bluuebunny/crossref_metadata_2025 huggingface dataset:
Orange Peel Waste as Feedstock for the Production of Glycerol-Free Biodiesel by the Microalgae Nannochloropsis oculata
Authors: Tardiolo Giuseppe , Nicolò Marco Sebastiano , Drago Carmelo , Genovese Claudia , Fava Giovanni , Gugliandolo Concetta , D’Antona Nicola
Published: September 2023

The bioconversion of agri-food waste into high-value products is gaining growing interest worldwide. Orange peel waste (OPW) is the main by-product of orange juice production and contains high levels of moisture and carbohydrates. In this study, the orange waste extract (OWE) obtained through acid hydrolysis of OPW was used as a substrate in the cultivation of the marine microalgae Nannochloropsis oculata. Photoheterotrophic (PH) and Photoautotrophic (PA) cultivations were performed in OWE medium and f/2 medium (obtained by supplementing OWE with macro- and micronutrients of f/2 medium), respectively, for 14 days. The biomass yields in PA and PH cultures were 390 mg L−1 and 450 mg L−1, while oil yields were 15% and 28%, respectively. The fatty acid (FA) profiles of PA cultures were mostly represented by saturated (43%) and monounsaturated (46%) FAs, whereas polyunsaturated FAs accounted for about 10% of the FAs. In PH cultures, FA profiles changed remarkably, with a strong increase in monounsaturated FAs (77.49%) and reduced levels of saturated (19.79%) and polyunsaturated (2.72%) FAs. Lipids obtained from PH cultures were simultaneously extracted and converted into glycerol-free biodiesel using an innovative microwave-assisted one-pot tandem protocol. FA methyl esters were then analyzed, and the absence of glycerol was confirmed. The FA profile was highly suitable for biodiesel production and the microwave-assisted one-pot tandem protocol was more effective than traditional extraction techniques. In conclusion, N. oculata used OWE photoheterotrophically, resulting in increased biomass and oil yield. Additionally, a more efficient procedure for simultaneous oil extraction and conversion into glycerol-free biodiesel is proposed.
A Detailed Comparative Analysis of the Structural Stability and Electron-Phonon Properties of ZrO2: Mechanisms of Water Adsorption on t-ZrO2 (101) and t-YSZ (101) Surfaces
Authors: Nematov Dilshod D. , Burhonzoda Amondulloi S. , Kholmurodov Kholmirzo T. , Lyubchyk Andriy I. , Lyubchyk Sergiy I.
Published: September 2023

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO2), tetragonal (t-ZrO2), and monoclinic (m-ZrO2) phases of ZrO2. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO2. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO2, the Fermi level first shifts by 0.125 eV toward higher energies, and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO2, t-ZrO2, and m-ZrO2 are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y2O3 onto the m-ZrO2 structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies the further stabilization of monoclinic ZrO2 and an increase in its defectiveness. A doping-induced and concentration-dependent phase transition in ZrO2 under the influence of Y2O3 was discovered, due to which the position of the Fermi level changes and the energy gap decreases. It has been established that the main contribution to the formation of the conduction band is made by the p-states of electrons, not only for pure systems, but also those doped with Y2O3. The t-ZrO2 (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO2 (101) and t-YSZ (101) showed that H2O on unstabilized t-ZrO2 (101) is adsorbed dissociatively with an energy of −1.22 eV, as well as by the method of molecular chemisorption with an energy of −0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of −1.84 eV. Dissociative adsorption of water occurs at an energy of −1.23 eV, near the yttrium atom. The results show that ab initio approaches are able to describe the mechanism of doping-induced phase transitions in (ZrO2+Y2O3)-like systems, based on which it can be assumed that DFT calculations can also flawlessly evaluate other physical and chemical properties of YSZ, which have not yet been studied quantum chemical research. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation, and can be used in designing humidity-to-electricity converters and in creating solid oxide fuel cells based on ZrO2.
The Application of Microfibrous Entrapped Activated Carbon Composite Material for the Sarin Simulant Dimethyl Methylphosphonate Adsorption
Authors: Xie Yucong , Zheng Chao , Lan Liang , Song Hua , Kang Jian , Kang Kai , Bai Shupei
Published: September 2023

Granular activated carbon (GAC) has proven to be an effective adsorbent for removing the chemical warfare agent sarin (GB) and simulants like Dimethyl methylphosphonate (DMMP). However, it comes with certain limitations, including inadequate contact efficiency, notable mass transfer resistance, and lower bed utilization efficiency. This study synthesized steel fiber-entrapped activated carbon composites (SFEACs), which exhibited a maximum adsorption capacity of 285.3 mg/g at 303 K. Compared with the packed bed (PB) filled with GAC, while the adsorption capacity of SFEACS decreased, there was a substantial increase in the adsorption mass transfer rate. These SFEACs were combined with GAC to create a structural fixed bed (SFB), which demonstrated excellent performance in DMMP removal. Under identical experimental conditions, the DMMP breakthrough curve of SFB exhibited a steeper profile compared to the packed bed (PB) filled with GAC at the same bed height, and the breakthrough time against DMMP vapor could be extended by 13.8%. Furthermore, the adsorption rate constant of the Yoon-Nelson model increased by more than 17.6%, and the unused bed length, according to the Wheeler–Jonas model, decreased by more than 14%.
Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity
Authors: Kisiolek Jacob N. , Flores Victoria A. , Ramani Arjun , Butler Blake , Haughian James M. , Stewart Laura K.
Published: September 2023

Background: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. Methods: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. Results: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). Conclusions: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.
Red Rice Seed Coat Targeting SPHK2 Ameliorated Alcoholic Liver Disease via Restored Intestinal Barrier and Improved Gut Microbiota in Mice
Authors: Chen Yuxu , Zhao Zhiye , Guo Shancheng , Li Yaxian , Yin Haiaolong , Tian Lei , Cheng Guiguang , Li Ye
Published: September 2023

Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativa L.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.
Black Goji Berry (Lycium ruthenicum Murray): A Review of Its Pharmacological Activity
Authors: Lee Ho Seon , Choi Chang-Ik
Published: September 2023

Lycium ruthenicum Murray (LRM; commonly known as black goji berry or black wolfberry), a plant in the Solanaceae family, grows in the deserts of China’s Qinghai–Tibet plateau. LRM is widely consumed in traditional Chinese medicine, and its fruits are frequently used as herbal remedies to treat heart disease, fatigue, inflammation, and other conditions. Many studies have reported that LRM is rich in functional phytochemicals, such as anthocyanins and polysaccharides, and has various pharmacological actions. This article reviews research on the biological and pharmacological effects of the constituents of LRM fruits. LRM has various pharmacological properties, such as antioxidant, anti-inflammatory, anti-radiation, immune-enhancing, anti-tumor, and protective effects. LRM has much promise as a dietary supplement for preventing many types of chronic metabolic disease.
Whole-Grain Highland Barley Attenuates Atherosclerosis Associated with NLRP3 Inflammasome Pathway and Gut Microbiota in ApoE−/− Mice
Authors: Wu Tong , Yu Qinye , Luo Yingting , Dai Zijian , Zhang Yuhong , Wang Chao , Shen Qun , Xue Yong
Published: September 2023

The efficacy and mechanism of highland barley in the treatment of atherosclerosis have received little attention. Herein, we aimed to explore whether highland barley supplementation can prevent atherosclerosis progression and improve gut microbiota disorder in apolipoprotein E knockout (ApoE−/−) mice. Male ApoE−/− mice were fed a high-fat diet with whole-grain highland barley (WHB) or refined highland barley for 18 weeks. WHB substantially inhibited the formation of atherosclerotic plaques, reduced serum tumor necrosis factor-α, and downregulated the expression of NLRP3 in the aorta. Furthermore, the 16S rRNA analysis revealed that highland barley supplementation helped to restore the dysregulation of the gut microbiota, as evidenced by an increase in the relative abundance of specific beneficial bacteria known for their anti-inflammatory properties, such as Lachnospiraceae, Lactobacillus, Muribaculaceae, and Bifidobacterium. Highland barley supplementation might alleviate atherosclerotic plaque formation by modulating the NLRP3 inflammasome pathway and the synthesis of anti-inflammatory metabolites by the gut microbiota.
Use of Branched-Chain Amino Acids as a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease
Authors: Colosimo Santo , Bertoli Simona , Saffioti Francesca
Published: September 2023

Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer’s ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.
Serum Vitamin D3 Concentration, Sleep, and Cognitive Impairment among Older Adults in China
Authors: Xie Yuning , Bai Chen , Feng Qiushi , Gu Danan
Published: September 2023

Background: Cognitive decline in older adults has become one of the critical challenges to global health. This study aims to examine both cross-sectional and longitudinal associations of levels of serum 25-hydroxyvitamin D3 (25(OH)D3) (briefed as VD3) concentration and sleep quality/duration, especially their interactions, with risk of cognitive impairment among older adults in China. Methods: We utilized a special subsample of adults aged 65–105 years (individuals = 3412, observations = 4816) from eight provinces in China derived from the 2011/2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Cognitive impairment was measured by the Mini-Mental State Examination scale. Sleep quality was classified as good versus fair/poor, and sleep duration was classified into short (<7 h), normal (≥7 but <9 h), and long (≥9 h). The VD3 concentration was divided into three levels: deficiency (VD3 < 25 nmol/L), insufficiency (25 nmol/L ≤ VD3 < 50 nmol/L), and sufficiency (VD3 ≥ 50 nmol/L). A wide set of covariates that include demographics, socioeconomic status, family support, health practice, and health conditions was adjusted for robust findings. Multilevel random intercept logit regression models were used to examine the cross-sectional associations between VD3, sleep, and cognitive impairment, whereas logit regression models were applied to investigate the longitudinal associations. Results: In the cross-sectional analyses, when all covariates were adjusted, VD3 sufficiency was significantly associated with a 33% lower risk of cognitive impairment compared with VD3 deficiency; good sleep quality was associated with 34% lower odds of cognitive impairment compared with fair/poor sleep quality; sleep hours were not associated with cognitive impairment, although a long sleep duration (≥9 h) was associated with 30% higher odds of being cognitively impaired when baseline health was not controlled. Interaction analyses reveal that VD3 sufficiency could help to additionally reduce the risk of cognitive impairment for good sleep quality and normal sleep hours. In the longitudinal analyses, the association of VD3 sufficiency remains significant, whereas sleep quality and sleep duration were not significant associates. Conclusions: Good sleep quality, normal sleep hours, and VD3 sufficiency are positively associated with good cognitive function. VD3 sufficiency could enhance the associations between sleep and cognitive impairment.
Patterns and Predictors of Low-Calorie Sweetener Consumption during Pregnancy: Findings from a National Survey
Authors: Gebremichael Bereket , Lassi Zohra S. , Begum Mumtaz , Mittinty Murthy , Zhou Shao-Jia
Published: September 2023

Recently, the World Health Organization recommended avoiding low-calorie sweeteners (LCS) during pregnancy due to concerns that it may be linked to adverse pregnancy outcomes and offspring wellbeing. This study examined the patterns and predictors of LCS consumption among pregnant women in Australia. A survey was conducted among 422 pregnant women aged 18–50 years. Sociodemographic, lifestyle, dietary intake including LCS consumption, pregnancy-related characteristics, and awareness about the health effects of LCS were assessed. We used latent class analysis and multinomial logistic regression to identify LCS consumption patterns and predictors of consumption patterns, respectively. The mean (SD) age of the women was 30 (4.6) years. Three LCS consumption patterns were identified: infrequent or non-consumers representing 50% of the women, moderate consumers encompassing 40% of the women, and the remaining were habitual consumers. Over two-thirds (71%) of women were not aware of the potential adverse effects of LCS, and only a quarter of them were concerned about the possible adverse effects on their health and their offspring. Increasing age and living with a medical condition decreased the likelihood of moderate consumption by 7% and 55%, respectively. Frequent sugar-sweetened beverage consumption and gestational diabetes predicted habitual LCS consumption. This research suggested widespread LCS consumption among pregnant women in Australia, but lower awareness of its potential adverse health effects. Interventions to increase awareness of potential adverse effects are warranted.
Potent Bile Acid Microbial Metabolites Modulate Clostridium perfringens Virulence
Authors: Alenezi Tahrir , Fu Ying , Alrubaye Bilal , Alanazi Thamer , Almansour Ayidh , Wang Hong , Sun Xiaolun
Published: September 2023

Clostridium perfringens is a versatile pathogen, inducing diseases in the skin, intestine (such as chicken necrotic enteritis (NE)), and other organs. The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced NE by inhibiting C. perfringens virulence signaling pathways. To evaluate the hypothesis, C. perfringens strains CP1 and wild-type (WT) HN13 and its mutants were cultured with different bile acids, including DCA and isoallolithocholic acid (isoalloLCA). Growth, hydrogen sulfide (H2S) production, and virulence gene expression were measured. Notably, isoalloLCA was more potent in reducing growth, H2S production, and virulence gene expression in CP1 and WT HN13 compared to DCA, while other bile acids were less potent compared to DCA. Interestingly, there was a slightly different impact between DCA and isoalloLCA on the growth, H2S production, and virulence gene expression in the three HN13 mutants, suggesting possibly different signaling pathways modulated by the two bile acids. In conclusion, DCA and isoalloLCA reduced C. perfringens virulence by transcriptionally modulating the pathogen signaling pathways. The findings could be used to design new strategies to prevent and treat C. perfringens-induced diseases.
Focal Adhesion Kinase Binds to the HPV E2 Protein to Regulate Initial Replication after Infection
Authors: Jose Leny , Gonzalez Jessica , Kessinger Emma , Androphy Elliot J. , DeSmet Marsha
Published: September 2023

Human papillomaviruses are small DNA tumor viruses that infect cutaneous and mucosal epithelia. The viral lifecycle is linked to the differentiation status of the epithelium. During initial viral infection, the genomes replicate at a low copy number but the mechanism(s) the virus uses to control the copy number during this stage is not known. In this study, we demonstrate that the tyrosine kinase focal adhesion kinase (FAK) binds to and phosphorylates the high-risk viral E2 protein, the key regulator of HPV replication. The depletion of FAK with a specific PROTAC had no effect on viral DNA content in keratinocytes that already maintain HPV-16 and HPV-31 episomes. In contrast, the depletion of FAK significantly increased HPV-16 DNA content in keratinocytes infected with HPV-16 quasiviruses. These data imply that FAK prevents the over-replication of the HPV genome after infection through the interaction and phosphorylation of the E2 protein.
Special Issue for “3D Printing of Drug Formulations”
Authors: Ehtezazi Touraj
Published: September 2023

Three-dimensional printing (3DP) is rapidly innovating the manufacturing process and provides opportunities that have never been seen before [...]
Quality, Safety and Biological Studies on Campylanthus glaber Aerial Parts
Authors: Lima Katelene , Malmir Maryam , Camões Sérgio P. , Hasan Kamrul , Gomes Samuel , Moreira da Silva Isabel , Figueira Maria Eduardo , Miranda Joana P. , Serrano Rita , Duarte Maria Paula , Silva Olga
Published: September 2023

In Cabo Verde, several endemic species are used in traditional medicine. However, no scientific studies have been conducted on the quality, efficacy, and safety of most of these plants. This study focused on establishing the botanical and chemical identification parameters required for a quality monograph of Campylanthus glaber Benth. aerial parts, a medicinal plant of Cabo Verde traditionally used to treat fever and muscular pain. In addition, in vitro antioxidant and antihyperglycemic activity, cytotoxicity, and genotoxicity were assessed for this medicinal plant. Optical microscopy, LC/UV-DAD-ESI/MS, and colorimetric assays were used for botanical, chemical, and biological studies, respectively. Cytotoxicity was assessed by the MTT assay with HepG2 cells, and genotoxicity by the Ames test. Microscopically, the xeromorphic leaf of C. glaber presents a thick cuticle (13.6–25.5 µm), thick-walled epidermal cells, anomocytic-type stomata, glandular trichomes (stalk length = 49.4–120.8 µm), and idioblasts containing calcium oxalate microcrystals. The chemical screening of aqueous and hydroethanolic extracts of this medicinal plant revealed the presence of organic acids, iridoids, phenylethanoids, and flavonoids as the main classes of marker compounds, with malic acid, citric acid, and verbascoside being the main marker compounds identified. Both extracts showed similar LC/UV-DAD/ESI-MS qualitative profiles and DPPH radical scavenger activity (IC50 = 130.9 ± 1.4; 134.3 ± 3.1 µg/mL). The hydroethanolic extract inhibited both α-amylase and α-glucosidase enzymes in a dose-dependent manner. Both extracts showed no cytotoxicity (up to 1000 µg/mL) by the MTT assay and no genotoxic potential with or without metabolic activation up to 5 mg /plate. The results obtained are an important contribution to the monographic quality assessment of C. glaber aerial parts and suggest that this medicinal plant may be safe and potentially used as an herbal drug raw material for pharmaceutical purposes.
Study of Mono and Di-O-caffeoylquinic Acid Isomers in Acmella oleracea Extracts by HPLC-MS/MS and Application of Linear Equation of Deconvolution Analysis Algorithm for Their Characterization
Authors: Bellumori Maria , Pallecchi Marco , Zonfrillo Beatrice , Lucio Luigi , Menicatti Marta , Innocenti Marzia , Mulinacci Nadia , Bartolucci Gianluca
Published: September 2023

Chlorogenic acids, the esters of caffeic and quinic acids, are the main phenolic acids detected in Acmella oleracea extracts and have gained increasing interest in recent years due to their important biological activities. Given their structural similarity and instability, the correct analysis and identification of these compounds in plants is challenging. This study aimed to propose a simple and rapid determination of the A. oleracea caffeoylquinic isomers, applying an HPLC-MS/MS method supported by a mathematical algorithm (Linear Equation of Deconvolution Analysis (LEDA)). The three mono- and the three di-caffeoylquinic acids in roots of Acmella plants were studied by an ion trap MS analyzer. A separation by a conventional chromatographic method was firstly performed and an MS/MS characterization by energetic dimension of collision-induced dissociation mechanism was carried out. The analyses were then replicated using a short HPLC column and a fast elution gradient (ten minutes). Each acquired MS/MS data were processed by LEDA algorithm which allowed to assign a relative abundance in the reference ion signal to each isomer present. Quantitative results showed no significant differences between the two chromatographic systems proposed, proving that the use of LEDA algorithm allowed the distinction of the six isomers in a quarter of the time.
Computational Discovery of Marine Molecules of the Cyclopeptide Family with Therapeutic Potential
Authors: Flores-Holguín Norma , Salas-Leiva Joan S. , Glossman-Mitnik Daniel
Published: September 2023

Stellatolides are natural compounds that have shown promising biological activities, including antitumor, antimicrobial, and anti-inflammatory properties, making them potential candidates for drug development. Chemical Reactivity Theory (CRT) is a branch of chemistry that explains and predicts the behavior of chemical reactions based on the electronic structure of molecules. Conceptual Density Functional Theory (CDFT) and Computational Peptidology (CP) are computational approaches used to study the behavior of atoms, molecules, and peptides. In this study, we present the results of our investigation of the chemical reactivity and ADMET properties of Stellatolides A-H using a novel computational approach called Conceptual DFT-based Computational Peptidology (CDFT-CP). Our study uses CDFT and CP to predict the reactivity and stability of molecules and to understand the behavior of peptides at the molecular level. We also predict the ADMET properties of the Stellatolides A–H to provide insight into their effectiveness, potential side effects, and optimal dosage and route of administration, as well as their biological targets. This study sheds light on the potential of Stellatolides A–H as promising candidates for drug development and highlights the potential of CDFT-CP for the study of other natural compounds and peptides.
Galangal–Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 MPro, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation
Authors: El-Hosari Doaa G. , Hussein Wesam M. , Elgendy Marwa O. , Elgendy Sara O. , Ibrahim Ahmed R. N. , Fahmy Alzhraa M. , Hassan Afnan , Mokhtar Fatma Alzahraa , Hussein Modather F. , Abdelrahim Mohamed E. A. , Haggag Eman G.
Published: September 2023

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal–cinnamon mixture in the inhibition of SARS-CoV-2’s different protein targets. The potential antiviral effect of galangal–cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 MPro. The GCAE showed a significant antiviral effect against HCoV-229E (IC50 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract.
Unlocking the Power of Onion Peel Extracts: Antimicrobial and Anti-Inflammatory Effects Improve Wound Healing through Repressing Notch-1/NLRP3/Caspase-1 Signaling
Authors: Mounir Rafik , Alshareef Walaa A. , El Gebaly Eman A. , El-Haddad Alaadin E. , Ahmed Abdallah M. Said , Mohamed Osama G. , Enan Eman T. , Mosallam Shaimaa , Tripathi Ashootosh , Selim Heba Mohammed Refat M. , Bukhari Sarah I. , Alfaraj Rihaf , Ragab Ghada M. , El-Gazar Amira A. , El-Emam Soad Z.
Published: September 2023

Onion peels are often discarded, representing an unlimited amount of food by-products; however, they are a valuable source of bioactive phenolics. Thus, we utilized UPLC-MS/MS to analyze the metabolomic profiles of red (RO) and yellow (YO) onion peel extracts. The cytotoxic (SRB assay), anti-inflammatory (Griess assay), and antimicrobial (sensitivity test, MIC, antibiofilm, and SP-SDS tests) properties were assessed in vitro. Additionally, histological analysis, immunohistochemistry, and ELISA tests were conducted to investigate the healing potential in excisional skin wound injury and Candida albicans infection in vivo. RO extract demonstrated antibacterial activity, limited skin infection with C. albicans, and improved the skin’s appearance due to the abundance of quercetin and anthocyanin derivatives. Both extracts reduced lipopolysaccharide-induced nitric oxide release in vitro and showed a negligible cytotoxic effect on MCF-7 and HT29 cells. When extracts were tested in vivo for their ability to promote tissue regeneration, it was found that YO peel extract had the greatest impact. Further biochemical analysis revealed that YO extract suppressed NLRP3/caspase-1 signaling and decreased inflammatory cytokines. Furthermore, YO extract decreased Notch-1 levels and boosted VEGF-mediated angiogenesis. Our findings imply that onion peel extract can effectively treat wounds by reducing microbial infection, reducing inflammation, and promoting tissue regeneration.
Rheological and Viscoelastic Analysis of Hybrid Formulations for Topical Application
Authors: Calienni Maria Natalia , Martínez Luis Manuel , Izquierdo Maria Cecilia , Alonso Silvia del Valle , Montanari Jorge
Published: September 2023

The rheological and viscoelastic properties of hybrid formulations composed of vehicles designed for cutaneous topical application and loaded with ultradeformable liposomes (UDL) were assessed. UDL were selected for their established ability to transport both lipophilic and hydrophilic compounds through the skin, and are applicable in pharmaceuticals and cosmetics. Formulations underwent flow analysis and were fitted to the Herschel–Bulkley model due to their prevalent non-Newtonian behavior in most cases. Linear viscoelastic regions (LVR) were identified, and G′ and G″ moduli were determined via frequency sweep steps, considering the impact of temperature and aging. The formulations exhibited non-Newtonian behavior with pseudoplastic traits in most cases, with UDL incorporation inducing rheological changes. LVR and frequency sweep tests indicated predominantly elastic solid behavior, with G′ higher than G″, at different temperatures and post-production times. Tan δ values also illustrated a predominant solid-like behavior over liquid. This study provides pivotal insights into the rheological and viscoelastic features of topical formulations, emphasizing the crucial role of meticulous vehicle and formulation selection when incorporating UDL or analogous liposomal drug delivery systems.
Comparative Safety Analysis of Empagliflozin in Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease versus Normal Kidney Function: A Nationwide Cohort Study in Korea
Authors: Jang Ha Young , Kim In-Wha , Oh Jung Mi
Published: September 2023

Background: Empagliflozin has been shown to reduce cardiovascular morbidity and mortality in patients with type 2 diabetes. Various research on its efficacy in patients with chronic kidney disease (CKD) have been actively conducted. So far, few studies have investigated the safety of these adverse effects specifically in Asians with CKD. We aim to address these safety concerns on a patient population of Asian CKD patients using real-world data. Methods: We conducted a retrospective cohort study using health insurance data from the Korean Health Insurance Review & Assessment Service and compared safety outcomes between empagliflozin and sitagliptin in 26,347 CKD patients diagnosed with diabetes. Adverse outcomes, including major adverse cardiac events (MACEs), all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF), among others, were assessed. Results: Among a 1:1 matched cohort (6170 on empagliflozin, 6170 on sitagliptin), empagliflozin was associated with a significant reduction in MACEs, all-cause mortality, MI, hospitalization for unstable angina, coronary revascularization, HHF, hypoglycemic events, and urinary tract infections, but increased the risk of genital tract infections. No significant changes were observed for transient ischemic attack, acute kidney injury, volume depletion, diabetic ketoacidosis, thromboembolic events, and fractures. Conclusions: The usage of empagliflozin in diabetic CKD patients shows a significant reduction in many adverse outcomes compared to sitagliptin, but with an increased risk of genital tract infections. These findings provide evidence for future clinical decision-making around the use of empagliflozin in Asian CKD patients.
Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds
Authors: Šebek Viktor , Anzenbacher Pavel , Rejman Dominik , Špičáková Alena , Kolář Milan
Published: September 2023

Lipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacterial cytoplasmic membrane of prokaryotic cells, with limited effect on eukaryotic cells. First-generation LPPOs showed excellent bactericidal activity against Gram-positive species, including multiresistant strains. Second-generation LPPOs broaden the antibiotic effect also against Gram-negative bacteria. However, both first- and second-generation LPPOs lose their antibacterial activity in the presence of serum albumin. LEGO-LPPOs were found to be active against both Gram-positive and Gram-negative bacteria, have better selectivity as compared to first- and second-generation resistance to LEGO-LPPOs was also not observed, and are active even in the presence of serum albumin. Second-generation LPPOs have been studied as antimicrobial additives in bone cement and as nanofiber dressing components in the treatment of wound infections in mice. Second-generation LPPOs and LEGO-LPPOs were also tested to treat ex vivo simulated endodontic infections in dental root canals. The results of all these studies were encouraging and suggested further investigation of LPPOs in these indications. This paper aims to review and compile published data on LPPOs.
Challenges in Permeability Assessment for Oral Drug Product Development
Authors: Koziolek Mirko , Augustijns Patrick , Berger Constantin , Cristofoletti Rodrigo , Dahlgren David , Keemink Janneke , Matsson Pär , McCartney Fiona , Metzger Marco , Mezler Mario , Niessen Janis , Polli James E. , Vertzoni Maria , Weitschies Werner , Dressman Jennifer
Published: September 2023

Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed.
Performance Analysis of Soft-Switching FSO/THz-RF Dual-Hop AF-NOMA Link Based on Cognitive Radio
Authors: Liu Rongpeng , Wang Ziyang , Wang Xuerui , Lu Jingwei , Wang Yawei , Zhuo Yizhou , Wu Ruihuan , Wei Zhongchao , Liu Hongzhan
Published: September 2023

This paper presents a promising solution to address the scarcity of spectrum resources and enhance spectrum efficiency in the context of cognitive radio (CR)-based soft-switching free-space optical (FSO)/terahertz (THz) radio frequency (RF) dual-hop amplify-and-forward (AF)–non-orthogonal multiple access (ROMANO) links. The impact of maximum tolerable interference power in the primary network, transmit power in the secondary transmitter, and maximum relay transmission power on the link are thoroughly studied. The numerical results ultimately validate the effectiveness of this link in improving performance, and a comparative analysis is conducted with the without-CR scheme, highlighting the distinctive characteristics of the proposed link.
Waveguide Properties of Homogeneously Aligned Liquid Crystal Layers between ITO Electrodes and Thin Alignment Films
Authors: Palto Serguei P. , Geivandov Artur R.
Published: September 2023

Numerical studies of the waveguide properties of liquid crystal layers bounded by substrates with indium tin oxide (ITO) electrodes using the finite difference time-domain (FDTD) method are carried out. On the basis of the experimental transmittance spectra of ITO-coated glass substrates in the visible and near-infrared ranges, a Lorentz model describing the dielectric properties of the ITO electrodes is created. Then, by numerical modeling, optical systems including a homogeneously aligned LC layer between the thin alignment films and the ITO electrodes on the quartz substrates are studied. It is shown that, in the case of the use of traditional alignment films or their absence, the ITO electrodes lead to significant resonant losses in the waveguide mode for both TE- and TM-polarized light. The losses mechanism based on a phase-synchronized mode coupling occurring in relatively narrow spectral ranges is discussed. We also propose a method to control and exclude the losses using thin alignment films with a proper thickness and low refractive index.
Characterization of MicroRNAs and Gene Expression in ACC Oxidase RNA Interference-Based Transgenic Bananas
Authors: Xia Yan , Lai Zhongxiong , Do Yi-Yin , Huang Pung-Ling
Published: September 2023

Banana (Musa acuminata, AAA group) is a typically respiratory climacteric fruit. Previously, genes encoding ACC oxidase, one of the key enzymes in ethylene biosynthesis, Mh-ACO1 and Mh-ACO2 in bananas were silenced individually using RNAi interference technology, and fruit ripening of transgenic bananas was postponed. Here, the differential expression of miRNAs and their targeted mRNAs were analyzed in the transcriptomes of fruits at the third ripening stage, peel color more green than yellow, from the untransformed and RNAi transgenic bananas. Five significantly differentially expressed miRNAs (mac-miR169a, mac-miR319c-3p, mac-miR171a, mac-miR156e-5p, and mac-miR164a-5p) were identified. The predicted miRNA target genes were mainly enriched in six KEGG pathways, including ‘sulfur relay system’, ‘protein digestion and absorption’, ‘histidine metabolism’, ‘pathogenic E. coli infection’, ‘sulfur metabolism’, and ‘starch and sucrose metabolism’. After ethylene treatment, the expression of ACC oxidase silencing-associated miRNAs was down-regulated, and that of their target genes was up-regulated along with fruit ripening. The evolutionary clustering relationships of miRNA precursors among 12 gene families related to fruit ripening were analyzed. The corresponding expression patterns of mature bodies were mainly concentrated in flowers, fruits, and leaves. Our results indicated that ethylene biosynthesis is associated with miRNAs regulating the expression of sulfur metabolism-related genes in bananas.
Teline monspessulana Can Harm the Chilean Native Tree Nothofagus obliqua: Effects on Germination and Initial Growth
Authors: Aguilera Narciso , Guedes Lubia M. , Alvarado Ulises , Sáez-Carrillo Katia
Published: September 2023

Teline monspessulana is highly invasive in several countries around the world. This species pressurizes and displaces several native and endemic tree species in south-central Chile such as Nothofagus obliqua, the native species of greatest timber interest. We determined the effects induced by allelochemical stress of T. monspessulana on N. obliqua germination and initial growth. Germination was evaluated under in vitro conditions and in natural substrate obtained from sites inhabited by N. obliqua and from nearby areas invaded by T. monspessulana. Controls irrigated with tap water and treatments with aqueous extracts of aerial organs of the invasive species were used. Morphometric and morphological variables were evaluated, and the composition of alkaloids and phenols from the plant organs used for the aqueous extracts was determined. The substrates were also chemically characterized. Allelochemicals synthesized by T. monspessulana caused germination and growth inhibition and tissue-level alterations, as well as leaf and root damage in N. obliqua seedlings. In the aerial organs of T. monspessulana, the quinolizidine alkaloids aphylline, caulophylline, anagyrine, and sophocarpine were mainly detected. In addition, 21 phenolic compounds were identified, including gallic acid, vanillic acid, chlorogenic acid, p-coumaric acid, and quercetin. The phytotoxic potential of T. monspessulana can compromise the natural multiplication of N. obliqua and its survival from its first phenological stages. This interdisciplinary study model facilitated the clarification of the plant–plant relationship mediated by allelochemicals. The model can be replicated to investigate other interspecific interactions between invasive and native species.
Biochemical Response and Gene Expression to Water Deficit of Croatian Grapevine Cultivars (Vitis vinifera L.) and a Specimen of Vitis sylvestris
Authors: Lukšić Katarina , Mucalo Ana , Smolko Ana , Brkljačić Lidija , Marinov Luka , Hančević Katarina , Ozretić Zoković Maja , Bubola Marijan , Maletić Edi , Karoglan Kontić Jasminka , Karoglan Marko , Salopek-Sondi Branka , Zdunić Goran
Published: September 2023

The biochemical response and gene expression in different grapevine cultivars to water deficit are still not well understood. In this study, we investigated the performance of four traditional Croatian Vitis vinifera L. cultivars (‘Plavac mali crni’, ‘Istrian Malvasia’, ‘Graševina’, and ‘Tribidrag’), and one wild (Vitis vinifera subsp. sylvestris) genotype exposed to water deficit (WD) for nine days under semi-controlled conditions in the greenhouse. Sampling for biochemical and gene expression analyses was performed at days six and nine from the beginning of WD treatment. The WD affected the accumulation of metabolites with a significant increase in abscisic acid (ABA), salicylic acid (SA), and proline in the leaves of the stressed genotypes when the WD continued for nine days. Lipid peroxidation (MDA) was not significantly different from that of the control plants after six days of WD, whereas it was significantly lower (297.40 nmol/g dw) in the stressed plants after nine days. The cultivar ‘Istrian Malvasia’ responded rapidly to the WD and showed the highest and earliest increase in ABA levels (1.16 ng mg−1 dw, i.e., 3.4-fold increase compared to control). ‘Graševina’ differed significantly from the other genotypes in SA content at both time points analyzed (six and nine days, 47.26 and 49.63 ng mg−1 dw, respectively). Proline level increased significantly under WD (up to 5-fold at day nine), and proline variation was not genotype driven. The expression of aquaporin genes (TIP2;1 and PIP2;1) was down-regulated in all genotypes, coinciding with the accumulation of ABA. The gene NCED1 (9-cis-epoxycarotenoid dioxygenase) related to ABA was up-regulated in all genotypes under stress conditions and served as a reliable marker of drought stress. This work suggests that the stress response in metabolite synthesis and accumulation is complex, treatment- and genotype-dependent.
Essential Oils of Artemisia frigida Plants (Asteraceae): Conservatism and Lability of the Composition
Authors: Zhigzhitzhapova Svetlana V. , Dylenova Elena P. , Zhigzhitzhapov Bato V. , Goncharova Danaya B. , Tykheev Zhargal A. , Taraskin Vasiliy V. , Anenkhonov Oleg A.
Published: September 2023

Plants of arid regions have adapted to harsh environments during the long span of their evolution and have developed a set of features necessary for their survival in water-limited conditions. Artemisia frigida Willd. (Asteraceae) is a widely distributed species possessing significant cenotic value in steppe ecosystems due to its high frequency and abundance. This study examines different patterns of formation of essential oil composition in A. frigida plants under the influence of heterogeneous factors, including climate and its integral characteristics (HTC, Cextr, SPEI and others). The work is based on the results of our research conducted in Russia (Republic of Buryatia, Irkutsk region), Mongolia, and China, from 1998 to 2021. A total of 32 constant compounds have been identified in the essential oil of A. frigida throughout its habitat range in Eurasia, from Kazakhstan to Qinghai Province, China. Among them, camphor, 1,8-cineol and bornyl acetate are the dominant components, contained in 93–95% of the samples. Among the sesquiterpenoids, germacrene D is the dominant component in 67% of the samples. The largest variability within the composition of the essential oils of A. frigida is associated with significant differences in the climatic parameters when plants grow in high-altitude and extrazonal conditions.