bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Activities of Grape Seed By-Products and Their Potential Use as Natural Sources of Food Additives in the Production of Balady Bread
Authors: Elkatry Haiam O. , Ahmed Abdelrahman R. , El-Beltagi Hossam S. , Mohamed Heba I. , Eshak Nareman S.
Published: July 2022

The biological function of bioactive compounds found in plant by-products has triggered expanded interest in recent years. This study aims to produce balady bread enriched with dietary fiber, mineral, and phenolic compounds by the addition of grape seeds powder (GSP) at different levels (5%, 10%, and 15% as a partial substitute for wheat flour). The results show that balady bread (Bb) and grape seed powder have ash contents of about 1.97% and 3.04%, lipid contents of 3.22% and 17.15%, protein contents of 11.16% and 12.10%, fiber contents of 1.06% and 44.90%, and carbohydrates contents of 56.52% and 29%, respectively. Moreover, grape seed powder contains a higher level of iron and zinc about 30.02 and 9.43 mg/kg than the Bb control sample which contains about 8.19 and 7.25 mg/kg respectively. The findings revealed that balady bread fortified with grape seed powder contains a high amount of total polyphenols content (TPC), total flavonoid content (TF), and antioxidant capacity. The farinograph test results showed that increasing the GSP concentration in the flour above 10% reduced dough development, stability, and farinograph quality number. The addition of GSP to wheat flour accelerated the dough’s water absorption and mixing tolerance. Grape seed incorporation levels up to 10% (w/w) had no negative effect on dough rheological performance. The sensory evaluation of bread showed that samples that were enriched with grape seeds powder at up to 10% had good quality. Based on these findings, it is recommended to replace up to 10% GSP in the manufacturing of fortified balady bread with satisfactory physical and sensory characteristics and high TPC and antioxidant activity.
The Regulation of Micro-Organisms’ Extra-Cellular Polysaccharides on Immunity: A Meta-Analysis
Authors: Zhang Jin , Chen Yirui , Zhang Jiaqi , Wang Yitong , Liu Yanan
Published: July 2022

Extra-cellular polysaccharides (EPSs) have excellent immunomodulatory functions. In order to further promote their application, we studied the ability of extra-cellular polysaccharides from different sources to regulate immunity. We studied the association of extra-cellular polysaccharides with immune factors (Interleukin (IL-2, IL-4, IL-10), Interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), Immunoglobulin A (IgA), and Immunoglobulin G (IgG)) and different concentrations of EPSs and interfering media on experimental results by using a forest plot under fixed-effect or random-effects models. Through Google, PubMed, Embase, ScienceDirect, and Medline, from 2000 to 2021, 12 articles were included. We found that exopolysaccharides (from bacteria or fungi) could significantly increase the immune index of spleen and thymus, spleen index (SMD: 2.11, ‘95%CI: [1.15, 3.08]’; p < 0.01), and thymus index (SMD: 1.62, ‘95%CI: [0.93, 2.32]’; p = 0.01 < 0.05). In addition, exopolysaccharides had a significant effect on TNF-α (SMD: 0.94, ‘95%CI: [0.29, 1.59]’; p = 0.01 < 0.05). For IL-4 (SMD: 0.49, ‘95%CI: [0.01, 0.98]’; p = 0.046 < 0.05), extra-cellular polysaccharides had a statistically significant effect on immunity. Although the data of other immune factors were not ideal, the comprehensive analysis showed that exopolysaccharides also had an effect on the release of these five immune factors. In the sub-group analysis, different concentrations of EPSs affected the results of experiments on the spleen and thymus, and the CY intervention had a relatively significant effect on immune regulation. Taken together, our study highlighted that EPSs have a significant impact on immune regulation.
Application of Emulsion Gels as Fat Substitutes in Meat Products
Authors: Ren Yuqing , Huang Lu , Zhang Yinxiao , Li He , Zhao Di , Cao Jinnuo , Liu Xinqi
Published: July 2022

Although traditional meat products are highly popular with consumers, the high levels of unsaturated fatty acids and cholesterol present significant health concerns. However, simply using plant oil rich in unsaturated fatty acids to replace animal fat in meat products causes a decline in product quality, such as lower levels of juiciness and hardness. Therefore, it is necessary to develop a fat substitute that can ensure the sensory quality of the product while reducing its fat content. Consequently, using emulsion gels to produce structured oils or introducing functional ingredients has attracted substantial attention for replacing the fat in meat products. This paper delineated emulsion gels into protein, polysaccharide, and protein–polysaccharide compound according to the matrix. The preparation methods and the application of the three emulsion gels as fat substitutes in meat products were reviewed. Since it displayed a unique separation structure, the double emulsion was highly suitable for encapsulating bioactive substances, such as functional oils, flavor components, and functional factors, while it also exhibited significant potential for developing low-fat or functional healthy meat products. This paper summarized the studies involving the utilization of double emulsion and gelled double emulsion as fat replacement agents to provide a theoretical basis for related research and new insight into the development of low-fat meat products.
Advances in Optimization and Nonlinear Analysis
Authors: Treanţă Savin
Published: July 2022

There are many applications of optimization and nonlinear analysis in various fields of basic science, engineering, and natural phenomena [...]
Oxostephanine, Thalmiculine, and Thaliphyline—Three Isoquinoleine Alkaloids That Inhibit L-Type Voltage-Gated Ca2+ Channels
Authors: Frangieh Jacinthe , Legendre Claire , Bréard Dimitri , Richomme Pascal , Henrion Daniel , Fajloun Ziad , Mattei César , Le Ray Anne-Marie , Legros Christian
Published: July 2022

The isoquinoline alkaloids (IAs) represent a large and diverse subfamily of phytochemicals in terms of structures and pharmacological activities, including ion channel inhibition. Several IAs, such as liriodenine (an oxoaporphine) and curine (a bisbenzylisoquinoline (BBIQ), inhibit the L-type voltage-gated Ca2+ channels (LTCC). In this study, we aimed to search for new blockers of LTCC, which are therapeutic targets in neurological and cardiovascular diseases. We set up a screening assay using the rat pituitary GH3b6 cell line, which expresses two LTCC isoforms, CaV1.2 and CaV1.3. Both LTCC subtypes can be indirectly activated by KCl concentration elevation or directly by the dihydropyridine (DHP), BAY K8644, leading to an increase in the intracellular Ca2+ concentration ([Ca2+]i). These Ca2+ responses were completely blocked by the selective LTCC DHP inhibitor, nifedipine. Thereby, 16 selected IAs were tested for their ability to inhibit KCl and BAY K8644-induced Ca2+ responses. We then identified three new potent LTCC blockers, namely, oxostephanine, thaliphyline, and thalmiculine. They inhibited LTCC with IC50 values in the micromolar range through interaction to a binding site different to that of dihydropyridines. The two subfamilies of IAs, oxoaporphine with oxostephanine, and BBIQs with both thalyphilline and thalmiculine, constitute interesting pharmacophores for the development of future therapeutic leads for neurological and cardiovascular diseases.
Application of Xanthan Gum and Hyaluronic Acid as Dermal Foam Stabilizers
Authors: Falusi Fanni , Berkó Szilvia , Kovács Anita , Budai-Szűcs Mária
Published: July 2022

Foams are increasingly popular in the field of dermatology due to their many advantages such as easy spreading, good skin sensation, and applicability in special skin conditions. One of the critical points of foam formulation is the choice of the appropriate stabilizing ingredients. One of the stability-increasing strategies is retarding the liquid drainage of liquid films from the foam structure. Therefore, our aim was the application of different hydrogel-forming polymers in order to retain the stabilizing liquid film. Dexpanthenol and niacinamide-containing foams were formulated, where xanthan gum and hyaluronic acid were used as foam-stabilizing polymers. Amplitude (LVE range) and frequency sweep (G’, G”, tanδ, and frequency dependency) were applied as structure- and stability-indicating rheological parameters. The rheological data were compared with the results of the cylinder method, microscopical images, and the spreadability measurements. The application of the gel-forming polymers increased the stability of the dermal foams (increased LVE range, G’ values, and decreased frequency dependency). These results were in correlation with the results of the cylinder and spreadability tests. It was concluded that in terms of both foam formation and stability, the combination of xanthan gum and dexpanthenol can be ideal.
Effect of Developmental Stages on Genes Involved in Middle and Downstream Pathway of Volatile Terpene Biosynthesis in Rose Petals
Authors: Kong Ying , Wang Huan , Lang Lixin , Dou Xiaoying , Bai Jinrong
Published: July 2022

Terpenoids are economically and ecologically important compounds, and they are vital constituents in rose flower fragrance and rose essential oil. The terpene synthase genes (TPSs), trans-prenyltransferases genes (TPTs), NUDX1 are involved in middle and downstream pathway of volatile terpene biosynthesis in rose flowers. We identified 7 complete RcTPTs, 49 complete RcTPSs, and 9 RcNUDX1 genes in the genome of Rosachinensis. During the flower opening process of butterfly rose (Rosachinensis ‘Mutabilis’, MU), nine RcTPSs expressed in the petals of opening MU flowers exhibited two main expression trends, namely high and low, in old and fresh petals. Five short-chain petal-expressed RcTPTs showed expression patterns corresponding to RcTPSs. Analysis of differential volatile terpenes and differential expressed genes indicated that higher emission of geraniol from old MU petals might be related to the RcGPPS expression. Comprehensive analysis of volatile emission, sequence structure, micro-synteny and gene expression suggested that RcTPS18 may encode (E,E)-α-farnesene synthase. These findings may be useful for elucidating the molecular mechanism of terpenoid metabolism in rose and are vital for future studies on terpene regulation.
The Effects of Catabolism Relationships of Leucine and Isoleucine with BAT2 Gene of Saccharomyces cerevisiae on High Alcohols and Esters
Authors: Zhang Lin , Zhang Yiqian , Hu Zhongqiu
Published: July 2022

This study sought to provide a theoretical basis for effectively controlling the content of higher alcohols and esters in fermented foods. In this work, isoleucine (Ile) or leucine (Leu) at high levels was used as the sole nitrogen source for a BAT2 mutant and its parental Saccharomyces. cerevisiae 38 to investigate the effects of the addition of amounts of Ile or Leu and BAT2 on the aroma components in the flavor profile using gas chromatography mass spectrometer (GC-MS). The results showed that 2-methyl-butyraldehyde, 2-methyl-1-butanol, and 2-methylbutyl-acetate were the products positively correlated with the Ile addition amount. In addition, 3-methyl-butyraldehyde, 3-methyl-1-butanol, and 3-methylbutyl-acetate were the products positively correlated with Leu addition amount. BAT2 deletion resulted in a significant decline in the yields of 2-methyl-butyraldehyde, 3-methyl-butyraldehyde,2-methyl-1-butanol, and 3-methyl-1-butanol, but also an increase in the yields of 2-methylbutyl-acetate and 3-methylbutyl-acetate. We speculated that BAT2 regulated the front and end of this metabolite chain in a feedback manner. Improved metabolic chain analyses, including the simulated energy metabolism of Ile or Leu, indicated that reducing the added amount of branched-chain amino acids, BAT mutation, and eliminating the role of energy cofactors such as NADH/NAD+ were three important ways to control the content of high alcohols and esters in fermented foods.
A Distribution-Free Model for Longitudinal Metagenomic Count Data
Authors: Luo Dan , Liu Wenwei , Chen Tian , An Lingling
Published: July 2022

Longitudinal metagenomics has been widely studied in the recent decade to provide valuable insight for understanding microbial dynamics. The correlation within each subject can be observed across repeated measurements. However, previous methods that assume independent correlation may suffer from incorrect inferences. In addition, methods that do account for intra-sample correlation may not be applicable for count data. We proposed a distribution-free approach, namely CorrZIDF, which extends the current method to model correlated zero-inflated metagenomic count data, offering a powerful and accurate solution for detecting significance features. This method can handle different working correlation structures without specifying each margin distribution of the count data. Through simulation studies, we have shown the robustness of CorrZIDF when selecting a working correlation structure for repeated measures studies to enhance the efficiency of estimation. We also compared four methods using two real datasets, and the new proposed method identified more unique features that were reported previously on the relevant research.
Enhancement of Geoheritage and Development of Geotourism: Comparison and Inferences from Different Experiences of Communication through Art
Authors: Valentini Laura , Guerra Veronica , Lazzari Maurizio
Published: July 2022

Geoheritage is a geotourism resource that could lead to the sustainable development of society, and could contribute to information on geological and geomorphological characteristics, education, public awareness on geoconservation, and landscape protection. Understanding this cultural wealth is still limited, since the information available is often specialized. Communication addressed to the emotional sphere can profoundly engage people, and technical information can be transmitted more effectively. For several years, our research group dealt with geoheritage and geotourism in central Italy. This work aimed to investigate different communication methods, such as publications, announcements through social media, conferences, live performances, and field excursions aimed at the emotional involvement of the public. Furthermore, the emotional response of the public was explored through a digital survey. These communication methodologies enabled a broad public reach, without any distinction based on social origin, cultural background, or age. Narrating the landscape through different forms of art creates a personal relationship with the audience. The emotional participation of the people demonstrates the effectiveness of the method in transmitting scientific and cultural themes, such as the origin of the geological landforms, the culture and the traditions that the site generated, and the problems pertaining to its protection and conservation.
Multi-Parameter Observations of Seismogenic Phenomena Related to the Tokyo Earthquake (M = 5.9) on 7 October 2021
Authors: Hayakawa Masashi , Schekotov Alexander , Izutsu Jun , Yang Shih-Sian , Solovieva Maria , Hobara Yasuhide
Published: July 2022

Multi-parameter observations, powerful for the study of lithosphere–atmosphere–ionosphere coupling (LAIC), have been performed for a recent Tokyo earthquake (EQ) with a moderate magnitude (M = 5.9) and rather larger depth (~70 km) on 7 October 2021, in the hope of predicting the next Kanto (Tokyo) huge EQ, such as the 1923 Great Kanto EQ (with a magnitude greater than 7). Various possible precursors have been searched during the two-month period of 1 September to 31 October 2021, based on different kinds of data sets: (i) ULF (ultra-low frequency) magnetic data from Kakioka, Japan, (ii) ULF/ELF (extremely low frequency) magnetic field data from the Chubu University network, (iii) meteorological data (temperature and humidity) from the Japan Meteorological Agency (JMA), (iv) AGW (atmospheric gravity wave) ERA5 data provided by the European Centre for Medium-Range Weather Forecast (ECMWF), (v) subionospheric VLF/LF (very low frequency/low frequency) data from Russia and Japan, (vi) ionosonde Japanese data, and (vii) GIM (global ionosphere map) TEC (total electron content) data. After extensive analyses of all of the above data, we have found that there are a few obvious precursors: (i) ULF/ELF electromagnetic radiation in the atmosphere, and (ii) lower ionospheric perturbations (with two independent tools from the ULF depression and subionospheric VLF anomaly) which took place just two days before the EQ. Further, ULF/ELF atmospheric electromagnetic radiation has been observed from approximately one week before the EQ until a few days after the EQ, which seems to be approximately synchronous in time to the anomalous variation in meteorological parameters (a combination of temperature and humidity, atmospheric chemical potential). On the other hand, there have been no clear anomalies detected in the stratospheric AGW activity, and in the NmF2 and TEC data for the upper F region ionosphere. So, it seems that the lithospheric origin is not strong enough to perturb the upper F region. Finally, we discuss the possible hypothesis for the LAIC process, and we can conclude that the AGW hypothesis might be ruled out, but other possible channels such as the chemical channel (radon emanation) and the associated effects might be in operation, at least, for this Tokyo EQ.
Active Triclinic Transtension in a Volcanic Arc: A Case of the El Salvador Fault Zone in Central America
Authors: Alonso-Henar Jorge , Fernández Carlos , Álvarez-Gómez José Antonio , Canora Carolina , Staller Alejandra , Díaz Manuel , Hernández Walter , García Ángela Valeria , Martínez-Díaz José Jesús
Published: July 2022

The El Salvador Fault Zone (ESFZ) is part of the Central American Volcanic Arc and accommodates the oblique separation movement between the forearc sliver and the Chortis block (Caribbean Plate). In this work, a triclinic transtension model was applied to geological (fault-slip inversion, shape of volcanic calderas), seismic (focal mechanisms) and geodetic (GPS displacements) data to evaluate the characteristics of the last stages of the kinematic evolution of the arc. The El Salvador Fault Zone constitutes a large band of transtensional deformation whose direction varies between N90° E and N110° E. Its dip is about 70° S because it comes from the reactivation of a previous extensional stage. A protocol consisting of three successive steps was followed to compare the predictions of the model with the natural data. The results show a simple shear direction plunging between 20° and 50° W (triclinic flow) and a kinematic vorticity number that is mostly higher than 0.81 (simple-shearing-dominated flow). The direction of shortening of the coaxial component would be located according to the dip of the deformation band. It was concluded that this type of analytical model could be very useful in the kinematic study of active volcanic arcs, even though only information on small deformation increments is available.
Of Force? Plasticity, Annihilation and Change
Authors: Cree Dylan Jeffrey
Published: July 2022

Catherine Malabou’s conception of plasticity as potentially having a creative or destructive form provides both philosophy and the neurosciences with a dynamic and generative concept for describing the workings and transformations of psychological, social, and material phenomena. Exploring the dynamism of Malabou’s plasticity, I question: how is plasticity, whether as a giving or receiving form, constituted to be so dynamic? Drawing somewhat from Heidegger’s account of change, I propose thinking of form as existing within a world of forces, to be a force, and be composed of force(s). The problem being, though somewhat presupposed and even alluded to in her elaborations of form and destructive plasticity, Malabou doesn’t conceptualize force nor advance it as a necessity for conceptualizing plasticity. Nevertheless, developing upon Christopher Watkin’s idea for engaging Malabou’s plasticity relationally within a broader ecology, we come to see how, whether ontically or ontologically, force(s) appear to be what makes plasticity dynamic. As a result, in order to address the figure of force as being integral to form, I argue that Malabou will need to somehow transfigure her conception of plasticity. Ultimately, in my estimation, such elaboration may lead to plasticity’s conceptual re-birth in the form of a mediating force.
The COVID-19 Pandemic in Romania: A Comparative Description with Its Border Countries
Authors: Enciu Bianca Georgiana , Tănase Alina Andreea , Drăgănescu Anca Cristina , Aramă Victoria , Pițigoi Daniela , Crăciun Maria-Dorina
Published: July 2022

The COVID-19 pandemic continues to be a major public health problem in most countries of the world, especially in developing countries with an underfunded healthcare system. We aim to present a comparative profile of the epidemiological characteristics of the COVID-19 pandemic in Romania and neighboring countries, which have similar onset and a similar socio-cultural pattern. A descriptive comparative study was performed using COVID-19 data collected from various official websites regarding demography, morbidity, mortality, vaccination, and testing capacity. The countries included in the study were Romania, Bulgaria, Hungary, Republic of Moldova, Serbia, and Ukraine. The study period was from week 09/2020 to week 46/2021. Overall, these countries have reported 8,382,441 cases and 216,014 deaths (during the study period). The highest cumulative incidence rate of cases has been recorded in Serbia (17,801.5) and the highest mortality rate has been recorded in Bulgaria (391.0). Romania is in fourth place regarding the cumulative incidence rate of cases/100,000 inhabitants but in third place regarding the mortality due to COVID-19 (case–fatality rate of 3.1%). Although the World Health Organization and EU co-ordinate the COVID-19 response, each state makes its own decisions regarding SARS-CoV-2 mitigation measures, the epidemiological indicators directing us about the effectiveness of responses.
Impact of the COVID-19 Pandemic on the Work Engagement of UK Active Employees
Authors: Romero-Martín Macarena , Gómez-Salgado Juan , Alcaide-Carrasco Miriam , Rodríguez-Jiménez Lucas , Ortega-Moreno Mónica , López-López Daniel , Ruiz-Frutos Carlos
Published: July 2022

The objective of this investigation was to describe the work engagement perceived by UK workers during the COVID-19 pandemic. A descriptive cross-sectional study was conducted. The sample included 1085 participants, aged 18 years and older, living in the UK during the COVID-19 pandemic, who were active workers. Data were collected using an online questionnaire and the UWES-9. They were analysed using descriptive statistics, a t-test for equality of means or ANOVA, and the Chi-squared Automatic Interaction Detection method. The mean value in the UWES-9 was 3.46 (SD = 1.11). Participants with lower satisfaction (21.8%) gave significantly low or very low UWES-9 scores in 58.5% of the cases. Greater work engagement was obtained with more resources and less conflict, risk, and stress. In cases where there had been contact with COVID-19, this was associated with slightly lower levels of work engagement. These results could motivate and guide companies to adopt risk prevention measures and protocols to return to normal working conditions after the initial crisis phase of the pandemic.
Role of PPAR Receptor and Ligands in the Pathogenesis and Therapy of Hematologic Malignancies
Authors: Wu Jian , Zhang Min , Faircloth Allison
Published: July 2022

The Peroxisome proliferator-activated receptors (PPARs) play vital roles in regulating cellular differentiation, proliferation, and caspase-mediated cell death pathways. They are regarded as promising targets for anti-tumor drug development, particularly for multiple myeloma (MM) and different hematological malignancies. Several early section clinical trials are conducted to measure the clinical practicableness of PPAR agonists, notably PPARα and PPARγ agonists, against various cancers. A spread of studies has investigated PPARs expression in metabolic regulation. Furthermore, it has been suggested that careful designing of partial agonists for PPARs may show improvement with side effects and increase the therapeutic value. This review summarizes the organic chemistry and metabolic actions of PPARs, and the therapeutic potential of their agonists underneath clinical development. It investigates therapeutic agents for hematologic malignancies.
Squash Yield, Water-Use Efficiency and Nitrate Accumulation as Influenced by the Application of Humic Acid, Geobacillus stearothermophilus SSK-2018 and Wheat Straw in an Arid Land Condition
Authors: Bello Suleiman K. , AL-Solaimani Samir G. , Abo-Elyousr Kamal A. M.
Published: July 2022

The importance of inorganic fertilizers in squash crop productivity is enormous. However, the continuous use of inorganic fertilizers constitutes a serious problem to the environment and human health due to nitrate accumulation. Thus, two seasons (2020 and 2021) of field trials were carried out to investigate the effects of bio-organic amendments on squash under arid land conditions in Saudi Arabia. The bio-organic amendments were comprised of humic acid (HA) at three levels (0, 50 and 100 L/ha), inoculation of a cellulose-decomposing bacterium (CDB; Geobacillus stearothermophilus SSK-2018) and wheat straw at four levels (0, 20 and 30 t/ha and NPK 20:20:20 at 600 kg/ha as a positive control). A randomized split-split plot design replicated three times was used in laying out the field trials. The independent application of HA, CDB and wheat straw significantly (p ≤ 0.05) improved squash growth, yield and water-use efficiency in both seasons. Furthermore, HA significantly (p ≤ 0.05) reduced fruits’ nitrate content. HA (100 L/ha) reduced nitrate content in squash fruits by 87% and 71.6% compared to the control in 2020 and 2021, respectively. The application of 20 t/ha of wheat straw significantly (p ≤ 0.05) reduced nitrate accumulation in fruits compared to the positive control (NPK) by 5.9% and 13.6% in 2019/20 and 2020/21, respectively. Regression analysis shows that increased nitrate accumulation in fruits results in decreased squash growth and fruit yield. This study demonstrates the significance of bio-organic amendments in improving squash growth and yield while reducing nitrate accumulation in fruits.
Development of a Mortality Prediction Model in Hospitalised SARS-CoV-2 Positive Patients Based on Routine Kidney Biomarkers
Authors: Boss Anna N. , Banerjee Abhirup , Mamalakis Michail , Ray Surajit , Swift Andrew J. , Wilkie Craig , Fanstone Joseph W. , Vorselaars Bart , Cole Joby , Weeks Simonne , Mackenzie Louise S.
Published: July 2022

Acute kidney injury (AKI) is a prevalent complication in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive inpatients, which is linked to an increased mortality rate compared to patients without AKI. Here we analysed the difference in kidney blood biomarkers in SARS-CoV-2 positive patients with non-fatal or fatal outcome, in order to develop a mortality prediction model for hospitalised SARS-CoV-2 positive patients. A retrospective cohort study including data from suspected SARS-CoV-2 positive patients admitted to a large National Health Service (NHS) Foundation Trust hospital in the Yorkshire and Humber regions, United Kingdom, between 1 March 2020 and 30 August 2020. Hospitalised adult patients (aged ≥ 18 years) with at least one confirmed positive RT-PCR test for SARS-CoV-2 and blood tests of kidney biomarkers within 36 h of the RT-PCR test were included. The main outcome measure was 90-day in-hospital mortality in SARS-CoV-2 infected patients. The logistic regression and random forest (RF) models incorporated six predictors including three routine kidney function tests (sodium, urea; creatinine only in RF), along with age, sex, and ethnicity. The mortality prediction performance of the logistic regression model achieved an area under receiver operating characteristic (AUROC) curve of 0.772 in the test dataset (95% CI: 0.694–0.823), while the RF model attained the AUROC of 0.820 in the same test cohort (95% CI: 0.740–0.870). The resulting validated prediction model is the first to focus on kidney biomarkers specifically on in-hospital mortality over a 90-day period.
Genome Assembly and Analysis of the Flavonoid and Phenylpropanoid Biosynthetic Pathways in Fingerroot Ginger (Boesenbergia rotunda)
Authors: Taheri Sima , Teo Chee How , Heslop-Harrison John S. , Schwarzacher Trude , Tan Yew Seong , Wee Wei Yee , Khalid Norzulaani , Biswas Manosh Kumar , Mutha Naresh V. R. , Mohd-Yusuf Yusmin , Gan Han Ming , Harikrishna Jennifer Ann
Published: July 2022

Boesenbergia rotunda (Zingiberaceae), is a high-value culinary and ethno-medicinal plant of Southeast Asia. The rhizomes of this herb have a high flavanone and chalcone content. Here we report the genome analysis of B. rotunda together with a complete genome sequence as a hybrid assembly. B. rotunda has an estimated genome size of 2.4 Gb which is assembled as 27,491 contigs with an N50 size of 12.386 Mb. The highly heterozygous genome encodes 71,072 protein-coding genes and has a 72% repeat content, with class I TEs occupying ~67% of the assembled genome. Fluorescence in situ hybridization of the 18 chromosome pairs at the metaphase showed six sites of 45S rDNA and two sites of 5S rDNA. An SSR analysis identified 238,441 gSSRs and 4604 EST-SSRs with 49 SSR markers common among related species. Genome-wide methylation percentages ranged from 73% CpG, 36% CHG and 34% CHH in the leaf to 53% CpG, 18% CHG and 25% CHH in the embryogenic callus. Panduratin A biosynthetic unigenes were most highly expressed in the watery callus. B rotunda has a relatively large genome with a high heterozygosity and TE content. This assembly and data (PRJNA71294) comprise a source for further research on the functional genomics of B. rotunda, the evolution of the ginger plant family and the potential genetic selection or improvement of gingers.
Studies on Lotus Genomics and the Contribution to Its Breeding
Authors: Qi Huanhuan , Yu Feng , Deng Jiao , Yang Pingfang
Published: July 2022

Lotus (Nelumbo nucifera), under the Nelumbonaceae family, is one of the relict plants possessing important scientific research and economic values. Because of this, much attention has been paid to this species on both its biology and breeding among the scientific community. In the last decade, the genome of lotus has been sequenced, and several high-quality genome assemblies are available, which have significantly facilitated functional genomics studies in lotus. Meanwhile, re-sequencing of the natural and genetic populations along with different levels of omics studies have not only helped to classify the germplasm resources but also to identify the domestication of selected regions and genes controlling different horticultural traits. This review summarizes the latest progress of all these studies on lotus and discusses their potential application in lotus breeding.
MicroRNA Methylome Signature and Their Functional Roles in Colorectal Cancer Diagnosis, Prognosis, and Chemoresistance
Authors: Baharudin Rashidah , Rus Bakarurraini Nurul Qistina , Ismail Imilia , Lee Learn-Han , Ab Mutalib Nurul Syakima
Published: July 2022

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite significant advances in the diagnostic services and patient care, several gaps remain to be addressed, from early detection, to identifying prognostic variables, effective treatment for the metastatic disease, and the implementation of tailored treatment strategies. MicroRNAs, the short non-coding RNA species, are deregulated in CRC and play a significant role in the occurrence and progression. Nevertheless, microRNA research has historically been based on expression levels to determine its biological significance. The exact mechanism underpinning microRNA deregulation in cancer has yet to be elucidated, but several studies have demonstrated that epigenetic mechanisms play important roles in the regulation of microRNA expression, particularly DNA methylation. However, the methylation profiles of microRNAs remain unknown in CRC patients. Methylation is the next major paradigm shift in cancer detection since large-scale epigenetic alterations are potentially better in identifying and classifying cancers at an earlier stage than somatic mutations. This review aims to provide insight into the current state of understanding of microRNA methylation in CRC. The new knowledge from this study can be utilized for personalized health diagnostics, disease prediction, and monitoring of treatment.
In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
Authors: Barbon Silvia , Stocco Elena , Rajendran Senthilkumar , Zardo Lorena , Macchi Veronica , Grandi Claudio , Tagariello Giuseppe , Porzionato Andrea , Radossi Paolo , De Caro Raffaele , Parnigotto Pier Paolo
Published: July 2022

In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production. The cells were cultured in an inductive medium enriched with endothelial growth factors for up to 21 days. In addition to significantly responding to the chemotactic endothelial stimuli, the cell populations started to form capillary-like structures and up-regulated the expression of specific endothelial markers (CD34, PDGFRα, VEGFR2, VE-cadherin, CD31, and vWF). A dot blot protein study detected the presence of FVIII in culture media collected from both unstimulated and stimulated Ad-MSCs. Remarkably, the activated partial thromboplastin time test demonstrated that the clot formation was accelerated, and FVIII activity was enhanced when FVIII deficient plasma was mixed with culture media from the untreated/stimulated Ad-MSCs. Overall, the collected evidence supported a possible Ad-MSC contribution to HA correction via specific stimulation by the endothelial microenvironment and without any need for gene transfection.
Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells
Authors: Tiong Tung-Yu , Weng Pei-Wei , Wang Chun-Hua , Setiawan Syahru Agung , Yadav Vijesh Kumar , Pikatan Narpati Wesa , Fong Iat-Hang , Yeh Chi-Tai , Hsu Chia-Hung , Kuo Kuang-Tai
Published: July 2022

Background: Lung cancer remains a leading cause of cancer-related death, with an annual global mortality rate of 18.4%. Despite advances in diagnostic and therapeutic technologies, non–small cell lung carcinoma (NSCLC) continues to be characterized by a poor prognosis. This may be associated with the enrichment of cancer stem cells (CSCs) and the development of chemoresistance—a double-edged challenge that continues to impede the improvement of long-term outcomes. Metabolic reprogramming is a new hallmark of cancer. Sterol regulatory element-binding proteins (SREBPs) play crucial regulatory roles in the synthesis and uptake of cholesterol, fatty acids, and phospholipids. Recent evidence has demonstrated that SREBP-1 is upregulated in several cancer types. However, its role in lung cancer remains unclear. Objective: This study investigated the role of SREBP-1 in NSCLC biology, progression, and therapeutic response and explored the therapeutic exploitability of SREBP-1 and SREBP-1-dependent oncometabolic signaling and miRNA epigenetic regulation. Methods: We analyzed SREBP-1 levels and biological functions in clinical samples and the human NSCLC cell lines H441 and A549 through shRNA-based knock down of SREBP function, cisplatin-resistant clone generation, immunohistochemical staining of clinical samples, and cell viability, sphere-formation, Western blot, and quantitative PCR assays. We conducted in-silico analysis of miRNA expression in NSCLC samples by using the Gene Expression Omnibus (GSE102286) database. Results: We demonstrated that SREBP-1 and SCAP are highly expressed in NSCLC and are positively correlated with the aggressive phenotypes of NSCLC cells. In addition, downregulation of the expression of tumor-suppressing hsa-miR-497-5p, which predictively targets SREBP-1, was observed. We also demonstrated that SREBP-1/SCAP/FASN lipogenic signaling plays a key role in CSCs-like and chemoresistant NSCLC phenotypes, especially because the fatostatin or shRNA targeting of SREBP-1 significantly suppressed the viability, cisplatin resistance, and cancer stemness of NSCLC cells and because treatment induced the expression of hsa-miR-497. Conclusion: Targeting the SREBP-1/hsa-miR-497 signaling axis is a potentially effective anticancer therapeutic strategy for NSCLC.
Flt3 Signaling in B Lymphocyte Development and Humoral Immunity
Authors: Medina Kay L.
Published: July 2022

The Class III receptor tyrosine kinase Flt3 and its ligand, the Flt3-ligand (FL), play an integral role in regulating the proliferation, differentiation, and survival of multipotent hematopoietic and lymphoid progenitors from which B cell precursors derive in bone marrow (BM). More recently, essential roles for Flt3 signaling in the regulation of peripheral B cell development and affinity maturation have come to light. Experimental findings derived from a multitude of mouse models have reinforced the importance of molecular and cellular regulation of Flt3 and FL in lymphohematopoiesis and adaptive immunity. Here, we provide a comprehensive review of the current state of the knowledge regarding molecular and cellular regulation of Flt3/FL and the roles of Flt3 signaling in hematopoietic stem cell (HSC) activation, lymphoid development, BM B lymphopoiesis, and peripheral B cell development. Cumulatively, the literature has reinforced the importance of Flt3 signaling in B cell development and function. However, it has also identified gaps in the knowledge regarding Flt3-dependent developmental-stage specific gene regulatory circuits essential for steady-state B lymphopoiesis that will be the focus of future studies.
Characterization of Mitochondrial Prohibitin in Opsariichthys bidens and Its Potential Functions in Spermatogenesis
Authors: Wang Li , Wang Jingqian , Gao Xinming , Du Chen , Hou Congcong , Zhang Chundan , Zhu Junquan , Tang Daojun
Published: July 2022

Spermatogenesis is the intricate and coordinated process by which spermatogonia develop into haploid differentiated spermatozoa. Mitochondria are essential for spermatogenesis, and prohibitin (PHB) is closely associated with mitochondrial structure and function during spermatogenesis. Although PHB has been implicated in spermatogenesis in some taxa, its roles in Opsariichthys bidens have not been determined. In this study, the expression patterns and potential functions of PHB in spermatogenesis in O. bidens were characterized using histological microscopic observations, PCR cloning, real-time quantitative PCR (qPCR), Western blotting (WB) and immunofluorescence (IF). The full-length cDNA of Ob-phb was 1500 bp encoding 271 amino acids. A sequence alignment demonstrated that the PHB protein is conserved among different animals. qPCR revealed that phb mRNA is widely distributed in O. bidens and highly expressed in the testes at stages IV and V. WB revealed that Ob-PHB is located in the mitochondria of testes. IF revealed the colocalization of PHB signals and mitochondria. Signals were detected around nuclei in spermatogonia and spermatocytes, gradually moving to the tail region during spermiogenesis, and finally aggregating in the midpiece. These results indicate that Ob-PHB was expressed in the mitochondria during spermatogenesis. In addition, this study proposed Ob-PHB may participate in the degradation of mitochondria and cell differentiation during spermatogenesis.
Roles of Fatty Acids in Microglial Polarization: Evidence from In Vitro and In Vivo Studies on Neurodegenerative Diseases
Authors: Sanjay  , Park Miey , Lee Hae-Jeung
Published: July 2022

Microglial polarization to the M1 phenotype (classically activated) or the M2 phenotype (alternatively activated) is critical in determining the fate of immune responses in neurodegenerative diseases (NDs). M1 macrophages contribute to neurotoxicity, neuronal and synaptic damage, and oxidative stress and are the first line of defense, and M2 macrophages elicit an anti-inflammatory response to regulate neuroinflammation, clear cell debris, and promote neuroregeneration. Various studies have focused on the ability of natural compounds to promote microglial polarization from the M1 phenotype to the M2 phenotype in several diseases, including NDs. However, studies on the roles of fatty acids in microglial polarization and their implications in NDs are a rare find. Most of the studies support the role of polyunsaturated fatty acids (PUFAs) in microglial polarization using cell and animal models. Thus, we aimed to collect data and provide a narrative account of microglial types, markers, and studies pertaining to fatty acids, particularly PUFAs, on microglial polarization and their neuroprotective effects. The involvement of only PUFAs in the chosen topic necessitates more in-depth research into the role of unexplored fatty acids in microglial polarization and their mechanistic implications. The review also highlights limitations and future challenges.
Degradation Mechanism of Autophagy-Related Proteins and Research Progress
Authors: Zhou Yanhui , Manghwar Hakim , Hu Weiming , Liu Fen
Published: July 2022

In all eukaryotes, autophagy is the main pathway for nutrient recycling, which encapsulates parts of the cytoplasm and organelles in double-membrane vesicles, and then fuses with lysosomes/vacuoles to degrade them. Autophagy is a highly dynamic and relatively complex process influenced by multiple factors. Under normal growth conditions, it is maintained at basal levels. However, when plants are subjected to biotic and abiotic stresses, such as pathogens, drought, waterlogging, nutrient deficiencies, etc., autophagy is activated to help cells to survive under stress conditions. At present, the regulation of autophagy is mainly reflected in hormones, second messengers, post-transcriptional regulation, and protein post-translational modification. In recent years, the degradation mechanism of autophagy-related proteins has attracted much attention. In this review, we have summarized how autophagy-related proteins are degraded in yeast, animals, and plants, which will help us to have a more comprehensive and systematic understanding of the regulation mechanisms of autophagy. Moreover, research progress on the degradation of autophagy-related proteins in plants has been discussed.
Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives
Authors: Saltarella Ilaria , Altamura Concetta , Lamanuzzi Aurelia , Apollonio Benedetta , Vacca Angelo , Frassanito Maria Antonia , Desaphy Jean-François
Published: July 2022

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.
Electrostatic Map of the SARS-CoV-2 Virion Specifies Binding Sites of the Antiviral Cationic Photosensitizer
Authors: Fedorov Vladimir , Kholina Ekaterina , Khruschev Sergei , Kovalenko Ilya , Rubin Andrew , Strakhovskaya Marina
Published: July 2022

Electrostatics is an important part of virus life. Understanding the detailed distribution of charges over the surface of a virus is important to predict its interactions with host cells, antibodies, drugs, and different materials. Using a coarse-grained model of the entire viral envelope developed by D. Korkin and S.-J. Marrink’s scientific groups, we created an electrostatic map of the external surface of SARS-CoV-2 and found a highly heterogeneous distribution of the electrostatic potential field of the viral envelope. Numerous negative patches originate mainly from negatively charged lipid domains in the viral membrane and negatively charged areas on the “stalks” of the spike (S) proteins. Membrane (M) and envelope (E) proteins with the total positive charge tend to colocalize with the negatively charged lipids. In the E protein pentamer exposed to the outer surface, negatively charged glutamate residues and surrounding lipids form a negative electrostatic potential ring around the channel entrance. We simulated the interaction of the antiviral octacationic photosensitizer octakis(cholinyl)zinc phthalocyanine with the surface structures of the entire model virion using the Brownian dynamics computational method implemented in ProKSim software (version r661). All mentioned negatively charged envelope components attracted the photosensitizer molecules and are thus potential targets for reactive oxygen generated in photosensitized reactions.
Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
Authors: Liu Min , Tan Xu , Liu E , Hang Zhaofang , Song Ruiheng , Mu Shouhong , Han Weikai , Yue Qingwei , Sun Jinhao
Published: July 2022

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.