bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids
Authors: Buckett Lance , Schönberger Sabrina , Spindler Veronika , Sus Nadine , Schoergenhofer Christian , Frank Jan , Frank Oliver , Rychlik Michael
Published: April 2022

Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood.
Correction: Cheng et al. Grating Couplers on Silicon Photonics: Design Principles, Emerging Trends and Practical Issues. Micromachines 2020, 11, 666
Authors: Cheng Lirong , Mao Simei , Li Zhi , Han Yaqi , Fu H. Y.
Published: April 2022

In the original publication [...]
Homologs of Phycobilisome Abundance Regulator PsoR Are Widespread across Cyanobacteria
Authors: Layer Alicia , Montgomery Beronda L.
Published: April 2022

During chromatic acclimation (CA), cyanobacteria undergo shifts in their physiology and metabolism in response to changes in their light environment. Various forms of CA, which involves the tuning of light-harvesting accessory complexes known as phycobilisomes (PBS) in response to distinct wavelengths of light, have been recognized. Recently, a negative regulator of PBS abundance, PsoR, about which little was known, was identified. We used sequence analyses and bioinformatics to predict the role of PsoR in cyanobacteria and PBS regulation and to examine its presence in a diverse range of cyanobacteria. PsoR has sequence similarities to the β-CASP family of proteins involved in DNA and RNA processing. PsoR is a putative nuclease widespread across Cyanobacteria, of which over 700 homologs have been observed. Promoter analysis suggested that psoR is co-transcribed with upstream gene tcpA. Multiple transcription factors involved in global gene regulation and stress responses were predicted to bind to the psoR-tcpA promoter. The predicted protein–protein interactions with PsoR homologs included proteins involved in DNA and RNA metabolism, as well as a phycocyanin-associated protein predicted to interact with PsoR from Fremyella diplosiphon (FdPsoR). The widespread presence of PsoR homologs in Cyanobacteria and their ties to DNA- and RNA-metabolizing proteins indicated a potentially unique role for PsoR in CA and PBS abundance regulation.
Myxobacteria: Physiology and Regulation
Authors: Whitworth David E.
Published: April 2022

Myxobacteria are fascinating and important prokaryotes [...]
Editorial for Special Issue “Colours in Minerals and Rocks”
Authors: Casas Lluís , Di Febo Roberta
Published: April 2022

Colour is one of the most eye-catching properties of some minerals and rocks [...]
Novel Bio-Functional Aloe vera Beverages Fermented by Probiotic Enterococcus faecium and Lactobacillus lactis
Authors: Cuvas-Limón Ruth B. , Ferreira-Santos Pedro , Cruz Mario , Teixeira José António , Belmares Ruth , Nobre Clarisse
Published: April 2022

Aloe vera has been medicinally used for centuries. Its bioactive compounds have been shown to be very effective in the treatment of numerous diseases. In this work, a novel functional beverage was developed and characterized to combine the health benefits of probiotic bacteria with the Aloe vera plant itself. Two Aloe vera juices were obtained by fermentation either by a novel isolated Enterococcus faecium or a commercial Lactococcus lactis. The extraction of Aloe vera biocompounds for further fermentation was optimized. Extraction with water plus cellulase enhanced the carbohydrates and phenolic compounds in the obtained extracts. The biotransformation of the bioactive compounds from the extracts during fermentation was assessed. Both probiotic bacteria were able to grow on the Aloe vera extract. Lactic acid and short-chain fatty acids (SCFA) together with fourteen individual phenolic compounds were quantified in the produced Aloe vera juice, mainly epicatechin, aloin, ellagic acid, and hesperidin. The amount of total phenolic compounds was maintained through fermentation. The antioxidant activity was significantly increased in the produced juice by the ABTS method. The novel produced Aloe vera juice showed great potential as a functional beverage containing probiotics, prebiotics, SCFA, and phenolic compounds in its final composition.
An Extensive Pharmacological Evaluation of New Anti-Cancer Triterpenoid (Nummularic Acid) from Ipomoea batatas through In Vitro, In Silico, and In Vivo Studies
Authors: Majid Muhammad , Farhan Anam , Asad Muhammad Imran , Khan Muhammad Rashid , Hassan Syed Shams ul , Haq Ihsan-ul , Bungau Simona
Published: April 2022

Prostate cancer (PCa) is the most common cancer in men, accounting for approximately 10% of all new cases in the United States. Plant-derived bioactive compounds, such as pentacyclic triterpenoids (PTs), have the ability to inhibit PCa cell proliferation. We isolated and characterized nummularic acid (NA), a potent PT, as a major chemical constituent of Ipomoea batatas, a medicinal food plant used in ethnomedicine for centuries. In the current study, in vitro antiproliferative potential against PCa cells (DU145 and PC3) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; Western blot protein expression analysis; absorption, distribution, metabolism, excretion (ADME); pharmacokinetic prediction studies; and bisphenol A (BPA)-induced prostate inhibition in Sprague Dawley rats were conducted to gauge the anti-cancer ability of NA. Significant (p < 0.05 and p < 0.01) time- and dose-dependent reductions in proliferation of PCa cells, reduced migration, invasion, and increased apoptotic cell population were recorded after NA treatment (3–50 µM). After 72 h of treatment, NA displayed significant IC50 of 21.18 ± 3.43 µM against DU145 and 24.21 ± 3.38 µM against PC3 cells in comparison to the controls cabazitaxel (9.56 ± 1.45 µM and 12.78 ± 2.67 µM) and doxorubicin (10.98 ± 2.71 µM and 15.97 ± 2.77 µM). Further deep mechanistic studies reveal that NA treatment considerably increased the cleavage of caspases and downstream PARP, upregulated BAX and P53, and downregulated BCL-2 and NF-κB, inducing apoptosis in PCa cells. Pharmacokinetic and ADME characterization indicate that NA has a favorable physicochemical nature, with high gastrointestinal absorption, low blood–brain barrier permeability, no hepatotoxicity, and cytochrome inhibition. BPA-induced perturbations of prostate glands in Sprague Dawley rats show a potential increase (0.478 ± 0.28 g) in prostate weight compared to the control (0.385 ± 0.13 g). Multi-dose treatment with NA (10 mg/kg) significantly reduced the prostate size (0.409 ± 0.21 g) in comparison to the control. NA-treated groups exhibited substantial restoration of hematological and histological parameters, reinstatement of serum hormones, and suppression of inflammatory markers. This multifaceted analysis suggests that NA, as a novel small molecule with a strong pharmacokinetic and pharmacological profile, has the potential to induce apoptosis and death in PCa cells.
Monitoring Farmed Fish Welfare by Measurement of Cortisol as a Stress Marker in Fish Feces by Liquid Chromatography Coupled with Tandem Mass Spectrometry
Authors: Meling Vanessa Andrea , Berge Kjetil , Knudsen David Lausten , Rønning Per Ola , Brede Cato
Published: April 2022

The aquaculture industry has become a sustainable source of food for humans. Remaining challenges include disease issues and ethical concerns for the discomfort and stress of farmed fish. There is a need for reliable biomarkers to monitor welfare in fish, and the stress hormone cortisol has been suggested as a good candidate. This study presents a novel method for measurement of cortisol in fish feces based on enzymatic hydrolysis, liquid–liquid extraction, derivatization, and finally instrumental analysis by liquid chromatography coupled with tandem mass spectrometry. Hydrolysis and extraction conditions were optimized. Cortisol appeared to be mostly conjugated to sulfate and less conjugated to glucuronic acid in the studied samples of feces from farmed Atlantic salmon. The method was suitable for quantification of cortisol after enzymatic deconjugation by either combined glucuronidase and sulfatase activity, or by glucuronidase activity alone. The limit of detection was 0.15 ng/g, the limit of quantification was 0.34 ng/g, and the method was linear (R2 > 0.997) up to 380 ng/g, for measurement of cortisol in wet feces. Method repeatability and intermediate precision were acceptable, both with a coefficient of variation (CV) of 11%. Stress level was high in fish released into seawater, and significantly reduced after eight days.
Spaghetti Enriched with Inulin: Effect of Polymerization Degree on Quality Traits and α-Amylase Inhibition
Authors: Cardullo Nunzio , Muccilli Vera , Di Stefano Vita , Bonacci Sonia , Sollima Lucia , Melilli Maria Grazia
Published: April 2022

Inulin is considered a dietary fiber and represents a noteworthy ingredient for food biofortification due to its health effects and its neutral taste. The aim of the work was the evaluation of the quality of pasta produced using whole-meal flours of two ancient Sicilian landraces (Senatore Cappelli-CAP and Timilia—TIM) fortified with two types of inulin (long-chain topinambur inulin IT and low-chain chicory inulin IC), at two different levels of substitution (2 and 4%) to evaluate its possible effect on α-amylase inhibition. The color indices L* and a* were mainly influenced by cultivars, while IT improved the sensory attributes, mainly the elasticity sensation, and influenced less the other sensory attributes: adhesiveness, color, odor, taste, and Over Quality Score for both landraces. The cooking quality was linked mainly to the landrace used, due to the very different gluten matrix of CAP and TIM. IC and IT showed promising α-Amy inhibitory activity with comparable IC50 values of 0.45 ± 0.04 and 0.50 ± 0.06 mg/mL. The enrichment of spaghetti with inulin with an inhibitory effect on α-amylase determined the hypoglycemic properties of pasta, thus lowering the corresponding IC50 value.
Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation
Authors: Okumura Hisashi , Itoh Satoru G.
Published: April 2022

Alzheimer’s disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-β (Aβ) peptides. This review article presents molecular dynamics (MD) simulation studies of Aβ peptides and Aβ fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of Aβ, a β-hairpin structure promotes the formation of intermolecular β-sheet structures. Aβ peptides tend to exist at hydrophilic/hydrophobic interfaces and form more β-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of Aβ peptides, interact with Aβ. An MD simulation study of the Aβ amyloid fibrils in equilibrium is also presented: the Aβ amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer’s disease using MD simulations.
Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ25–35-Induced Mice by Inhibiting the NLRP3 Inflammasome
Authors: Guo Pengli , Zeng Mengnan , Wang Shengchao , Cao Bing , Liu Meng , Zhang Yuhan , Jia Jufang , Zhang Qinqin , Zhang Beibei , Wang Ru , Zheng Xiaoke , Feng Weisheng
Published: April 2022

(1) Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is now widely accepted that neuroinflammation plays a key role in its pathogenesis. Eriodictyol (Eri) and homoeriodictyol (Hom), dihydroflavonoids extracted from a variety of plants, have been confirmed to display a relationship with neuroprotection. (2) Methods: An AD mouse model was constructed by intracerebroventricular (ICV) injection of the Aβ25–35 peptide, and Eri and Hom were administered orally for 4 weeks. UPLC-MS/MS was used to determine whether Eri and Hom cross the blood–brain barrier to exert their therapeutic effects. Histological changes in the brain and levels of Aβ were evaluated, and Y-maze and new object recognition experiments were conducted to assess the effects of Eri and Hom on Aβ25–35-induced memory impairment in mice. The levels of oxidative stress and apoptosis in peripheral immune cells and progenitor cells in the hippocampal region were analyzed by flow cytometry and in vitro assays. Western blotting and enzyme-linked immunosorbent assays (ELISA) were used to measure the expression levels of NLRP3 inflammasome-related proteins and inflammatory factors in the brain. The effect of nigericin (an agonist of the NLRP3 inflammasome) on Eri and Hom intervention in LPS-induced N9 microglia was examined using a High Content Screening System. (3) Results: Eri and Hom reduced neuronal damage in mouse brain tissue, decreased Aβ levels in the brain, downregulated oxidative stress and apoptosis levels, and improved learning and memory capacity by crossing the blood–brain barrier to exert its effects. Moreover, Eri and Hom inhibited NLRP3 inflammasome activation and ameliorated immune cell disorder. Furthermore, the effect of Eri and Hom on LPS-induced N9 microglia disappeared after the addition of nigericin to agonize NLRP3 receptors. (4) Conclusions: Eri and Hom improved Aβ25–35-induced memory impairment in mice by inhibiting the NLRP3 inflammasome.
Effects of Cations on HPTS Fluorescence and Quantification of Free Gadolinium Ions in Solution; Assessment of Intracellular Release of Gd3+ from Gd-Based MRI Contrast Agents
Authors: Scarciglia Angelo , Di Gregorio Enza , Aime Silvio , Ferrauto Giuseppe
Published: April 2022

8-Hydroxypyrene-1,3,6-trisulfonate (HPTS) is a small, hydrophilic fluorescent molecule. Since the pKa of the hydroxyl group is close to neutrality and quickly responds to pH changes, it is widely used as a pH-reporter in cell biology for measurements of intracellular pH. HPTS fluorescence (both excitation and emission spectra) at variable pH was measured in pure water in the presence of NaCl solution or in the presence of different buffers (PBS or hepes in the presence or not of NaCl) and in a solution containing BSA. pKa values have been obtained from the sigmoidal curves. Herein, we investigated the effect of mono-, di-, and trivalent cations (Na+, Ca2+, La3+, Gd3+) on fluorescence changes and proposed its use for the quantification of trivalent cations (e.g., gadolinium ions) present in solution as acqua-ions. Starting from the linear regression, the LoD value of 6.32 µM for the Gd3+ detection was calculated. The effects on the emission were also analyzed in the presence of a combination of Gd3+ at two different concentrations and the previously indicated mono and di-valent ions. The study demonstrated the feasibility of a qualitative method to investigate the intracellular Gd3+ release upon the administration of Gd-based contrast agents in murine macrophages.
Food Ingredients Derived from Lemongrass Byproduct Hydrodistillation: Essential Oil, Hydrolate, and Decoction
Authors: Rodrigues Luís , Coelho Elisabete , Madeira Renata , Teixeira Pedro , Henriques Isabel , Coimbra Manuel A.
Published: April 2022

Essential oil (EO), hydrolate, and nondistilled aqueous phase (decoction) obtained from the hydrodistillation of lemongrass byproducts were studied in terms of their potential as food ingredients under a circular economy. The EO (0.21%, dry weight basis) was composed mainly of monoterpenoids (61%), the majority being citral (1.09 g/kg). The minimal inhibitory concentrations (MIC) of lemongrass EO against Escherichia coli, Salmonella enterica, and Staphylococcus aureus, were 617, 1550, and 250 μg/mL, respectively. This effect was dependent on the citral content. Particularly for Gram-negative bacteria, a synergism between citral and the remaining EO compounds enhanced the antimicrobial activity. The polymeric material obtained from the nondistilled aqueous phase was composed of phenolic compounds (25% gallic acid equivalents) and carbohydrates (22%), mainly glucose (66 mol%). This polymeric material showed high antioxidant activity due to bound phenolic compounds, allowing its application as a functional dietary fiber ingredient. Matcha green tea formulations were successfully mixed with lemongrass hydrolate containing 0.21% EO (dry weight basis) with 58% of monoterpenoids, being citral at 0.73 g/kg, minimizing matcha astringency with a citrus flavor and extending the product shelf life. This holistic approach to essential oils’ hydrodistillation of Cymbopogon citratus byproducts allows for valorizing of the essential oil, hydrolate, and decoction for use as food ingredients.
Comparative Preparation Method and Associated Cost of Lignin–Cellulose Nanocrystals
Authors: Zhang Yi , Haque Abu Naser Md Ahsanul , Naebe Maryam
Published: April 2022

Lignin is a natural source of UV-shielding materials, though its recalcitrant and heterogeneous structure makes the extraction and purification processes complex. However, lignin’s functionality can be directly utilised when it stays as native with cellulose and hemicellulose in plant biomass, rather than being separated. The fabrication process of this native lignin is sustainable, as it consumes less energy and chemicals compared to purified lignin; thus, it is an economic and more straightforward approach. In this study, the properties of native and purified lignin–cellulose nanocrystals (L–CNCs) sourced from hemp hurd waste were compared to explore the differences in their morphology, UV-shielding properties and chemical structure affected by their distinct fabrication process. These two kinds of L–CNCs were further added into polyvinyl alcohol (PVA) to evaluate their reinforcement characteristics. The resulting native L–CNCs/PVA film showed stronger UV-shielding ability than purified L–CNCs. Moreover, the native L–CNCs showed better compatibility with PVA, while the purified L–CNCs/PVA interfaces showed phase separation. The phase separation in purified L–CNCs/PVA films reduced the films’ tensile strength and Young’s modulus and increased the water vapour transmission. The laboratory-scale cost of native L–CNCs production (~AUD 80/kg) was only 10% of purified L–CNCs (~AUD 850/kg), resulting in a comparatively lower cost for preparing native L–CNCs/PVA composite films. Overall, this study shows that the proposed method of production and use of native L–CNCs can be an economic approach to deliver UV-shielding properties for potential applications, such as food packaging.
Multi-Role Surface Modification of Single-Crystalline Nickel-Rich Lithium Nickel Cobalt Manganese Oxides Cathodes with WO3 to Improve Performance for Lithium-Ion Batteries
Authors: Ou Limin , Nong Shengheng , Yang Ruoxi , Li Yaoying , Tao Jinrong , Zhang Pan , Huang Haifu , Liang Xianqing , Lan Zhiqiang , Liu Haizhen , Huang Dan , Guo Jin , Zhou Wenzheng
Published: April 2022

Compared with the polycrystalline system, the single-crystalline ternary cathode material has better cycle stability because the only primary particles without grain boundaries effectively alleviate the formation of micro/nanocracks and retain better structural integrity. Therefore, it has received extensive research attention. There is no consistent result whether tungsten oxide acts as doping and/or coating from the surface modification of the polycrystalline system. Meanwhile, there is no report on the surface modification of the single-crystalline system by tungsten oxide. In this paper, multirole surface modification of single-crystalline nickel-rich ternary cathode material LiNi0.6Co0.2Mn0.2O2 by WO3 is studied by a simple method of adding WO3 followed by calcination. The results show that with the change in the amount of WO3 added, single-crystalline nickel-rich ternary cathode material can be separately doped, separately coated, and both doped and coated. Either doping or coating effectively enhances the structural stability, reduces the polarization of the material, and improves the lithium-ion diffusion kinetics, thus improving the cycle stability and rate performance of the battery. Interestingly, both doping and coating (for SC-NCM622-0.5%WO3) do not show a more excellent synergistic effect, while the single coating (for SC-NCM622-1.0%WO3) after eliminating the rock-salt phase layer performs the most excellent modification effect.
Analysis of Low-Frequency 1/f Noise Characteristics for MoTe2 Ambipolar Field-Effect Transistors
Authors: Zhang Bing , Hu Congzhen , Xin Youze , Li Yaoxin , Xie Yiyun , Xing Qian , Guo Zhuoqi , Xue Zhongming , Li Dan , Zhang Guohe , Geng Li , Ke Zungui , Wang Chi
Published: April 2022

Low-frequency electronic noise is an important parameter used for the electronic and sensing applications of transistors. Here, we performed a systematic study on the low-frequency noise mechanism for both p-channel and n-channel MoTe2 field-effect transistors (FET) at different temperatures, finding that low-frequency noise for both p-type and n-type conduction in MoTe2 devices come from the variable range hopping (VRH) transport process where carrier number fluctuations (CNF) occur. This process results in the broad distribution of the waiting time of the carriers between successive hops, causing the noise to increase as the temperature decreases. Moreover, we found the noise magnitude for p-type MoTe2 FET hardly changed after exposure to the ambient conditions, whereas for n-FET, the magnitude increased by nearly one order. These noise characteristics may provide useful guidelines for developing high-performance electronics based on the emerging transition metal dichalcogenides.
New Fabrication Method of Silicon Sub-Micron Beams with Monolithic Contacts for Thermoelectric Transport Properties Analysis
Authors: Stranz Andrej , Salleras Marc , Fonseca Luis
Published: April 2022

Micromachined devices were developed and fabricated using complementary metal-oxide-semiconductor (CMOS)/micro-electro-mechanical systems (MEMS) technology allowing for the analysis of transport properties of silicon sub-micron beams having monolithic contacts. The beams were fabricated by a combination of deep reactive ion etching (RIE) and potassium hydroxide (KOH) etching techniques on standard p and n silicon bulk and silicon-on-insulator (SOI) wafers. Simultaneous fabrication of many devices on one wafer allows for the extraction of statistical information to properly compare the different layers and contacts. Fabricated devices are presented, underlining the feasibility of the proposed microdevice. The methods used to manipulate the geometry and the surface roughness of the single crystalline silicon beams are described. The presented measurement device offers the possibility to determine simultaneously all the main transport values, thermal, and electrical conductivities as well as the Seebeck coefficient.
Facile Gold-Nanoparticle Boosted Graphene Sensor Fabrication Enhanced Biochemical Signal Detection
Authors: Meng Shuaishuai , Wang Li , Ji Xixi , Yu Jie , Ma Xing , Zhang Jiaheng , Zhao Weiwei , Ji Hongjun , Li Mingyu , Feng Huanhuan
Published: April 2022

Graphene has been considered as an excellent biochemical sensors’ substrate material because of its excellent physical and chemical properties. Most of these sensors have employed enzymes, antibodies, antigens, and other biomolecules with corresponding recognition ability as recognition elements, to convert chemical signals into electrical signals. However, oxidoreductase enzymes that grow on graphene surfaces are affected significantly by the environment and are easily inactivated, which hinders the further improvement of detection sensitivity and robusticity. A gold-boosted graphene sensor was fabricated by the in situ electrochemical deposition of inorganic gold nanoparticles on vertical graphene nanosheets. This approach solves the instability of biological enzymes and improves the detection performance of graphene-based sensors. The uric acid sensitivity of the gold-boosted electrode was 6230 µA mM−1 cm−2, which is 6 times higher than the original graphene electrode. A 7 h GNSs/CC electrode showed an impressive detection performance for ascorbic acid, dopamine, and uric acid, simultaneously. Moreover, it exhibited a reliable detection performance in human serum in terms of uric acid. The possible reason could be that the vertical aliened graphene nanosheet acts as a reaction active spot. This 3D graphene-nanosheet-based doping approach can be applied to a wide variety of inorganic catalytic materials to enhance their performance and improve their durability in aspects such as single-atom catalysis and integration of multiple catalytic properties.
Inflammatory Bowel Disease and Reproductive Health: From Fertility to Pregnancy—A Narrative Review
Authors: Ronchetti Camilla , Cirillo Federico , Di Segni Noemi , Cristodoro Martina , Busnelli Andrea , Levi-Setti Paolo Emanuele
Published: April 2022

Despite the fact that knowledge on obstetrical management of Inflammatory Bowel Diseases (IBDs) has greatly improved over the years, many patients still actively avoid pregnancy for fear of adverse maternal or neonatal outcomes, of adverse effects of pregnancy on the disease activity, of eventual IBD inheritance, or of an increased risk of congenital malformations. Indeed, though data prove that fertility is hardly affected by the disease, a reduced birth rate is nevertheless observed in patients with IBD. Misconceptions on the safety of drugs during gestation and breastfeeding may influence patient choice and negatively affect their serenity during pregnancy or lactation. Moreover, physicians often showed concerns about starting IBD medications before and during pregnancy and did not feel adequately trained on the safety of IBD therapies. IBD-expert gastroenterologists and gynecologists should discuss pregnancy and breastfeeding issues with patients when starting or changing medications in order to provide appropriate information; therefore, pre-conception counselling on an individualized basis should be mandatory for all patients of reproductive age to reassure them that maintaining disease remission and balancing the eventual obstetrical risks is possible.
Cycling for Weight Loss May Clear Carbohydrates Rather Than Fat, Irrespective of Normal or Mildly Reduced Normobaric Oxygen
Authors: Schreurs Victor V. A. M. , Maas Tjieu , van den Borne Joost J. G. C. , Keijer Jaap
Published: April 2022

A single-center randomized, controlled cross-over exercise intervention in 20 women willing to reduce weight (20–40 y, BMI: 27.4 ± 2.1), with the aim to examine potential benefits for weight loss under normal (N-Ox: 20.9%) and mildly reduced (R-Ox: 17.0%) normobaric oxygen in an “Altitude Simulation Chamber”. O2 consumption (VO2), CO2 production (VCO2), blood oxygen saturation (SaO2), blood glucose and lactate (mM) were studied before, during and after cycling for 22 min at a mean personalized workload of 54.2 ± 11.7 watts, about 40% of VO2max. Despite lower absolute SaO2 values and a greater decline from rest to exercise under R-Ox (time x treatment interaction p < 0.01), VO2 did not differ from N-Ox (time x treatment interaction p = 0.178). Average net VO2, 13.8 mL O2 per watt, reflected fairly normal aerobic cycling, irrespective of O2 regime. The Respiratory Exchange Ratio (RER; VO2/VCO2), 0.83 at rest, increased for both treatments to a ratio close to or beyond unity during and directly after exercise (treatment effect p = 0.407). The tendency of cycling for weight loss to clear carbohydrates rather than fat, irrespective of normal or mildly reduced normobaric oxygen, is discussed as a lactate-mediated and phenotype-specific consequence of apparent anaerobic glycolysis with adverse perspectives for weight loss and metabolic health.
Investigation of Cross-Reactivity of Anti-Ephrin-B2 Antibody to Other Ephrin-B Members in an Immunohistochemical Study in a Cohort of Oral Squamous Cell Carcinoma
Authors: Sapkota Dipak , Vallenari Evan M. , Tamatam Dhanalakshmi , Schreurs Olaf Joseph Franciscus , Pandey Sushma , Søland Tine Merete , Costea Daniela-Elena , Tokozlu Burcu , Åsheim Hans-Christian
Published: April 2022

Ephrin-B1,-B2 and -B3 proteins share a high degree of sequence similarity. Investigation of these proteins as putative prognostic markers in human cancers including oral squamous cell carcinoma (OSCC) has been limited by challenges in generating specific antibodies against them. The current study examined the reactivity of a polyclonal anti-human ephrin-B2 antibody (HPA008999) against ephrin-B proteins and investigated the prognostic significance of immunoreactivity of the same antibody at different intra-tumor sites in OSCC specimens. By amino acid sequence comparison, immunocytochemistry and Western blot analysis on cell lysates and precipitates from HEK-293T cells transfected with EFNB1, EFNB2, or EFNB3 expression constructs, we demonstrated that HPA008999 reacted to all ephrin-B proteins. Using immunohistochemistry (IHC) with the HPA008999 antibody in a cohort (n = 131) of OSCC, we showed high immunoreactivity at the tumor center, but not at the tumor invading front, was significantly associated with worse 5-year overall survival probabilities. In conclusion, the HPA008999 antibody reacted to all ephrin-B proteins and the immunoreactivity at the tumor center might be useful as a prognostic marker in OSCC. These data underscore the need for the investigation of antibodies for cross-reactivity to similar protein members for obtaining reliable and meaningful results in IHC based biomarker studies.
Comparative Evaluation of Six SARS-CoV-2 Real-Time RT-PCR Diagnostic Approaches Shows Substantial Genomic Variant–Dependent Intra- and Inter-Test Variability, Poor Interchangeability of Cycle Threshold and Complementary Turn-Around Times
Authors: Kogoj Rok , Korva Misa , Knap Nataša , Resman Rus Katarina , Pozvek Patricija , Avšič-Županc Tatjana , Poljak Mario
Published: April 2022

Several professional societies advise against using real-time Reverse-Transcription PCR (rtRT-PCR) cycle threshold (Ct) values to guide clinical decisions. We comparatively assessed the variability of Ct values generated by six diagnostic approaches by testing serial dilutions of well-characterized isolates of 10 clinically most relevant SARS-CoV-2 genomic variants: Alpha, Beta, Gamma, Delta, Eta, Iota, Omicron, A.27, B.1.258.17, and B.1 with D614G mutation. Comparison of three fully automated rtRT-PCR analyzers and a reference manual rtRT-PCR assay using RNA isolated with three different nucleic acid isolation instruments showed substantial inter-variant intra-test and intra-variant inter-test variability. Ct value differences were dependent on both the rtRT-PCR platform and SARS-CoV-2 genomic variant. Differences ranging from 2.0 to 8.4 Ct values were observed when testing equal concentrations of different SARS-CoV-2 variants. Results confirm that Ct values are an unreliable surrogate for viral load and should not be used as a proxy of infectivity and transmissibility, especially when different rtRT-PCR assays are used in parallel and multiple SARS-CoV-2 variants are circulating. A detailed turn-around time (TAT) comparative assessment showed substantially different TATs, but parallel use of different diagnostic approaches was beneficial and complementary, allowing release of results for more than 81% of non-priority samples within 8 h after admission.
Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression
Authors: Malyshev Anton V. , Sukhanova Iuliia A. , Ushakova Valeria M. , Zorkina Yana A. , Abramova Olga V. , Morozova Anna Y. , Zubkov Eugene A. , Mitkin Nikita A. , Pavshintsev Vsevolod V. , Doronin Igor I. , Gedzun Vasilina R. , Babkin Gennady A. , Sanchez Sergio A. , Baker Miah D. , Haile Colin N.
Published: April 2022

We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant.
The Importance of Endoplasmic Reticulum Stress as a Novel Antidepressant Drug Target and Its Potential Impact on CNS Disorders
Authors: Jóźwiak-Bębenista Marta , Sokołowska Paulina , Siatkowska Małgorzata , Panek Cecilia Analia , Komorowski Piotr , Kowalczyk Edward , Wiktorowska-Owczarek Anna
Published: April 2022

Many central nervous system (CNS) diseases, including major depressive disorder (MDD), are underpinned by the unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress. New, more efficient, therapeutic options for MDD are needed to avoid adverse effects and drug resistance. Therefore, the aim of the work was to determine whether UPR signalling pathway activation in astrocytes may serve as a novel target for antidepressant drugs. Among the tested antidepressants (escitalopram, amitriptyline, S-ketamine and R-ketamine), only S-ketamine, and to a lesser extent R-ketamine, induced the expression of most ER stress-responsive genes in astrocytes. Furthermore, cell viability and apoptosis measuring assays showed that (R-)S-ketamine did not affect cell survival under ER stress. Under normal conditions, S-ketamine played the key role in increasing the release of brain-derived neurotrophic factor (BDNF), indicating that the drug has a complex mechanism of action in astrocytes, which may contribute to its therapeutic effects. Our findings are the first to shed light on the relationship between old astrocyte specifically induced substance (OASIS) stabilized by ER stress and (R-)S-ketamine; however, the possible involvement of OASIS in the mechanism of therapeutic ketamine action requires further study.
Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
Authors: Bouchenaki Hichem , Bernard Amandine , Bessaguet Flavien , Frachet Simon , Richard Laurence , Sturtz Franck , Magy Laurent , Bourthoumieu Sylvie , Demiot Claire , Danigo Aurore
Published: April 2022

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN.
CRISPR/Cas9 in Planta Hairy Root Transformation: A Powerful Platform for Functional Analysis of Root Traits in Soybean
Authors: Niazian Mohsen , Belzile François , Torkamaneh Davoud
Published: April 2022

Sequence and expression data obtained by next-generation sequencing (NGS)-based forward genetics methods often allow the identification of candidate causal genes. To provide true experimental evidence of a gene’s function, reverse genetics techniques are highly valuable. Site-directed mutagenesis through transfer DNA (T-DNA) delivery is an efficient reverse screen method in plant functional analysis. Precise modification of targeted crop genome sequences is possible through the stable and/or transient delivery of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) reagents. Currently, CRISPR/Cas9 is the most powerful reverse genetics approach for fast and precise functional analysis of candidate genes/mutations of interest. Rapid and large-scale analyses of CRISPR/Cas-induced mutagenesis is achievable through Agrobacterium rhizogenes-mediated hairy root transformation. The combination of A. rhizogenes hairy root-CRISPR/Cas provides an extraordinary platform for rapid, precise, easy, and cost-effective “in root” functional analysis of genes of interest in legume plants, including soybean. Both hairy root transformation and CRISPR/Cas9 techniques have their own complexities and considerations. Here, we discuss recent advancements in soybean hairy root transformation and CRISPR/Cas9 techniques. We highlight the critical factors required to enhance mutation induction and hairy root transformation, including the new generation of reporter genes, methods of Agrobacterium infection, accurate gRNA design strategies, Cas9 variants, gene regulatory elements of gRNAs and Cas9 nuclease cassettes and their configuration in the final binary vector to study genes involved in root-related traits in soybean.
Characterization of PISTILLATA-like Genes and Their Promoters from the Distyly Fagopyrum esculentum
Authors: You Wei , Chen Xiangjian , Zeng Lingtian , Ma Zhiyuan , Liu Zhixiong
Published: April 2022

Arabidopsis PISTILLATA (PI) encodes B-class MADS-box transcription factor (TF), and works together with APETALA3 (AP3) to specify petal and stamen identity. However, a small-scale gene duplication event of PI ortholog was observed in common buckwheat and resulted in FaesPI_1 and FaesPI_2. FaesPI_1 and FaesPI_2 were expressed only in the stamen of dimorphic flower (thrum and pin) of Fagopyrum esculentum. Moreover, intense beta-glucuronidase (GUS) staining was found in the entire stamen (filament and anther) in pFaesPI_1::GUS transgenic Arabidopsis, while GUS was expressed only in the filament of pFaesPI_2::GUS transgenic Arabidopsis. In addition, phenotype complementation analysis suggested that pFaesPI_1::FaesPI_1/pFaesPI_2::FaesPI_2 transgenic pi-1 Arabidopsis showed similar a flower structure with stamen-like organs or filament-like organs in the third whorl. This suggested that FaesPI_2 only specified filament development, but FaesPI_1 specified stamen development. Meanwhile, FaesPI_1 and FaesPI_2 were shown to function redundantly in regulating filament development, and both genes work together to require a proper stamen identity. The data also provide a clue to understanding the roles of PI-like genes involved in floral organ development during the early evolution of core eudicots and also suggested that FaesPI_1 and FaesPI_2 hold the potential application in bioengineering to develop a common buckwheat male sterile line.
Optimal Growth Conditions for Azolla pinnata R. Brown: Impacts of Light Intensity, Nitrogen Addition, pH Control, and Humidity
Authors: da Silva Maria Emelia Jesus , Mathe Lebani Oarabile Joy , van Rooyen Ignatius Leopoldus , Brink Hendrik Gideon , Nicol Willie
Published: April 2022

Nitrogen pollution from agriculture is a major challenge facing our society today. Biological nitrogen fixation is key to combat the damage that is caused by synthetic nitrogen. Azolla spp. are ideal candidates for fast nitrogen fixation. This study aimed to investigate the optimal growth conditions for Azolla pinnata R. Brown. The growth conditions that were investigated included the growth medium type and strength, light intensity, the presence/absence of nitrogen in the medium, pH control, and humidity. Higher light intensities increased plant growth by 32%, on average. The highest humidity (90%) yielded higher growth rate values than lower humidity values (60% and 75%). The presence of nitrogen in the medium had no significant effect on the growth rate of the plants. pH control was critical under the fast growth conditions of high light intensity and high humidity, and it reduced algal growth (from visual observation). The optimal growth rate that was achieved was 0.321 day−1, with a doubling time of 2.16 days. This was achieved by using a 15% strength of the Hoagland solution, high light intensity (20,000 lx), nitrogen present in the medium, and pH control at 90% humidity. These optimised conditions could offer an improvement to the existing phytoremediation systems of Azolla pinnata and aid in the fight against synthetic nitrogen pollution.
Scale-up of Emulsion Polymerisation up to 100 L and with a Polymer Content of up to 67 wt%, Monitored by Photon Density Wave Spectroscopy
Authors: Jacob Laurence Isabelle , Pauer Werner
Published: April 2022

The scale-up process of the high solid content (up to 67 wt%) emulsion polymerisation of vinyl acetate and Versa®10 from 1 L over 10 L to 100 L was investigated. An emulsion copolymerisation of vinyl acetate and neodecanoic acid vinyl ester in a molar ratio of 9:1 was carried out in a starved-fed semi-batch operation. As a radical source, a redox initiator system consisting of L-ascorbic acid, tert-butyl hydroperoxide and ammonium iron (III) sulphate was used. The process parameters, such as the required stirring speed and heat dissipation, were determined and adjusted beforehand via reaction calorimetry to ensure a successful scale-up without safety issues. In addition, the emulsion polymerisation was monitored inline by Raman (qualitative monomer accumulation), as well as Photon Density Wave spectroscopy (particle size and scattering coefficient) and temperature measurements. The data provided by Raman spectroscopy and temperature measurements revealed mixing difficulties due to an insufficient stirring rate, while the inline measurement with Photon Density Wave spectroscopy offered an insight into the development of the product properties. It proved to be reliable and precise throughout the entire scale-up process, especially compared to conventional offline methods, such as dynamic light scattering or sedimentation analysis by means of a disc centrifuge, both of which encountered issues when using higher polymer contents.
Zr-Based Biocomposite Materials as an Alternative for Fluoride Removal, Preparation and Characteristics
Authors: Robledo-Peralta Adriana , García-Quiñonez Linda Viviana , Rodríguez-Beltrán René I. , Reynoso-Cuevas Liliana
Published: April 2022

The development of biocomposite materials used as adsorbents to remove ions in aqueous media has become an attractive option. The biomasses (base materials) are chemically treated and impregnated with metal cations, becoming competitive for fluoride-capture capacity. In this research, Valence orange (Citrus sinensis) and Red Delicious apple (Malus Domestica) peels were modified by alkaline treatment, carboxylation, and impregnation with zirconium (Zr). These materials were characterized morphologically and structurally to understand the modifications in the treated biomasses and the mechanism of fluoride adsorption. The results show changes in surface area and composition, most notably, an increment in roughness and Zr impregnation of the bioadsorbents. After batch experimentation, the maximum capacity of the materials was determined to be 4.854 and 5.627 mg/g for the orange and apple peel bioadsorbent, respectively, at pH 3.5. The experimental data fitted the Langmuir model, suggesting that chemisorption occurs in monolayers. Finally, the characterization of the bioadsorbents in contact with fluoride allowed the replacement of OH species by fluoride or the formation of hydrogen bonds between them as an adsorption mechanism. Therefore, these bioadsorbents are considered viable and can be studied in a continuous system.
Chloride-Derived Bimetallic Cu-Fe Nanoparticles for High-Selective Nitrate-to-Ammonia Electrochemical Catalysis
Authors: Tang Zixuan , Bai Zehui , Li Xin , Ding Le , Zhang Bin , Chang Xinghua
Published: April 2022

Cu-based bimetallic materials have been widely reported as efficient catalysts for electrocatalytic nitrate reduction. However, the faradaic efficiency and selectivity are still far from satisfactory. Herein, Cu-Fe bimetallic nanoalloys with adjustable Cu/Fe ratios are successfully prepared through a reactive mechanical milling approach with CuCl2, FeCl3 and Na as the starting materials. The optimized Cu3Fe exhibits excellent nitrate conversion efficiency of 81.1% and 70.3% ammonia selectivity at −0.7 V vs. RHE within 6 h under 0.1 M Na2SO4 and 100 ppm NO3−. The Fe-introduction-induced upshift of the d-band center is identified to be beneficial for promoting nitrate adsorption on Cu3Fe. Moreover, favorable H generation under the assistance of Fe could effectively accelerate the stepwise hydrogenation during electrocatalytic nitrate reduction, resulting in significantly improved NH4+ selectivity. This work supplies valuable insights for the rational design of transition-metal-based bimetallic catalysts for electrocatalytic nitrate reduction.