bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Brain Angiogenesis Inhibitor-3 (BAI3) G-Protein Coupled Receptor in Mice Regulates Adaptive Thermogenesis by Enhancing Energy Expenditure
Authors: Alsharif Haifa , Latimer Mary N. , Perez Katherine C. , Alexander Justin , Rahman Md Mostafizur , Challa Anil K. , Kim Jeong-A. , Ramanadham Sasanka , Young Martin , Bhatnagar Sushant
Published: May 2023

Effective energy expenditure is critical for maintaining body weight (BW). However, underlying mechanisms contributing to increased BW remain unknown. We characterized the role of brain angiogenesis inhibitor-3 (BAI3/ADGRB3), an adhesion G-protein coupled receptor (aGPCR), in regulating BW. A CRISPR/Cas9 gene editing approach was utilized to generate a whole-body deletion of the BAI3 gene (BAI3−/−). In both BAI3−/− male and female mice, a significant reduction in BW was observed compared to BAI3+/+ control mice. Quantitative magnetic imaging analysis showed that lean and fat masses were reduced in male and female mice with BAI3 deficiency. Total activity, food intake, energy expenditure (EE), and respiratory exchange ratio (RER) were assessed in mice housed at room temperature using a Comprehensive Lab Animal Monitoring System (CLAMS). While no differences were observed in the activity between the two genotypes in male or female mice, energy expenditure was increased in both sexes with BAI3 deficiency. However, at thermoneutrality (30 °C), no differences in energy expenditure were observed between the two genotypes for either sex, suggesting a role for BAI3 in adaptive thermogenesis. Notably, in male BAI3−/− mice, food intake was reduced, and RER was increased, but these attributes remained unchanged in the female mice upon BAI3 loss. Gene expression analysis showed increased mRNA abundance of thermogenic genes Ucp1, Pgc1α, Prdm16, and Elov3 in brown adipose tissue (BAT). These outcomes suggest that adaptive thermogenesis due to enhanced BAT activity contributes to increased energy expenditure and reduced BW with BAI3 deficiency. Additionally, sex-dependent differences were observed in food intake and RER. These studies identify BAI3 as a novel regulator of BW that can be potentially targeted to improve whole-body energy expenditure.
Free Radicals and Obesity-Related Chronic Inflammation Contrasted by Antioxidants: A New Perspective in Coronary Artery Disease
Authors: Caiati Carlo , Stanca Alessandro , Lepera Mario Erminio
Published: May 2023

We are surrounded by factors called free radicals (FR), which attach to the molecules our body is made of, first among them the endothelium. Even though FR are to a certain extent a normal factor, nowadays we face an escalating increase in these biologically aggressive molecules. The escalating formation of FR is linked to the increased usage of man-made chemicals for personal care (toothpaste, shampoo, bubble bath, etc.), domestic laundry and dish-washer detergents, and also an ever wider usage of drugs (both prescription and over the counter), especially if they are to be used long-term (years). In addition, tobacco smoking, processed foods, pesticides, various chronic infectious microbes, nutritional deficiencies, lack of sun exposure, and, finally, with a markedly increasing impact, electromagnetic pollution (a terribly destructive factor), can increase the risk of cancer, as well as endothelial dysfunction, owing to the increased production of FR that they cause. All these factors create endothelial damage, but the organism may be able to repair such damage thanks to the intervention of the immune system supported by antioxidants. However, one other factor can perpetuate the state of inflammation, namely obesity and metabolic syndrome with associated hyperinsulinemia. In this review, the role of FR, with a special emphasis on their origin, and of antioxidants, is explored from the perspective of their role in causing atherosclerosis, in particular at the coronary level.
A Compact MIMO Multiband Antenna for 5G/WLAN/WIFI-6 Devices
Authors: Ali Ayyaz , Munir Mehr E , Marey Mohamed , Mostafa Hala , Zakaria Zahriladha , Al-Gburi Ahmed Jamal Abdullah , Bhatti Farooq Ahmed
Published: May 2023

This research work presents a compact design of a Multiple-Input Multiple-Output (MIMO) multiband antenna along with high-isolation characteristics. The presented antenna was designed for 3.50 GHz, 5.50 GHz, and 6.50 GHz frequencies for 5G cellular, 5G WiFi, and WiFi-6, respectively. The fabrication of the aforementioned design was undertaken using FR-4 (1.6 mm thickness) substrate material with a loss tangent and relative permittivity of about 0.025 and 4.30, respectively. The two-element MIMO multiband antenna was miniaturized to 16 × 28 × 1.6 mm3, making it desirable for devices operating in 5G bands. High isolation (>15 dB) was attained with thorough testing without employing a decoupling scheme in the design. Laboratory measurements resulted in a peak gain of 3.49 dBi and an efficiency of around 80% in the entire operating band. The evaluation of the presented MIMO multiband antenna was carried out in terms of the envelope correlation coefficient (ECC), diversity gain (DG), total active reflection coefficient (TARC), and Channel Capacity Loss (CCL). The measured ECC was less than 0.04, and the DG was well above 9.50. The observed TARC was also lower than −10 dB, and the CCL was below 0.4 bits/s/Hz in the entire operating band. The presented MIMO multiband antenna was analyzed and simulated using CST Studio Suite 2020.
Spiral Chiral Metamaterial Structure Shape for Optical Activity Improvements
Authors: Maruyama Kohei , Mizuna Miyako , Kosuge Takuya , Takeda Yuki , Iwase Eiji , Kan Tetsuo
Published: May 2023

We report on a spiral structure suitable for obtaining a large optical response. We constructed a structural mechanics model of the shape of the planar spiral structure when deformed and verified the effectiveness of the model. As a verification structure, we fabricated a large-scale spiral structure that operates in the GHz band by laser processing. Based on the GHz radio wave experiments, a more uniform deformation structure exhibited a higher cross-polarization component. This result suggests that uniform deformation structures can improve circular dichroism. Since large-scale devices enable speedy prototype verification, the obtained knowledge can be exported to miniaturized-scale devices, such as MEMS terahertz metamaterials.
Multidirectional Piezoelectric Vibration Energy Harvester Based on Cam Rotor Mechanism
Authors: Jiang Xin , Liu Yan , Wei Jiaming , Yang Haotian , Yin Bin , Qin Hongbo , Wang Weidong
Published: May 2023

The techniques that harvest mechanical energy from low-frequency, multidirectional environmental vibrations have been considered a promising strategy to implement a sustainable power source for wireless sensor networks and the Internet of Things. However, the obvious inconsistency in the output voltage and operating frequency among different directions may bring a hindrance to energy management. To address this issue, this paper reports a cam-rotor-based approach for a multidirectional piezoelectric vibration energy harvester. The cam rotor can transform vertical excitation into a reciprocating circular motion, producing a dynamic centrifugal acceleration to excite the piezoelectric beam. The same beam group is utilized when harvesting vertical and horizontal vibrations. Therefore, the proposed harvester reveals similar characterization in its resonant frequency and output voltage at different working directions. The structure design and modeling, device prototyping and experimental validation are conducted. The results show that the proposed harvester can produce a peak voltage of up to 42.4 V under a 0.2 g acceleration with a favorable power of 0.52 mW, and the resonant frequency for each operating direction is stable at around 3.7 Hz. Practical applications in lighting up LEDs and powering a WSN system demonstrate the promising potential of the proposed approach in capturing energy from ambient vibrations to construct self-powered engineering systems for structural health monitoring, environmental measuring, etc.
Late Ordovician High Ba-Sr Intrusion in the Eastern North Qilian Orogen: Implications for Crust–Mantle Interaction and Proto-Tethys Ocean Evolution
Authors: Zhao Shaoqing , Hai Lianfu , Liu Bin , Dong Huan , Mei Chao , Xu Qinghai , Mu Caixia , Wei Xiangcheng
Published: May 2023

High Ba-Sr granitic rocks are widespread in Phanerozoic orogenic systems, and their petrogenesis is important for revealing the evolutionary process of the Proto-Tethys Ocean in the North Qilian orogenic belt. This paper presents a combination of zircon U-Pb age, whole-rock major and trace element concentrations, and Sr-Nd-Hf isotopic data for Caowa high Ba-Sr dioritic intrusion from the eastern part of the North Qilian orogenic belt, aiming to decipher its petrogenesis and tectonic setting. LA-ICP-MS zircon U-Pb dating yield an emplacement age of 450 ± 2 Ma for the Caowa intrusion, indicating a magmatic activity of the Late Ordovician. The Caowa quartz diorites contain moderate contents of SiO2, MgO, Mg#, and resultant high concentrations of Na2O + K2O, Fe2O3T, and Al2O3, displaying calc-alkaline and metaluminous characteristics. The studied samples have relatively elevated Ba (up to 1165 ppm) and Sr (561 to 646 ppm) contents, with obvious enrichment in LILEs (e.g., Ba, Th, U) and depletions in HFSEs (e.g., Nb, Ta, Ti), resembling those of typical high Ba-Sr granitoids in subduction zones. Together with enriched Sr-Nd isotopic composition [(87Sr/86Sr)i = 0.7082–0.7086, εNd(t) = −5.1 to −4.9], and the wide ranges of zircon εHf(t) values (−13.2 to +8.5), it suggests that these high Ba-Sr quartz diorites were derived from a mixture magma source between the ancient crust materials and the enriched lithospheric mantle metasomatized by fluid released from subducted oceanic crust or sediment. Taking into account the ophiolites, high pressure metamorphic rocks, and arc magmatic rocks in the region, we infer that due to the influence of the northward subduction of the Qilian Proto-Tethys Ocean, the Laohushan oceanic crust of the North Qilian back-arc basin was subducted during the Late Ordovician and resulted in extensive metasomatism of lithospheric mantle by fluids derived from oceanic crust or sediments, and the Caowa high Ba-Sr quartz diorites were generated in the process of crust–mantle interaction during the Late Ordovician.
Development of High-Energy µ-X-ray Fluorescence and X-ray Absorption Fine Structure for the Distribution and Speciation of Rare Earth Elements in Natural Samples
Authors: Nagasawa Makoto , Sekizawa Oki , Nitta Kiyofumi , Kashiwabara Teruhiko , Takahashi Yoshio
Published: May 2023

Micro-X-ray fluorescence and X-ray absorption fine structure (µ-XRF-XAFS) is one of the most powerful tools to identify the distribution and speciation of trace elements in natural samples with µm spatial resolution. However, conventional µ-XRF-XAFS studies applied to rare earth elements (REEs: lanthanide elements + Y in this study) are mainly limited to their L-edges and L lines (except for Y) that are subject to strong interferences from other elements (mainly transition metals). In this study, we extend µ-XRF-XAFS to the higher energy region (HE-µ-XRF-XAFS) by using an incident X-ray microbeam (size: ca. 1 × 1 µm2) between 38 and 54 keV to realize K-edge excitation lanthanide analysis without interferences from other elements at the BL37XU beamline, SPring-8 (Japan). This method enables us to simultaneously analyze (i) REE patterns (from La to Dy), (ii) XAFS spectra, and (iii) µm-scale distribution of each REE in the natural sample. The proposed method also realizes the simultaneous application of µ-XAFS at low (e.g., Fe K-edge) and high (lanthanide K-edges) energy at the same spot without changing the setup of the µ-XRF-XAFS system using the detuning technique.
Recursive Feature Elimination and Neural Networks Applied to the Forecast of Mass and Metallurgical Recoveries in A Brazilian Phosphate Mine
Authors: Niquini Fernanda Gontijo Fernandes , Branches André Miranda Brito , Costa João Felipe Coimbra Leite , Moreira Gabriel de Castro , Schneider Claudio Luiz , Araújo Florence Cristiane de , Capponi Luciano Nunes
Published: May 2023

Geometallurgical models are commonly built by combining explanatory variables to obtain the response that requires prediction. This study presented a phosphate plant with three concentration steps: magnetic separation, desliming and flotation, where the yields and recoveries corresponding to each process unit were predicted. These output variables depended on the ore composition and the collector concentration utilized. This paper proposed a solution based on feature engineering to select the best set of explanatory variables and a subset of them able to keep the model as simple as possible but with enough precision and accuracy. After choosing the input variables, two neural network models were developed to simultaneously forecast the seven geometallurgical variables under study: the first, using the best set of variables; and the second, using the reduced set of inputs. The forecasts obtained in both scenarios were compared, and the results showed that the mean squared error and the root mean squared error increase in all output variables evaluated in the test set was smaller than 2.6% when the reduced set was used. The trade-off between simplicity and the quality of the model needs to be addressed when choosing the final neural network to be used in a 3D-block model.
The Paleoproterozoic Evolution of Basement Rocks of the Taebaeksan Basin, Korean Peninsula, and Their Correlation to Those of the Paleoproterozoic Massifs in the Korean Peninsula
Authors: Lee Bo Young , Cho Deung-Lyong , Oh Chang Whan , Lee Byung Choon , Lee Seung Hwan
Published: May 2023

The Korean Peninsula mainly comprises the Paleoproterozoic Gwanmo, Nangnim, Gyeonggi, and Yeongnam massifs from north to south. The Paleoproterozoic basement is rarely exposed in the Paleozoic Taebaeksan basin, which is located in the northeastern part of the Okcheon belt between the Gyeonggi and Yeongnam massifs. One of the most important issues in the tectonic interpretation of the Korean Peninsula is whether Paleoproterozoic rocks in the Taebaeksan basin have an affinity with those in the Gyeonggi or Yeongnam massifs. To solve this problem, we focused on the petrogenesis of the Imgye gabbroic diorite, Jungbongsan granite, and Jangsan quartzite in the Imgye area of the Taebaeksan basin. The Imgye gabbroic diorite shows mafic to intermediate compositions with slightly enriched LREEs compared to HREEs, slightly positive Rb, K, and Pb anomalies, and negative Ta, Nb, and P anomalies. The Imgye gabbroic diorite formed in a volcanic arc tectonic setting. The geochemical compositions of the Jungbongsan granite show enriched LREEs compared to HREEs with negative Eu anomalies, and reveal strong positive Rb, Th, K, and Pb anomalies with negative Ba, Ta, Nb, Sr, P, Eu, and Ti anomalies. This Jungbongsan granite also formed in an arc tectonic setting like the Imgye gabbroic diorite. LA-ICP-MS zircon age dating of the Imgye gabbroic diorite gives an intrusion age of 1948 ± 21 Ma, whereas SHRIMP U–Pb zircon age dating on the Jungbongsan granite yields an emplacement age of 1873 ± 14 Ma. The εHf(t) values of the Imgye gabbroic diorite are from 3.5 to 9.7, whereas those of the Jungbongsan granite are from −2.9 to 0.6. These data imply that the Imgye gabbroic diorite formed from a depleted mantle in the arc tectonic environment, whereas the Jungbongsan granite formed by reworking pre-existing crust material in the arc environment. The detrital zircons in the Jangsan quartzite show ages ranging from 3.06 to 1.85 Ga, with a peak concentration of ca. 2.5 Ga. Previous studies have suggested that the northern Gyeonggi and Nangnim massifs underwent collision-related magmatism and metamorphism at ca. 1.93–1.90 Ga, and then post-collisional magmatism and metamorphism at ca. 1.89–1.83 Ga, whereas the southern Gyeonggi massif underwent subduction-related magmatism and metamorphism at ca. 1.94–1.92 Ga, and then post-collision-related magmatism and metamorphism at ca. 1.84–1.78 Ga. By contrast, subduction-related events were recognized in the northern Yeongnam massif at ca 2.02–1.96 Ga and 1.90–1.85 Ga. This work, combined with the previous studies, suggests that the Paleoproterozoic basement in the Imgye area of the Taebaeksan basin can be correlated with the Paleoproterozoic basement of the northern Yeongnam massif rather than with those of the Nangnim and Gyeonggi massifs.
Analysis of Silver Nanoparticles in Ground Beef by Single Particle Inductively Coupled Plasma Mass Spectrometry (SP-ICP-MS)
Authors: Chalifoux Alexandre , Hadioui Madjid , Amiri Nesrine , Wilkinson Kevin J.
Published: May 2023

The regulation and characterization of nanomaterials in foods are of great interest due to the potential risks associated with their exposure and the increasing number of applications where they are used within the food industry. One factor limiting the scientifically rigorous regulation of nanoparticles in foods is the lack of standardized procedures for the extraction of nanoparticles (NPs) from complex matrices without alteration of their physico-chemical properties. To this end, we tested and optimized two sample preparation approaches (enzymatic- and alkaline-based hydrolyses) in order to extract 40 nm of Ag NP, following their equilibration with a fatty ground beef matrix. NPs were characterized using single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). Fast sample processing times (<20 min) were achieved using ultrasonication to accelerate the matrix degradation. NP losses during the sample preparation were minimized by optimizing the choice of enzymes/chemicals, the use of surfactants, and the product concentration and sonication. The alkaline approach using TMAH (tetramethylammonium hydroxide) was found to have the highest recoveries (over 90%); however, processed samples were found to be less stable than the samples processed using an enzymatic digestion based upon pork pancreatin and lipase (≈60 % recovery). Low method detection limits (MDLs) of 4.8 × 106 particles g−1 with a size detection limit (SDL) of 10.9 nm were achieved for the enzymatic extraction whereas an MDL of 5.7 × 107 particles g−1 and an SDL of 10.5 nm were obtained for the alkaline hydrolysis.
Single and Binary Removals of Pb(II) and Cd(II) with Chemically Modified Opuntia ficus indica Cladodes
Authors: Lavado-Meza Carmencita , Fernandez-Pezua Miguel C. , Gamarra-Gómez Francisco , Sacari-Sacari Elisban , Angeles-Suazo Julio , Dávalos-Prado Juan Z.
Published: May 2023

In this study, cladodes of Opuntia ficus indica (OFIC), chemically modified with NaOH (OFICM), have been prepared, characterized, and tested as an effective biomass to remove Pb(II) and/or Cd(II) from aqueous media. At an optimum pH of 4.5, the adsorption capacity, qe, of treated OFICM was almost four times higher than that of untreated OFIC. The maximum adsorption capacities (qmax) in the single removal of Pb(II) and Cd(II) were 116.8 and 64.7 mg g−1, respectively. These values were 12.1% and 70.6% higher than those for the corresponding qmax in binary removal, which indicates the strong inhibitive effect of Pb(II) on the co-cation Cd(II) in a binary system. Structural and morphological characterization have been carried out by FTIR, SEM/EDX, and point of zero charge (pHPZC) measurements. The SEM/EDX results confirmed that the metals are adsorbed on the surface. The presence of C-O, C=O, and COO- functional groups were identified by FTIR on both OFIC and OFICM surfaces. On the other hand, we found that the adsorption processes followed the pseudo-second-order kinetics for both single and binary systems, with a fast biosorption rate of Pb(II) and Cd(II). The equilibrium data (adsorption isotherms) were better described by Langmuir and modified-Langmuir models for single and binary systems, respectively. A good regeneration of OFICM was obtained with an eluent of 0.1 M HNO3. Therefore, OFICM can be efficiently reused to remove Pb or Cd, up to three times.
Gold Nanoparticles Functionalized with 2-Thiouracil for Antiproliferative and Photothermal Therapies in Breast Cancer Cells
Authors: Lorenzana-Vázquez Génesis , Pavel Ioana , Meléndez Enrique
Published: May 2023

Nanoparticles have been used to transport drugs to various body parts to treat cancer. Our interest is in gold nanoparticles (AuNPs) since they have the capacity to absorb light and convert it to heat, inducing cellular damage. This property is known as photothermal therapy (PTT) and has been studied in cancer treatment. In the present study, biocompatible citrate-reduced AuNPs were functionalized with a biologically active compound, 2-thiouracil (2-TU), of potential anticancer activity. Both the unfunctionalized (AuNPs) and functionalized (2-TU-AuNPs) were purified and characterized by UV–Vis absorption spectrophotometry, Zeta potential, and Transmission Electron Microscopy. Results showed monodispersed, spherical AuNPs with a mean core diameter of 20 ± 2 nm, a surface charge of −38 ± 5 mV, and a localized surface plasmon resonance peak at 520 nm. As a result of functionalization, the mean core diameter of 2-TU-AuNPs increased to 24 ± 4 nm, and the surface charge increased to −14 ± 1 mV. The functionalization of AuNPs and the load efficiency were further established through Raman spectroscopy and UV–Vis absorption spectrophotometry. The antiproliferative activities of AuNPs, 2-TU and 2-TU-AuNPs were examined by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the MDA-MB-231 breast cancer cell line. It was established that AuNPs significantly enhanced the antiproliferative activity of 2-TU. Furthermore, the irradiation of the samples with visible light at 520 nm decreased the half-maximal inhibitory concentration by a factor of 2. Thus, the 2-TU drug concentration and its side effect during treatments could be significantly reduced by synergistically exploiting the antiproliferative activity of 2-TU loaded onto AuNPs and the PTT effect of AuNPs.
Carbon Nanocomposites in Aerospace Technology: A Way to Protect Low-Orbit Satellites
Authors: Weerasinghe Janith , Prasad Karthika , Mathew Joice , Trifoni Eduardo , Baranov Oleg , Levchenko Igor , Bazaka Kateryna
Published: May 2023

Recent advancements in space technology and reduced launching cost led companies, defence and government organisations to turn their attention to low Earth orbit (LEO) and very low Earth orbit (VLEO) satellites, for they offer significant advantages over other types of spacecraft and present an attractive solution for observation, communication and other tasks. However, keeping satellites in LEO and VLEO presents a unique set of challenges, in addition to those typically associated with exposure to space environment such as damage from space debris, thermal fluctuations, radiation and thermal management in vacuum. The structural and functional elements of LEO and especially VLEO satellites are significantly affected by residual atmosphere and, in particular, atomic oxygen (AO). At VLEO, the remaining atmosphere is dense enough to create significant drag and quicky de-orbit satellites; thus, thrusters are needed to keep them on a stable orbit. Atomic oxygen-induced material erosion is another key challenge to overcome during the design phase of LEO and VLEO spacecraft. This review covered the corrosion interactions between the satellites and the low orbit environment, and how it can be minimised through the use of carbon-based nanomaterials and their composites. The review also discussed key mechanisms and challenges underpinning material design and fabrication, and it outlined the current research in this area.
Relationship between Serum Selenium Level and Self-Reported History of Kidney Stone
Authors: Wang Anni , Wang Ningrui , Zhang Dongfeng , Wen Jing , Wang Weijing
Published: May 2023

A relationship may exist between selenium and kidney calculi, but there is a lack of research in this field at present. Our study explored the relationship between the serum selenium level and a medical history of adult kidney calculi. We utilized data from the National Health and Nutrition Examination Survey conducted between 2011 and 2016. Participants self-reported their history of kidney stones, while serum selenium levels were measured using inductively coupled plasma dynamic reaction cell mass spectrometry. Our findings indicate a negative correlation between serum selenium levels and the risk of kidney stone history. In the multiple-adjusted model, the lowest serum selenium level group had a higher risk than the other groups. The odds ratio (95% confidence interval) of ever having kidney stones for the highest serum selenium level group was 0.54 (0.33–0.88). In the results of stratified analysis, this relationship was still significant in the groups of women and those 40–59 years. We also found that as a nonlinear dose–response relationship between serum selenium levels and the history of kidney stones disease. In our research, we found that people with higher serum selenium levels had a lower risk of having a history of kidney stones. We concluded that selenium may have a protective effect on kidney stones. In the future, more population studies are needed to explore the relationship between selenium and kidney stones.
β-Hydroxy-β-methyl Butyrate Regulates the Lipid Metabolism, Mitochondrial Function, and Fat Browning of Adipocytes
Authors: Duan Geyan , Zheng Changbing , Yu Jiayi , Zhang Peiwen , Wan Mengliao , Zheng Jie , Duan Yehui
Published: May 2023

A growing number of in vivo studies demonstrated that β-hydroxy-β-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H+ leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity.
Annona muricate Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice
Authors: Lee Heaji , Kim Sun Yeou , Lim Yunsook
Published: May 2023

Type 2 diabetes mellitus (T2DM) is related with the incidence of sarcopenia and cognitive impairment that reduces quality of life in the elderly. Recent evidence has demonstrated that sarcopenia is associated with cognitive dysfunction, and muscle-derived endocrine factors might contribute to cognitive function by the skeletal muscle–brain endocrine loop. This study investigated the beneficial effects of Annona muricata (AM, graviola) on multi-organ energy metabolism with muscle–brain connectivity via brain function-related myokines in mice. Body composition, fasting blood glucose level, insulin, HbA1c%, histopathological changes, and the protein levels of insulin-signaling, energy metabolism, neuroprotection, inflammation, and protein-degradation pathways were measured. AM extract (AME) treatment selectively enhanced insulin signaling in the skeletal muscle and hippocampus of T2DM mice. Furthermore, AME treatment effectively increased muscle-derived fibroblast growth factor 21 (FGF21), cathepsin-B (CTSB), irisin, brain-derived neurotrophic factor (BDNF), and liver-derived FGF21 that contribute to whole-body energy homeostasis. In particular, AME increased the levels of circulating myokines (FGF21, BDNF, irisin, and CTSB), and these were accordance with the hippocampal neurotrophic factors (BDNF and CTSB) in T2DM mice. In conclusion, we suggest that AME would be a potential nutraceutical for improving the energy metabolism associated with muscle–brain connectivity via brain function-related myokines in T2DM.
“The Role of Vitamin D in Cancer Prevention”: Some New Clues on a Fascinating Subject
Authors: Martin-Moreno Jose M. , Martin-Gorgojo Alejandro
Published: May 2023

Increasing evidence from experimental animal nutrition studies suggests that vitamin D may potentially influence apoptosis and tumor-associated angiogenesis, reduce the initiation of carcinogenesis, and delay the multiplication and proliferation of tumor cells [...]
The Effects of a Very-Low-Calorie Ketogenic Diet on the Intestinal Barrier Integrity and Function in Patients with Obesity: A Pilot Study
Authors: Linsalata Michele , Russo Francesco , Riezzo Giuseppe , D’Attoma Benedetta , Prospero Laura , Orlando Antonella , Ignazzi Antonia , Di Chito Martina , Sila Annamaria , De Nucci Sara , Rinaldi Roberta , Giannelli Gianluigi , De Pergola Giovanni
Published: May 2023

The very-low-calorie ketogenic diet (VLCKD) is effective and safe for obese individuals, but limited information exists on its impact on the intestinal barrier. This study analyzed the effects of 8 weeks of VLCKD on 24 obese patients (11M/13F). Carbohydrate intake was fixed at 20–50 g/day, while protein and lipid intake varied from 1–1.4 g/kg of ideal body weight and 15–30 g per day, respectively. Daily calorie intake was below 800 kcal. The lactulose–mannitol absorption test assessed small intestinal permeability. Multiple markers, such as serum and fecal zonulin, fatty acid-binding protein, diamine oxidase concentrations, urinary dysbiosis markers (indican and skatole), and circulating lipopolysaccharide levels, were analyzed. Inflammation markers (serum interleukin 6, 8, 10, and tumor necrosis factor-α concentrations) were also evaluated. The results showed significant reductions in weight, BMI, and waist circumference post-diet. However, the lactulose–mannitol ratio increased by 76.5%, and a significant increase in dysbiosis markers at the end of the diet occurred. This trend was particularly evident in a subgroup of patients. Despite initial benefits, the VLCKD might negatively affect the intestinal barrier function in obese patients, potentially worsening their compromised intestinal balance.
The Effect of Probiotic Bacteria on Composition and Metabolite Production of Faecal Microbiota Using In Vitro Batch Cultures
Authors: Eastwood Jessica , van Hemert Saskia , Poveda Carlos , Elmore Stephen , Williams Claire , Lamport Daniel , Walton Gemma
Published: May 2023

Probiotic supplements are increasingly being used to target the gut microbiome with a view to improving cognitive and psychological function via the gut-brain axis. One possible mechanism behind the effect of probiotics is through alterations to microbially-derived metabolites including short-chain fatty acids (SCFA) and neurotransmitters. However, research to date has largely been conducted in animal models or under conditions irrelevant to the human gastrointestinal tract (GIT). The aim of the current work was therefore to use anaerobic, pH controlled in vitro batch cultures to (a) assess the production of neuroactive metabolites in human faecal microbiota under conditions relevant to the human GIT, and (b) to explore how several pre-selected probiotic strains may affect bacterial composition and metabolite production. Enumeration of bacteria was assessed using fluorescence in situ hybridisation with flow cytometry, and concentrations of SCFAs and neurotransmitters were measured using gas chromatography and liquid chromatography mass spectroscopy, respectively. GABA, serotonin, tryptophan, and dopamine were successfully detected, suggesting some level of microbial derivation. The addition of Lactococcus lactis W58 and Lactobacillus rhamnosus W198 resulted in a significant increase in lactate after 8 h of fermentation, while no significant effect of probiotics on bacterial composition or neurotransmitter production was found.
Muscle Protein Synthesis with a Hybrid Dairy and Plant-Based Protein Blend (P4) Is Equal to Whey Protein in a Murine Ageing Model after Fasting
Authors: Dijk Francina J. , Hofman Zandrie , Luiking Yvette C. , Furber Matthew J. W. , Roberts Justin D. , van Helvoort Ardy , van Dijk Miriam
Published: May 2023

P4, a specific combination of dairy proteins (whey and casein) and plant-based protein isolates (pea and soy), has been shown to provide a more balanced amino acid (AA) profile than its single constituent proteins; however, less is known about how this translates to muscle protein synthesis (MPS). The aim of this study was to investigate the effect of P4 compared to whey or casein against fasted control on MPS. C57BL/6J mice, aged 25 months, were fasted overnight, followed by oral gavage of either whey, P4, casein, or water as a fasted control. Thirty minutes after ingestion, puromycin (0.04 µmol∙g−1 bodyweight) was subcutaneously injected; 30-min thereafter, mice were sacrificed. MPS was measured by the SUnSET method, and signalling proteins were determined in the left-tibialis anterior (TA) muscle by the WES technique. AA composition was determined in plasma and right-TA muscle. Dried blood spots (DBS) were analysed for postprandial AA dynamics at 10, 20, 45, 60 min. MPS was 1.6-fold increased with whey (p = 0.006) and 1.5-fold with P4 compared to fasted (p = 0.008), while no change was seen with casein. This was confirmed by a significant increase of phosphorylated/total ratio of 4E-BP1 for both whey (p = 0.012) and P4 (p = 0.001). No changes were observed in p70S6K and mTOR phosphorylation/total ratio with whey or P4. Intramuscular leucine levels were lower for P4 (0.71 µmol∙g dry weight−1) compared to whey (0.97 µmol∙g dry weight−1) (p = 0.0007). Ten minutes postprandial, DBS showed significantly increased blood AA levels of BCAAs, histidine, lysine, threonine, arginine, and tyrosine for P4 versus fasted. In conclusion, a hybrid mix of dairy and plant-based proteins (P4) resulted in a MPS response that was similar to whey protein in aged mice after fasting. This suggests that other anabolic triggers beyond leucine or the well-balanced amino acid profile and bioavailability of the blend benefit stimulation of MPS.
Assessing the Quality of Simulated Food Patterns with Reduced Animal Protein Using Meal Data from NHANES 2017–2018
Authors: Vasiloglou Maria F. , Elortegui Pascual Paloma , Scuccimarra Eric A. , Plestina Roko , Mainardi Fabio , Mak Tsz-Ning , Ronga Frédéric , Drewnowski Adam
Published: May 2023

The nutritional consequences of progressively replacing meat products with plant-based foods need to be systematically evaluated. Modeling analyses provide insights into the predicted food consumption and nutritional adequacy of plant-based diets. We developed a novel methodology to simulate food patterns and evaluate diet quality. Meal data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 was used to create 100 7-day meal plans subject to various nutrient and food group optimization criteria. Omnivore (reference diet), flexitarian, pescatarian, and vegetarian food patterns were modeled using mixed integer linear programming. The modeled food patterns used the 25th and 75th percentiles of the US Usual Dietary Intakes to set the optimization constraints. The diet quality was determined using the Healthy Eating Index 2015 (HEI-2015). The modeled vegetarian, pescatarian, and flexitarian food patterns outperformed the omnivore diet on the HEI-2015, with the vegetarian pattern achieving the highest score (82 for females, 78 for males). Modeled flexitarian patterns, with a 25 to 75% reduction in animal protein, offer viable options for those seeking to reduce but not eliminate their animal protein intake while supporting the transition from omnivore to fully plant-based diets. This methodology could be applied to evaluate the nutrient and diet quality of different dietary patterns with various constraints.
Endothelial Glycocalyx Preservation—Impact of Nutrition and Lifestyle
Authors: Franceković Paula , Gliemann Lasse
Published: May 2023

The endothelial glycocalyx (eGC) is a dynamic hair-like layer expressed on the apical surface of endothelial cells throughout the vascular system. This layer serves as an endothelial cell gatekeeper by controlling the permeability and adhesion properties of endothelial cells, as well as by controlling vascular resistance through the mediation of vasodilation. Pathogenic destruction of the eGC could be linked to impaired vascular function, as well as several acute and chronic cardiovascular conditions. Defining the precise functions and mechanisms of the eGC is perhaps the limiting factor of the missing link in finding novel treatments for lifestyle-related diseases such as atherosclerosis, type 2 diabetes, hypertension, and metabolic syndrome. However, the relationship between diet, lifestyle, and the preservation of the eGC is an unexplored territory. This article provides an overview of the eGC’s importance for health and disease and describes perspectives of nutritional therapy for the prevention of the eGC’s pathogenic destruction. It is concluded that vitamin D and omega-3 fatty acid supplementation, as well as healthy dietary patterns such as the Mediterranean diet and the time management of eating, might show promise for preserving eGC health and, thus, the health of the cardiovascular system.
Selenylated Imidazo [1,2-a]pyridine Induces Apoptosis and Oxidative Stress in 2D and 3D Models of Colon Cancer Cells
Authors: Gomes Giovana Bicudo , Zubieta Claudia Stutz , Guilhermi Jhefferson dos Santos , Toffoli-Kadri Mônica Cristina , Beatriz Adilson , Rafique Jamal , Parisotto Eduardo Benedetti , Saba Sumbal , Perdomo Renata Trentin
Published: May 2023

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research.
Correction: Liu et al. Apigenin Ameliorates Hyperuricemia and Renal Injury through Regulation of Uric Acid Metabolism and JAK2/STAT3 Signaling Pathway. Pharmaceuticals 2022, 15, 1442
Authors: Liu Tianyuan , Gao Huimin , Zhang Yueyi , Wang Shan , Lu Meixi , Dai Xuan , Liu Yage , Shi Hanfen , Xu Tianshu , Yin Jiyuan , Gao Sihua , Wang Lili , Zhang Dongwei
Published: May 2023

In the original publication [...]
Chaperone Activity and Protective Effect against Aβ-Induced Cytotoxicity of Artocarpus camansi Blanco and Amaranthus dubius Mart. ex Thell Seed Protein Extracts
Authors: Sanchez-Rodriguez David , Gonzalez-Figueroa Idsa , Alvarez-Berríos Merlis P.
Published: May 2023

Alzheimer’s disease (AD) is the most common type of dementia and is listed as the sixth-leading cause of death in the United States. Recent findings have linked AD to the aggregation of amyloid beta peptides (Aβ), a proteolytic fragment of 39–43 amino acid residues derived from the amyloid precursor protein. AD has no cure; thus, new therapies to stop the progression of this deadly disease are constantly being searched for. In recent years, chaperone-based medications from medicinal plants have gained significant interest as an anti-AD therapy. Chaperones are responsible for maintaining the three-dimensional shape of proteins and play an important role against neurotoxicity induced by the aggregation of misfolded proteins. Therefore, we hypothesized that proteins extracted from the seeds of Artocarpus camansi Blanco (A. camansi) and Amaranthus dubius Mart. ex Thell (A. dubius) could possess chaperone activity and consequently may exhibit a protective effect against Aβ1–40-induced cytotoxicity. To test this hypothesis, the chaperone activity of these protein extracts was measured using the enzymatic reaction of citrate synthase (CS) under stress conditions. Then, their ability to inhibit the aggregation of Aβ1–40 using a thioflavin T (ThT) fluorescence assay and DLS measurements was determined. Finally, the neuroprotective effect against Aβ1–40 in SH-SY5Y neuroblastoma cells was evaluated. Our results demonstrated that A. camansi and A. dubius protein extracts exhibited chaperone activity and inhibited Aβ1–40 fibril formation, with A. dubius showing the highest chaperone activity and inhibition at the concentration assessed. Additionally, both protein extracts showed neuroprotective effects against Aβ1–40-induced toxicity. Overall, our data demonstrated that the plant-based proteins studied in this research work can effectively overcome one of the most important characteristics of AD.
Antiviral Peptides Delivered by Chitosan-Based Nanoparticles to Neutralize SARS-CoV-2 and HCoV-OC43
Authors: Mali Avinash , Franci Gianluigi , Zannella Carla , Chianese Annalisa , Anthiya Shubaash , López-Estévez Ana M. , Monti Alessandra , De Filippis Anna , Doti Nunzianna , Alonso María José , Galdiero Massimiliano
Published: May 2023

The COVID-19 pandemic has made it clear that there is a crucial need for the design and development of antiviral agents that can efficiently reduce the fatality rate caused by infectious diseases. The fact that coronavirus mainly enters through the nasal epithelial cells and spreads through the nasal passage makes the nasal delivery of antiviral agents a promising strategy not only to reduce viral infection but also its transmission. Peptides are emerging as powerful candidates for antiviral treatments, showing not only a strong antiviral activity, but also improved safety, efficacy, and higher specificity against viral pathogens. Based on our previous experience on the use of chitosan-based nanoparticles to deliver peptides intra-nasally the current study aimed to explore the delivery of two-novel antiviral peptides making use of nanoparticles consisting of HA/CS and DS/CS. The antiviral peptides were chemically synthesized, and the optimal conditions for encapsulating them were selected through a combination of physical entrapment and chemical conjugation using HA/CS and DS/CS nanocomplexes. Finally, we evaluated the in vitro neutralization capacity against SARS-CoV-2 and HCoV-OC43 for potential use as prophylaxis or therapy.
Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy
Authors: Navarro-Becerra J. Angel , Borden Mark A.
Published: May 2023

Microbubbles are 1–10 μm diameter gas-filled acoustically-active particles, typically stabilized by a phospholipid monolayer shell. Microbubbles can be engineered through bioconjugation of a ligand, drug and/or cell. Since their inception a few decades ago, several targeted microbubble (tMB) formulations have been developed as ultrasound imaging probes and ultrasound-responsive carriers to promote the local delivery and uptake of a wide variety of drugs, genes, and cells in different therapeutic applications. The aim of this review is to summarize the state-of-the-art of current tMB formulations and their ultrasound-targeted delivery applications. We provide an overview of different carriers used to increase drug loading capacity and different targeting strategies that can be used to enhance local delivery, potentiate therapeutic efficacy, and minimize side effects. Additionally, future directions are proposed to improve the tMB performance in diagnostic and therapeutic applications.
Novel Multi-Responsive Hyperbranched Polyelectrolyte Polyplexes as Potential Gene Delivery Vectors
Authors: Selianitis Dimitrios , Katifelis Hector , Gazouli Maria , Pispas Stergios
Published: May 2023

In this work, we investigate the complexation behavior of poly(oligo(ethylene glycol)methyl methacrylate)-co-poly(2-(diisopropylamino)ethyl methacrylate), P(OEGMA-co-DIPAEMA), hyperbranched polyelectrolyte copolymers, synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization, with short-linear DNA molecules. The synthesized hyperbranched copolymers (HBC), having a different chemical composition, are prepared in order to study their ability to bind with a linear nucleic acid at various N/P ratios (amine over phosphate groups). Specifically, the three pH and thermo-responsive P(OEGMA-co-DIPAEMA) hyperbranched copolymers were able to form polyplexes with DNA, with dimensions in the nanoscale. Using several physicochemical methods, such as dynamic and electrophoretic light scattering (DLS, ELS), as well as fluorescence spectroscopy (FS), the complexation process and the properties of formed polyplexes were explored in response to physical and chemical stimuli such as temperature, pH, and ionic strength. The mass and the size of polyplexes are shown to be affected by the hydrophobicity of the copolymer utilized each time, as well as the N/P ratio. Additionally, the stability of polyplexes in the presence of serum proteins is found to be excellent. Finally, the multi-responsive hyperbranched copolymers were evaluated regarding their cytotoxicity via in vitro experiments on HEK 293 non-cancerous cell lines and found to be sufficiently non-toxic. Based on our results, these polyplexes could be useful candidates for gene delivery and related biomedical applications.