bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects
Authors: Al-Khazaleh Ahmad K. , Zhou Xian , Bhuyan Deep Jyoti , Münch Gerald W. , Al-Dalabeeh Elaf Adel , Jaye Kayla , Chang Dennis
Published: January 2024

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.
A Statistical Physics Approach to Understanding the Adsorption of Methylene Blue onto Cobalt Oxide Nanoparticles
Authors: Dehbi Ali , Dehmani Younes , Franco Dison S. P. , Omari Hind , Georgin Jordana , Brahmi Younes , Elazhari Kaoutar , Messaoudi Mohammed , Aadnan Imane , Lamhasni Taibi , Alrashdi Awad A. , Abdallaoui Abdelaziz , Abouarnadasse Sadik , Lamini Adil
Published: January 2024

The production of cobalt oxide nanoparticles and their use in the adsorption of methylene blue (MB) from solution is described in the paper. The X-ray diffraction patterns show that the synthesized cobalt oxide nanoparticles have a crystalline cubic structure. The study of the adsorption of methylene blue onto the cobalt oxide nanoparticles involved determining the contact time and initial concentration of the adsorption of MB on the adsorbent. The kinetics of adsorption were analyzed using two kinetic models (pseudo-first order and pseudo-second order), and the pseudo-second-order model was found to be the most appropriate for describing the behavior of the adsorption. This study indicates that the MLTS (monolayer with the same number of molecules per site) model is the most suitable model for describing methylene blue/cobalt oxide systems, and the parameter values help to further understand the adsorption process with the steric parameters. Indicating that methylene blue is horizontally adsorbed onto the surface of the cobalt oxide, which is bonded to two different receptor sites. Regarding the temperature effect, it was found that the adsorption capacity increased, with the experimental value ranging from 313.7 to 405.3 mg g−1, while the MLTS predicted 313.32 and 408.16 mg g−1. From the thermodynamic functions, high entropy was found around 280 mg L−1 concentration. For all concentrations and temperatures examined, the Gibbs free energy and enthalpy of adsorption were found to be negative and positive, respectively, suggesting that the system is spontaneous and endothermic. According to this study’s findings, methylene blue adsorption onto cobalt oxide nanoparticles happens via the creation of a monolayer, in which the same amount of molecules are adsorbed at two distinct locations. The findings shed light on the methylene blue adsorption process onto cobalt oxide nanoparticles, which have a variety of uses, including the remediation of wastewater.
Portable Mid-Infrared Spectroscopy Combined with Chemometrics to Diagnose Fibromyalgia and Other Rheumatologic Syndromes Using Rapid Volumetric Absorptive Microsampling
Authors: Nuguri Shreya Madhav , Hackshaw Kevin V. , de Lamo Castellvi Silvia , Bao Haona , Yao Siyu , Aziz Rija , Selinger Scott , Mikulik Zhanna , Yu Lianbo , Osuna-Diaz Michelle M. , Sebastian Katherine R. , Giusti M. Monica , Rodriguez-Saona Luis
Published: January 2024

The diagnostic criteria for fibromyalgia (FM) have relied heavily on subjective reports of experienced symptoms coupled with examination-based evidence of diffuse tenderness due to the lack of reliable biomarkers. Rheumatic disorders that are common causes of chronic pain such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and chronic low back pain are frequently found to be comorbid with FM. As a result, this can make the diagnosis of FM more challenging. We aim to develop a reliable classification algorithm using unique spectral profiles of portable FT-MIR that can be used as a real-time point-of-care device for the screening of FM. A novel volumetric absorptive microsampling (VAMS) technique ensured sample volume accuracies and minimized the variation introduced due to hematocrit-based bias. Blood samples from 337 subjects with different disorders (179 FM, 158 non-FM) collected with VAMS were analyzed. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. The OPLS-DA algorithm enabled the classification of the spectra into their corresponding classes with 84% accuracy, 83% sensitivity, and 85% specificity. The OPLS-DA regression plot indicated that spectral regions associated with amide bands and amino acids were responsible for discrimination patterns and can be potentially used as spectral biomarkers to differentiate FM and other rheumatic diseases.
A Synthetic Pathway for the Production of Benzylsuccinate in Escherichia coli
Authors: Mock Johanna , Schühle Karola , Linne Uwe , Mock Marco , Heider Johann
Published: January 2024

(R)-Benzylsuccinate is generated in anaerobic toluene degradation by the radical addition of toluene to fumarate and further degraded to benzoyl-CoA by a β-oxidation pathway. Using metabolic modules for benzoate transport and activation to benzoyl-CoA and the enzymes of benzylsuccinate β-oxidation, we established an artificial pathway for benzylsuccinate production in Escherichia coli, which is based on its degradation pathway running in reverse. Benzoate is supplied to the medium but needs to be converted to benzoyl-CoA by an uptake transporter and a benzoate-CoA ligase or CoA-transferase. In contrast, the second substrate succinate is endogenously produced from glucose under anaerobic conditions, and the constructed pathway includes a succinyl-CoA:benzylsuccinate CoA-transferase that activates it to the CoA-thioester. We present first evidence for the feasibility of this pathway and explore product yields under different growth conditions. Compared to aerobic cultures, the product yield increased more than 1000-fold in anaerobic glucose-fermenting cultures and showed further improvement under fumarate-respiring conditions. An important bottleneck to overcome appears to be product excretion, based on much higher recorded intracellular concentrations of benzylsuccinate, compared to those excreted. While no export system is known for benzylsuccinate, we observed an increased product yield after adding an unspecific mechanosensitive channel to the constructed pathway.
Phomopsterone B Alleviates Liver Fibrosis through mTOR-Mediated Autophagy and Apoptosis Pathway
Authors: Peng Mei-Lin , Zhang Li-Jie , Luo Yan , Xu Shi-Ying , Long Xing-Mei , Ao Jun-Li , Liao Shang-Gao , Zhu Qin-Feng , He Xun , Xu Guo-Bo
Published: January 2024

Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-β1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 μM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells’ apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-β1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis.
6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress
Authors: Yang Ah Young , Kim Kiryeong , Kwon Hyun Hee , Leem Jaechan , Song Jeong Eun
Published: January 2024

Non-alcoholic steatohepatitis (NASH) is becoming an increasingly serious global health threat, distinguished by hepatic lipid accumulation, inflammation, and fibrosis. There is a lack of approved pharmaceutical interventions for this disease, highlighting the urgent need for effective treatment. This study explores the hepatoprotective potential of 6-shogaol, a natural compound derived from ginger, in a methionine- and choline-deficient (MCD) dietary mouse model of NASH. Male C57BL/6J mice were subjected to the MCD diet for 4 weeks to induce NASH, with concurrent intraperitoneal administration of 6-shogaol (20 mg/kg) three times a week. While 6-shogaol did not impact body weight, liver weight, or hepatic lipid accumulation, it effectively mitigated liver injury, inflammation, and fibrosis in MCD diet-fed mice. Mechanistically, 6-shogaol inhibited lipid and DNA oxidation, restored hepatic glutathione levels, and regulated the expression of pro-oxidant and antioxidant enzymes. Furthermore, 6-shogaol inhibited apoptosis and necroptosis, as indicated by a decrease in TUNEL-stained cells and downregulation of apoptosis- and necroptosis-associated proteins. Additionally, 6-shogaol alleviated endoplasmic reticulum (ER) stress, as demonstrated by decreased expression of molecules associated with unfolded protein response pathways. These findings underscore the potential of 6-shogaol as a therapeutic intervention for NASH by targeting pathways related to oxidative stress, cell death, and ER stress.
CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues
Authors: Ruparelia Ketan C. , Zeka Keti , Beresford Kenneth J. M. , Wilsher Nicola E. , Potter Gerry A. , Androutsopoulos Vasilis P. , Brucoli Federico , Arroo Randolph R. J.
Published: January 2024

Naturally occurring stilbenoids, such as the (E)-stilbenoid resveratrol and the (Z)-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were assessed, using the MTT cell proliferation assay on a panel of human breast cell lines. Breast tumour cell lines that express CYP1 were significantly more strongly affected by the resveratrol analogues than the cell lines that did not have CYP1 activity. Metabolism studies using isolated CYP1 enzymes provided further evidence that (E)-stilbenoids can be substrates for these enzymes. Structures of metabolic products were confirmed by comparison with synthetic standards and LC-MS co-elution studies. The most promising stilbenoid was (E)-4,3′,4′,5′-tetramethoxystilbene (DMU212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, DMU212 selectively affects proliferation of cells that express CYP1 enzymes.
Three-Dimensional Hydrogen-Bonded Porous Metal-Organic Framework for Natural Gas Separation with High Selectivity
Authors: Dan Wenyan , Wei Guangfeng , Fang Xiangdong
Published: January 2024

A 3D hydrogen-bonded metal-organic framework, [Cu(apc)2]n (TJU-Dan-5, Hapc = 2-aminopyrimidine-5-carboxylic acid), was synthesized via a solvothermal reaction. The activated TJU-Dan-5 with permanent porosity exhibits a moderate uptake of 1.52 wt% of hydrogen gas at 77 K. The appropriate BET surface areas and decoration of the internal polar pore surfaces with groups that form extensive hydrogen bonds offer a more favorable environment for selective C2H6 adsorption, with a predicted selectivity for C2H6/CH4 of around 101 in C2H6/CH4 (5:95, v/v) mixtures at 273 K under 100 kPa. The molecular model calculation demonstrates a C–H···π interaction and a van der Waals host–guest interaction of C2H6 with the pore walls. This work provides a strategy for the construction of 3D hydrogen-bonded MOFs, which may have great potential in the purification of natural gas.
Plasma-Engineered CeOx Nanosheet Array with Nitrogen-Doping and Porous Architecture for Efficient Electrocatalysis
Authors: Wang Zhou , Li Tong , Wang Qi
Published: January 2024

Surface engineering has been proved efficient and universally applicable in improving the performance of CeO2 in various fields. However, previous approaches have typically required high-temperature calcination or tedious procedures, which makes discovery of a moderate and facile modification approach for CeO2 an attractive subject. In this paper, porous CeO2 nanosheets with effective nitrogen-doping were synthesized via a low-temperature NH3/Ar plasma treatment and exhibited boosted hydrogen evolution reaction performance with low overpotential (65 mV) and long-term stability. The mechanism of the elevated performance was investigated by introducing Ar-plasma-treated CeO2 with no nitrogen-doping as the control group, which revealed the dominant role of nitrogen-doping by providing abundant active sites and improving charge transfer characteristics. This work illuminates further investigations into the surface engineering methodologies boosted by plasma and the relative mechanism of the structure–activity relationship.
Geometrical Stabilities and Electronic Structures of Rh5 Nanoclusters on Rutile TiO2 (110) for Green Hydrogen Production
Authors: Alotaibi Moteb
Published: January 2024

Addressing the urgent need for sustainable energy sources, this study investigates the intricate relationship between rhodium (Rh5) nanoclusters and TiO2 rutile (110) surfaces, aiming to advance photocatalytic water splitting for green hydrogen production. Motivated by the imperative to transition from conventional fossil fuels, this study employs density functional theory (DFT) with DFT-D3 and HSE06 hybrid functionals to analyse the geometrical stabilities and electronic structures of Rh5 nanoclusters on TiO2 rutile (110). TiO2, a prominent photocatalyst, faces challenges such as limited visible light absorption, leading researchers to explore noble metals like Rh as cocatalysts. Our results show that bipyramidal Rh5 nanoclusters exhibit enhanced stability and charge transfer when adsorbed on TiO2 rutile (110) compared to trapezoidal configurations. The most stable adsorption induces the oxidation of the nanocluster, altering the electronic structure of TiO2. Extending the analysis to defective TiO2 surfaces, this study explores the impact of Rh5 nanoclusters on oxygen vacancy formation, revealing the stabilisation of TiO2 and increased oxygen vacancy formation energy. This theoretical exploration contributes insights into the potential of Rh5 nanoclusters as efficient cocatalysts for TiO2-based photocatalytic systems, laying the foundation for experimental validations and the rational design of highly efficient photocatalysts for sustainable hydrogen production. The observed effects on electronic structures and oxygen vacancy formation emphasize the complex interactions between Rh5 nanoclusters and the TiO2 surface, guiding future research in the quest for clean energy alternatives.
Enhancing the Properties of Photo-Generated Metallized Nanocomposite Coatings through Thermal Annealing
Authors: Dabert Marine , Papanastasiou Dorina T. , Vidal Loïc , Hajjar-Garreau Samar , Bellet Daniel , Lougnot Daniel , Balan Lavinia
Published: January 2024

In this work, the effect of thermal annealing on silver nanoparticles@polymer (AgNPs@polymer) nanocomposite coatings was investigated. These photo-generated metallized coatings have a spatial distribution of metal nanoparticles, with a depth-wise decrease in their concentration. During annealing, both structural and morphological variations, as well as a spatial reorganization of AgNPs, were observed, both at the surface and in the core of the AgNPs@polymer coating. Owing to their increased mobility, the polymer chains reorganize spontaneously, and, at the same time, a hopping diffusion process, caused by the minimization of the surface energy, promotes the migration and coalescence of the silver nanoparticles towards the surface. The layer of discrete nanoparticles gradually transforms from a weakly percolative assembly to a denser and more networked structure. Consequently, the surface of the coatings becomes significantly more electrically conductive, hydrophobic, and reflective. The general trend is that the thinner the nanohybrid coating, the more pronounced the effect of thermal annealing on its spatial reorganization and properties. These results open up interesting prospects in the field of metallized coating technology and pave the way for integration into a wide variety of devices, e.g., efficient and inexpensive reflectors for energy-saving applications, electrically conductive microdevices, and printed electronic microcircuits.
Zein/Polysaccharide Nanoscale Electrostatic Complexes: Preparation, Drug Encapsulation and Antibacterial Properties
Authors: Lotos Elena-Daniela , Mihai Marcela , Vasiliu Ana-Lavinia , Rosca Irina , Mija Alice , Simionescu Bogdan C. , Pispas Stergios
Published: January 2024

Characterization of zein aqueous solutions, as a function of the ethanol content and pH, was performed, giving information on the zein aggregation state for the construction of complexes. The aggregation state and surface charge of zein was found to depend on the mixed solvent composition and pH. Nonstoichiometric complex nanoparticles (NPECs) were prepared by electrostatically self-assembling zein, as the polycation, and sodium alginate or chondroitin sulfate, as the polyanions, at a pH of 4. A wide range of parameters were investigated: the alcohol–water content in the zein solutions, the charge molar ratios, the solution addition order and the addition rate. The resulting nanoparticles were characterized by dynamic and electrophoretic light scattering, circular dichroism and scanning electron microscopy. The smallest size for the NPECs (100 nm) was obtained when the polysaccharides acted as the titrate with an addition rate of 0.03 mL·min−1. The NPECs with the best characteristics were selected for loading with ciprofloxacin and then deposited on a cellulosic material in order to evaluate their antibacterial activity. Substantial drug encapsulation with desired drug release profiles were found together with notable antibacterial efficiency, showing the tunability of the properties for both the zein and its complexes with polysaccharides, together with their application potential in the biomedical field.
A Survey on Routing Solutions for Low-Power and Lossy Networks: Toward a Reliable Path-Finding Approach
Authors: Almutairi Hanin , Zhang Ning
Published: January 2024

Low-Power and Lossy Networks (LLNs) have grown rapidly in recent years owing to the increased adoption of Internet of Things (IoT) and Machine-to-Machine (M2M) applications across various industries, including smart homes, industrial automation, healthcare, and smart cities. Owing to the characteristics of LLNs, such as Lossy channels and limited power, generic routing solutions designed for non-LLNs may not be adequate in terms of delivery reliability and routing efficiency. Consequently, a routing protocol for LLNs (RPL) was designed. Several RPL objective functions have been proposed to enhance the routing reliability in LLNs. This paper analyses these solutions against performance and security requirements to identify their limitations. Firstly, it discusses the characteristics and security issues of LLN and their impact on packet delivery reliability and routing efficiency. Secondly, it provides a comprehensive analysis of routing solutions and identifies existing limitations. Thirdly, based on these limitations, this paper highlights the need for a reliable and efficient path-finding solution for LLNs.
Host Choice and Feeding Behaviours of Glossina morsitans Offspring Whose Parents Were Fed on Different Host Species
Authors: Mdee Filbert E. , Lyatuu Jeremiah , Mafie Eliakunda , Mnyone Ladslaus L.
Published: January 2024

The success of any tsetse control program depends on the knowledge of their behaviour. This study assessed the host choice and feeding behaviours of Glossina morsitans siblings whose parents were bloodfed on rabbits, guinea pigs, rodents, and squirrels. Each individual host was placed in a screen cage, which allowed flies to enter through openings on each side. The groups of flies (20 per replicate), which were colour-marked differently based on their parents’ blood meal hosts, were released from the centre of large semi-field cage. The released flies were aspirated after 24 h and then sorted based on their location, feeding status, and parents’ blood meal. A total of 213 flies (72.95% of those recovered) were attracted to the hosts. The numbers of flies attracted to different hosts varied significantly (χ24 = 33.685, p = 0.0001): rodents (n = 80, p = 0.006), rabbits (n = 59, p = 0.331), guinea pigs (n = 49, p = 0.057), and squirrels (n = 25, p = 0.005). The numbers of flies attracted to their parent’s blood meal source varied significantly (χ212 = 56.476, p < 0.001): rabbits (n = 35, 59.32%, p < 0.001), rodents (n = 25, 31.25%, p = 0.043), and guinea pigs (n = 19, 38.78%, p = 0.45). But only 39 flies (18.31% of the total attracted) bloodfed on the hosts, including guinea pigs (n = 10, 25.64%), rodents (n = 23, 58.97%), rabbits (n = 6, 15.38%), and squirrels (n = 0, 0.0%). There was significant variation in the number of flies that fed successively across hosts (χ24 = 49.478, p < 0.001). The findings from this study confirm the presence of differential attractiveness of the hosts to flies and the so-called “Hopkins host selection principle” or “pre-imaginal conditioning”. Therefore, the study attracts the need for detailed investigation on the influence of blood meal sources on tsetse fly siblings’ behaviours across filial generations using small mammals or other large mammal species.
First Report of Benzimidazole Resistance in Field Population of Haemonchus contortus from Sheep, Goats and Cattle in Bosnia and Herzegovina
Authors: Kapo Naida , Omeragić Jasmin , Goletić Šejla , Šabić Emina , Softić Adis , Smajlović Ahmed , Mujezinović Indira , Škapur Vedad , Goletić Teufik
Published: January 2024

Haemonchus contortus is a globally significant parasitic nematode in ruminants, with widespread resistance to benzimidazole due to its excessive and prolonged use. Given the extensive use of benzimidazole anthelmintics in Bosnia and Herzegovina, we hypothesized that resistance is prevalent. The aim of this study was to identify the presence of anthelmintic resistance to benzimidazole in H. contortus from naturally infected sheep, goats and cattle in Bosnia and Herzegovina through the detection of the Phe/Tyr polymorphism in the amino acid at position 200 of the β-tubulin protein. From 19 locations in Bosnia and Herzegovina, a total of 83 adult H. contortus were collected from the abomasum of ruminants. Among these, 45 H. contortus specimens were isolated from sheep, 19 from goats and 19 from cattle. Results showed that 77.8% of H. contortus in sheep exhibited homozygous resistant genotypes at position 200 of the β-tubulin gene, with 15.5% being heterozygous. In goats, all tested H. contortus (100%) were homozygous resistant, and no heterozygous resistant or homozygous sensitive genotypes were found. Cattle had 94.7% homozygous resistant H. contortus, with no heterozygous resistant genotypes detected. In H. contortus from sheep and cattle, 6.7% and 5.3%, respectively, displayed homozygous sensitive genotypes. This study, for the first time, highlights the presence of a resistant population of H. contortus in sheep, goats and cattle in Bosnia and Herzegovina, using the rt-qPCR method. The resistance likely spread from sheep or goats to cattle, facilitated by shared pastures and the practice of transhumance, indicating a widespread and growing issue of anthelmintic resistance.
Mycoplasma gallisepticum and Mycoplasma synoviae in Turkeys in Poland
Authors: Kursa Olimpia , Tomczyk Grzegorz , Sieczkowska Agata , Kostka Sylwia , Sawicka-Durkalec Anna
Published: January 2024

The pathogenic mycoplasmas are among the bacteria causing significant losses in the poultry industry worldwide. Mycoplasma gallisepticum (MG) and M. synoviae (MS) are economically important pathogens causing chronic respiratory disease, decreased growth, egg production and hatchability rates, and significant downgrading of carcasses. Effective diagnosis of infection with these species in poultry is highly requisite considering their two routes of spreading—horizontal and vertical. Their prevalence and molecular epidemiology were investigated in 184 turkey flocks in Poland. Tracheal samples were selected from 144 broiler flocks and 40 turkey breeder flocks collected in 2015–2023. The prevalence of MG was determined by real-time PCR targeting the 16S rRNA gene and PCR targeting the mgc2 gene, and MS was determined by a 16–23S rRNA real-time PCR and a vlhA gene PCR. Further identification and molecular characterization were carried out using PCR and sequencing. M. gallisepticum and M. synoviae were found in 8.33% and 9.72% of turkey broiler flocks respectively. The phylogenetic analysis of MG isolates in most cases showed high similarity to the ts-11-like strains. MS isolates showed high similarity to strains isolated from flocks of laying hens causing EAA. Additional tests detected Ornithobacterium rhinotracheale, Gallibacterium anatis, Enterococcus faecalis and Enterococcus faecium, Staphylococcus aureus and Riemerella anatipestifer. These secondary pathogens could have significantly heightened the pathogenicity of the mycoplasma infections studied.
Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network
Authors: Huang Miao , Wang Long , Zhang Qianhui , Zhou Ling , Liao Rui , Wu Anguo , Wang Xinle , Luo Jiesi , Huang Feihong , Zou Wenjun , Wu Jianming
Published: January 2024

Interleukins, a diverse family of cytokines produced by various cells, play crucial roles in immune responses, immunoregulation, and a wide range of physiological and pathological processes. In the context of megakaryopoiesis, thrombopoiesis, and platelet function, interleukins have emerged as key regulators, exerting significant influence on the development, maturation, and activity of megakaryocytes (MKs) and platelets. While the therapeutic potential of interleukins in platelet-related diseases has been recognized for decades, their clinical application has been hindered by limitations in basic research and challenges in drug development. Recent advancements in understanding the molecular mechanisms of interleukins and their interactions with MKs and platelets, coupled with breakthroughs in cytokine engineering, have revitalized the field of interleukin-based therapeutics. These breakthroughs have paved the way for the development of more effective and specific interleukin-based therapies for the treatment of platelet disorders. This review provides a comprehensive overview of the effects of interleukins on megakaryopoiesis, thrombopoiesis, and platelet function. It highlights the potential clinical applications of interleukins in regulating megakaryopoiesis and platelet function and discusses the latest bioengineering technologies that could improve the pharmacokinetic properties of interleukins. By synthesizing the current knowledge in this field, this review aims to provide valuable insights for future research into the clinical application of interleukins in platelet-related diseases.
Cofilin Inhibitor Improves Neurological and Cognitive Functions after Intracerebral Hemorrhage by Suppressing Endoplasmic Reticulum Stress Related-Neuroinflammation
Authors: Almarghalani Daniyah A. , Bahader Ghaith A. , Ali Mohammad , Tillekeratne L. M. Viranga , Shah Zahoor A.
Published: January 2024

Neuroinflammation after intracerebral hemorrhage (ICH) is a crucial factor that determines the extent of the injury. Cofilin is a cytoskeleton-associated protein that drives neuroinflammation and microglia activation. A novel cofilin inhibitor (CI) synthesized and developed in our lab has turned out to be a potential therapeutic agent for targeting cofilin-mediated neuroinflammation in an in vitro model of ICH and traumatic brain injury. The current study aims to examine the therapeutic potential of CI in a mouse collagenase model of ICH and examine the neurobehavioral outcomes and its mechanism of action. Male mice were subjected to intrastriatal collagenase injection to induce ICH, and sham mice received needle insertion. Various concentrations (25, 50, and 100 mg/kg) of CI were administered to different cohorts of the animals as a single intravenous injection 3 h following ICH and intraperitoneally every 12 h for 3 days. The animals were tested for neurobehavioral parameters for up to 7 days and sacrificed to collect brains for hematoma volume measurement, Western blotting, and immunohistochemistry. Blood was collected for cofilin, TNF-α, and IL-1β assessments. The results indicated that 50 mg/kg CI improved neurological outcomes, reversed post-stroke cognitive impairment, accelerated hematoma resolution, mitigated cofilin rods/aggregates, and reduced microglial and astrocyte activation in mice with ICH. Microglia morphological analysis demonstrated that CI restored the homeostasis ramification pattern of microglia in mice treated with CI. CI suppressed endoplasmic reticulum stress-related neuroinflammation by inhibiting inflammasomes and cell death signaling pathways. We also showed that CI prevented synaptic loss by reviving the pre- and post-synaptic markers. Our results unveil a novel therapeutic approach to treating ICH and open a window for using CI in clinical practice.
Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses
Authors: Abdelwahab Walid M. , Auclair Sarah , Borgogna Timothy , Siram Karthik , Riffey Alexander , Bazin Hélène G. , Cottam Howard B. , Hayashi Tomoko , Evans Jay T. , Burkhart David J.
Published: January 2024

Co-delivery of antigens and adjuvants to the same antigen-presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNP) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNP of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed >90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNP (INI-4001/A-SNP) formulations was improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30–50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen-only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.
The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability
Authors: Wang Lili , Ding Zhuang , Wang Zhengping , Zhao Yanna , Wu Hengqian , Wei Qipeng , Gao Lingfeng , Han Jun
Published: January 2024

Paxlovid®, a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we developed a liquid formulation containing NRV and RTV by adopting strategies that used co-solvents and surfactants to enhance the solubility and inhibit possible recrystallization. The in vitro release results showed that NRV and RTV could be maintained at high concentrations in solution for a certain period in the investigated media. In vivo studies in rats showed that the oral bioavailability of NRV/RTV solution was significantly enhanced. Compared to Paxlovid® tablets, the AUC(0–t) of NRV and RTV increased by 6.1 and 3.8 times, respectively, while the Cmax increased by 5.5 times for both. Furthermore, the promoting effect of the absorption of RTV on the bioavailability of NRV was confirmed. Experiments with a beagle showed a similar trend. Stability studies were also conducted at 4 °C, 25 °C, and 40 °C for 90 days, indicating that the oral liquid formulation was physically and chemically stable. This study can be used as a valuable resource for developing and applying oral liquid NRV/RTV formulations in a clinical context.
Virtue, Environmental Ethics, Nonhuman Values, and Anthropocentrism
Authors: Di Paola Marcello
Published: January 2024

This article discusses the encounter between virtue ethics and environmental ethics and the ways in which environmental virtue ethics confronts nonhuman axiology and the controversial theme of moral anthropocentrism. It provides a reasoned review of the relevant literature and a historical–conceptual rendition of how environmental and virtue ethics came to converge as well as the ways in which they diverge. It explains that contrary to important worries voiced by some non-anthropocentric environmental ethicists, environmental virtue ethics enables and requires a rich and nuanced engagement with nonhuman values of all sorts—intrinsic as well as extrinsic, moral as well as nonmoral, anthropocentric as well as non-anthropocentric—and neither presupposes nor implies moral anthropocentrism in its normativity. Finally, the article considers the fortunes of, and some challenges for, environmental virtue ethics in its application to the ethics of climate change, an increasingly central topic in environmental ethics. This article proceeds as follows: the first section introduces virtue ethics; the second section looks at axiological and normative themes in environmental ethics; the third section discusses environmental virtue ethics; and the fourth section considers its application to climate change. The fifth section draws some conclusions.
Screening for Resistance Resources against Bacterial Wilt in Wild Potato
Authors: He Wenfeng , Wang Bingsen , Huang Mengshu , Meng Chengzhen , Wu Jiahui , Du Juan , Song Botao , Chen Huilan
Published: January 2024

Potato is an important crop, used not only for food production but also for various industrial applications. With the introduction of the potato as a staple food strategy, the potato industry in China has grown rapidly. However, issues related to bacterial wilt, exacerbated by factors such as seed potato transportation and continuous cropping, have become increasingly severe in the primary potato cultivation regions of China, leading to significant economic losses. The extensive genetic diversity of Ralstonia solanacearum (R. solanacearum), which is the pathogen of bacterial wilt, has led to a lack of highly resistant potato genetic resources. There is a need to identify and cultivate potato varieties with enhanced resistance to reduce the adverse impact of this disease on the industry. We screened 55 accessions of nine different wild potato species against the bacterial wilt pathogen R. solanacearum PO2-1, which was isolated from native potato plants and belongs to phylotype II. Three accessions of two species (ACL24-2, PNT880-3, and PNT204-23) were identified with high resistance phenotypes to the tested strains. We found these accessions also showed high resistance to different phylotype strains. Among them, only PNT880-3 was capable of flowering and possessed viable pollen, and it was diploid. Consistent with the high resistance, decreased growth of R. solanacearum was detected in PNT880-3. All these findings in our study reveal that the wild potato PNT880-3 was a valuable resistance source to bacterial wilt with breeding potential.
Expanding the Distribution of Prosthechea jauana (Orchidaceae) in the Pantepui and Highlighting the Urgent Need for Conservation Strategies in the Region in Face of Climate Change
Authors: Vieira Tiago L. , Barbosa-Silva Rafael G. , Acosta André L. , van den Berg Cássio
Published: January 2024

Prosthechea jauana has been recognized as an orchid species endemic to the Venezuelan tepui. The first record of P. jauana in Brazil is presented here, also from a tepui in the Southern phytogeographical district of Pantepui in the Serra do Aracá, at the northern border of the Amazonas state. A detailed morphological description and images of the specimen are presented, as well as an updated distribution map, preliminary conservation status assessment, and taxonomic notes about the species. In addition, we provide species’ distribution models for P. jauana based on current and future bioclimatic data. Future projections suggest that the geographic distribution of P. jauana will likely be severely affected, with ~79% of its suitable habitat being reduced by 2041–2060 and ~92% by 2061–2080. Prosthechea jauana could represent a flag species and an example of how climate change may affect the endemic Pantepui flora.
Effect of Bacteria Inoculation on Colonization of Roots by Tuber melanosporum and Growth of Quercus ilex Seedlings
Authors: Giorgi Veronica , Amicucci Antonella , Landi Lucia , Castelli Ivan , Romanazzi Gianfranco , Peroni Cristiano , Ranocchi Bianca , Zambonelli Alessandra , Neri Davide
Published: January 2024

Tuber melanosporum is an ascomycete that forms ectomycorrhizal (ECM) symbioses with a wide range of host plants, producing edible fruiting bodies with high economic value. The quality of seedlings in the early symbiotic stage is important for successful truffle cultivation. Numerous bacterial species have been reported to take part in the truffle biological cycle and influence the establishment of roots symbiosis in plant hosts and the development of the carpophore. In this work, three different bacteria formulations were co-inoculated in Quercus ilex L. seedlings two months after T. melanosporum inoculation. At four months of bacterial application, the T. melanosporum ECM root tip rate of colonization and bacterial presence were assessed using both morphological and molecular techniques. A 2.5-fold increase in ECM colonization rate was found in the presence of Pseudomonas sp. compared to the seedlings inoculated only with T. melanosporum. The same treatment caused reduced plant growth either for the aerial and root part. Meanwhile, the ECM colonization combined with Bradyrhizobium sp. and Pseudomonas sp. + Bradyrhizobium sp. reduced the relative density of fibrous roots (nutrient absorption). Our work suggests that the role of bacteria in the early symbiotic stages of ECM colonization involves both the mycorrhizal symbiosis rate and plant root development processes, both essential for improve the quality of truffle-inoculated seedlings produced in commercial nurseries.
Effects of Exogenous Abscisic Acid on the Physiological and Biochemical Responses of Camellia oleifera Seedlings under Drought Stress
Authors: Yang Dayu , Chen Yongzhong , Wang Rui , He Yimin , Ma Xiaofan , Shen Jiancai , He Zhilong , Lai Hanggui
Published: January 2024

This study comprehensively investigates the physiological and molecular regulatory mechanisms of Camellia oleifera seedlings under drought stress with a soil moisture content of about 30%, where exogenous abscisic acid (ABA) was applied via foliar spraying at concentrations of 50 µg/L, 100 µg/L, and 200 µg/L. The results demonstrated that appropriate concentrations of ABA treatment can regulate the physiological state of the seedlings through multiple pathways, including photosynthesis, oxidative stress response, and osmotic balance, thereby aiding in the restructuring of their drought response strategy. ABA treatment effectively activated the antioxidant system by reducing stomatal conductance and moderately inhibiting the photosynthetic rate, thus alleviating oxidative damage caused by drought stress. Additionally, ABA treatment promoted the synthesis of osmotic regulators such as proline, maintaining cellular turgor stability and enhancing the plant’s drought adaptability. The real-time quantitative PCR results of related genes indicated that ABA treatment enhanced the plant’s response to the ABA signaling pathway and improved disease resistance by regulating the expression of related genes, while also enhancing membrane lipid stability. A comprehensive evaluation using a membership function approach suggested that 50 µg/L ABA treatment may be the most-effective in mitigating drought effects in practical applications, followed by 100 µg/L ABA. The application of 50 µg/L ABA for 7 h induced significant changes in various biochemical parameters, compared to a foliar water spray. Notably, superoxide dismutase activity increased by 17.94%, peroxidase activity by 30.27%, glutathione content by 12.41%, and proline levels by 25.76%. The content of soluble sugars and soluble proteins rose by 14.79% and 87.95%, respectively. Additionally, there was a significant decrease of 31.15% in the malondialdehyde levels.
The Novel Invader Salpichroa origanifolia Modifies the Soil Seed Bank of a Mediterranean Mesophile Forest
Authors: Arduini Iduna , Alessandrini Viola
Published: January 2024

The composition and structure of soil seed banks provide insight into the long-term implications of plant invasions on resident communities. The effect of Salpichroa origanifolia (Sa) on the seed bank of a coastal mesophile forest (Tuscany) was studied by growing Sa-rhizomes in soils from low and high invaded sites, in full sun and canopy shade. Sa growth patterns, and the composition, biomass, nitrogen, and phosphorus contents of seedlings which emerged from seed banks were determined. Seed bank abundance and richness were also determined from under and 2 m apart established Sa populations. Sa plants’ leaf traits and biomass allocation changed in response to light conditions. The germination of seed bank seedlings was not affected or even promoted by Sa, while their biomass as well as N and P uptake were more than halved in both light conditions, leading to a progressive depletion of the forest seed bank. Richness was lower under established Sa populations. Sa seedlings exerted a greater suppression on residents than Sa adults, and these appeared more competitive against their own seedlings than on residents. Sa is an invader of concern for Mediterranean forests because of its adaptability to shaded conditions, the competitiveness of its seedlings, and its vegetative spread by means of rhizomes.
Germination Behavior and Geographical Information System-Based Phenotyping of Root Hairs to Evaluate the Effects of Different Sources of Black Soldier Fly (Hermetia illucens) Larval Frass on Herbaceous Crops
Authors: Labella Rosanna , Bochicchio Rocco , Addesso Rosangela , Labella Donato , Franco Antonio , Falabella Patrizia , Amato Mariana
Published: January 2024

Insect larval frass has been proposed as a fertilizer and amendment, but methods for testing its effects on plants are poorly developed and need standardization. We obtained different types of black soldier fly (Hermetia illucens) frass via the factorial combination of (a) two insect diets, as follows: G (Gainesville = 50% wheat bran, 30% alfalfa meal, 20% maize meal) and W (43% sheep whey + 57% seeds); (b) two frass thermal treatments: NT = untreated and T = treated at 70 °C for 1 h. We tested the effects on the germination of cress (Lepidium sativum L.) and wheat (Triticum durum Desf.) by applying 1:2 w:w water extracts at 0, 25, 50, 75 and 100% concentration. Standardizing frass water content before extraction affected chemical composition. Frass extracts showed high electrical conductivity (8.88 to 13.78 mS cm−1). The W diet was suppressive towards Escherichia coli and showed a lower content of nitrates (e.g., WNT 40% lower than GNT) and a concentration-dependent phytotoxic effect on germinating plants. At 25% concentration, germination indices of G were 4.5 to 40-fold those at 100%. Root and shoot length and root hair area were affected by diet and concentration of frass extracts (e.g., root and shoot length in cress at 25% were, respectively, 4.53 and 2 times higher than at 100%), whereas the effects of the thermal treatment were few or inconclusive. On barley (Hordeum vulgare L.) grown in micropots on a silty loam soil, root mass was reduced by 37% at high extract concentration. A quick procedure for root hair surface area was developed based on the geographic information system (GIS) and may provide a fast method for incorporating root hair phenotyping in frass evaluation. The results indicate that below-ground structures need to be addressed in research on frass effects. For this, phyotoxicity tests should encompass different extract dilutions, and frass water content should be standardized before extraction in the direction of canonical procedures to allow comparisons.