bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine—From Theory to Practice
Authors: Domitrz Izabela , Cegielska Joanna
Published: March 2022

So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium–migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation.
Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents
Authors: Barranco Alejandro , Garcia Llenalia , Gruart Agnes , Delgado-Garcia Jose Maria , Rueda Ricardo , Ramirez Maria
Published: March 2022

β-hydroxy β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.
Assessing the Causal Effects of Adipokines on Uric Acid and Gout: A Two-Sample Mendelian Randomization Study
Authors: Cong Ruyi , Zhang Xiaoyu , Song Zihong , Chen Shanshan , Liu Guanhua , Liu Yizhi , Pang Xiuyu , Dong Fang , Xing Weijia , Wang Youxin , Xu Xizhu
Published: March 2022

Previous observational studies have highlighted associations between adipokines and hyperuricemia, as well as gout, but the causality and direction of these associations are not clear. Therefore, we attempted to assess whether there are causal effects of specific adipokines (such as adiponectin (ADP) and soluble leptin receptors (sOB-R)) on uric acid (UA) or gout in a two-sample Mendelian randomization (MR) analysis, based on summary statistics from large genome-wide association studies. The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (including MR-Egger regression, weighted median, penalized weighted median, and MR pleiotropy residual sum and outlier methods) were also performed, to ensure reliable results. In the IVW models, no causal effect was found for sOB-R (odds ratios (OR), 1.002; 95% confidence intervals (CI), 0.999–1.004; p = 0.274) on UA, or ADP (OR, 1.198; 95% CI, 0.865–1.659; p = 0.277) or sOB-R (OR, 0.988; 95% CI, 0.940–1.037; p = 0.616) on gout. The results were confirmed in sensitivity analyses. There was no notable directional pleiotropy or heterogeneity. This study suggests that these specific adipokines may not play causal roles in UA or gout development.
Potential “Therapeutic” Effects of Tocotrienol-Rich Fraction (TRF) and Carotene “Against” Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB Signaling Pathways
Authors: Lu Yifei , Zhang Yihan , Pan Zhenyu , Yang Chao , Chen Lin , Wang Yuanyuan , Xu Dengfeng , Xia Hui , Wang Shaokang , Chen Shiqing , Hao Yoong Jun , Sun Guiju
Published: March 2022

Background: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF. Aim: The potential “therapeutic” effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-β/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Design/Methods: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues. Results: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-β1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats. Conclusion: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.
Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders
Authors: Saini Nipun , Virdee Manjot S. , Helfrich Kaylee K. , Kwan Sze Ting Cecilia , Mooney Sandra M. , Smith Susan M.
Published: March 2022

Prenatal alcohol exposure (PAE) causes fetal growth restrictions. A major driver of fetal growth deficits is maternal metabolic disruption; this is under-investigated following PAE. Untargeted metabolomics on the dam and fetus exposed to alcohol (ALC) revealed that the hepatic metabolome of ALC and control (CON) dams were distinct, whereas that of ALC and CON fetuses were similar. Alcohol reduced maternal hepatic glucose content and enriched essential amino acid (AA) catabolites, N-acetylated AA products, urea content, and free fatty acids. These alterations suggest an attempt to minimize the glucose gap by increasing gluconeogenesis using AA and glycerol. In contrast, ALC fetuses had unchanged glucose and AA levels, suggesting an adequate draw of maternal nutrients, despite intensified stress on ALC dams. Maternal metabolites including glycolytic intermediates, AA catabolites, urea, and one-carbon-related metabolites correlated with fetal liver and brain weights, whereas lipid metabolites correlated with fetal body weight, indicating they may be drivers of fetal weight outcomes. Together, these data suggest that ALC alters maternal hepatic metabolic activity to limit glucose availability, thereby switching to alternate energy sources to meet the high-energy demands of pregnancy. Their correlation with fetal phenotypic outcomes indicates the influence of maternal metabolism on fetal growth and development.
(–)-Epicatechin Improves Vasoreactivity and Mitochondrial Respiration in Thermoneutral-Housed Wistar Rat Vasculature
Authors: Chun Ji Hye , Henckel Melissa M. , Knaub Leslie A. , Hull Sara E. , Pott Greg B. , Walker Lori A. , Reusch Jane E.-B. , Keller Amy C.
Published: March 2022

Cardiovascular disease (CVD) is a global health concern. Vascular dysfunction is an aspect of CVD, and novel treatments targeting vascular physiology are necessary. In the endothelium, eNOS regulates vasodilation and mitochondrial function; both are disrupted in CVD. (–)-Epicatechin, a botanical compound known for its vasodilatory, eNOS, and mitochondrial-stimulating properties, is a potential therapy in those with CVD. We hypothesized that (–)-epicatechin would support eNOS activity and mitochondrial respiration, leading to improved vasoreactivity in a thermoneutral-derived rat model of vascular dysfunction. We housed Wistar rats at room temperature or in thermoneutral conditions for a total of 16 week and treated them with 1mg/kg body weight (–)-epicatechin for 15 day. Vasoreactivity, eNOS activity, and mitochondrial respiration were measured, in addition to the protein expression of upstream cellular signaling molecules including AMPK and CaMKII. We observed a significant improvement of vasodilation in those housed in thermoneutrality and treated with (–)-epicatechin (p < 0.05), as well as dampened mitochondrial respiration (p < 0.05). AMPK and CaMKIIα and β expression were lessened with (–)-epicatechin treatment in those housed at thermoneutrality (p < 0.05). The opposite was observed with animals housed at room temperature supplemented with (–)-epicatechin. These data illustrate a context-dependent vascular response to (–)-epicatechin, a candidate for CVD therapeutic development.
Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study
Authors: Sánchez Enric , Kerkeni Mohsen , Hernández Marta , Gavaldà Ricard , Rius Ferran , Sauret Ariadna , Torres Gerard , Bermúdez-López Marcelino , Fernández Elvira , Castro-Boqué Eva , Purroy Francisco , Mauricio Dídac , Farràs-Sallés Cristina , Buti Miquel , Godoy Pere , Pamplona Reinald , Lecube Albert
Published: March 2022

A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m2, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population.
Prevalence and Predictors of Insufficient Plasma Vitamin C in a Subtropical Region and Its Associations with Risk Factors of Cardiovascular Diseases: A Retrospective Cross-Sectional Study
Authors: Lin Yao-Tsung , Wang Li-Kai , Hung Kuo-Chuan , Chang Chia-Yu , Wu Li-Ching , Ho Chung-Han , Chen Jen-Yin
Published: March 2022

Background: to evaluate the prevalence and predictors of insufficient plasma vitamin C among adults in a subtropical region and its associations with cardiovascular disease risk factors including dyslipidemia and lipid-independent markers, namely homocysteine, high-sensitivity C-reactive protein (hs-CRP) and lipoprotein(a). Methods: Data of this retrospective cross-sectional study were extracted from electronic medical database of a Medical Center. Based on plasma vitamin C status, subjects were split into two groups—subjects with sufficient and insufficient plasma vitamin C levels (<50 µmol/L, ≤8.8 mg/L). Results: Prevalence of insufficient plasma vitamin C in 3899 adults was 39%. Multivariate logistic regression identified male gender, high body mass index, age 20–39, and winter/spring as independent predictors of insufficient vitamin C among all subjects. Greater proportions of subjects with insufficient plasma vitamin C had lower high-density lipoprotein cholesterol levels and elevated levels of triglyceride, homocysteine and hs-CRP (all p < 0.001). There were no differences in total cholesterol, low-density lipoprotein cholesterol and lipoprotein(a) between groups. Conclusions: There was a high prevalence of insufficient plasma vitamin C in the subtropical region, which indicates that insufficient plasma vitamin C remains a public health issue. Further study is needed to confirm these findings and to determine the underlying mechanisms.
Modified Vaccinia Virus Ankara as a Potential Biosafety Level 2 Surrogate for African Swine Fever Virus in Disinfectant Efficacy Tests
Authors: Rhee Chae Hong , Her Moon , Jeong Wooseog
Published: March 2022

In South Korea, despite the increase in emerging viral pathogens in the veterinary industry, only efficacy-tested, virus-specific disinfectants are allowed to be used. Moreover, domestic testing of disinfectants for their virucidal efficacies against foreign, malignant, infectious pathogens that are unreported within the country and/or contagious livestock diseases that require special attention regarding public hygiene are legally restricted. Therefore, the Animal and Plant Quarantine Agency (APQA) designed a study to select a potential biosafety level 2 surrogate of African swine fever virus (ASFV) for efficacy testing to improve the disinfectant approval procedures. For this, the modified vaccinia virus Ankara (MVA) was compared to ASFV in terms of its susceptibility to disinfectants. Effective concentrations of active substances of disinfectants (potassium peroxymonosulfate, sodium dichloroisocyanurate, malic acid, citric acid, glutaraldehyde, and benzalkonium chloride) against ASFV and MVA were compared; similarly, efficacies of APQA-listed commercial disinfectants were examined. Tests were performed according to APQA guidelines, and infectivities of ASFV and MVA were confirmed by hemadsorption and cytopathic effect, respectively. The results reveal that the disinfectants are effective against MVA at similar or higher concentrations than those against ASFV, validating the use of MVA as a potential biosafety level 2 surrogate for ASFV in efficacy testing of veterinary disinfectants.
Rethinking Protein Drug Design with Highly Accurate Structure Prediction of Anti-CRISPR Proteins
Authors: Park Ho-Min , Park Yunseol , Vankerschaver Joris , Van Messem Arnout , De Neve Wesley , Shim Hyunjin
Published: March 2022

Protein therapeutics play an important role in controlling the functions and activities of disease-causing proteins in modern medicine. Despite protein therapeutics having several advantages over traditional small-molecule therapeutics, further development has been hindered by drug complexity and delivery issues. However, recent progress in deep learning-based protein structure prediction approaches, such as AlphaFold2, opens new opportunities to exploit the complexity of these macro-biomolecules for highly specialised design to inhibit, regulate or even manipulate specific disease-causing proteins. Anti-CRISPR proteins are small proteins from bacteriophages that counter-defend against the prokaryotic adaptive immunity of CRISPR-Cas systems. They are unique examples of natural protein therapeutics that have been optimized by the host-parasite evolutionary arms race to inhibit a wide variety of host proteins. Here, we show that these anti-CRISPR proteins display diverse inhibition mechanisms through accurate structural prediction and functional analysis. We find that these phage-derived proteins are extremely distinct in structure, some of which have no homologues in the current protein structure domain. Furthermore, we find a novel family of anti-CRISPR proteins which are structurally similar to the recently discovered mechanism of manipulating host proteins through enzymatic activity, rather than through direct inference. Using highly accurate structure prediction, we present a wide variety of protein-manipulating strategies of anti-CRISPR proteins for future protein drug design.
Development of Nanocrystal Compressed Minitablets for Chronotherapeutic Drug Delivery
Authors: Sreeharsha Nagaraja , Naveen Nimbagal Raghavendra , Anitha Posina , Goudanavar Prakash S. , Ramkanth Sundarapandian , Fattepur Santosh , Telsang Mallikarjun , Habeebuddin Mohammed , Answer Md. Khalid
Published: March 2022

The present work aimed to develop a chronotherapeutic system of valsartan (VS) using nanocrystal formulation to improve dissolution. VS nanocrystals (VS-NC) were fabricated using modified anti-solvent precipitation by employing a Box–Behnken design to optimize various process variables. Based on the desirability approach, a formulation containing 2.5% poloxamer, a freezing temperature of −25 °C, and 24 h of freeze-drying time can fulfill the optimized formulation’s requirements to result in a particle size of 219.68 nm, 0.201 polydispersity index, and zeta potential of −38.26 mV. Optimized VS-NC formulation was compressed (VNM) and coated subsequently with ethyl cellulose and HPMC E 5. At the same time, fast dissolving tablets of VS were designed, and the best formulation was loaded with VNM into a capsule size 1 (average fill weight—400–500 mg, lock length—19.30 mm, external diameter: Cap—6.91 mm; Body—6.63 mm). The final tab in cap (tablet-in-capsule) system was studied for in vitro dissolution profile to confirm the chronotherapeutic release of VS. As required, a bi-pulse release of VS was identified with a lag time of 5 h. The accelerated stability studies confirmed no significant changes in the dissolution profiles of the tab in cap system (f2 similarity profile: >90). To conclude, the tab in cap system was successfully developed to induce a dual pulsatile release, which will ensure bedtime dosing with release after a lag-time to match with early morning circadian spikes.
The Inhibition of the Small-Conductance Ca2+-Activated Potassium Channels Decreases the Sinus Node Pacemaking during Beta-Adrenergic Activation
Authors: Bitay Gergő , Tóth Noémi , Déri Szilvia , Szlovák Jozefina , Kohajda Zsófia , Varró András , Nagy Norbert
Published: March 2022

Sinus pacemaking is based on tight cooperation of intracellular Ca2+ handling and surface membrane ion channels. An important player of this synergistic crosstalk could be the small-conductance Ca2+-activated K+-channel (ISK) that could contribute to the sinoatrial node (SAN) pacemaking driven by the intracellular Ca2+ changes under normal conditions and beta-adrenergic activation, however, the exact role is not fully clarified. SK2 channel expression was verified by immunoblot technique in rabbit SAN cells. Ionic currents and action potentials were measured by patch-clamp technique. The ECG R-R intervals were obtained by Langendorff-perfusion method on a rabbit heart. Apamin, a selective inhibitor of SK channels, was used during the experiments. Patch-clamp experiments revealed an apamin-sensitive current. When 100 nM apamin was applied, we found no change in the action potential nor in the ECG R-R interval. In experiments where isoproterenol was employed, apamin increased the cycle length of the SAN action potentials and enhanced the ECG R-R interval. Apamin did not amplify the cycle length variability or ECG R-R interval variability. Our data indicate that ISK has no role under normal condition, however, it moderately contributes to the SAN automaticity under beta-adrenergic activation.
Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study
Authors: Alcoforado Luciana , Paiva Dulciane Nunes , Ari Arzu , Barcelar Jacqueline de Melo , Brandão Simone Cristina Soares , Fink James B. , Dornelas de Andrade Armele
Published: March 2022

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; p = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC (p < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities (p < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC (p < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC (p < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.
Mixed Polymeric Micelles for Rapamycin Skin Delivery
Authors: Le Guyader Guillaume , Do Bernard , Rietveld Ivo B. , Coric Pascale , Bouaziz Serge , Guigner Jean-Michel , Secretan Philippe-Henri , Andrieux Karine , Paul Muriel
Published: March 2022

Facial angiofibromas (FA) are one of the most obvious cutaneous manifestations of tuberous sclerosis complex. Topical rapamycin for angiofibromas has been reported as a promising treatment. Several types of vehicles have been used hitherto, but polymeric micelles and especially those made of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) seem to have shown better skin bioavailability of rapamycin than the so far commonly used ointments. To better understand the influence of polymeric micelles on the behavior of rapamycin, we explored it through mixed polymeric micelles combining TPGS and poloxamer, evaluating stability and skin bioavailability to define an optimized formulation to effectively treat FA. Our studies have shown that TPGS improves the physicochemical behavior of rapamycin, i.e., its solubility and stability, due to a strong inclusion in micelles, while poloxamer P123 has a more significant influence on skin bioavailability. Accordingly, we formulated mixed-micelle hydrogels containing 0.1% rapamycin, and the optimized formulation was found to be stable for up to 3 months at 2–8 °C. In addition, compared to hydroalcoholic gel formulations, the studied system allows for better biodistribution on human skin.
Pharmaceutical Development of Film-Coated Mini-Tablets with Losartan Potassium for Epidermolysis Bullosa
Authors: Elezaj Valentinë , Lura Ard , Canha Luis , Breitkreutz Jörg
Published: March 2022

Epidermolysis bullosa is a genetically heterogenous skin fragility disorder with multiorgan involvement appearing already in newborn children. Severe progressive fibrosis follows skin blistering, mucosa lesions, and wound healing, favouring development of highly aggressive squamous cell carcinomas. Losartan potassium (LP) has been described to show positive effects; therefore, it was of clinical interest to develop 2 mm mini-tablets with LP for treatment of the affected children. Several challenges emerged during development: limited flowability and sticking to punches were observed in the first tableting experiments due to a high drug load, and a bitter taste of the LP was reported. Sticking to punches was reduced by using SMCC 50 and a combination of different lubricants; however, direct compression trials on a Korsch XM 12 rotary press were not successful due to compaction phenomena in the hopper. Thus, an intermediate dry granulation was successfully introduced. Two final formulations of the mini-tablets complied with the requirements of the European Pharmacopoeia regarding disintegration times (<15 min) and friability (<1.0%); mean tensile strengths amounted to about 1 MPa as a compromise between manufacturability and sufficient mechanical strength for further coating studies. The subsequent coating step succeeded delaying the initial drug release for more than 2 min. An acceptance value ≤15 was matched for the coated mini-tablets, and stability studies showed a promising shelf life.
Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery
Authors: McCrorie Phoebe , Rowlinson Jonathan , Scurr David J. , Marlow Maria , Rahman Ruman
Published: March 2022

Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetration of label-free drugs, an absence of efficacy typically hampers clinical translational potential, rather than encourage re-formulation of drug compounds using nanocarriers to achieve greater tissue penetration. OrbiSIMS, a next-generation analytical instrument for label-free imaging, combines the high resolving power of an OrbiTrapTM mass spectrometer with the relatively high spatial resolution of secondary ion mass spectrometry. Here, we develop an ex vivo pipeline using OrbiSIMS to accurately detect brain penetration of drug compounds. Secondary ion spectra were acquired for a panel of drugs (etoposide, olaparib, gemcitabine, vorinostat and dasatinib) under preclinical consideration for the treatment of isocitrate dehydrogenase-1 wild-type glioblastoma. Each drug demonstrated diagnostic secondary ions (all present molecular ions [M-H]− which could be discriminated from brain analytes when spiked at >20 µg/mg tissue. Olaparib/dasatinib and olaparib/etoposide dual combinations are shown as exemplars for the capability of OrbiSIMS to discriminate distinct drug ions simultaneously. Furthermore, we demonstrate the imaging capability of OrbiSIMS to simultaneously illustrate label-free drug location and brain chemistry. Our work encourages the neuro-oncology community to consider mass spectrometry imaging modalities to complement in vivo efficacy studies, as an analytical tool to assess brain distribution of systemically administered drugs, or localised brain penetration of drugs released from micro- or nano-scale biomaterials.
A Brain-Targeted Approach to Ameliorate Memory Disorders in a Sporadic Alzheimer’s Disease Mouse Model via Intranasal Luteolin-Loaded Nanobilosomes
Authors: Elsheikh Manal A. , El-Feky Yasmin A. , Al-Sawahli Majid Mohammad , Ali Merhan E. , Fayez Ahmed M. , Abbas Haidy
Published: March 2022

Impaired memory and cognitive function are the main features of Alzheimer’s disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.
Nanobionics in Crop Production: An Emerging Approach to Modulate Plant Functionalities
Authors: Ranjan Anuj , Rajput Vishnu D. , Kumari Arpna , Mandzhieva Saglara S. , Sushkova Svetlana , Prazdnova Evgenya V. , Zargar Sajad Majeed , Raza Ali , Minkina Tatiana , Chung Gyuhwa
Published: March 2022

The “Zero Hunger” goal is one of the key Sustainable Development Goals (SDGs) of the United Nations. Therefore, improvements in crop production have always been a prime objective to meet the demands of an ever-growing population. In the last decade, studies have acknowledged the role of photosynthesis augmentation and enhancing nutrient use efficiency (NUE) in improving crop production. Recently, the applications of nanobionics in crop production have given hope with their lucrative properties to interact with the biological system. Nanobionics have significantly been effective in modulating the photosynthesis capacity of plants. It is documented that nanobionics could assist plants by acting as an artificial photosynthetic system to improve photosynthetic capacity, electron transfer in the photosystems, and pigment content, and enhance the absorption of light across the UV-visible spectrum. Smart nanocarriers, such as nanobionics, are capable of delivering the active ingredient nanocarrier upon receiving external stimuli. This can markedly improve NUE, reduce wastage, and improve cost effectiveness. Thus, this review emphasizes the application of nanobionics for improving crop yield by the two above-mentioned approaches. Major concerns and future prospects associated with the use of nanobionics are also deliberated concisely.
Metabolic Profiling of Sugars and Organic Acids, and Expression Analyses of Metabolism-Associated Genes in Two Yellow-Peel Pitaya Species
Authors: Xie Fangfang , Chen Canbin , Chen Jiaxuan , Yuan Yuanju , Hua Qingzhu , Zhang Zhike , Zhao Jietang , Hu Guibing , Chen Jianye , Qin Yonghua
Published: March 2022

Sugar and organic acids are important factors determining pitaya fruit quality. However, changes in sugars and acids, and expressions of metabolism-associated genes during fruit maturation of yellow-peel pitayas are not well-documented. In this study, metabolic and expression analyses in pulps of different fruit developmental stages of ‘Wucihuanglong’ (‘WCHL’, Hylocereus undatus) and ‘Youcihuanglong’ pitaya (‘YCHL’, Hylocereus megalanthus) were used to explore the sugar and organic acid metabolic process. Total phenols and flavonoids were mainly accumulated at S1 in pitaya pulps. Ascorbic acid contents of ‘WCHL’ pitaya were higher than that of ‘YCHL’ pitaya during fruit maturation. Starch was mainly accumulated at early fruit development stages while soluble sugars were rich in late stages. Sucrose, fructose, and glucose were the main sugar components of ‘YCHL’ pitaya while glucose was dominant in ‘WCHL’ pitaya. Malic and citric acids were the main organic acids in ‘WCHL’ and ‘YCHL’ pitayas, respectively. Based on the transcriptome analyses, 118 genes involved in pitaya sugar and organic acid metabolism were obtained. Results from the correlation analyses between the expression profiling of candidate genes and the contents of sugar and organic acid showed that 51 genes had a significant correlation relationship and probably perform key role in pitaya sugar and organic acid metabolism processes. The finding of the present study provides new information for quality regulation of pitayas.
Rapid Creation of Interspecific Hybrid Progeny to Broaden Genetic Distance through Double Haploid (DH) Inducer in Brassica napus
Authors: Zhou Ying , Yang Meicui , Zhao Shihui , Shi Haoran , Li Yun , Gong Wanzhuo , Yang Jin , Wang Jisheng , Zou Qiong , Tao Lanrong , Kang Zeming , Tang Rong , Guo Shixing , Fu Shaohong
Published: March 2022

Interspecific hybridization of rapeseed is an important way to innovate breeding resources. This research used Brassica napus and Brassica rapa for artificial synthesis interspecific hybridization of F1. The F1 self-fruiting rate was particularly low. By comparing the fertilization rate and seed setting rate of nine crosses and selfing combinations of interspecific hybrid progeny F1 and control B. napus, the results proved that the genetic stability of egg cells was greater than that of sperm cells, so the F1 could get seed by artificial pollination with other normal pollen. Based on these results, interspecific maternal inbred offspring (induced F1) from egg cells was obtained by emasculation and pollination with the pollen of DH inducer Y3380. It was found through morphological analysis, flow cytometry identification, and meiotic observation of induced F1, the plants had most normal fertile tetraploid and the meiosis was normal. The FISH results showed that the induced F1 were B. napus (2n = 4x = 38, AACC), 20 A and 19 C chromosomes. The results of SNP chip detection and genetic cluster analysis found that the genetic variation between interspecies could be preserved or broadened in the induced F1. The use of DH inducer created special breeding resources for interspecific hybridization and distant hybridization of rapeseed while shortening time, improving efficiency, and providing a new insight into innovate breeding resources.
Recent Advances in Development of Waste-Based Polymer Materials: A Review
Authors: Formela Krzysztof , Kurańska Maria , Barczewski Mateusz
Published: March 2022

Limited petroleum sources, suitable law regulations, and higher awareness within society has caused sustainable development of manufacturing and recycling of polymer blends and composites to be gaining increasing attention. This work aims to report recent advances in the manufacturing of environmentally friendly and low-cost polymer materials based on post-production and post-consumer wastes. Sustainable development of three groups of materials: wood polymer composites, polyurethane foams, and rubber recycling products were comprehensively described. Special attention was focused on examples of industrially applicable technologies developed in Poland over the last five years. Moreover, current trends and limitations in the future “green” development of waste-based polymer materials were also discussed.
Combination of Ultrasound and Heat in the Extraction of Chia Seed (Salvia hispanica L.) Mucilage: Impact on Yield and Technological Properties
Authors: Wang Wen-Huei , Lu Chun-Ping , Kuo Meng-I
Published: March 2022

The effect of ultrasound in combination of heat on the extraction yield and technological properties of chia seed mucilage was investigated. Chia seeds were mixed with distilled water at a seed-to-water ratio of 1:30. The dispersion was adjusted to pH 9 and treated either with heat extraction by water bath or with heat/ultrasound extraction by probe-type sonication at 50 °C and 80 °C for 30 and 60 min. The yield and technological properties of mucilage samples were evaluated. The heat/ultrasound extraction gave a greater yield of mucilage (6.92–10.52%) as compared to the heat extraction (1.03–1.86%). Images obtained from Scanning Electron Microscope (SEM) have shown that during heat/ultrasound extraction, the amount of mucilage fibers on the surface of chia seed decreased with the increased extraction time. Thus, the yield of mucilage prepared with heat/ultrasound extraction for 60 min was significantly higher than that of mucilage extracted for 30 min. However, the difference between the seed samples treated with heat/ultrasound extraction at different temperatures was not apparent. The mucilage prepared with heat/ultrasound extraction at 50 °C for 60 min had the best technological properties. The amount of protein in the heat/ultrasound extracted mucilage diversified its technological property. Moreover, the mixture of mucilage and whey protein isolate had better miscibility. This study confirms the great potential of application of ultrasound in combination with heat in the extraction of chia seed mucilage.
Kinematic Model Pruning: A Design Optimization Technique for Simultaneous Optimization of Topology and Geometry
Authors: Gamper Hannes , Luthi Adrien , Gattringer Hubert , Mueller Andreas , Di Castro Mario
Published: March 2022

This paper presents a method of optimizing the design of robotic manipulators using a novel kinematic model pruning technique. The optimization departs from an predefined candidate linkage consisting of a initial topology and geometry. It allows simultaneously optimizing the degree of freedom, the link lengths and other kinematic or dynamic performance criteria, while enabling the manipulator to follow the desired end-effector position and avoid collisions with the environment or itself. Current methods for design optimization rely on dedicated and complex frameworks, and solve the design optimization only as decoupled from each other in separate optimization problems. The proposed method only requires the introduction of a simple function, called a pruning function, as an objective function of an optimization problem. The introduced pruning function transforms a discrete topology optimization problem into a continuous problem that then can be solved simultaneously with other continuous objectives, using readily available optimization schemes. Two applications are presented: the optimization of a manipulator for the inspection of radio frequency cavities and a manipulator for maintenance within the future circular collider (FCC).
ASTER and GF-5 Satellite Data for Mapping Hydrothermal Alteration Minerals in the Longtoushan Pb-Zn Deposit, SW China
Authors: Chen Qi , Zhao Zhifang , Zhou Jiaxi , Zhu Ruifeng , Xia Jisheng , Sun Tao , Zhao Xin , Chao Jiangqin
Published: March 2022

Hydrothermal alteration minerals are an effective prospecting indicator. Advanced spaceborne thermal emission and reflection radiometer (ASTER) satellite data are some of the most commonly adopted multispectral data for the mapping of hydrothermal alteration minerals. Compared to multispectral data, hyperspectral data have stronger ground object recognition ability. Chinese Gaofen-5 (GF-5) is the first hyperspectral satellite independently developed by China that has the advantages of both wide-width and high-spectral-resolution technology. However, the mapping ability of GF5 data for hydrothermal alteration minerals requires further study. In this study, ASTER and GF-5 satellite data were implemented to map hydrothermal alteration minerals in the Longtoushan Pb-Zn deposit, SW China. Selective principal component analysis (SPCA) technology was employed to map iron oxide/hydroxides, argillic, quartz, and carbonate minerals at the pixel level using ASTER data, and the mixture tuned matched filtering (MTMF) method was implemented for the extracted hematite, kaolinite, calcite, and dolomite at the sub-pixel level using GF-5 data. When mapping the hydrothermal alteration minerals, the distribution features of the hydrothermal alteration minerals from the Longtoushan Pb-Zn deposit were systematically revealed. A comprehensive field investigation and petrographic study were conducted to verify the extraction accuracy of the hydrothermal alteration minerals. The results showed that the overall accuracies for the ASTER and GF-5 data were 82.6 and 92.9 and that the kappa coefficients were 0.78 and 0.90, respectively. This indicates that the GF-5 data are able to map hydrothermal alteration minerals well and that they can be promoted as a hyperspectral data source for mapping systematic hydrothermal alteration minerals in the future.
Remote Sensing Products Validated by Flux Tower Data in Amazon Rain Forest
Authors: Paca Victor Hugo da Motta , Espinoza-Dávalos Gonzalo E. , da Silva Rodrigo , Tapajós Raphael , dos Santos Gaspar Avner Brasileiro
Published: March 2022

This work compares methods of climate measurements, such as those used to measure evapotranspiration, precipitation, net radiation, and temperature. The satellite products used were compared and evaluated against flux tower data. Evapotranspiration was validated against the SSEBop monthly and GLEAM daily and monthly products, respectively, and the results were RMSE = 24.144 mm/month, NRMSE = 0.223, r2 = 0.163, slope = 0.411; RMSE = 1.781 mm/day, NRMSE = 0.599, r2 = 0.000, slope = 0.006; RMSE = 36.17 mm/month, NRMSE = 0.401, r2 = 0.002, and slope = 0.026. Precipitation was compared with the CHIRPS data, K67 was not part of the CHIRPS station correction. The results for both the daily and monthly comparisons were RMSE = 18.777 mm/day, NRMSE = 1.027, r2 = 0.086, slope = 0.238 and RMSE = 130.713 mm/month, NRMSE = 0.706, r2 = 0.402, and slope = 0.818. The net radiation validated monthly with CERES was RMSE = 75.357 W/m2, NRMSE = 0.383, r2 = 0.422, and slope = 0.867. The temperature results, as compared to MOD11C3, were RMSE = 2.829 °C, NRMSE = 0.116, r2 = 0.153, and slope = 0.580. Comparisons between the remote sensing products and validation against the ground data were performed on a monthly basis. GLEAM and CHIRPS daily were the data sets with considerable discrepancy.
An Automatic Procedure for Forest Fire Fuel Mapping Using Hyperspectral (PRISMA) Imagery: A Semi-Supervised Classification Approach
Authors: Shaik Riyaaz Uddien , Laneve Giovanni , Fusilli Lorenzo
Published: March 2022

Natural vegetation provides various benefits to human society, but also acts as fuel for wildfires. Therefore, mapping fuel types is necessary to prevent wildfires, and hyperspectral imagery has applications in multiple fields, including the mapping of wildfire fuel types. This paper presents an automatic semisupervised machine learning approach for discriminating between wildfire fuel types and a procedure for fuel mapping using hyperspectral imagery (HSI) from PRISMA, a recently launched satellite of the Italian Space Agency. The approach includes sample generation and pseudolabelling using a single spectral signature as input data for each class, unmixing mixed pixels by a fully constrained linear mixing model, and differentiating sparse and mountainous vegetation from typical vegetation using biomass and DEM maps, respectively. Then the procedure of conversion from a classified map to a fuel map according to the JRC Anderson Codes is presented. PRISMA images of the southern part of Sardinia, an island off Italy, were considered to implement this procedure. As a result, the classified map obtained an overall accuracy of 87% upon validation. Furthermore, the stability of the proposed approach was tested by repeating the procedure on another HSI acquired for part of Bulgaria and we obtained an overall stability of around 84%. In terms of repeatability and reproducibility analysis, a degree of confidence greater than 95% was obtained. This study suggests that PRISMA imagery has good potential for wildfire fuel mapping, and the proposed semisupervised learning approach can generate samples for training the machine learning model when there is no single go-to dataset available, whereas this procedure can be implemented to develop a wildfire fuel map for any part of Europe using LUCAS land cover points as input.
Dominant Factors and Spatial Heterogeneity of Land Surface Temperatures in Urban Areas: A Case Study in Fuzhou, China
Authors: Yang Liuqing , Yu Kunyong , Ai Jingwen , Liu Yanfen , Yang Wufa , Liu Jian
Published: March 2022

The urban heat island (UHI) phenomenon caused by rapid urbanization has become an important global ecological and environmental problem that cannot be ignored. In this study, the UHI effect was quantified using Landsat 8 image inversion land surface temperatures (LSTs). With the spatial scale of street units in Fuzhou City, China, using ordinary least squares (OLS) regression, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR), we explored the spatial heterogeneities of the influencing factors and LST. The results indicated that, compared with traditional OLS models, GWR improved the model fit by considering spatial heterogeneity, whereas MGWR outperformed OLS and GWR in terms of goodness of fit by considering the effects of different bandwidths on LST. Building density (BD), normalized difference impervious surface index (NDISI), and the sky view factor (SVF) were important influences on elevated LST, while building height (BH), forest land percentage (Forest_per), and waterbody percentage (Water_per) were negatively correlated with LST. In addition, built-up percentage (Built_per) and population density (Pop_Den) showed significant spatial non-stationary characteristics. These findings suggest the need to consider spatial heterogeneity in analyses of impact factors. This study can be used to provide guidance on mitigation strategies for UHIs in different regions.