bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic, Antimicrobial, and Aphicidal Traits of Bacillus velezensis ATR2, and Its Biocontrol Potential against Ginger Rhizome Rot Disease Caused by Bacillus pumilus
Authors: Liang Leiqin , Fu Yajuan , Deng Sangsang , Wu Yan , Gao Meiying
Published: December 2021

Ginger rhizome rot disease, caused by the pathogen Bacilluspumilus GR8, could result in severe rot of ginger rhizomes and heavily threaten ginger production. In this study, we identified and characterized a new Bacillus velezensis strain, designated ATR2. Genome analysis revealed B. velezensis ATR2 harbored a series of genes closely related to promoting plant growth and triggering plant immunity. Meanwhile, ten gene clusters involved in the biosynthesis of various secondary metabolites (surfactin, bacillomycin, fengycin, bacillibactin, bacilysin, difficidin, macrolactin, bacillaene, plantazolicin, and amylocyclicin) and two clusters encoding a putative lipopeptide and a putative phosphonate which might be explored as novel bioactive compounds were also present in the ATR2 genome. Moreover, B. velezensis ATR2 showed excellent antagonistic activities against multiple plant pathogenic bacteria, plant pathogenic fungi, human pathogenic bacteria, and human pathogenic fungus. B. velezensis ATR2 was also efficacious in control of aphids. The antagonistic compound from B. velezensis ATR2 against B.pumilus GR8 was purified and identified as bacillomycin D. In addition, B. velezensis ATR2 exhibited excellent biocontrol efficacy against ginger rhizome rot disease on ginger slices. These findings showed the potential of further applications of B. velezensis ATR2 as a biocontrol agent in agricultural diseases and pests management.
Two-Dimensional Soil Geometric Tortuosity Model Based on Porosity and Particle Arrangement
Authors: Gan Jin , Yang Zhiquan , Zhang Zhiwei , Li Chaoyue , Yang Yi , Zhu Yingyan , Guo Yanhui , Wang Renchao , Zhang Bihua , Fang Yingchao , Yu Dongliang , Zhang Jie , Liu Hao , Su Jiankun
Published: December 2021

Porosity and particle arrangement are important parameters affecting soil tortuosity, so it is of great significance to determine the intrinsic relationship between them when studying soil permeability characteristics. Theoretical derivation and geometric analysis methods are used to derive a two-dimensional geometric tortuosity model. The model is a function of particle arrangement parameters (m and θ) and porosity. An analysis of the model and its parameters shows that: (1) The arrangement of particles is one of the reasons for the different functional relationship between tortuosity and porosity, which proved that the tortuosity is not only related to the porosity but also affected by the particle arrangement. (2) The greater the anisotropy parameter m is, the greater the tortuosity is, indicating m varies when fluid passes through the soil from different sides resulting in different values of permeability. (3) The tortuosity increases with the increase in the blocking parameters θ. (4) With increasing porosity, the influence of the parameters m and θ on the tortuosity gradually decreases, suggesting that the influence of particle arrangement on tortuosity gradually decreases. The results presented here increase the understanding of the physical mechanisms controlling tortuosity and, hence, the process of fluid seepage through soil.
Quantification of STEM Images in High Resolution SEM for Segmented and Pixelated Detectors
Authors: Konvalina Ivo , Paták Aleš , Zouhar Martin , Müllerová Ilona , Fořt Tomáš , Unčovský Marek , Materna Mikmeková Eliška
Published: December 2021

The segmented semiconductor detectors for transmitted electrons in ultrahigh resolution scanning electron microscopes allow observing samples in various imaging modes. Typically, two standard modes of objective lens, with and without a magnetic field, differ by their resolution. If the beam deceleration mode is selected, then an electrostatic field around the sample is added. The trajectories of transmitted electrons are influenced by the fields below the sample. The goal of this paper is a quantification of measured images and theoretical study of the capability of the detector to collect signal electrons by its individual segments. Comparison of measured and ray-traced simulated data were difficult in the past. This motivated us to present a new method that enables better comparison of the two datasets at the cost of additional measurements, so-called calibration curves. Furthermore, we also analyze the measurements acquired using 2D pixel array detector (PAD) that provide a more detailed angular profile. We demonstrate that the radial profiles of STEM and/or 2D-PAD data are sensitive to material composition. Moreover, scattering processes are affected by thickness of the sample as well. Hence, comparing the two experimental and simulation data can help to estimate composition or the thickness of the sample.
Synthesis of Atomically Thin h-BN Layers Using BCl3 and NH3 by Sequential-Pulsed Chemical Vapor Deposition on Cu Foil
Authors: Oh Hongseok , Yi Gyu-Chul
Published: December 2021

The chemical vapor deposition of hexagonal boron nitride layers from BCl3 and NH3 is highly beneficial for scalable synthesis with high controllability, yet multiple challenges such as corrosive reaction or by-product formation have hindered its successful demonstration. Here, we report the synthesis of polycrystalline hexagonal boron nitride (h-BN) layers on copper foil using BCl3 and NH3. The sequential pulse injection of precursors leads to the formation of atomically thin h-BN layers with a polycrystalline structure. The relationship between growth temperature and crystallinity of the h-BN film is investigated using transmission electron microscopy and Raman spectroscopy. Investigation on the initial growth mode achieved by the suppression of precursor supply revealed the formation of triangular domains and existence of preferred crystal orientations. The possible growth mechanism of h-BN in this sequential-pulsed CVD is discussed.
Effect of a Support on the Properties of Zinc Oxide Based Sorbents
Authors: Chomiak Maciej , Szyja Bartłomiej M. , Jędrysiak Marta , Trawczyński Janusz
Published: December 2021

We present the comparative analysis of three Zn-based sorbents for the process of sulphur removal from hot coal gas. The sorbents were prepared by a slurry impregnation of TiO2, SiO2 and Al2O3, resulting in complex, multiphase materials, with the dominant phases of Zn2TiO4, Zn2SiO4 and ZnAl2O4, respectively. We have analyzed the effect of supports on the phase composition, texture, reducibility and H2S sorption. We have found that the phase composition significantly influences the susceptibility of the investigated materials to reduction by hydrogen. Zn2TiO4 have been found to be the easiest to reduce which correlates with its ability to adsorb the largest amount of hydrogen sulphide—up to 4.2 gS/100 g—compared to the other sorbents, which absorb up to 2.2 gS/100 g. In the case of Zn2SiO4 and ZnAl2O4, this effect also correlates with reducibility—these sorbents have been found to be highly resistant to reduction by hydrogen and to absorb much less hydrogen sulphide. In addition, the capacity of ZnAl2O4 for H2S adsorption decreases in the subsequent work cycles—from 2.2 gS/100 g in the first cycle to 0.8 gS/100 g in the third one. Computational analysis on the DFT level has shown that these materials show different thermodynamic stability of sulphur sites within the unit cells of the sorbents. For Zn2TiO4 and Zn2SiO4, the adsorption is favorable in both the first and second layers of the former and only the top layer of the latter, while for zinc aluminate it is not favorable, which is consistent with the experimental findings.
Properties of Polysiloxane/Nanosilica Nanodielectrics for Wearable Electronic Devices
Authors: Radu Elena Ruxandra , Panaitescu Denis Mihaela , Andrei Laura , Ciuprina Florin , Nicolae Cristian Andi , Gabor Augusta Raluca , Truşcă Roxana
Published: December 2021

Polymer nanodielectrics characterized by good flexibility, processability, low dielectric loss and high dielectric permittivity are materials of interest for wearable electronic devices and intelligent textiles, and are highly in demand in robotics. In this study, an easily scalable and environmentally friendly method was applied to obtain polysiloxane/nanosilica nanocomposites with a large content of nanofiller, of up to 30% by weight. Nanosilica was dispersed both as individual particles and as agglomerates; in nanocomposites with a lower amount of filler, the former prevailed, and at over 20 wt% nanosilica the agglomerates predominated. An improvement of both the tensile strength and modulus was observed for nanocomposites with 5–15 wt% nanosilica, and a strong increase of the storage modulus was observed with the increase of nanofiller concentration. Furthermore, an increase of the storage modulus of up to seven times was observed in the nanocomposites with 30 wt% nanosilica. The tensile modulus was well fitted by models that consider the aggregation of nanoparticles and the role of the interface. The dielectric spectra showed an increase of the real part of the complex relative permittivity with 33% for 30 wt% nanosilica in nanocomposites at a frequency of 1 KHz, whereas the loss tangent values were lower than 0.02 for all tested nanodielectrics in the radio frequency range between 1 KHz and 1 MHz. The polysiloxane–nanosilica nanocomposites developed in this work showed good flexibility; however, they also showed increased stiffness along with a stronger dielectric response than the unfilled polysiloxane, which recommends them as dielectric substrates for wearable electronic devices.
Mild Choline Deficiency and MTHFD1 Synthetase Deficiency Interact to Increase Incidence of Developmental Delays and Defects in Mice
Authors: Christensen Karen E. , Malysheva Olga V. , Carlin Stephanie , Matias Fernando , MacFarlane Amanda J. , Jacobs René L. , Caudill Marie A. , Rozen Rima
Published: December 2021

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80–90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S+/+ and Mthfd1S+/− females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S+/− genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.
Long-Chain Polyunsaturated Fatty Acid Concentrations and Association with Weight Gain in Pregnancy
Authors: da Mota Santana Jerusa , Pereira Marcos , Carvalho Gisele , dos Santos Djanilson , Oliveira Ana
Published: December 2021

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women’s weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (−0.20, −0.12, and −0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).
Postpartum Weight Change in Relation to Pre-Pregnancy Weight and Gestational Weight Gain in Women in Low-Income Setting: Data from the KITE Cohort in the Northern Part of Ethiopia
Authors: Misgina Kebede Haile , Groen Henk , Bezabih Afework Mulugeta , Boezen Hendrika Marike , van der Beek Eline M.
Published: December 2021

(1) Background: Postpartum weight may increase compared to pre-pregnancy due to weight retention or decrease due to weight loss. Both changes could pose deleterious effects on maternal health and subsequent pregnancy outcomes. Therefore, this study aimed to assess postpartum weight change and its associated factors. (2) Methods: A total of 585 women from the KIlte-Awlaelo Tigray Ethiopia (KITE) cohort were included in the analysis. (3) Results: The mean pre-pregnancy body mass index and weight gain during pregnancy were 19.7 kg/m2 and 10.8 kg, respectively. At 18 to 24 months postpartum, the weight change ranged from −3.2 to 5.5 kg (mean = 0.42 kg [SD = 1.5]). In addition, 17.8% of women shifted to normal weight and 5.1% to underweight compared to the pre-pregnancy period. A unit increase in weight during pregnancy was associated with higher weight change (β = 0.56 kg, 95% CI [0.52, 0.60]) and increased probability to achieve normal weight (AOR = 1.65, 95% CI [1.37, 2.00]). Food insecurity (AOR = 5.26, 95% CI [1.68, 16.50]), however, was associated with a shift to underweight postpartum. Interestingly, high symptoms of distress (AOR = 0.13, 95% CI [0.03, 0.48]) also negatively impacted a change in weight category. (4) Conclusions: In low-income settings such as northern Ethiopia, higher weight gain and better mental health during pregnancy may help women achieve a better nutritional status after pregnancy and before a possible subsequent pregnancy.
Korean Red Ginseng Enhances Immunotherapeutic Effects of NK Cells via Eosinophils in Metastatic Liver Cancer Model
Authors: Kwon Hee Jung , Lee Sunyi , Lee Hwan Hee , Cho Hyosun , Jung Joohee
Published: December 2021

Metastasis decreases the survival rate of patients with liver cancer. Therefore, novel anti-metastatic strategies are needed. Korean Red Ginseng (KRG) is often ingested as a functional food with an immune-boosting effect. We investigated a combination of KRG and natural killer (NK) cells as a novel immunotherapy approach. SK-Hep1 cells were injected into the tail vein of NRGA mice to establish an experimental metastasis model. KRG, NK cells, or a combination of KRG and NK cells were administered. Tumor growth was observed using an in vivo imaging system, and metastatic lesions were evaluated by histological analysis and immunohistochemistry. Bioluminescence intensity was lower in the KRG and NK cell combination group than in the other groups, indicating that the combination treatment suppressed the progression of metastasis. CD56 expression was used as a NK cell marker and hematological analysis was performed. The combination treatment also decreased the expression of matrix metalloproteinases and the area of metastatic lesions in liver and bone tissues, as well as increased the eosinophil count. Expression of cytokines-related eosinophils and NK cells was determined by Western blotting analysis. The expression of interleukin 33 (IL33) was induced by the combination of KRG and NK cells. High IL33 expression was associated with prolonged overall survival in the Kaplan–Meier plotter. Our results suggest that KRG enhances the immune activity of NK cells by IL-33 through eosinophils and suppresses metastatic liver cancer progression.
Anti-Periodontitis Effect of Ethanol Extracts of Alpinia Katsumadai Seeds
Authors: Shin Seo Woo , Hwang Young Sun
Published: December 2021

Oral microbes are intimately associated with many oral and systemic diseases. Ongoing research is seeking to elucidate drugs that prevent and treat microbial diseases. Various functions of Alpinia Katsumadai seed extracts have been reported such as their anti-viral, anti-oxidant, anti-inflammatory, anti-puritic, anti-emetic, and cytoprotective effects. Here, we investigated the anti-periodontitis effect of an ethanol extract of Alpinia Katsumadai seeds (EEAKSs) on dental plaque bacteria (DPB)-induced inflammation and bone resorption. DPB and Porphyromonas gingivalis (P. gingivalis) were cultured and lipopolysaccharide (LPS) was extracted. Prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX-2) levels were estimated using ELISA. Cytotoxicity was also verified. Proteases were screened using a protease antibody array method. Osteoclastic bone resorption was also investigated. EEAKSs suppressed P. gingivalis growth on agar plates. LPS prepared from dental plaque bacteria (DPB-LPS) and P. gingivalis (PG-LPS) significantly increased PGE2 and COX2 levels in immortalized gingival fibroblasts (IGFs), immortalized human oral keratinocytes (IHOKs), and RAW264.7 macrophage cells. However, DPB-LPS and PG-LPS-induced PGE2 and COX-2 increases were effectively abolished by EEAKS treatment at non-cytotoxic concentrations. In the protease antibody array, matrix metalloproteinase (MMP)-2, MMP-3, MMP-7, kallikrein 10, cathepsin D, and cathepsin V levels were increased by PG-LPS stimulation. However, increases in protease levels except for cathepsin D were suppressed by EEAKS treatment. In addition, RANKL-induced osteoclast differentiation was significantly inhibited by EEAKS treatment, leading to reductions in resorption pit formation. These results suggest that EEAKSs exerted a beneficial oral health effect to help prevent DPB-mediated periodontal disease.
Microbiota and Metabolite Profiling as Markers of Mood Disorders: A Cross-Sectional Study in Obese Patients
Authors: Leyrolle Quentin , Cserjesi Renata , Demeure Romane , Neyrinck Audrey M. , Amadieu Camille , Rodriguez Julie , Kärkkäinen Olli , Hanhineva Kati , Paquot Nicolas , Cnop Miriam , Cani Patrice D. , Thissen Jean-Paul , Bindels Laure B. , Klein Olivier , Luminet Olivier , Delzenne Nathalie M.
Published: December 2021

Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort of obese patients. Psychological, biological characteristics and nutritional habits were evaluated in 94 obese subjects from the Food4Gut study stratified according to their mood score assessed by the Positive and Negative Affect Schedule (PANAS). The fecal gut microbiota and plasma non-targeted metabolomics were analysed. Obese subjects with increased negative mood display elevated levels of Coprococcus as well as decreased levels of Sutterella and Lactobacillus. Serum metabolite profile analysis reveals in these subjects altered levels of several amino acid-derived metabolites, such as an increased level of L-histidine and a decreased in phenylacetylglutamine, linked to altered gut microbiota composition and function rather than to differences in dietary amino acid intake. Regarding clinical profile, we did not observe any differences between both groups. Our results reveal new microbiota-derived metabolites that characterize the alterations of mood in obese subjects, thereby allowing to propose new targets to tackle mood disturbances in this context. Food4gut, clinicaltrial.gov: NCT03852069.
Potential Role of Omega-3 Polyunsaturated Fatty Acids in Pediatric Food Allergy
Authors: Sartorio Marco Ugo Andrea , Pendezza Erica , Coppola Serena , Paparo Lorella , D’Auria Enza , Zuccotti Gian Vincenzo , Berni Canani Roberto
Published: December 2021

Polyunsaturated fatty acids (PUFAs) are involved both in immune system regulation and inflammation. In particular, within the PUFAs category, omega-3 (ω-3) may reduce inflammation, whereas omega-6 (ω-6) PUFAs are generally considered to have a proinflammatory effect. Recent evidence highlights an imbalance in the ω-3:ω-6 ratio with an increased intake of ω-6, as a consequence of the shift towards a westernized diet. In critical age groups such as infants, toddlers and young children, as well as pregnant and lactating women or fish allergic patients, ω-3 intake may be inadequate. This review aims to discuss the potential beneficial effects of PUFAs on pediatric food allergy prevention and treatment, both at prenatal and postnatal ages. Data from preclinical studies with PUFAs supplementation show encouraging effects in suppressing allergic response. Clinical studies results are still conflicting about the best timing and dosages of supplementation and which individuals are most likely to benefit; therefore, it is still not possible to draw firm conclusions. With regard to food-allergic children, it is still debated whether PUFAs could slow disease progression or not, since consistent data are lacking. In conclusion, more data on the effects of ω-3 PUFAs supplementation alone or in combination with other nutrients are warranted, both in the general and food allergic population.
Underweight and Weight Change Increases End-Stage Renal Disease Risk in Patients with Diabetes: A Nationwide Population-Based Cohort Study
Authors: Bae Eun Hui , Oh Tae Ryom , Suh Sang Heon , Yang Eun Mi , Choi Hong Sang , Kim Chang Seong , Ma Seong Kwon , Kim Bongseong , Han Kyung-Do , Kim Soo Wan
Published: December 2021

Weight variability has known as a risk factor for cardiovascular events and mortality. However, its effect on end-stage renal disease (ESRD) development remains controversial. We investigated the relationship between weight change and ESRD risk. Overall, 97,029 patients with DM aged >20 years were selected from the Korean National Health Screening Program 2009–2012. Weight change was defined as differences in body weight from the index year to 2 years later. Newly diagnosed ESRD was observed until 2017 end. Over a 5.1-year median follow-up period, ESRD was newly diagnosed in 7932 (4.81%) DM patients. BMI < 18.5 kg/m2 and waist circumferences <85/80 and >100/95 cm were ESRD risk factors. ESRD risk increased with increasing weight change; ≥10% weight loss (hazard ratio [HR], 1.247) followed by ≥10% weight gain (1.247) was associated with a higher HR than ≤5% weight change after adjusting for several confounding factors. The association between weight change and ESRD risk in a subgroup analysis was significantly stronger in patients aged <65 years, without proteinuria, with BMI ≥ 25, with DM duration <5 years, and prescribed less than 3 classes of DM medication. Underweight patients showed higher ESRD risks than overweight patients. Weight loss >10% was associated with the fastest decline in renal function.
A Survey of Tick Infestation and Tick-Borne Piroplasm Infection of Cattle in Oudalan and Séno Provinces, Northern Burkina Faso
Authors: Adjou Moumouni Paul Franck , Minoungou Germaine Lim-Bamba , Dovonou Christian Enonkpon , Galon Eloiza May , Efstratiou Artemis , Tumwebaze Maria Agnes , Byamukama Benedicto , Vudriko Patrick , Umemiya-Shirafuji Rika , Suzuki Hiroshi , Xuan Xuenan
Published: December 2021

In this study, cattle farms located in Oudalan and Séno, two provinces in the Sahel region, northern Burkina Faso, were surveyed. Cattle owners were interviewed, cattle were examined for tick infestation, and ticks as well as blood samples were collected during the dry season (October). Blood DNA samples were tested for Babesia and Theileria infections using nested PCRs and sequencing. A total of 22 herds, 174 Zebu cattle were investigated at 6 different sites. Overall, 76 cattle (43.7 %) from 18 farms (81.8%) were found infested with ticks. Cattle in Séno, adult cattle (>5 years) and those owned by the Fulani ethnic group were significantly (p < 0.05) more likely to be tick-infested. A total of 144 adult ticks belonging to five species namely: Hyalomma impeltatum, Hyalomma impressum, Hyalomma rufipes, Rhipicephalus evertsi evertsi, and Rhipicephalus guilhoni were collected from the animals. Piroplasms were detected in the blood DNA of 23 (13.2%) cattle. The cattle in Séno and adult cattle were significantly more likely to be piroplasm-positive. Five pathogens diversely distributed were identified. Theileria mutans (12/174), Babesia bigemina (5/174), Theileria annulata (3/174), and Theileria velifera (3/174) were detected for the first time in northern Burkina Faso, whereas Babesia occultans (1/174) was found for the first time in cattle in West Africa. The analysis of the sequences, including B. bigemina RAP-1a, T. annulata Tams1 genes, and the 18S rRNA genes of all the five protozoa, revealed identities ranging from 98.4 to 100% with previously published sequences. Phylogenetic analysis based on the 18S rRNA gene sequences located north Burkina Faso piroplasms in the same clade as isolates from Africa and other regions of the world. Notably, T. mutans sequences were distributed in two clades: the T. mutans Intona strain clade and the Theileria sp. (strain MSD)/ Theileria sp. B15a clade, suggesting the presence of at least two strains in the area. These findings indicate that the control of ticks and tick-borne diseases should be taken into account in strategies to improve animal health in the Sahel region.
Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 2: TRPM4 in Health and Disease
Authors: Dienes Csaba , Kovács Zsigmond Máté , Hézső Tamás , Almássy János , Magyar János , Bányász Tamás , Nánási Péter P. , Horváth Balázs , Szentandrássy Norbert
Published: December 2021

Transient receptor potential melastatin 4 (TRPM4) is a unique member of the TRPM protein family and, similarly to TRPM5, is Ca2+ sensitive and permeable for monovalent but not divalent cations. It is widely expressed in many organs and is involved in several functions; it regulates membrane potential and Ca2+ homeostasis in both excitable and non-excitable cells. This part of the review discusses the currently available knowledge about the physiological and pathophysiological roles of TRPM4 in various tissues. These include the physiological functions of TRPM4 in the cells of the Langerhans islets of the pancreas, in various immune functions, in the regulation of vascular tone, in respiratory and other neuronal activities, in chemosensation, and in renal and cardiac physiology. TRPM4 contributes to pathological conditions such as overactive bladder, endothelial dysfunction, various types of malignant diseases and central nervous system conditions including stroke and injuries as well as in cardiac conditions such as arrhythmias, hypertrophy, and ischemia-reperfusion injuries. TRPM4 claims more and more attention and is likely to be the topic of research in the future.
An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue
Authors: Teitelbaum Jacob , Goudie Sarah
Published: December 2021

Chronic fatigue syndrome and fibromyalgia (CFS/FMS) affect 2.1% of the world’s population and ~10–25% of people who have had COVID-19. Previous clinical data suggested that a unique Panax ginseng (C.A. Meyer, family Araliaceae) root extract (HRG80™ Red Ginseng) often resulted in marked improvement. We aimed to study this hydroponic form of red ginseng root, containing high levels of rare ginsenosides, for improving energy, cognition, and stamina. This open-label prospective study included participants with severe CFS/FMS who took a daily supplement of HRG80 capsules (200–400 mg) or tablets (100–200 mg) for one month. A total of 188 subject patients completed the one-month treatment trial. Of these, 60.1% rated themselves as improved, with 13.3% rating themselves as being much better. In this group, the mean composite score improved from 11.9 to 18.8 (p < 0.001), with a 67% average increase in energy, 44% average increase in overall well-being, 48% average improvement in mental clarity, 58% average composite improvement in the previous three measurements (primary outcome measure), 46% average improvement in sleep, 33% average decrease in pain, and 72% average increase in stamina. Our study showed that HRG80 red ginseng root powder resulted in a marked improvement in people with CFS and fibromyalgia. This included the subgroup with post-viral CFS/FMS.
Development of DNA Aptamers to Visualize Release of Mycobacterial Membrane-Derived Extracellular Vesicles in Infected Macrophages
Authors: Das Soonjyoti , Jain Sapna , Ilyas Mohd , Anand Anjali , Kumar Saurabh , Sharma Nishant , Singh Kuljit , Mahlawat Rahul , Sharma Tarun Kumar , Atmakuri Krishnamohan
Published: December 2021

Extracellular vesicles (EVs) have emerged into a novel vaccine platform, a biomarker and a nano-carrier for approved drugs. Their accurate detection and visualization are central to their utility in varied biomedical fields. Owing to the limitations of fluorescent dyes and antibodies, here, we describe DNA aptamer as a promising tool for visualizing mycobacterial EVs in vitro. Employing SELEX from a large DNA aptamer library, we identified a best-performing aptamer that is highly specific and binds at nanomolar affinity to EVs derived from three diverse mycobacterial strains (pathogenic, attenuated and avirulent). Confocal microscopy revealed that this aptamer was not only bound to in vitro-enriched mycobacterial EVs but also detected EVs that were internalized by THP-1 macrophages and released by infecting mycobacteria. To the best of our knowledge, this is the first study that detects EVs released by mycobacteria during infection in host macrophages. Within 4 h, most released mycobacterial EVs spread to other parts of the host cell. We predict that this tool will soon hold huge potential in not only delineating mycobacterial EVs-driven pathogenic functions but also in harboring immense propensity to act as a non-invasive diagnostic tool against tuberculosis in general, and extra-pulmonary tuberculosis in particular.
Characterization and Stabilization of a New 64Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography
Authors: Matsumoto Hiroki , Igarashi Chika , Tachibana Tomoko , Hihara Fukiko , Waki Atsuo , Zhang Ming-Rong , Yoshida Sei , Naito Kenichiro , Kurihara Hiroaki , Ueno Makoto , Ito Kimiteru , Higashi Tatsuya , Yoshii Yukie
Published: December 2021

Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make 64Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and 64Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture 64Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and 64Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of 64Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of 64Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer.
CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials
Authors: Zhang Zhongkun , Kuo Jimmy Chun-Tien , Yao Siyu , Zhang Chi , Khan Hira , Lee Robert J.
Published: December 2021

CpG oligodeoxynucleotides (CpG ODNs), the artificial versions of unmethylated CpG motifs that were originally discovered in bacterial DNA, are demonstrated not only as potent immunoadjuvants but also as anticancer agents by triggering toll-like receptor 9 (TLR9) activation in immune cells. TLR9 activation triggered by CpG ODN has been shown to activate plasmacytoid dendritic cells (pDCs) and cytotoxic T lymphocytes (CTLs), enhancing T cell-mediated antitumor immunity. However, the extent of antitumor immunity carried by TLR agonists has not been optimized individually or in combinations with cancer vaccines, resulting in a decreased preference for TLR agonists as adjuvants in clinical trials. Although various combination therapies involving CpG ODNs have been applied in clinical trials, none of the CpG ODN-based drugs have been approved by the FDA, owing to the short half-life of CpG ODNs in serum that leads to low activation of natural killer cells (NK cells) and CTLs, along with increases of pro-inflammatory cytokine productions. This review summarized the current innovation on CpG ODNs that are under clinical investigation and explored the future direction for CpG ODN-based nanomedicine as an anticancer monotherapy.
Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles
Authors: Huang Li , Himawan Erico , Belhadj Soumaya , Pérez García Raúl Oswaldo , Paquet Durand François , Schipper Nicolaas , Buzgo Matej , Simaite Aiva , Marigo Valeria
Published: December 2021

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargos to the retina. The new formulation, based on a gel core and composite shell, allowed up to two-fold increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affected the particle surface charge, colloidal stability, and cell internalization profile. We validated SLNs as a drug delivery system by performing the encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analog, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with a size of ±250 nm, anionic charge > −20 mV, and an encapsulation efficiency of ±60%, criteria that are suitable for retinal delivery. In vitro studies using the ARPE-19 and 661W retinal cell lines revealed the relatively low toxicity of SLNs, even when a high particle concentration was used. More importantly, SLN could be taken up by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all the characteristics suitable for the drug delivery of small hydrophilic active molecules into retinal cells.
Bromelain and Nisin: The Natural Antimicrobials with High Potential in Biomedicine
Authors: Jančič Urška , Gorgieva Selestina
Published: December 2021

Infectious diseases along with various cancer types are among the most significant public health problems and the leading cause of death worldwide. The situation has become even more complex with the rapid development of multidrug-resistant microorganisms. New drugs are urgently needed to curb the increasing spread of diseases in humans and livestock. Promising candidates are natural antimicrobial peptides produced by bacteria, and therapeutic enzymes, extracted from medicinal plants. This review highlights the structure and properties of plant origin bromelain and antimicrobial peptide nisin, along with their mechanism of action, the immobilization strategies, and recent applications in the field of biomedicine. Future perspectives towards the commercialization of new biomedical products, including these important bioactive compounds, have been highlighted.
Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery
Authors: Yokoo Hidetomo , Oba Makoto , Uchida Satoshi
Published: December 2021

Messenger RNAs (mRNAs) were previously shown to have great potential for preventive vaccination against infectious diseases and therapeutic applications in the treatment of cancers and genetic diseases. Delivery systems for mRNAs, including lipid- and polymer-based carriers, are being developed for improving mRNA bioavailability. Among these systems, cell-penetrating peptides (CPPs) of 4–40 amino acids have emerged as powerful tools for mRNA delivery, which were originally developed to deliver membrane-impermeable drugs, peptides, proteins, and nucleic acids to cells and tissues. Various functionalities can be integrated into CPPs by tuning the composition and sequence of natural and non-natural amino acids for mRNA delivery. With the employment of CPPs, improved endosomal escape efficiencies, selective targeting of dendritic cells (DCs), modulation of endosomal pathways for efficient antigen presentation by DCs, and effective mRNA delivery to the lungs by dry powder inhalation have been reported; additionally, they have been found to prolong protein expression by intracellular stabilization of mRNA. This review highlights the distinctive features of CPP-based mRNA delivery systems.
Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers
Authors: Morin Maxim , Björklund Sebastian , Jankovskaja Skaidre , Moore Kieran , Delgado-Charro Maria Begoña , Ruzgas Tautgirdas , Guy Richard H. , Engblom Johan
Published: December 2021

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.
Rowan Berries: A Potential Source for Green Synthesis of Extremely Monodisperse Gold and Silver Nanoparticles and Their Antimicrobial Property
Authors: Singh Priyanka , Mijakovic Ivan
Published: December 2021

Rowanberries (Sorbus aucuparia) are omnipresent in Europe. The medicinal importance of rowanberries is widely known and corresponds to the active ingredients present in the fruits, mainly polyphenols, carotenoids, and organic acids. In the current study, we explored rowanberries for the reduction of gold and silver salts into nanoparticles. Rowanberries-mediated gold nanoparticles (RB-AuNPs) formed within 5 s at room temperature, and silver nanoparticles (RB-AgNPs) formed in 20 min at 90 °C. The produced nanoparticles were thoroughly characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), dynamic light scattering (DLS), single-particle inductively coupled plasma–mass spectrometry (sp-ICP-MS), thermogravimetric analysis (TGA), Fourier transform-infrared spectroscopy (FT-IR) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). The characterization confirmed that the nanoparticles are highly monodisperse, spherical, stable over long periods, and exhibit a high negative zeta potential values. The produced RB-AuNPs and RB-AgNPs were 90–100 nm and 20–30 nm in size with a thick biological corona layer surrounding them, providing extreme stability but lowering the antimicrobial activity. The antimicrobials study of RB-AgNPs revealed that the nanoparticles have antimicrobial potential with an MBC value of 100 µg/mL against P. aeruginosa and 200 µg/mL against E. coli.
Interpretation and Dynamics of the Lotka–Volterra Model in the Description of a Three-Level Laser
Authors: Aboites Vicente , Bravo-Avilés Jorge Francisco , García-López Juan Hugo , Jaimes-Reategui Rider , Huerta-Cuellar Guillermo
Published: December 2021

In this work, the Lotka–Volterra equations where applied to laser physics to describe population inversion and the number of emitted photons. Given that predation and stimulated emissions are analogous processes, two rate equations where obtained by finding suitable parameter transformations for a three-level laser. This resulted in a set of differential equations which are isomorphic to several laser models under accurate parameter identification. Furthermore, the steady state provided two critical points: one where light amplification stops and another where continuous-wave operation is achieved. Lyapunov’s first method of stability yielded the conditions for the convergence to the continuous-wave point, whereas a Lyapunov potential provided its stability regions. Finally, the Q-Switching technique was modeled by introducing a periodic variation of the quality Q of the cavity. This resulted in the transformation of the asymptotically stable fixed point into a limit cycle in the phase space.
Low-Frequency Content of THz Emission from Two-Color Femtosecond Filament
Authors: Shipilo Daniil E. , Panov Nikolay A. , Nikolaeva Irina A. , Ushakov Alexander A. , Chizhov Pavel A. , Mamaeva Kseniia A. , Bukin Vladimir V. , Garnov Sergey V. , Kosareva Olga G.
Published: December 2021

We experimentally investigate the low-frequency (below 1 THz) spectral content of broadband terahertz (THz) emission from two-color femtosecond filament formed by the 2.7-mJ, 40-fs, 800+400-nm pulse focused into air. For incoherent detection, we screened the Golay cell by the bandpass filters and measured the THz angular distributions at the selected frequencies ν=0.5, 1, 2 and 3 THz. The measured distributions of THz fluence were integrated over the forward hemisphere taking into account the transmittance of the filters, thus providing the estimation of spectral power at the frequencies studied. The spectral power decreases monotonically with the frequency increasing from 0.5 to 3 THz, thus showing that the maximum of THz spectrum is attained at ν≤0.5 THz. The THz waveform measured by electro-optical sampling (EOS) based on ZnTe crystal and transformed into the spectral domain shows that there exists the local maximum of the THz spectral power at ν≈1 THz. This disagrees with monotonic decrease of THz spectral power obtained from the filter-based measurements. We have introduced the correction to the spectral power reconstructed from EOS measurements. This correction takes into account different focal spot size for different THz frequencies contained in the broadband electromagnetic pulse. The corrected EOS spectral power is in semi-quantitative agreement with the one measured by a set of filters.
Silicon Mitigates Negative Impacts of Drought and UV-B Radiation in Plants
Authors: Mavrič Čermelj Anja , Golob Aleksandra , Vogel-Mikuš Katarina , Germ Mateja
Published: December 2021

Due to climate change, plants are being more adversely affected by heatwaves, floods, droughts, and increased temperatures and UV radiation. This review focuses on enhanced UV-B radiation and drought, and mitigation of their adverse effects through silicon addition. Studies on UV-B stress and addition of silicon or silicon nanoparticles have been reported for crop plants including rice, wheat, and soybean. These have shown that addition of silicon to plants under UV-B radiation stress increases the contents of chlorophyll, soluble sugars, anthocyanins, flavonoids, and UV-absorbing and antioxidant compounds. Silicon also affects photosynthesis rate, proline content, metal toxicity, and lipid peroxidation. Drought is a stress factor that affects normal plant growth and development. It has been frequently reported that silicon can reduce stress caused by different abiotic factors, including drought. For example, under drought stress, silicon increases ascorbate peroxidase activity, total soluble sugars content, relative water content, and photosynthetic rate. Silicon also decreases peroxidase, catalase, and superoxide dismutase activities, and malondialdehyde content. The effects of silicon on drought and concurrently UV-B stressed plants has not yet been studied in detail, but initial studies show some stress mitigation by silicon.
Corn Starch: Quality and Quantity Improvement for Industrial Uses
Authors: Yu Ju-Kyung , Moon Yong-Sun
Published: December 2021

Corn starch serves as food, feed, and a raw material for industrial use. Starch makes up most of the biomass of the corn hybrid and is the most important and main yield component in corn breeding programs. Starch is composed of two polymers, branched amylopectin and linear amylose, which normally constitute about 75% and 25% of the corn starch, respectively. Breeding for corn starch quality has become economically beneficial because of the development of niche markets for specialty grains. In addition, due to the increased demands of biofuel production, corn ethanol production is receiving more attention. Consequently, improving starch quantity has become one of the most important breeding objectives. This review will summarize the use of corn starch, and the genetics and breeding of grain quality and quantity for industrial applications.