bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis of Microbiomes and Metabolomics Reveals the Mechanism of Adaptation to Cadmium Stress in Rhizosphere Soil of Rhododendron decorum subsp. Diaprepes
Authors: Tang Ming , Chen Lanlan , Wang Li , Yi Yin , Wang Jianfeng , Wang Chao , Chen Xianlei , Liu Jie , Yang Yongsong , Malik Kamran , Gong Jiyi
Published: August 2024

The toxicity of cadmium (Cd) not only affects the growth and development of plants but also has an impact on human health. In this study, high-throughput sequencing and LC-MS were conducted to analyze the effect of CdCl2 treatment on the microbial community and soil metabolomics of rhizosphere soil in Rhododendron decorum subsp. diaprepes. The results showed that CdCl2 treatment reduced the quality of the rhizosphere soil by significantly decreasing the soil organic carbon (SOC) content, urease, and invertase activities, increasing the percentage of the exchangeable Cd fraction. CdCl2 treatment did not significantly change the Chao1 and Shannon indices of bacterial and fungal communities in the rhizosphere soil. R. decorum was more likely to recruit Cd-resistant bacteria (e.g., Proteobacteria, Chloroflexi) and increase the abundance of Cd-resistant fungi (e.g., Basidiomycota, Rozellomycota). Moreover, CdCl2 treatment decreased the content of secondary metabolites associated with plants’ resistance to Cd. Rhizosphere soil urease, invertase activities, alkaline phosphatase (ALP), SOC, total potassium (TK), Cd, and nitrate nitrogen (NN) were the main drivers of the composition of rhizosphere bacterial and fungal communities. CdCl2 treatment weakened the relationships among bacterial/fungi, differential metabolites, and physicochemical properties in rhizosphere soil.
Crop Nutrition and Soil Fertility Management in Organic Potato Production Systems
Authors: Ierna Anita , Distefano Miriam
Published: August 2024

Organic farming is a comprehensive production management system that fosters and improves the health of agroecosystems, encompassing biodiversity, biological cycles, and soil biological activity. The potato (Solanum tuberosum L.) is a crucial crop in organic farming systems, standing out as one of the most highly demanded organic products on the market. Among all crops, with potatoes, there is a very large yield gap between organic and conventional systems, attributable mainly to its intensive nutrient demands. The present review, considering the most relevant scientific literature worldwide, discusses the contemporary state of knowledge on crop nutrition and soil fertility management in organic potato crop production, analyzing the effects of animal manures, green manures, organic amendments, and biostimulants on organic potato tuber yield and quality. Overall, the main findings show a particular combination is needed to effectively maintain good soil fertility, satisfy the nutritional needs of the crop, and overcome the difference in potato yield between organic and conventional farming methods while meeting consumer demand. This combination entails using an animal manure or leguminous green manure with an organic soil amendment, and even better with a biofertilizer, such as a mycorrhizae-fungus-based one. It also emerged that more targeted studies are needed to select appropriate cultivars for organic potato farming systems to optimize this environmentally friendly production method.
Functional Identification of the Isopentenyl Diphosphate Isomerase Gene from Fritillaria unibracteata
Authors: Yu Xinyi , Chen Jiao , Yan Han , Huang Xue , Chen Jieru , Ma Zichun , Zhou Jiayu , Liao Hai
Published: August 2024

Isopentenyl diphosphate isomerase (IPI) is a key enzyme in the synthesis of isoprenoids. In this paper, the in vivo biological activity of the IPI gene from Fritillaria unibracteata (FuIPI) was investigated. Combining a color complementation experiment with High-Performance Liquid Chromatography analysis showed that the FuIPI gene could accumulate β-carotene in Escherichia coli, and Glu190 was identified as a key residue for its catalytic activity. Bioinformatics analysis together with subcellular localization indicated that the FuIPI protein was localized in chloroplasts. Compared with wild-type Arabidopsis thaliana, FuIPI transgenic plants had higher abscisic acid content and strengthening tolerance to drought and salt stress. Overall, these results indicated that the FuIPI gene had substantial biological activity in vivo, hopefully laying a foundation for its further research and application in liliaceous ornamental and medicinal plants.
Aruncus dioicus var. kamtschaticu: A Newly Identified Source of Lactucaxanthin (ε,ε-Carotene-3,3′-diol)
Authors: Saini Ramesh Kumar , Ko Eun-Young , Keum Young-Soo , Lee Ji-Ho , Chun Se Chul , Sivanesan Iyyakkannu
Published: August 2024

Green leafy vegetables are rich in lipophilic metabolites such as carotenoids, phytosterols, tocopherols, and fatty acids, known for their significant health benefits. Goat’s beard (Aruncus dioicus var. kamtschaticus), a wild leafy vegetable native to Ulleungdo Island, South Korea, is reported to possess various biological activities and bioactive compounds. However, the content and profiles of lipophilic metabolites, especially carotenoids, have not been reported. This study investigated the composition of lipophilic metabolites in the foliage of goat’s beard using liquid chromatography–diode-array detection–mass spectrometry, gas chromatography–mass spectrometry, and gas chromatography–flame ionization detection. Five carotenoids (violaxanthin, neoxanthin, lactucaxanthin, lutein, β-carotene) and α-tocopherol were identified and quantified using liquid chromatography–diode-array detection–mass spectrometry. Lactucaxanthin, previously discovered in lettuce, was identified for the first time in goat’s beard foliage, with a higher concentration (45.42 ± 0.80 µg/g FW) compared to red lettuce (19.05 ± 0.67 µg/g FW). Furthermore, total carotenoids and α-tocopherol contents were higher in goat’s beard than in red lettuce. Gas chromatography–mass spectrometry analysis showed the presence of three phytosterols, namely, campesterol (3.53 ± 0.20 µg/g FW), stigmasterol (65.30 ± 4.87 µg/g FW), and β-sitosterol (89.54 ± 2.46 µg/g FW). Gas chromatography–flame ionization detection analysis revealed the presence of five essential fatty acids, with α-linolenic acid (57.03 ± 0.47%) being the most abundant, contributing to a favorable polyunsaturated FA/saturated FA ratio. These findings underscore the nutritional potential of a goat’s beard, suggesting its promising use in dietary supplements and the commercial extraction of valuable lipophilic antioxidants, particularly lactucaxanthin, for nutraceuticals and functional foods.
Evaluation of the Resistance of Bitter Cucumber (Momordica charantia) to Saline Stress through Physical, Biochemical, and Physiological Analysis
Authors: Ostaci Ștefănica , Slabu Cristina , Marta Alina Elena , Jităreanu Carmenica Doina
Published: August 2024

Momordica charantia is a climbing plant often used in traditional medicine to treat a large number of diseases, including diabetes. Salinity is one of the main stressors faced by plants, affecting almost half of irrigated agricultural land and constantly increasing. The aim of this study was to determine the resistance of some bitter cucumber genotypes to salt stress by means of dry matter analysis, chlorophyll a, chlorophyll b, malondialdehyde content, chlorophyll fluorescence, and potassium (K)/silicon (Si) and calcium (Ca)/silicon (Si) atomic ratios. Two varieties of bitter cucumber and three experimental lines were used for the experiment. Treatments with different saline solutions (100 mM of NaCl and 200 mM of NaCl) were applied and compared with an untreated control (0 mM of NaCl). The analyses revealed an increase in the dry matter content of the varieties subjected to salt stress. The Line 4 genotype showed an increase of up to 37.2% compared to the control when treated with 200 mM of NaCl. Following the analysis of the chlorophyll a content, a 38% decrease in its amount compared to the control was observed when treated with 100 mM of saline and 58.6% when treated with 200 mM of NaCl in genotype Line 4. Line 3 showed an increase in the chlorophyll a content compared to the control by 53% in the case of saline treatment with 200 mM. After the analysis of the chlorophyll b content, a 44% decrease was revealed in the case of Line 4 in the variant treated with 100 mM compared to the control and a 61% decrease in the 200 mM NaCl treatment. The highest increase in the concentration of malondialdehyde was recorded in the case of Line 4 in the variant treated with 200 mM of NaCl by 41% compared to the control. The maximum quantum yield of PS II decreased in the treated variants compared to the control plants. The most pronounced difference compared to the control was registered in the case of Line 4, where the treatment with 100 mM of NaCl caused a decrease of 16%, and the treatment with 200 mM caused a decrease of 25%. In the case of the atomic ratio, significant decreases in K and Ca were observed in the NaCl-treated variants. The observed differences between the values obtained for each studied genotype highlight the different degrees of their resistance to salinity.
Optimizing Peat and Wood Fiber Blends: Impacts of Liming and Fertilization on Growth of Petunia (Petunia x hybrida Vilm.) and Basil (Ocimum basilicum L.)
Authors: Woznicki Tomasz L. , Sønsteby Anita , Aurdal Siv M. , Kusnierek Krzysztof , Haraldsen Trond K.
Published: August 2024

This study investigated the effects of substrates composed of various ratios of wood fiber and peat (0, 25, 50, 75, and 100% peat (v/v)) mixed with different amounts of lime (0, 2, 4, 6, and 8 g L−1) and start fertilizer (0, 2, and 4 g L−1 Multimix) on the growth and biomass accumulation of petunia (Petunia x hybrida Vilm ‘Finity F1 Purple’) and basil (Ocimum basilicum L. ‘Marian’) in an ebb-and-flow greenhouse system. Growth parameters included plant height, weight, canopy diameter, and chlorosis symptoms for petunia, along with substrate pH and EC measurements. Petunia showed optimal growth in substrates with higher peat content, while basil produced satisfactory biomass across a pH range of 5–7 regardless of substrate type. Optimal petunia cultivation in 100% wood fiber required a significant dose of start fertilizer without lime. Monitoring pH and EC using pour-through and press methods revealed a pH decrease in substrates with added start fertilizer, while substrates with higher wood fiber content were less acidic. Substrates with over 50% (v/v) wood fiber without lime showed a rapid pH increase over five weeks. The pour-through method generally underestimated EC values compared to the press method. These findings contribute to optimizing the wood fiber/peat blends for sustainable horticulture.
Chlorine Dioxide Delays Enzymatic Browning in Postharvest Cherimoya and Enables Establishment of Kinetics Substrate Model
Authors: Zheng Tianchang , Huang Chongxing , Jing Xianghai , Huang Huijie , Deng Rongrong , Fang Jingjing
Published: August 2024

Cherimoya (Annona squamosa L.) is a nutrient-rich fruit. However, it is not easy to store because of its susceptibility to browning. In order to prolong the storage period of cherimoya, the fruit was treated with chlorine dioxide (ClO2) at different concentrations (20, 40, 60, 80, and 100 mg L−1) and stored at 15 °C for 8 days. The quality and biochemical indexes of the fruit were investigated using a chromameter, high-performance liquid chromatography and scanning electron microscopy, etc. The results showed that all the treatments with various concentrations of ClO2 could delay the increase in the browning index, loss of weight, and decrease in hardness. Meanwhile, ClO2 treatment effectively reduced the consumption of starch, titratable acids, and phenolics as well as inhibited the polyphenol oxidase (PPO) activity and enzymatic oxidation. It can be seen from the Fourier transform infrared spectrum (FTIR) that the C=O stretching peak at 1731 cm−1 disappeared at a ClO2 concentration of 60 mg L−1. We think the ClO2 treatment may inhibit the oxidation of phenol to quinone. According to the Arrhenius formula, the values of the apparent activation energy (Ea) for enzymatic browning reaction were estimated. The Ea with catechol in cherimoya pericarp and flesh were 67.00 and 47.83 kJ mol−1, respectively. It was found that the phenolic enzyme reaction with catechol has a much smaller Ea and a higher affinity for PPO. Therefore, treatment with ClO2 at a suitable concentration for cherimoya stored at 15 °C could effectively maintain fruit quality and prolong the storage period; the most appropriate concentration is 60 mg L−1.
Drought Stress Effects and Ways for Improving Drought Tolerance in Impatiens walleriana Hook.f.—A Review
Authors: Milovančević Marija , Trifunović-Momčilov Milana , Radulović Olga , Milošević Snežana , Subotić Angelina
Published: August 2024

Drought is one of the main abiotic stresses affecting plant growth and development. Reduced plant yield and quality are primarily caused by the reductions in photosynthesis, mineral uptake, metabolic disorders, damages from the increased production of reactive oxygen species, and many other disruptions. Plants utilize drought resistance mechanisms as a defense strategy, and the systems’ activation is dependent upon several factors, including plant genotype, onthogenesis phase, drought intensity and duration, and the season in which the drought occurs. Impatiens walleriana is a worldwide popular flowering plant recognized for its vibrant flower colors, and is an indispensable plant in pots, gardens and other public areas. It prefers well-draining, moisturized soil, and does not perform well in overly dry or waterlogged conditions. Consequently, inadequate water supply is a common problem for this plant during production, transportation, and market placement, which has a substantial impact on plant performance overall. This review article outlines certain features of morphological, physiological, and molecular alterations induced by drought in ornamental, drought-sensitive plant species I. walleriana, as well as research carried out to date with the aim to improve the drought tolerance. Stress proteins aquaporins and dehydrins, whose molecular structure was described for the first time in this plant species, are highlighted specifically for their role in drought stress. Furthermore, the effective improvement of drought tolerance in I. walleriana by exogenous application of Plant Growth Regulators and Plant Growth-Promoting Bacteria is discussed in detail. Finally, this review can provide valuable insights for improving plant resilience and productivity in the face of water scarcity, which is critical for sustainable agriculture and horticulture.
Advancing Fruit Preservation: Ecofriendly Treatments for Controlling Fruit Softening
Authors: Mthembu Sisanda Sibusiso , Magwaza Lembe Samukelo , Tesfay Samson Zeray , Mditshwa Asanda
Published: August 2024

Textural softening is a major factor that limits the storage potential of fruit. Fresh produce markets incur severe financial losses due to excessive fruit softening. The application of preservation strategies aimed at mitigating fruit softening is crucial for optimising the marketability of fruit. Proposed preservation strategies include ecofriendly treatments, namely, hexanal, edible coatings, heat treatments, ozone and UV-C irradiation. These treatments optimise firmness retention by targeting the factors that affect fruit softening, such as ethylene, respiration rates, enzymes and pathogens. This review discusses the mechanisms by which ecofriendly treatments inhibit fruit softening, providing insights into their effect on ethylene biosynthesis, cell wall metabolism and disease resistance. Although ecofriendly treatments offer a promising and sustainable approach for delaying fruit softening, the optimisation of treatment application protocols is needed to improve their efficacy in retaining fruit firmness. Studies reporting on the molecular mechanisms by which ecofriendly treatments inhibit fruit softening are limited. Future studies should prioritise proteomic and transcriptome analyses to advance our understanding of the underlying molecular mechanisms by which ecofriendly treatments delay the fruit-softening process.
Industrial Decarbonization through Blended Combustion of Natural Gas and Hydrogen
Authors: Franco Alessandro , Rocca Michele
Published: August 2024

The transition to cleaner energy sources, particularly in hard-to-abate industrial sectors, often requires the gradual integration of new technologies. Hydrogen, crucial for decarbonization, is explored as a fuel in blended combustions. Blending or replacing fuels impacts combustion stability and heat transfer rates due to differing densities. An extensive literature review examines blended combustion, focusing on hydrogen/methane mixtures. While industrial burners claim to accommodate up to 20% hydrogen, theoretical support is lacking. A novel thermodynamic analysis methodology is introduced, evaluating methane/hydrogen combustion using the Wobbe index. The findings highlight practical limitations beyond 25% hydrogen volume, necessitating a shift to “totally hydrogen” combustion. Blended combustion can be proposed as a medium-term strategy, acknowledging hydrogen’s limited penetration. Higher percentages require burner and infrastructure redesign.
Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury
Authors: Angelin Leonidas Gomes , Carreño Marcelo Nelson Páez , Otoch Jose Pinhata , de Resende Joyce Cristina Ferreira , Arévalo Analía , Motta-Teixeira Lívia Clemente , Seelaender Marilia Cerqueira Leite , Lepski Guilherme
Published: August 2024

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin–eosin) and immunohistochemistry for NeuN, β-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for β-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in β-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.
Lignin Structural Characterization and Its Antioxidant Potential: A Comparative Evaluation by EPR, UV-Vis Spectroscopy, and DPPH Assays
Authors: Kozmelj Tina Ročnik , Voinov Maxim A. , Grilc Miha , Smirnov Alex I. , Jasiukaitytė-Grojzdek Edita , Lucia Lucian , Likozar Blaž
Published: August 2024

The natural aromatic polymer lignin and its lignin-like oligomeric fragments have attracted attention for their antioxidant capacity and free radical scavenging activities. In this study, a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was employed to assess the antioxidant capacity of fractionated and partially depolymerized organosolv lignin by electron paramagnetic resonance (EPR) and UV-Vis spectroscopy. The results show significant antioxidant activity for both the lignin and oligomeric fragments, with the EPR measurements demonstrating their efficiency in quenching the free radicals. The EPR data were analyzed to derive the kinetic rate constants. The radical scavenging activity (RSA) of lignins was then determined by UV-Vis spectroscopy and the results were compared with the EPR method. This two-method approach improves the reliability and understanding of the antioxidant potential of lignin and its derivatives and provides valuable insights for their potential applications in various industries, including pharmaceuticals, food preservation, and cosmetics.
Biological Roles of Lipids in Rice
Authors: Zhou Kun , Luo Zhengliang , Huang Weidong , Liu Zemin , Miao Xuexue , Tao Shuhua , Wang Jiemin , Zhang Jian , Wang Shiyi , Zeng Xiaoshan
Published: August 2024

Lipids are organic nonpolar molecules with essential biological and economic importance. While the genetic pathways and regulatory networks of lipid biosynthesis and metabolism have been extensively studied and thoroughly reviewed in oil crops such as soybeans, less attention has been paid to the biological roles of lipids in rice, a staple food for the global population and a model species for plant molecular biology research, leaving a considerable knowledge gap in the biological roles of lipids. In this review, we endeavor to furnish a current overview of the advancements in understanding the genetic foundations and physiological functions of lipids, including triacylglycerol, fatty acids, and very-long-chain fatty acids. We aim to summarize the key genes in lipid biosynthesis, metabolism, and transcriptional regulation underpinning rice’s developmental and growth processes, biotic stress responses, abiotic stress responses, fertility, seed longevity, and recent efforts in rice oil genetic improvement.
Identification and Characterization of Novel Founder Mutations in NDRG1: Refining the Genetic Landscape of Charcot–Marie–Tooth Disease Type 4D in Bulgaria
Authors: Atkinson Derek , Chamova Teodora , Candayan Ayse , Kastreva Kristina , Asenov Ognian , Litvinenko Ivan , Estrada-Cuzcano Alejandro , De Vriendt Els , Kukushev Georgi , Tournev Ivailo , Jordanova Albena
Published: August 2024

Charcot–Marie–Tooth neuropathy type 4D (CMT4D) is a rare genetic disorder of the peripheral nervous system caused by biallelic mutations in the N-Myc Downstream Regulated 1 gene (NDRG1). Patients present with an early onset demyelinating peripheral neuropathy causing severe distal muscle weakness and sensory loss, leading to loss of ambulation and progressive sensorineural hearing loss. The disorder was initially described in the Roma community due to a common founder mutation, and only a handful of disease-causing variants have been described in this gene so far. Here, we present genetic and clinical findings from a large Bulgarian cohort of demyelinating CMT patients harboring recurrent and novel variants in the NDRG1 gene. Notably, two splice-site variants are exclusive to Bulgarian Muslims and reside in ancestral haplotypes, suggesting a founder effect. Functional characterization of these novel variants implicates a loss-of-function mechanism due to shorter gene products. Our findings contribute to a deeper understanding of the genetic and clinical heterogeneity of CMT4D and highlight novel founder mutations in the ethnic minority of Bulgarian Muslims.
The Beneficial Effects of Prenatal Biotin Supplementation in a Rat Model of Intrauterine Caloric Restriction to Prevent Cardiometabolic Risk in Adult Female Offspring
Authors: Aguilera-Méndez Asdrubal , Figueroa-Fierros Ian , Ruiz-Pérez Xóchilt , Godínez-Hernández Daniel , Saavedra-Molina Alfredo , Rios-Chavez Patricia , Villafaña Santiago , Boone-Villa Daniel , Ortega-Cuellar Daniel , Gauthereau-Torres Marcia Yvette , Nieto-Aguilar Renato , Palomera-Sanchez Zoraya
Published: August 2024

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee’s index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee’s index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.
AAV-Mediated Expression of miR-17 Enhances Neurite and Axon Regeneration In Vitro
Authors: Almeida Raquel Alves , Ferreira Carolina Gomes , Matos Victor Ulysses Souza , Nogueira Julia Meireles , Braga Marina Pimenta , Caldi Gomes Lucas , Jorge Erika Cristina , Soriani Frederico Marianetti , Michel Uwe , Ribas Vinicius Toledo
Published: August 2024

Neurodegenerative disorders, including traumatic injuries to the central nervous system (CNS) and neurodegenerative diseases, are characterized by early axonal damage, which does not regenerate in the adult mammalian CNS, leading to permanent neurological deficits. One of the primary causes of the loss of regenerative ability is thought to be a developmental decline in neurons’ intrinsic capability for axon growth. Different molecules are involved in the developmental loss of the ability for axon regeneration, including many transcription factors. However, the function of microRNAs (miRNAs), which are also modulators of gene expression, in axon re-growth is still unclear. Among the various miRNAs recently identified with roles in the CNS, miR-17, which is highly expressed during early development, emerges as a promising target to promote axon regeneration. Here, we used adeno-associated viral (AAV) vectors to overexpress miR-17 (AAV.miR-17) in primary cortical neurons and evaluate its effects on neurite and axon regeneration in vitro. Although AAV.miR-17 had no significant effect on neurite outgrowth and arborization, it significantly enhances neurite regeneration after scratch lesion and axon regeneration after axotomy of neurons cultured in microfluidic chambers. Target prediction and functional annotation analyses suggest that miR-17 regulates gene expression associated with autophagy and cell metabolism. Our findings suggest that miR-17 promotes regenerative response and thus could mitigate neurodegenerative effects.
Evaluation of the Antidiabetic Potential of Xanthone-Rich Extracts from Gentiana dinarica and Gentiana utriculosa
Authors: Jovanović Jelena Arambašić , Krstić-Milošević Dijana , Vinterhalter Branka , Dinić Svetlana , Grdović Nevena , Uskoković Aleksandra , Rajić Jovana , Đorđević Marija , Sarić Ana , Vidaković Melita , Mihailović Mirjana
Published: August 2024

Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, the main secondary metabolites found in Gentiana dinarica and Gentiana utriculosa, display various biological activities. In in vitro cultured and particularly in genetically transformed G. dinarica and G. utriculosa roots, there is a higher content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of secondary metabolites (extracts) prepared from these two Gentiana species, cultured in vitro and genetically transformed with those collected from nature. We compare HPLC secondary metabolite profiles and the content of the main extract compounds of G. dinarica and G. utriculosa methanol extracts with their ability to scavenge DPPH free radicals and inhibit intestinal α-glucosidase in vitro. Anti-hyperglycemic activity of selected extracts was tested further in vivo on glucose-loaded Wistar rats. Our findings reveal that the most prominent radical scavenging potential and potential to control the rise in glucose level, detected in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin and norswertianin-1-O-primeveroside in G. dinarica and decussatin and decussatin-1-O-primeveroside in G. utriculosa.
Transient Adaptation of Toxoplasma gondii to Exposure by Thiosemicarbazone Drugs That Target Ribosomal Proteins Is Associated with the Upregulated Expression of Tachyzoite Transmembrane Proteins and Transporters
Authors: Semeraro Manuela , Boubaker Ghalia , Scaccaglia Mirco , Müller Joachim , Vigneswaran Anitha , Hänggeli Kai Pascal Alexander , Amdouni Yosra , Kramer Laura Helen , Vismarra Alice , Genchi Marco , Pelosi Giorgio , Bisceglie Franco , Heller Manfred , Uldry Anne-Christine , Braga-Lagache Sophie , Hemphill Andrew
Published: August 2024

Thiosemicarbazones and their metal complexes have been studied for their biological activities against bacteria, cancer cells and protozoa. Short-term in vitro treatment with one gold (III) complex (C3) and its salicyl-thiosemicarbazone ligand (C4) selectively inhibited proliferation of T. gondii. Transmission Electron Microscopy (TEM) detected transient structural alterations in the parasitophorous vacuole membrane and the tachyzoite cytoplasm, but the mitochondrial membrane potential appeared unaffected by these compounds. Proteins potentially interacting with C3 and C4 were identified using differential affinity chromatography coupled with mass spectrometry (DAC-MS). Moreover, long-term in vitro treatment was performed to investigate parasitostatic or parasiticidal activity of the compounds. DAC-MS identified 50 ribosomal proteins binding both compounds, and continuous drug treatments for up to 6 days caused the loss of efficacy. Parasite tolerance to both compounds was, however, rapidly lost in their absence and regained shortly after re-exposure. Proteome analyses of six T. gondii ME49 clones adapted to C3 and C4 compared to the non-adapted wildtype revealed overexpression of ribosomal proteins, of two transmembrane proteins involved in exocytosis and of an alpha/beta hydrolase fold domain-containing protein. Results suggest that C3 and C4 may interfere with protein biosynthesis and that adaptation may be associated with the upregulated expression of tachyzoite transmembrane proteins and transporters, suggesting that the in vitro drug tolerance in T. gondii might be due to reversible, non-drug specific stress-responses mediated by phenotypic plasticity.
Pyroptosis in Skeleton Diseases: A Potential Therapeutic Target Based on Inflammatory Cell Death
Authors: Wu Qian , Du Jiacheng , Bae Eun Ju , Choi Yunjung
Published: August 2024

Skeletal disorders, including fractures, osteoporosis, osteoarthritis, rheumatoid arthritis, and spinal degenerative conditions, along with associated spinal cord injuries, significantly impair daily life and impose a substantial burden. Many of these conditions are notably linked to inflammation, with some classified as inflammatory diseases. Pyroptosis, a newly recognized form of inflammatory cell death, is primarily triggered by inflammasomes and executed by caspases, leading to inflammation and cell death through gasdermin proteins. Emerging research underscores the pivotal role of pyroptosis in skeletal disorders. This review explores the pyroptosis signaling pathways and their involvement in skeletal diseases, the modulation of pyroptosis by other signals in these conditions, and the current evidence supporting the therapeutic potential of targeting pyroptosis in treating skeletal disorders, aiming to offer novel insights for their management.
Sex Differences in Antennal Transcriptome of Hyphantria cunea and Analysis of Odorant Receptor Expression Profiles
Authors: Ma Weichao , Li Yaning , Yang Lina , Yan Shanchun
Published: August 2024

Insects rely on olfaction for mating, finding oviposition sites, and locating hosts. Hyphantria cunea is a serious pest that severely damages forests. Differential expression analysis of olfactory-related genes between males and females is the basis for elucidating the functions of olfactory-related proteins in H. cunea. In this study, Illumina HiSeqTM 4000 high-throughput sequencing technology was used to perform transcriptome sequencing of the antennal tissues of adult male and female H. cunea. Functional annotation was conducted using the NR, Swiss-Prot, KOG, KEGG, and GO databases, and the results showed that the antennal transcriptome of adult H. cunea contained 50,158 unigenes. Differential expression analysis identified 3923 genes that were significantly differentially expressed between male and female antennae. A total of 221 olfactory-related genes were annotated, and 96 sex-biased genes were identified, including 13 odorant receptors (ORs), 48 odorant binding proteins (OBPs), 7 chemosensory proteins (CSPs), 10 ionotropic receptors (IRs), 10 sensory neuron membrane proteins (SNMPs), 2 gustatory receptors (GRs), and 6 odorant-degrading enzymes (ODEs), indicating that there were differences in olfaction between male and female H. cunea. Quantitative real-time PCR was used to verify the expression levels of 21 putative general odorant receptor genes in male and female antennae. HcunOR4 and HcunOR5 showed female-biased expression; HcunOR48, HcunOR49 and HcunOR50 showed male-biased expression. The results were consistent with the transcriptome differential analysis. The screening of male-biased odorant receptor genes might provide a theoretical basis for the functional characterization of odorant receptors for recognizing sex pheromones in H. cunea.
The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow
Authors: Scarpellino Giorgia , Brunetti Valentina , Berra-Romani Roberto , De Sarro Giovambattista , Guerra Germano , Soda Teresa , Moccia Francesco
Published: August 2024

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma. Herein, we review the role of eNOS in both the regulation of cerebral blood flow and of synaptic plasticity and discuss the mechanisms by which cerebrovascular endothelial cells may transduce synaptic inputs into a NO signal. We further suggest that eNOS could play a critical role in vascular-to-neuronal communication by integrating signals converging onto cerebrovascular endothelial cells from both the streaming blood and active neurons.
Estrogen Receptors: A New Frontier in Alzheimer’s Disease Therapy
Authors: Cipriano Giovanni Luca , Mazzon Emanuela , Anchesi Ivan
Published: August 2024

Alzheimer’s disease (AD) is a long-term neurodegenerative condition that leads to the deterioration of neurons and synapses in the cerebral cortex, resulting in severe dementia. AD is significantly more prevalent in postmenopausal women, suggesting a neuroprotective role for estrogen. Estrogen is now known to regulate a wide array of physiological functions in the body by interacting with three known estrogen receptors (ERs) and with the β-amyloid precursor protein, a key factor in AD pathogenesis. Recent experimental evidence indicates that new selective ER modulators and phytoestrogens may be promising treatments for AD for their neuroprotective and anti-apoptotic properties. These alternatives may offer fewer side effects compared to traditional hormone therapies, which are associated with risks such as cardiovascular diseases, cancer, and metabolic dysfunctions. This review sheds light on estrogen-based treatments that may help to partially prevent or control the neurodegenerative processes characteristic of AD, paving the way for further investigation in the development of estrogen-based treatments.
The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects
Authors: Alves Luana de Fátima , Moore J. Bernadette , Kell Douglas B.
Published: August 2024

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety of cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters and receptors display micromolar binding constants; these are consistent with its typically micromolar tissue concentrations but far above its serum/plasma concentration (normally tens of nanomolar), suggesting large gaps in our knowledge of its transport and mechanisms of action, in that the main influx transporters characterized to date are equilibrative, not concentrative. In addition, it is a substrate of a known anion efflux pump (ABCC4), whose in vivo activity is largely unknown. Exogeneous addition of L-tryptophan or L-kynurenine leads to the production of KYNA but also to that of many other co-metabolites (including some such as 3-hydroxy-L-kynurenine and quinolinic acid that may be toxic). With the exception of chestnut honey, KYNA exists at relatively low levels in natural foodstuffs. However, its bioavailability is reasonable, and as the terminal element of an irreversible reaction of most tryptophan degradation pathways, it might be added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show that it has valuable bioactivity. Given the above, we review its potential utility as a nutraceutical, finding it significantly worthy of further study and development.
Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells
Authors: Alhasan Bashar , Gladova Yana A. , Sverchinsky Dmitry V. , Aksenov Nikolai D. , Margulis Boris A. , Guzhova Irina V.
Published: August 2024

Proteostasis mechanisms, such as proteotoxic-stress response and autophagy, are increasingly recognized for their roles in influencing various cancer hallmarks such as tumorigenesis, drug resistance, and recurrence. However, the precise mechanisms underlying their coordination remain not fully elucidated. The aim of this study is to investigate the molecular interplay between Hsp70 and autophagy in lung adenocarcinoma cells and elucidate its impact on the outcomes of anticancer therapies in vitro. For this purpose, we utilized the human lung adenocarcinoma A549 cell line and genetically modified it by knockdown of Hsp70 or HSF1, and the H1299 cell line with knockdown or overexpression of Hsp70. In addition, several treatments were employed, including treatment with Hsp70 inhibitors (VER-155008 and JG-98), HSF1 activator ML-346, or autophagy modulators (SAR405 and Rapamycin). Using immunoblotting, we found that Hsp70 negatively regulates autophagy by directly influencing AMPK activation, uncovering a novel regulatory mechanism of autophagy by Hsp70. Genetic or chemical Hsp70 overexpression was associated with the suppression of AMPK and autophagy. Conversely, the inhibition of Hsp70, genetically or chemically, resulted in the upregulation of AMPK-mediated autophagy. We further investigated whether Hsp70 suppression-mediated autophagy exhibits pro-survival- or pro-death-inducing effects via MTT test, colony formation, CellTiter-Glo 3D-Spheroid viability assay, and Annexin/PI apoptosis assay. Our results show that combined inhibition of Hsp70 and autophagy, along with cisplatin treatment, synergistically reduces tumor cell metabolic activity, growth, and viability in 2D and 3D tumor cell models. These cytotoxic effects were exerted by substantially potentiating apoptosis, while activating autophagy via rapamycin slightly rescued tumor cells from apoptosis. Therefore, our findings demonstrate that the combined inhibition of Hsp70 and autophagy represents a novel and promising therapeutic approach that may disrupt the capacity of refractory tumor cells to withstand conventional therapies in NSCLC.
Wastewater Treatment with Bacterial Representatives of the Thiothrix Morphotype
Authors: Gureeva Maria V. , Muntyan Maria S. , Ravin Nikolai V. , Grabovich Margarita Yu.
Published: August 2024

Bacteria of the Thiothrix morphotype, comprising the genera Thiothrix, Thiolinea and Thiofilum, are frequently encountered in domestic and industrial wastewater treatment systems, but they are usually not clearly differentiated due to the marked similarity in their morphologies. Methods ranging from light microscopy, FISH and PCR to modern high-throughput sequencing are used to identify them. The development of these bacteria in wastewater treatment systems has both advantages and disadvantages. On the one hand, the explosive growth of these bacteria can lead to activated sludge bulking or clogging of the treatment system’s membranes, with a consequent decrease in the water treatment efficiency. On the other hand, members of the Thiothrix morphotype can improve the quality of granular sludge and increase the water treatment efficiency. This may be due to their capacity for sulfide oxidation, denitrification combined with the oxidation of reduced sulfur compounds, enhanced biological phosphate removal and possibly denitrifying phosphate removal. The recently obtained pangenome of the genus Thiothrix allows the explanation, at the genomic level, of the experimental results of various studies. Moreover, this review summarizes the data on the factors affecting the proliferation of representatives of the Thiothrix morphotype.
Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage
Authors: Martin Lee J. , Koh Shannon J. , Price Antionette , Park Dongseok , Kim Byung Woo
Published: August 2024

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene that encodes copper/zinc superoxide dismutase (SOD1). SOD1 is known mostly as a cytosolic antioxidant protein, but SOD1 is also in the nucleus of non-transgenic (tg) and human SOD1 (hSOD1) tg mouse MNs. SOD1’s nuclear presence in different cell types and subnuclear compartmentations are unknown, as are the nuclear functions of SOD1. We examined hSOD1 nuclear localization and DNA damage in tg mice expressing mutated and wildtype variants of hSOD1 (hSOD1-G93A and hSOD1-wildtype). We also studied ALS patient-derived induced pluripotent stem (iPS) cells to determine the nuclear presence of SOD1 in undifferentiated and differentiated MNs. In hSOD1-G93A and hSOD1-wildtype tg mice, choline acetyltransferase (ChAT)-positive MNs had nuclear hSOD1, but while hSOD1-wildtype mouse MNs also had nuclear ChAT, hSOD1-G93A mouse MNs showed symptom-related loss of nuclear ChAT. The interneurons had preserved parvalbumin nuclear positivity in hSOD1-G93A mice. hSOD1-G93A was seen less commonly in spinal cord astrocytes and, notably, oligodendrocytes, but as the disease emerged, the oligodendrocytes had increased mutant hSOD1 nuclear presence. Brain and spinal cord subcellular fractionation identified mutant hSOD1 in soluble nuclear extracts of the brain and spinal cord, but mutant hSOD1 was concentrated in the chromatin nuclear extract only in the spinal cord. Nuclear extracts from mutant hSOD1 tg mouse spinal cords had altered protein nitration, footprinting peroxynitrite presence, and the intact nuclear extracts had strongly increased superoxide production as well as the active NADPH oxidase marker, p47phox. The comet assay showed that MNs from hSOD1-G93A mice progressively (6–14 weeks of age) accumulated DNA single-strand breaks. Ablation of the NCF1 gene, encoding p47phox, and pharmacological inhibition of NADPH oxidase with systemic treatment of apocynin (10 mg/kg, ip) extended the mean lifespan of hSOD1-G93A mice by about 25% and mitigated genomic DNA damage progression. In human postmortem CNS, SOD1 was found in the nucleus of neurons and glia; nuclear SOD1 was increased in degenerating neurons in ALS cases and formed inclusions. Human iPS cells had nuclear SOD1 during directed differentiation to MNs, but mutant SOD1-expressing cells failed to establish wildtype MN nuclear SOD1 levels. We conclude that SOD1 has a prominent nuclear presence in the central nervous system, perhaps adopting aberrant contexts to participate in ALS pathobiology.