility of genomic information was evaluated to predict the hybrid performance of BC-NAM populations. Two agronomically elite BC-NAM populations were chosen for evaluation in which elite inbred RTx436 was the recurrent parent. Each BC1F3 line was evaluated in hybrid combination with an elite tester in two locations with phenotypes of grain yield, plant height, and days to anthesis collected on all test cross hybrids. Lines from both populations were found to outperform their recurrent parent. Efforts to utilize genetic distance based on genotyping-by-sequence (GBS) as a predictive tool for hybrid performance was ineffective. However, utilizing genomic prediction models using additive and dominance GBLUP kernels to screen germplasm appeared to be an effective method to eliminate inferior-performing lines that will not be useful in a hybrid breeding program.
Analysis of Corn Yield Prediction Potential at Various Growth Phases Using a Process-Based Model and Deep Learning
Authors: Ren Yiting , Li Qiangzi , Du Xin , Zhang Yuan , Wang Hongyan , Shi Guanwei , Wei Mengfan
Published: January 2023

Early and accurate prediction of grain yield is of great significance for ensuring food security and formulating food policy. The exploration of key growth phases and features is beneficial to improving the efficiency and accuracy of yield prediction. In this study, a hybrid approach using the WOFOST model and deep learning was developed to forecast corn yield, which analysed yield prediction potential at different growth phases and features. The World Food Studies (WOFOST) model was used to build a comprehensive simulated dataset by inputting meteorological, soil, crop and management data. Different feature combinations at various growth phases were designed to forecast yield using machine learning and deep learning methods. The results show that the key features of corn’s vegetative growth stage and reproductive growth stage were growth state features and water-related features, respectively. With the continuous advancement of the crop growth stage, the ability to predict yield continued to improve. Especially after entering the reproductive growth stage, corn kernels begin to form, and the yield prediction performance is significantly improved. The performance of the optimal yield prediction model in flowering (R2 = 0.53, RMSE = 554.84 kg/ha, MRE = 8.27%), in milk maturity (R2 = 0.89, RMSE = 268.76 kg/ha, MRE = 4.01%), and in maturity (R2 = 0.98, RMSE = 102.65 kg/ha, MRE = 1.53%) were given. Thus, our method improves the accuracy of yield prediction, and provides reliable analysis results for predicting yield at various growth phases, which is helpful for farmers and governments in agricultural decision making. This can also be applied to yield prediction for other crops, which is of great value to guide agricultural production.
Microbes vs. Nematodes: Insights into Biocontrol through Antagonistic Organisms to Control Root-Knot Nematodes
Authors: Bhat Adil Ameen , Shakeel Adnan , Waqar Sonia , Handoo Zafar Ahmad , Khan Abrar Ahmed
Published: January 2023

Root-knot nematodes (Meloidogyne spp.) are sedentary endoparasites that cause severe economic losses to agricultural crops globally. Due to the regulations of the European Union on the application of nematicides, it is crucial now to discover eco-friendly control strategies for nematode management. Biocontrol is one such safe and reliable method for managing these polyphagous nematodes. Biocontrol agents not only control these parasitic nematodes but also improve plant growth and induce systemic resistance in plants against a variety of biotic stresses. A wide range of organisms such as bacteria, fungi, viruses, and protozoans live in their natural mode as nematode antagonists. Various review articles have discussed the role of biocontrol in nematode management in general, but a specific review on biocontrol of root-knot nematodes is not available in detail. This review, therefore, focuses on the biocontrol of root-knot nematodes by discussing their important known antagonists, modes of action, and interactions.