bluuebunny/crossref_metadata_2025 huggingface dataset:
The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways
Authors: Liu Xiaoyao , Wang Yuxi , Tian Yuan , Hu Jiahui , Liu Zhen , Ma Yuncheng , Xu Wenhui , Wang Weiling , Gao Jian , Wang Ting
Published: April 2024

Rhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.
Lactylation Modification in Cardiometabolic Disorders: Function and Mechanism
Authors: Li Xu , Cai Pingdong , Tang Xinyuan , Wu Yingzi , Zhang Yue , Rong Xianglu
Published: April 2024

Cardiovascular disease (CVD) is recognized as the primary cause of mortality and morbidity on a global scale, and developing a clear treatment is an important tool for improving it. Cardiometabolic disorder (CMD) is a syndrome resulting from the combination of cardiovascular, endocrine, pro-thrombotic, and inflammatory health hazards. Due to their complex pathological mechanisms, there is a lack of effective diagnostic and treatment methods for cardiac metabolic disorders. Lactylation is a type of post-translational modification (PTM) that plays a regulatory role in various cellular physiological processes by inducing changes in the spatial conformation of proteins. Numerous studies have reported that lactylation modification plays a crucial role in post-translational modifications and is closely related to cardiac metabolic diseases. This article discusses the molecular biology of lactylation modifications and outlines the roles and mechanisms of lactylation modifications in cardiometabolic disorders, offering valuable insights for the diagnosis and treatment of such conditions.
Improving the Quality of Laser Drilling by Assisted Process Methods of Static Solution and Mist Blowing
Authors: Tao Yuan , Wang Zhiwei , Hu Shanshan , Feng Yufei , Yang Fan , Li Guangliang
Published: April 2024

The use of static solution-assisted laser drilling can effectively improve hole roundness, decrease taper angle, and reduce recast layer thickness and hole wall slag adhesion. However, the enormous energy of the laser will evaporate the solution to form a suspension droplet and reduce the quality and efficiency of laser drilling. To deal with this defect, the mist-blowing method was used to reduce the influence of droplets on the taper angle and recast layer. In this work, the effect of wind speed on drilling quality was examined, and laser drilling in air, water, and NaCl solution was carried out to analyse the effect of solution composition on hole wall morphology. The results showed that a speed fan with a proper wind speed that disperses the droplets formed in the processing area can significantly reduce the refraction and scattering of the laser, and the taper angle and roundness of the drilling hole were also reduced by 15.6% and improved by 2.4%, respectively, under the wind speed of 2 m/s. The hole wall morphology showed a thicker recast layer and cracking in air, while it was thinner in water and there was little or no layer in the NaCl solution in the same current. When drilling in NaCl, the taper angle and roundness of the drilling hole were reduced by 4.13% and improved by 2.11%, respectively, compared to water. Due to the mechanical effect of the laser in the NaCl solution, the impact force on the material was much greater than that in water. The solution cavitation effect, generated by the absorption of laser energy, caused an explosive impact on the molten material adhered to the surface of the hole wall. Above all, drilling in the NaCl solution with a current of 200 A and a wind speed of 2 m/s was the optimal condition for obtaining the best processing quality.
Improvement Performance of p-GaN Gate High-Electron-Mobility Transistors with GaN/AlN/AlGaN Barrier Structure
Authors: Liu An-Chen , Huang Yu-Wen , Chen Hsin-Chu , Kuo Hao-Chung
Published: April 2024

This study demonstrates a particular composited barrier structure of high-electron-mobility transistors (HEMTs) with an enhancement mode composed of p-GaN/GaN/AlN/AlGaN/GaN. The purpose of the composite barrier structure device is to increase the maximum drain current, reduce gate leakage, and achieve lower on-resistance (Ron) performance. A comparison was made between the conventional device without the composited barrier and the device with the composited barrier structure. The maximum drain current is significantly increased by 37%, and Ron is significantly reduced by 23%, highlighting the synergistic impact of the composite barrier structure on device performance improvement. This reason can be attributed to the undoped GaN (u-GaN) barrier layer beneath p-GaN, which was introduced to mitigate Mg diffusion in the capping layer, thus addressing its negative effects. Furthermore, the AlN barrier layer exhibits enhanced electrical properties, which can be attributed to the critical role of high-energy-gap properties that increase the 2DEG carrier density and block leakage pathways. These traps impact the device behavior mechanism, and the simulation for a more in-depth analysis of how the composited barrier structure brings improvement is introduced using Synopsys Sentaurus TCAD.
A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1
Authors: Vijayaraghavan Christina Sathyanathan , Raman Lakshmi Sundaram , Surenderan Shanmugapriya , Kaur Harpreet , Chinambedu Mohanapriya Dandapani , Thyagarajan Sadras Panchatcharam , Gnanambal Krishnan Mary Elizabeth
Published: April 2024

The cannabinoid-type I (CB1) receptor functions as a double-edged sword to decide cell fate: apoptosis/survival. Elevated CB1 receptor expression is shown to cause acute ceramide accumulation to meet the energy requirements of fast-growing cancers. However, the flip side of continual CB1 activation is the initiation of a second ceramide peak that leads to cell death. In this study, we used ovarian cancer cells, PA1, which expressed CB1, which increased threefold when treated with a natural compound, bis(palmitoleic acid) ester of a glycerol (C2). This novel compound is isolated from a marine snail, Conus inscriptus, using hexane and the structural details are available in the public domain PubChem database (ID: 14275348). The compound induced two acute ceramide pools to cause G0/G1 arrest and killed cells by apoptosis. The compound increased intracellular ceramides (C:16 to 7 times and C:18 to 10 times), both of which are apoptotic inducers in response to CB1 signaling and thus the compound is a potent CB1 agonist. The compound is not genotoxic because it did not induce micronuclei formation in non-cancerous Chinese hamster ovarian (CHO) cells. Since the compound induced the cannabinoid pathway, we tested if there was a psychotropic effect in zebrafish models, however, it was evident that there were no observable neurobehavioral changes in the treatment groups. With the available data, we propose that this marine compound is safe to be used in non-cancerous cells as well as zebrafish. Thus, this anticancer compound is non-toxic and triggers the CB1 pathway without causing psychotropic effects.
Sterol Derivatives Specifically Increase Anti-Inflammatory Oxylipin Formation in M2-like Macrophages by LXR-Mediated Induction of 15-LOX
Authors: Ohno Reiichi , Mainka Malwina , Kirchhoff Rebecca , Hartung Nicole M. , Schebb Nils Helge
Published: April 2024

The understanding of the role of LXR in the regulation of macrophages during inflammation is emerging. Here, we show that LXR agonist T09 specifically increases 15-LOX abundance in primary human M2 macrophages. In time- and dose-dependent incubations with T09, an increase of 3-fold for ALOX15 and up to 15-fold for 15-LOX-derived oxylipins was observed. In addition, LXR activation has no or moderate effects on the abundance of macrophage marker proteins such as TLR2, TLR4, PPARγ, and IL-1RII, as well as surface markers (CD14, CD86, and CD163). Stimulation of M2-like macrophages with FXR and RXR agonists leads to moderate ALOX15 induction, probably due to side activity on LXR. Finally, desmosterol, 24(S),25-Ep cholesterol and 22(R)-OH cholesterol were identified as potent endogenous LXR ligands leading to an ALOX15 induction. LXR-mediated ALOX15 regulation is a new link between the two lipid mediator classes sterols, and oxylipins, possibly being an important tool in inflammatory regulation through anti-inflammatory oxylipins.
Nanoscale Evaluation of the Degradation Stability of Black Phosphorus Nanosheets Functionalized with PEG and Glutathione-Stabilized Doxorubicin Drug-Loaded Gold Nanoparticles in Real Functionalized System
Authors: Gunathilaka Thisari Maleesha , Shimomura Masaru
Published: April 2024

Two-dimensional black phosphorus (2D BP) has attracted significant research interest in the field of biomedical applications due to its unique characteristics, including high biocompatibility, impressive drug-loading efficiency, phototherapeutic ability, and minimal side effects. However, its puckered honeycomb lattice structure with lone-pair electrons of BP leads to higher sensitivity and chemical reactivity towards H2O and O2 molecules, resulting in the degradation of the structure with physical and chemical changes. In our study, we synthesize polyethylene glycol (PEG) and glutathione-stabilized doxorubicin drug-assembled Au nanoparticle (Au-GSH-DOX)-functionalized BP nanosheets (BP-PEG@Au-GSH-DOX) with improved degradation stability, biocompatibility, and tumor-targeting ability. Transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy indicate the nanoscale degradation behavior of synthesized nanoconjugates in three different environmental exposure conditions, and the results demonstrate the remarkable nanoscale stability of BP-PEG@Au-GSH-DOX against the degradation of BP, which provides significant interest in employing 2D BP-based nanotherapeutic agents for tumor-targeted cancer phototherapy.
The Impact of Different Drying Methods on the Metabolomic and Lipidomic Profiles of Arthrospira platensis
Authors: Mróz Marika , Parchem Karol , Jóźwik Joanna , Domingues M. Rosário , Kusznierewicz Barbara
Published: April 2024

Drying is an inseparable part of industrial microalgae production. In this work, the impacts of eight different drying methods on the metabolome and lipidome of Arthrospira platensis were investigated. The studied drying methods were freeze drying (FD), sun drying (SD), air drying at 40 and 75 °C (AD′ and AD″), infrared drying at 40 and 75 °C (IRD′ and IRD″), and vacuum drying at 40 and 75 °C (VD′ and VD″). Results gathered by reversed-phase liquid chromatography separation coupled with high-resolution tandem mass spectrometry with electrospray ionization (RP-LC-ESI-Orbitrap HRMS/MS) analysis allowed researchers to identify a total of 316 metabolites (including lipids) in aqueous and ethanolic extracts. The compounds identified in ethanolic extracts were mainly lipids, such as neutral and polar lipids, chlorophylls and carotenoids, while the compounds identified in the aqueous extracts were mainly amino acids and dipeptides. Among the identified compounds, products of enzymatic and chemical degradation, such as pyropheophytins, monoacylglycerols and lysophosphatidylcholines were also identified and their amounts depended on the drying method. The results showed that except for FD method, recognized as a control, the most protective method was AD′. Contrary to this, VD′ and VD″, under the conditions used, promoted the most intense degradation of valuable metabolites.
Diverse Co(II) Coordination Polymers with the Same Mixed Ligands: Evaluation of Chemical Stability and Structural Transformation
Authors: Lee Chia-Yi , Ye Yu-Hui , Wang Song-Wei , Chen Jhy-Der
Published: April 2024

Reactions of Co(OAc)2·4H2O, N‚N’-bis(3-pyridylmethyl)oxalamide (L) and 4,4′-sulfonyldibenzoic acid (H2SDA) afforded four coordination polymers with the same mixed ligands, {[Co(L)(SDA)(H2O)2]·H2O·CH3OH}n, 1, {[Co(L)0.5(SDA)]·2H2O·0.5L}n, 2, {[Co(L)1.5(SDA)(H2O)]·H2O}n, 3, and {[Co2(L)1.5(SDA)2(H2O)2]·4H2O}n, 4, which have been structurally characterized using single-crystal X-ray crystallography. Complexes 1–4 are 2D layers, revealing topologies of sql, 2,6L1, (4,4)Ia, and 6L12, respectively, and demonstrating that the metal-to-ligand ratio, solvent system, and reaction temperature are important in determining the structural diversity. The immersion of these complexes into various solvents shows that the structural types govern the chemical stabilities of 1–4. Reversible structural transformation is shown for complexes 1 and 2 upon solvent removal and adsorption, while those of 3 and 4 are irreversible.
Detecting Pathogenic Phytophthora Species Using Volatile Organic Compounds
Authors: Sherwood Patrick , Nordström Ida , Woodward Steve , Bohman Björn , Cleary Michelle
Published: April 2024

There are several highly damaging Phytophthora species pathogenic to forest trees, many of which have been spread beyond their native range by the international trade of live plants and infested materials. Such introductions can be reduced through the development of better tools capable of the early, rapid, and high-throughput detection of contaminated plants. This study utilized a volatilomics approach (solid-phase microextraction coupled to gas chromatography–mass spectrometry) to differentiate between several Phytophthora species in culture and discriminate between healthy and Phytophthora-inoculated European beech and pedunculate oak trees. We tentatively identified 14 compounds that could differentiate eight Phytophthora species from each other in vitro. All of the Phytophthora species examined, except Phytophthora cambivora, uniquely produced at least one compound not observed in the other species; however, most detected compounds were shared between multiple species. Phytophthora polonica had the most unique compounds and was the least similar of all the species examined. The inoculated seedlings had qualitatively different volatile profiles and could be distinguished from the healthy controls by the presence of isokaurene, anisole, and a mix of three unknown compounds. This study supports the notion that volatiles are suitable for screening plant material, detecting tree pathogens, and differentiating between healthy and diseased material.
Effects of Torulaspora delbrueckii and Saccharomyces cerevisiae Co-Fermentation on the Physicochemical and Flavor Compounds of Huaniu Apple Cider
Authors: Zeng Chaozhen , Mu Yuwen , Yuan Jing , Zhang Haiyan , Song Juan , Kang Sanjiang
Published: April 2024

The effects of different fermentation methods utilizing Torulaspora delbrueckii 1004 and Saccharomyces cerevisiae 32169 on the physicochemical properties, organic acid content, polyphenol and flavonoid concentrations, antioxidant activity, and volatile aroma compounds of Huaniu apple cider were investigated in this study. Employing methods of single inoculation, co-inoculation, and sequential inoculation, it was found that sequential fermentation exhibited strong fermentative power in the initial stages, effectively reducing the content of soluble solids and achieving a balanced composition of malic, succinic, and citric acids while maintaining a lower titratable acidity. Sequential inoculation was observed to significantly enhance the total polyphenols and flavonoids, as well as the antioxidant capacity (p < 0.05). Specifically, in the synthesis of volatile aroma compounds, sequential inoculation significantly enhanced the richness and diversity of the Huaniu apple cider’s aromas, particularly in terms of the concentration of ester compounds (p < 0.05). Principal component analysis further confirmed the superiority of sequential inoculation in terms of aroma component diversity and richness. The findings of this study suggest that sequential inoculation of fermentation with non-Saccharomyces and S. cerevisiae is an effective strategy for optimizing the flavor characteristics of Huaniu apple cider, offering valuable theoretical support and practical guidance for enhancing cider quality and fostering the development of new products.
Wondrous Yellow Molecule: Are Hydrogels a Successful Strategy to Overcome the Limitations of Curcumin?
Authors: Stachowiak Magdalena , Mlynarczyk Dariusz T. , Dlugaszewska Jolanta
Published: April 2024

Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential.
Hydrocarbon Transportation in Heterogeneous Shale Pores by Molecular Dynamic Simulation
Authors: Sun Shuo , Gao Mingyu , Liang Shuang , Liu Yikun
Published: April 2024

Shale oil in China is widely distributed and has enormous resource potential. The pores of shale are at the nanoscale, and traditional research methods encounter difficulty in accurately describing the fluid flow mechanism, which has become a bottleneck restricting the industrial development of shale oil in China. To clarify the distribution and migration laws of fluid microstructure in shale nanopores, we constructed a heterogeneous inorganic composite shale model and explored the fluid behavior in different regions of heterogeneous surfaces. The results revealed the adsorption capacity for alkanes in the quartz region was stronger than that in the illite region. When the aperture was small, solid–liquid interactions dominated; as the aperture increased, the bulk fluid achieved a more uniform and higher flow rate. Under conditions of small aperture/low temperature/low pressure gradient, the quartz region maintained a negative slip boundary. Illite was more hydrophilic than quartz; when the water content was low, water molecules formed a “liquid film” on the illite surface, and the oil flux percentages in the illite and quartz regions were 87% and 99%, respectively. At 50% water content, the adsorbed water in the illite region reached saturation, the quartz region remained unsaturated, and the difference in the oil flux percentage of the two regions decreased. At 70% water content, the adsorbed water in the two regions reached a fully saturated state, and a layered structure of “water–two-phase region–water” was formed in the heterogeneous nanopore. This study is of great significance for understanding the occurrence characteristics and flow mechanism of shale oil within inorganic nanopores.
How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography
Authors: Porfetye Arthur T. , Stege Patricia , Rebollido-Rios Rocio , Hoffmann Daniel , Schrader Thomas , Vetter Ingrid R.
Published: April 2024

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon-shaped molecule. Due to their marked preference for basic amino acids and the fully reversible binding mode, molecular tweezers are able to counteract pathologic protein aggregation and are currently being developed as disease-modifying therapies against neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. We analyzed the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme Δ1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH) and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.
Evaluation of Urtica dioica Phytochemicals against Therapeutic Targets of Allergic Rhinitis Using Computational Studies
Authors: Culhuac Erick Bahena , Bello Martiniano
Published: April 2024

Allergic rhinitis (AR) is a prevalent inflammatory condition affecting millions globally, with current treatments often associated with significant side effects. To seek safer and more effective alternatives, natural sources like Urtica dioica (UD) are being explored. However, UD’s mechanism of action remains unknown. Therefore, to elucidate it, we conducted an in silico evaluation of UD phytochemicals’ effects on known therapeutic targets of allergic rhinitis: histamine receptor 1 (HR1), neurokinin 1 receptor (NK1R), cysteinyl leukotriene receptor 1 (CLR1), chemoattractant receptor-homologous molecule expressed on type 2 helper T cells (CRTH2), and bradykinin receptor type 2 (BK2R). The docking analysis identified amentoflavone, alpha-tocotrienol, neoxanthin, and isorhamnetin 3-O-rutinoside as possessing a high affinity for all the receptors. Subsequently, molecular dynamics (MD) simulations were used to analyze the key interactions; the free energy of binding was calculated through Generalized Born and Surface Area Solvation (MMGBSA), and the conformational changes were evaluated. Alpha-tocotrienol exhibited a high affinity while also inducing positive conformational changes across all targets. Amentoflavone primarily affected CRTH2, neoxanthin targeted NK1R, CRTH2, and BK2R, and isorhamnetin-3-O-rutinoside acted on NK1R. These findings suggest UD’s potential to treat AR symptoms by inhibiting these targets. Notably, alpha-tocotrienol emerges as a promising multi-target inhibitor. Further in vivo and in vitro studies are needed for validation.
Tellurium and Nano-Tellurium: Medicine or Poison?
Authors: Sári Daniella , Ferroudj Aya , Semsey Dávid , El-Ramady Hassan , Brevik Eric C. , Prokisch József
Published: April 2024

Tellurium (Te) is the heaviest stable chalcogen and is a rare element in Earth’s crust (one to five ppb). It was discovered in gold ore from mines in Kleinschlatten near the present-day city of Zlatna, Romania. Industrial and other applications of Te focus on its inorganic forms. Tellurium can be toxic to animals and humans at low doses. Chronic tellurium poisoning endangers the kidney, liver, and nervous system. However, Te can be effective against bacteria and is able to destroy cancer cells. Tellurium can also be used to develop redox modulators and enzyme inhibitors. Soluble salts that contain Te had a role as therapeutic and antimicrobial agents before the advent of antibiotics. The pharmaceutical use of Te is not widespread due to the narrow margin between beneficial and toxic doses, but there are differences between the measure of toxicity based on the Te form. Nano-tellurium (Te-NPs) has several applications: it can act as an adsorptive agent to remove pollutants, and it can be used in antibacterial coating, photo-catalysis for the degradation of dyes, and conductive electronic materials. Nano-sized Te particles are the most promising and can be produced in both chemical and biological ways. Safety assessments are essential to determine the potential risks and benefits of using Te compounds in various applications. Future challenges and directions in developing nano-materials, nano-alloys, and nano-structures based on Te are still open to debate.
The Asymmetry Observed between the Effects of Photon–Phonon Coupling and Crystal Field on the Fine Structure of Fluorescence and Spontaneous Four-Wave Mixing in Ion-Doped Microcrystals
Authors: Fan Huanrong , Zhang Zhongtai , Hussain Iqbal , Yang Qinyue , Majeed Muhammad Kashif , Imran Muhammad , Raza Faizan , Li Peng , Zhang Yanpeng
Published: April 2024

In this paper, we explore the asymmetry observed between the effects of photon–phonon coupling (nested-dressing) and a crystal field (CF) on the fine structure of fluorescence (FL) and spontaneous four-wave mixing (SFWM) in Eu3+: BiPO4 and Eu3+: NaYF4. The competition between the CF and the strong photon–phonon dressing leads to dynamic splitting in two directions. The CF leads to static splitting in one direction under weak phonon dressing. The evolution from strong dressing to weak dressing results in spectral asymmetry. This spectral asymmetry includes out-of-phase FL and in-phase SFWM. Further, the large ratio between the dressing Rabi frequency and the de-phase rate leads to strong FL and SFWM asymmetry due to photon–phonon constructive dressing. Moreover, the experimental results suggest the analogy of a spectra asymmetry router with a channel equalization ratio of 96.6%.
Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial
Authors: Alba Claudio , Carrera Marta , Álvarez-Calatayud Guillermo , Arroyo Rebeca , Fernández Leónides , Rodríguez Juan M.
Published: April 2024

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 107 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.
Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance
Authors: Duelo Adriana , Comas-Basté Oriol , Sánchez-Pérez Sònia , Veciana-Nogués M. Teresa , Ruiz-Casares Eva , Vidal-Carou M. Carmen , Latorre-Moratalla M. Luz
Published: April 2024

A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants.
Pathotyping Systems and Pathotypes of Plasmodiophora brassicae—Navigating toward the Optimal Classification
Authors: Zamani-Noor Nazanin , Jędryczka Małgorzata
Published: April 2024

Plasmodiophora brassicae Woronin, an obligate biotrophic soil-borne pathogen, poses a significant threat to cruciferous crops worldwide by causing the devastating disease known as clubroot. Pathogenic variability in P. brassicae populations has been recognized since the 1930s based on its interactions with Brassica species. Over time, numerous sets of differential hosts have been developed and used worldwide to explore the pathogenic variability within P. brassicae populations. These sets encompass a range of systems, including the Williams system, the European Clubroot Differential set (ECD), the Brassica napus set, the Japanese Clubroot Differential Set, the Canadian Clubroot Differential Set (CCS), the Korean Clubroot Differential Set, and the Chinese Sinitic Clubroot Differential set (SCD). However, all existing systems possess both advantages as well as limitations regarding the detection of pathotypes from various Brassica species and their corresponding virulence pattern on Brassica genotypes. This comprehensive review aims to compare the main differential systems utilized in classifying P. brassicae pathotypes worldwide. Their strengths, limitations, and implications are evaluated, thereby enhancing our understanding of pathogenic variability.
The Transmission of Campylobacter Strains in Dairy Herds in Different Housing Systems
Authors: Wysok Beata , Rudowska Małgorzata , Wiszniewska-Łaszczych Agnieszka
Published: April 2024

Cattle are frequent carriers of Campylobacter spp.; therefore, these bacteria may be transmitted to humans through meat or milk. Campylobacter spp. in raw milk derives most commonly from secondary fecal contamination during the milking process; however, the udder excretion of Campylobacter may be a cause of milk-borne infection. Studies were carried out on a Campylobacter-positive farm with two different housing systems (with free-stall and tie-stall systems). The sampling process comprised several stages, including samples being taken from animals, such as from raw milk and feces, and from the environment, such as the from floor in the milking parlor and from teat cups. None of the individual raw milk samples or swabs from the floor in the parlor before the milking process were positive for Campylobacter spp. Simultaneously, Campylobacter spp. was isolated from all swabs from the floor after the milking process and in the bulk tank milk samples from the two farms. The incidence of Campylobacter isolated from fecal and teat swab samples ranged from 15.4% to 26.7% and from 8.9% to 25%, respectively. Altogether, 59 recovered Campylobacter isolates were classified, based on sequencing of the flaA short variable region, showing 15 different allele types, and the majority of them were distributed among one farm. Analysis of the virulence and antimicrobial properties showed that genes related to adherence, invasion and cytotoxicity were widely distributed among the Campylobacter recovered strains. In relation to AMR, multidrug resistance was noted in 16.1% of strains.
Clinical Strains of Mycobacterium tuberculosis Representing Different Genotype Families Exhibit Distinct Propensities to Adopt the Differentially Culturable State
Authors: Gordhan Bhavna Gowan , Padarath Kiyasha , Sewcharran Astika , McIvor Amanda , VanNieuwenhze Michael S. , Waja Ziyaad , Martinson Neil , Kana Bavesh Davandra
Published: April 2024

Growing evidence points to the presence of differentially culturable tubercle bacteria (DCTB) in clinical specimens from individuals with active tuberculosis (TB) disease. These bacteria are unable to grow on solid media but can resuscitate in liquid media. Given the epidemiological success of certain clinical genotype families of Mycobacterium tuberculosis, we hypothesize that different strains may have distinct mechanisms of adaptation and tolerance. We used an in vitro carbon starvation model to determine the propensity of strains from lineages 2 and 4 that included the Beijing and LAM families respectively, to generate DCTB. Beijing strains were associated with a greater propensity to produce DCTB compared to LAM strains. Furthermore, LAM strains required culture filtrate (CF) for resuscitation whilst starved Beijing strains were not dependent on CF. Moreover, Beijing strains showed improved resuscitation with cognate CF, suggesting the presence of unique growth stimulatory molecules in this family. Analysis of starved Beijing and LAM strains showed longer cells, which with resuscitation were restored to a shorter length. Cell wall staining with fluorescent D-amino acids identified strain-specific incorporation patterns, indicating that cell surface remodeling during resuscitation was distinct between clinical strains. Collectively, our data demonstrate that M. tuberculosis clinical strains from different genotype lineages have differential propensities to generate DCTB, which may have implications for TB treatment success.
Reasons Why Dog Owners Stop Feeding Raw Meat-Based Diets (RMBDs)—An Online Survey
Authors: Baum Lilly Laurea , Zablotski Yury , Busch Kathrin , Koelle Petra
Published: April 2024

Feeding raw meat-based diets (RMBDs) is becoming increasingly popular among dog owners. The concerns of veterinarians and scientists about this feeding method and its risks are topic of many publications. The present study aimed to determine why dog owners stop feeding raw diets and whether this change in diet is connected to health issues in dogs. The survey was conducted using an online questionnaire in the German language. The survey included questions about the signalment and health status of the dog, past RMBDs, and the reasons behind the change in the diet or discontinuation of an RMBD. Questionnaires answered by 802 pet owners, each describing a single dog, were included in the final analysis. The three primary reasons to stop feeding an RMBD were intolerance of the diet (24%, n = 196/802), which was expressed exclusively in gastrointestinal signs, disease (20%, n = 163/802), which was a gastrointestinal disease in 64% (n = 104/163) of cases (13%, n = 104/802), and an unwillingness to eat the raw diet (15%, n = 117/802). Overall, 37% (n = 300) of all participants terminated feeding an RMBD due to gastrointestinal problems. Gastrointestinal problems are a significant reason for discontinuation of the RMBD. In cases of gastrointestinal complaints, a detailed diet history should be asked for, and a diet change should be considered as a solution.
Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis
Authors: Spathakis Michail , Dovrolis Nikolas , Filidou Eirini , Kandilogiannakis Leonidas , Tarapatzi Gesthimani , Valatas Vassilis , Drygiannakis Ioannis , Paspaliaris Vasilis , Arvanitidis Konstantinos , Manolopoulos Vangelis G. , Kolios George , Vradelis Stergios
Published: April 2024

Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand–receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify possible interactions with inflammatory and fibrotic pathways in the intestine. RNA-sequencing datasets containing 643 Crohn’s disease (CD) patients, 467 ulcerative colitis (UC) patients and 295 HIs, and 4 Campylobacter jejuni-infected individuals were retrieved from the Sequence Read Archive, and differential expression was performed using the RaNA-seq online platform. The identified differentially expressed MR genes were used for correlation analysis with up- and downregulated genes in IBD, as well as functional enrichment analysis using a R based pipeline. Overall, 15 MR genes exhibited dysregulated expression in IBD. In inflamed CD, the hydroxycarboxylic acid receptors 2 and 3 (HCAR2, HCAR3) were upregulated and were associated with the recruitment of innate immune cells, while, in the non-inflamed CD ileum, the cannabinoid receptor 1 (CNR1) and the sphingosine-1-phospate receptor 4 (S1PR4) were downregulated and were involved in the regulation of B-cell activation. In inflamed UC, the upregulated receptors HCAR2 and HCAR3 were more closely associated with the process of TH-17 cell differentiation, while the pregnane X receptor (NR1I2) and the transient receptor potential vanilloid 1 (TRPV1) were downregulated and were involved in epithelial barrier maintenance. Our results elucidate the landscape of metabolite receptor expression in IBD, highlighting associations with disease-related functions that could guide the development of new targeted therapies.
A Green HPLC Approach to Florfenicol Analysis in Pig Urine
Authors: Šandor Ksenija , Perak Junaković Eleonora , Terzić Svjetlana , Žarković Irena , Vujnović Anja , Fajdić Dominika , Pehnec Mirta , Sinković Sonja , Ćaleta Irena , Andrišić Miroslav
Published: April 2024

Florfenicol (FF) is a broad-spectrum antibiotic used to treat gastrointestinal and respiratory infections in domestic animals. Considering FF’s rapid elimination via urine after drug treatment, its use increases concerns about environmental contamination. The objective of the study was to establish a sustainable chromatographic method for simple analysis of FF in pig urine to investigate the urinary excretion of FF after a single intramuscular administration of 20 mg FF/kg body weight. The urine sample was prepared using a centrifuge and regenerated cellulose filter, and the diluted sample was analyzed. The method was validated in terms of linearity, the limit of detection (0.005 µg/mL) and quantitation (0.016 µg/mL), repeatability and matrix effect (%RSD ranged up to 2.5), accuracy (varied between 98% and 102%), and stability. The concentration-time profile of pig urine samples collected within 48 h post-drug administration showed that 63% of FF’s dose was excreted. The developed method and previously published methods used to qualify FF in the urine of animal origin were evaluated by the National Environmental Method Index (NEMI), Green Analytical Procedure Index (GAPI) and Analytical GREENness Metric Approach (AGREE). The greenness profiles of published methods revealed problems with high solvents and energy consumption, while the established method was shown to be more environmentally friendly.
Cell Membrane-Coated Biomimetic Nanoparticles in Cancer Treatment
Authors: Zhang Shu , Zhang Xiaojuan , Gao Huan , Zhang Xiaoqin , Sun Lidan , Huang Yueyan , Zhang Jie , Ding Baoyue
Published: April 2024

Nanoparticle-based drug delivery systems hold promise for cancer treatment by enhancing the solubility and stability of anti-tumor drugs. Nonetheless, the challenges of inadequate targeting and limited biocompatibility persist. In recent years, cell membrane nano-biomimetic drug delivery systems have emerged as a focal point of research and development, due to their exceptional traits, including precise targeting, low toxicity, and good biocompatibility. This review outlines the categorization and advantages of cell membrane bionic nano-delivery systems, provides an introduction to preparation methods, and assesses their applications in cancer treatment, including chemotherapy, gene therapy, immunotherapy, photodynamic therapy, photothermal therapy, and combination therapy. Notably, the review delves into the challenges in the application of various cell membrane bionic nano-delivery systems and identifies opportunities for future advancement. Embracing cell membrane-coated biomimetic nanoparticles presents a novel and unparalleled avenue for personalized tumor therapy.
68Ga-DOTA-D-Alanine-BoroPro Radiotracer for Imaging of the Fibroblast Activation Protein in Malignant and Non-Malignant Diseases
Authors: Trujillo-Benítez Diana , Luna-Gutiérrez Myrna , Aguirre-De Paz José G. , Cruz-Nova Pedro , Bravo-Villegas Gerardo , Vargas-Ahumada Joel E. , Vallejo-Armenta Paola , Morales-Avila Enrique , Jiménez-Mancilla Nallely , Oros-Pantoja Rigoberto , Santos-Cuevas Clara , Azorín-Vega Erika , Ocampo-García Blanca , Ferro-Flores Guillermina
Published: April 2024

Recently, we reported a new fibroblast activation protein (FAP) inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-HYNIC-D-Alanine-BoroPro)(99mTc-HYNIC-iFAP) structure for tumor microenvironment SPECT imaging. This research aimed to synthesize 68Ga-[2,2′,2″,2‴-(2-(4-(2-(5-(((S)-1-((S)-2-boronopyrrolidin-1-yl)-1-oxopropan-2-yl)carbamoyl)pyridin-2-yl)hydrazine-1-carbothioamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid] (68Ga-DOTA-D-Alanine-BoroPro)(68Ga-iFAP) as a novel radiotracer for PET imaging and evaluate its usefulness for FAP expression in malignant and non-malignant tissues. The coupling of p-SCN-benzene DOTA with HYNIC-iFAP was used for the chemical synthesis and further labeling with 68Ga. Radiochemical purity was verified by radio-HPLC. The specificity of 68Ga-iFAP was evaluated in HCT116 cells, in which FAP expression was verified by immunofluorescence and Western blot. Biodistribution and biokinetic studies were performed in murine models. 68Ga-iFAP uptake at the myocardial level was assessed in mice with induced infarction. First-in-human images of 68Ga-iFAP in healthy subjects and patients with myocardial infarction, glioblastoma, prostate cancer, and breast cancer were also obtained. DOTA-D-Alanine BoroPro was prepared with a chemical purity of 98% and was characterized by UPLC mass spectroscopy, FT-IR, and UV-vis. The 68Ga-iFAP was obtained with a radiochemical purity of >95%. In vitro and in vivo studies demonstrated 68Ga-iFAP-specific recognition for FAP, rapid renal elimination, and adequate visualization of the glioblastoma, breast tumor, prostate cancer, and myocardial infarction sites. The results of this research justify further dosimetry and clinical trials to establish the specificity and sensitivity of 68Ga-iFAP PET for FAP expression imaging.
Color and Chemical Stability of 3D-Printed and Thermoformed Polyurethane-Based Aligners
Authors: Šimunović Luka , Čekalović Agović Sara , Marić Antun Jakob , Bačić Ivana , Klarić Eva , Uribe Flavio , Meštrović Senka
Published: April 2024

The significant rise in the use of clear aligners for orthodontic treatment is attributed to their aesthetic appeal, enhancing patient appearance and self-confidence. The aim of this study is to evaluate the aligners’ response to common staining agents (coffee, black tea, Coca-Cola, and Red Bull) in color and chemical stability. Polyurethane-based thermoformed and 3D-printed aligners from four brands were exposed to common beverages to assess color change using a VITA Easyshade compact colorimeter after 24 h, 48 h, 72 h, and 7 days, as well as chemical stability using ATR-FTIR spectroscopy. The brand, beverage, and manufacturing method significantly influence color stability. ATR-FTIR analysis revealed compositional differences, with variations in response to beverage exposure affecting the integrity of polymer bonds. Color change analysis showed coffee as the most potent staining agent, particularly affecting Tera Harz TC85 aligners, while ClearCorrect aligners exhibited the least susceptibility. 3D-printed aligners showed a greater color change compared to thermoformed ones. Aligners with a PETG outer layer are more resistant to stains and chemical alterations than those made of polyurethane. Additionally, 3D-printed polyurethane aligners stain more than thermoformed ones. Therefore, PETG-layered aligners are a more reliable choice for maintaining the aesthetic integrity of aligners.