bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased Soil Microbial Biomass and Changed Microbial Community Composition following a Defoliation Event by the Forest Tent Caterpillar
Authors: Dansereau-Macias Éléonore , Despland Emma , Handa Ira Tanya
Published: April 2023

With climate change projected to increase the frequency and severity of episodic insect outbreak events, assessing potential consequences for soil microbial communities and nutrient dynamics is of importance for understanding forest resilience. The forest tent caterpillar (Malacosoma disstria) is an important defoliator of deciduous tree species in temperate and mixed forests of eastern North America with an invasion cycle every 10–12 years and outbreak events that can last 3–6 years. Following a defoliation episode on trembling aspen (Populus tremuloides) from 2015 to 2017 in Abitibi-Témiscamingue, QC, Canada, we sought to test if defoliation resulted in changes to soil bacterial and fungal communities. We hypothesized an increase in soil microbial biomass due to increased caterpillar frass inputs and potential changes in community structure following the event. Soils were sampled in August 2018, May 2019 and July 2019 from sites that had been subjected to defoliation during the outbreak and from sites where no defoliation had been recorded. We assessed soil microbial biomass and fungal to total microbial activity ratio on all sampling dates, and Community Level Physiological Profiles (CLPPs) for 2018 only using a substrate-induced respiration method. Contrary to our hypothesis, we observed a significant 50% decrease in microbial biomass (μg biomass-C g−1 soil hour−1) in defoliated stands, suggesting tree carbon normally allocated towards root exudates was reallocated towards foliage regeneration. We noted a differentiated carbon-based substrate usage following defoliation, but no change in the fungal to total microbial activity ratio. The observed changes in the two years following the defoliation event suggest that defoliation episodes above-ground could trigger changes in soil chemistry below-ground with effects on soil microbial communities that may, in turn, feedback to influence forest plant dynamics.
Synonymous Codon Usage Bias in the Chloroplast Genomes of 13 Oil-Tea Camellia Samples from South China
Authors: Chen Jing , Ma Wuqiang , Hu Xinwen , Zhou Kaibing
Published: April 2023

Synonymous codon usage (SCU) bias in oil-tea camellia cpDNAs was determined by examining 13 South Chinese oil-tea camellia samples and performing bioinformatics analysis using GenBank sequence information, revealing conserved bias among the samples. GC content at the third position (GC3) was the lowest, with a preference for A or T, suggesting weak SCU bias. The GC contents at the first two codon positions (GC1 and GC2) were extremely significantly correlated with one another but not with the expected number of codons (ENC). GC3 was not correlated with GC1 and GC2 but was extremely significantly correlated with ENC. Of the 30 high-frequency codons, 15, 14, 1 and 0 codons had U, A, G and C at the third position, respectively. The points for most genes were distributed above the neutrality plot diagonal. The points for 20 genes, accounting for 37.74% of all coding sequences (CDSs), were distributed on or near the ENC plot standard curve, and the ENC ratio ranged from −0.05–0.05. However, those of the other genes were under the standard curve, with higher ENC ratios. The points for most genes were distributed in the lower part of the PR2 plot, especially the bottom right corner. Twenty-eight highly expressed codons were screened and 11, 9, 7 and 1 codons had U, A, C and G as the third base, respectively. Twenty optimal codons were screened by comparing high-frequency codons and 11, 8, 0 and 1 codons had U, A, C and G as the third base, respectively. All samples were divided into six clades (r2 = 0.9190, d = 0.5395) according to a relative synonymous codon usage (RSCU)-based phylogenetic tree. Camellia gauchowensis, C. vietnamensis, an undetermined oil-tea camellia species from Hainan province, and C. osmantha belonged to the same clade; the genetic relationships between C. gauchowensis, C. vietnamensis and the undetermined species were the closest. In summary, SCU bias is influenced by selection, while the influence of mutation cannot be ignored. As the SCU bias differed between species, this feature can be used to identify plant species and infer their genetic relationships. For example, C. vietnamensis and C. gauchowensis can be merged into one species, and the undetermined species can be considered C. vietnamensis. The results described here provide a basis for studying cpDNA gene expression and the development of cpDNA genetic engineering.
The Importance of Initial Seedling Characteristics in Controlling Allocation to Growth and Reserves under Different Soil Moisture Conditions
Authors: Landhäusser Simon M. , Wiley Erin T. , Solarik Kevin A. , Kulbaba Shaun P. , Goeppel Alexander E.
Published: April 2023

After disturbance, forest regeneration and resiliency depend on the ability of seedlings to respond, survive, and grow under a variety of stress conditions, including drought. Despite recent efforts to improve our fundamental knowledge surrounding plant response mechanisms to stress and their application in seedling quality research, initial seedling characteristics are often ignored when exploring seedling responses to stress in field plantings or ecophysiological studies. Here, we explore how initial differences in size, biomass allocation, and non-structural carbohydrate (NSC) storage affect the subsequent partitioning of new biomass, growth potential, and drought response in seedlings of a deciduous broad-leaved (Populus tremuloides) and an evergreen coniferous species (Pinus banksiana). We exposed seedlings of both species to different growing conditions in their first growing season in order to manipulate the aforementioned seedling characteristics. In a second growing season, we exposed these different seedling types to a subsequent drought stress. While drought reduced both structural growth and NSC storage in all seedling types, the expected shift in allocation favoring roots was only observed in seedling types with initially low root:shoot or root:stem ratios. Overall, we also found that the traits associated with greater growth were quite different between pine and aspen. While larger seedlings led to greater growth in pine, it was the smallest seedling type in aspen with the largest root:stem ratio that produced the most new growth. In aspen, this smaller seedling type was the only one that did not undergo a shift in biomass relative to its initial allometry, suggesting that adjustments in biomass allocation made by other, larger seedling types must have come at the cost of lower growth. In contrast, adjustments in allocation did not appear to negatively impact pine, possibly because reduced root:shoot ratios of larger seedlings did not reduce NSC storage, as it did in aspen. Our results highlight (1) the complexity of how differences in biomass allocation and changes in seedling size may alter storage and the response of species to drought, and (2) the importance of accounting for initial seedling characteristics (both morphological and physiological) when predicting seedling growth and the impacts of environmental stressors.
Enhancement of Enzymatic Hydrolysis of Sugarcane Bagasse by the Combination of Delignification Pretreatment and Polysorbate 80
Authors: Zhang Hongdan , Dai Tao , Huang Shihang , Xie Jun
Published: April 2023

Delignification pretreatment with alkali under various conditions (25–160 °C for 1–12 h) or sodium chlorite at 75 °C for 4 h was applied to improve the enzymatic digestibility of sugarcane bagasse by removing hemicellulose and lignin. Compared with the elimination of hemicellulose, delignification contributed more in achieving a higher glucose yield. In addition, the characterization of untreated and pretreated sugarcane bagasse was conducted to determine the influence of hemicellulose and lignin degradation on subsequent enzymatic digestibility. Furthermore, Polysorbate 80 was added to reduce the enzyme loading, shorten the hydrolysis time, and enhance the efficiency of enzymatic hydrolysis, suggesting that the glucose yield of 92.2% was obtained with enzyme loading of 5 FPU/g substrate. However, the increased yield of glucose with Polysorbate 80 occurred with an increased lignin content and a reduction of enzyme loading, and the yield decreased sharply as the hydrolysis time was prolonged from 6 h to 24 h.
Optimal Production of Ganoderma formosanum Mycelium with Anti-Melanogenic Activity
Authors: Liu Yen-Wenn , Liu Chi-Mei , Chen Hung-Yueh , Khumsupan Darin , Hsu Hsien-Yi , Lin Hui-Wen , Hsieh Chang-Wei , Cheng Kuan-Chen
Published: April 2023

Ganoderma formosanum is a medicinal mushroom endemic to Taiwan. The extraction of G. formosanum mycelium using ethyl acetate showed a significant reduction of melanin activity due to the inhibition of tyrosinase. To optimize the production of G. formosanum mycelium with anti-melanogenic activity, different variables (carbon sources and concentrations, initial pH value, and temperature) were investigated. According to the results, the optimal conditions included the utilization of 50 g/L lactose as the carbon source at pH 7 and 25 °C for 9 days. Afterward, the G. formosanum ethanolic extracts-optimized (GFE-O) was used to study the anti-melanogenic activity in vitro and in vivo. In B16-F10 melanoma cells treated with GFE-O (0.1 mg/mL), the intracellular melanin content was reduced to 76% compared to the control group. By applying GFE-O (0.05 mg/mL) in vivo on zebrafish embryo, hypopigmentation was observed, and the melanin content was reduced to 62% compared to the control with no toxicological effects. The results showed that the optimal inoculation conditions can provide the basis for future large-scale production of G. formosanum mycelium to maximize the extraction of anti-melanogenic ingredients.
Shear Strengthening and Repairing of Reinforced Concrete Deep Beams Damaged by Heat Using NSM–CFRP Ropes
Authors: Al-khreisat Ahmad , Abdel-Jaber Mu’tasime , Ashteyat Ahmed
Published: April 2023

This study investigates experimentally the shear strengthening and repairing of reinforced concrete (RC) deep beams damaged by heat utilizing near-surface mounted carbon fiber reinforced polymers (NSM-CFRP) ropes. The main parameters adopted in this research are rope orientation (45°, 90°) and rope spacing (150 mm, 200 mm). For this purpose, ten RC deep beams were cast and tested until failure was reached. The test results showed that using NSM-CFRP ropes with various configurations significantly enhanced the shear capacity for repaired and strengthened deep beams. All the tested beams enhanced the ultimate load capacity for the strengthened beams ranging between 19% to 46%, while for the repaired beams, the values ranged between 40.8% to 64.6%. The CFRP ropes oriented at 45° recorded the highest enhancement result in shear capacity. Notably, all tested beams had a satisfactory rise in the enhancement ratio. Consequently, the economic aspect should have priority.
Ovule Transcriptome Analysis Discloses Deregulation of Genes and Pathways in Sexual and Apomictic Limonium Species (Plumbaginaceae)
Authors: Caperta Ana D. , Fernandes Isabel , Conceição Sofia I. R. , Marques Isabel , Róis Ana S. , Paulo Octávio S.
Published: April 2023

The genus Limonium Mill. (sea lavenders) includes species with sexual and apomixis reproductive strategies, although the genes involved in these processes are unknown. To explore the mechanisms beyond these reproduction modes, transcriptome profiling of sexual, male sterile, and facultative apomictic species was carried out using ovules from different developmental stages. In total, 15,166 unigenes were found to be differentially expressed with apomictic vs. sexual reproduction, of which 4275 were uniquely annotated using an Arabidopsis thaliana database, with different regulations according to each stage and/or species compared. Gene ontology (GO) enrichment analysis indicated that genes related to tubulin, actin, the ubiquitin degradation process, reactive oxygen species scavenging, hormone signaling such as the ethylene signaling pathway and gibberellic acid-dependent signal, and transcription factors were found among differentially expressed genes (DEGs) between apomictic and sexual plants. We found that 24% of uniquely annotated DEGs were likely to be implicated in flower development, male sterility, pollen formation, pollen-stigma interactions, and pollen tube formation. The present study identifies candidate genes that are highly associated with distinct reproductive modes and sheds light on the molecular mechanisms of apomixis expression in Limonium sp.
Transcriptome Profiling of Different Developmental Stages on Longissimus Dorsi to Identify Genes Underlying Intramuscular Fat Content in Wannanhua Pigs
Authors: Li Xiaojin , Yang Yanan , Li Lei , Ren Man , Zhou Mei , Li Shenghe
Published: April 2023

Intramuscular fat (IMF) is a key index to measure the tenderness and flavor of pork. Wannanhua pig, a famous indigenous pig breed in Anhui Province, is renowned for its high lipid deposition and high genetic divergence, making it an ideal model for investigating the lipid position trait mechanisms in pigs. However, the regulatory mechanisms of lipid deposition and development in pigs remain unclear. Furthermore, the temporal differences in gene regulation are based on muscle growth and IMF deposition. The purpose of this study was to study the expression changes of longissimus dorsi (LD) at different growth stages of WH pigs at the molecular level, to screen the candidate genes and signaling pathways related to IMF during development by transcriptome sequencing technology, and to explore the transcriptional regulation mechanism of IMF deposition-related genes at different development stages. In total, 616, 485, and 1487 genes were differentially expressed between LD60 and LD120, LD120 and LD240, and LD60 and LD240, respectively. Numerous differentially expressed genes (DEGs) associated with lipid metabolism and muscle development were identified, and most of them were involved in IMF deposition and were significantly up-regulated in LD120 and LD240 compared to LD60. STEM (Short Time-series Expression Miner) analysis indicated significant variations in the mRNA expression across distinct muscle development stages. The differential expression of 12 selected DEGs was confirmed by RT-qPCR. The results of this study contribute to our understanding of the molecular mechanism of IMF deposition and provide a new way to accelerate the genetic improvement of pork quality.
The Vindolanda Vessel: pXRF and Microphotography of an Enamel-Painted Roman Gladiator Glass
Authors: Campbell Louisa
Published: April 2023

Roman glass is well studied and known to have been produced from a mineral soda source and calcareous sand with variation between elements relating to naturally occurring minerals in the sands. While the common characteristics of colourants and opacifiers used in opaque and translucent glasses are well understood, the diverse elemental composition of colouring agents associated with the highly specialised, and largely unexplored, technique of enamel-painted glass has never been firmly established. There remains a significant gap in knowledge of pigments used for this technological innovation which is here addressed through the deployment of non-invasive portable X-Ray Flourescence (pXRF) analysis and microphotography on a unique Roman enamel-painted gladiator glass from Vindolanda fort. This vanguard research has successfully established, for the first time, a palette of pigments associated with this specialist technique. It is now possible to unravel previously unknown information on complex manufacturing processes and significantly expand the repertoire of the pigments bound up in enamelling recipes used to depict the striking iconographic scenes on the Vindolanda vessel and, potentially, other Roman enamelled glassware. The detection of Cinnabar, Egyptian blue, Orpiment and other pigments are ground-breaking discoveries that will have a transformative impact on early glassmaking studies and push the boundaries of scholarship into new directions of analytical approaches in heritage materials science to complement recent success in this field with Raman spectroscopy and other techniques. The methodology is unprecedented and has been validated through the high quality of the resulting data which permits the extrapolation of elemental compositions of enamelling materials from those associated with the base vessel. This unique approach provides remarkable insights that will revolutionise our understanding of enamelling technologies using the Vindolanda vessel as the investigative platform for forgotten practice.
Loss Assessment during Postharvest and Handling of Thai Garlic Used for Processing
Authors: Sunanta Piyachat , Kontogiorgos Vassilis , Leksawasdi Noppol , Phimolsiripol Yuthana , Wangtueai Sutee , Wongkaew Malaiporn , Sommano Sarana Rose
Published: April 2023

Garlic is one of the most economically important crops cultivated and consumed worldwide. The rising demand for garlic in the functional food market is driven by the growing interest in using processed products and supplements for benefits in health and wellbeing. Prior to processing, freshly harvested Thai garlic undergoes six distinct curing procedures; however, the losses and initial quality evaluation of the cured garlics have never been assessed. The research aims to evaluate losses and types of biomass during post-harvest processing using lab scale waste composition and mass–flow analyses, which align with the bio-circular green economic approach. Qualitative process flow diagrams (PFD) of each curing procedure were outlined, and the volume of post-harvest loss and types of biomasses were recorded. The study found that the overall losses during garlic curing were significantly higher than those associated with curing the bulb with root attached and the bulb alone. Moisture loss (>60%) was the greatest type of loss, followed by through biomass during initial and minimal processing. The aerial part accounted for >40% of total biomass loss, while root and skin were variable, depending on whether the initial process was conducted before or after curing. In terms of quality, the study found that the total phenolic and flavonoid content of garlic decreased after curing, and the level of total reducing sugar significantly decreased from the day of harvest. This result can be used as the criterion for handling Thai garlic after harvest. In addition, the biomass produced by postharvest processing can be utilised as a raw material for biorefinery extraction.
Bacterial Contamination of Antiseptics, Disinfectants, and Hand Hygiene Products Used in Healthcare Settings in Low- and Middle-Income Countries—A Systematic Review
Authors: Lompo Palpouguini , Agbobli Esenam , Heroes Anne-Sophie , Van den Poel Bea , Kühne Vera , Kpossou Cyprien M. Gutemberg , Zida Adama , Tinto Halidou , Affolabi Dissou , Jacobs Jan
Published: April 2023

We conducted a systematic review of healthcare-associated outbreaks and cross-sectional surveys related to the contamination of antiseptics, disinfectants, and hand hygiene products in healthcare settings in low- and middle-income countries (PROSPERO CRD42021266271). Risk of bias was assessed by selected items of the ORION and MICRO checklists. From 1977 onwards, 13 outbreaks and 25 cross-sectional surveys were found: 20 from Asia and 13 from Africa. Products most associated with outbreaks were water-based chlorhexidine, chlorhexidine-quaternary ammonium compound combinations (7/13), and liquid soap products (4/13). Enterobacterales (including multidrug-resistant Enterobacter cloacae, Klebsiella pneumoniae, and Serratia marcescens) and non-fermentative Gram-negative rods were found in 5 and 7 outbreaks and in 34.1% and 42.6% of 164 isolates, respectively, from cross-sectional surveys. Risk factors included preparation (place, utensils, or tap water high and incorrect dilutions), containers (reused, recycled, or inadequate reprocessing), and practices (topping-up or too long use). Potential biases were microbiological methods (neutralizers) and incomplete description of products’ identity, selection, and denominators. External validity was compromised by low representativeness for remote rural settings and low-income countries in sub-Saharan Africa. Outstanding issues were water quality, biofilm control, field-adapted containers and reprocessing, in-country production, healthcare providers’ practices, and the role of bar soap. A list of “best practices” to mitigate product contamination was compiled.
Assessment of Ecosystem Service Value in Response to LULC Changes Using Geospatial Techniques: A Case Study in the Merbil Wetland of the Brahmaputra Valley, Assam, India
Authors: Lahon Durlov , Sahariah Dhrubajyoti , Debnath Jatan , Nath Nityaranjan , Meraj Gowhar , Kumar Pankaj , Hashimoto Shizuka , Farooq Majid
Published: April 2023

The alteration of land use and land cover caused by human activities on a global scale has had a notable impact on ecosystem services at regional and global levels, which are crucial for the survival and welfare of human beings. Merbil, a small freshwater wetland located in the Brahmaputra basin in Assam, India, is not exempt from this phenomenon. In the present study, we have estimated and shown a spatio-temporal variation of ecosystem service values in response to land use and land cover alteration for the years 1990, 2000, 2010, and 2021, and predicted the same for 2030 and 2040. Supervised classification and the CA-Markov model were used in this study for land-use and land-cover classification and future projection, respectively. The result showed a significant increase in built-up areas, agricultural land, and aquatic plants and a decrease in open water and vegetation during 1990–2040. The study area experienced a substantial rise in ecosystem service values during the observed period (1990–2021) due to the rapid expansion of built-up areas and agricultural and aquatic land. Although the rise of built-up and agricultural land is economically profitable and has increased the study site’s overall ecosystem service values, decreasing the area under open water and vegetation cover may have led to an ecological imbalance in the study site. Hence, we suggest that protecting the natural ecosystem should be a priority in future land-use planning. The study will aid in developing natural resource sustainability management plans and provide useful guidelines for preserving the local ecological balance in small wetlands over the short to medium term.
Gender Differences in Cortisol and Cortisol Receptors in Depression: A Narrative Review
Authors: Teo Chuin Hau , Wong Ally Chai Hui , Sivakumaran Rooba Nair , Parhar Ishwar , Soga Tomoko
Published: April 2023

Stress is known to have a significant impact on mental health. While gender differences can be found in stress response and mental disorders, there are limited studies on the neuronal mechanisms of gender differences in mental health. Here, we discuss gender and cortisol in depression as presented by recent clinical studies, as well as gender differences in the role of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in stress-associated mental disorders. When examining clinical studies drawn from PubMed/MEDLINE (National Library of Medicine) and EMBASE, salivary cortisol generally showed no gender correlation. However, young males were reported to show heightened cortisol reactivity compared to females of similar age in depression. Pubertal hormones, age, early life stressors, and types of bio-samples for cortisol measurement affected the recorded cortisol levels. The role of GRs and MRs in the HPA axis could be different between males and females during depression, with increased HPA activity and upregulated MR expression in male mice, while the inverse happened in female mice. The functional heterogeneity and imbalance of GRs and MRs in the brain may explain gender differences in mental disorders. This knowledge and understanding will support the development of gender-specific diagnostic markers involving GRs and MRs in depression.
Glucocorticoid Receptor and β-Catenin Interact in Prostate Cancer Cells and Their Co-Inhibition Attenuates Tumorsphere Formation, Stemness, and Docetaxel Resistance
Authors: Martinez Shannalee R. , Elix Catherine C. , Ochoa Pedro T. , Sanchez-Hernandez Evelyn S. , Alkashgari Hossam R. , Ortiz-Hernandez Greisha L. , Zhang Lubo , Casiano Carlos A.
Published: April 2023

Therapy resistance hinders the efficacy of anti-androgen therapies and taxane-based chemotherapy for advanced prostate cancer (PCa). Glucocorticoid receptor (GR) signaling mediates resistance to androgen receptor signaling inhibitors (ARSI) and has also been recently implicated in PCa resistance to docetaxel (DTX), suggesting a role in therapy cross-resistance. Like GR, β-catenin is upregulated in metastatic and therapy-resistant tumors and is a crucial regulator of cancer stemness and ARSI resistance. β-catenin interacts with AR to promote PCa progression. Given the structural and functional similarities between AR and GR, we hypothesized that β-catenin also interacts with GR to influence PCa stemness and chemoresistance. As expected, we observed that treatment with the glucocorticoid dexamethasone promotednuclear accumulation of GR and active β-catenin in PCa cells. Co-immunoprecipitation studies showed that GR and β-catenin interact in DTX-resistant and DTX-sensitive PCa cells. Pharmacological co-inhibition of GR and β-catenin, using the GR modulator CORT-108297 and the selective β-catenin inhibitor MSAB, enhanced cytotoxicity in DTX-resistant PCa cells grown in adherent and spheroid cultures and decreased CD44+/CD24– cell populations in tumorspheres. These results indicate that GR and β-catenin influence cell survival, stemness, and tumorsphere formation in DTX-resistant cells. Their co-inhibition could be a promising therapeutic strategy to overcome PCa therapy cross-resistance.
Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26
Authors: He Sirong , He Peiting , Wu Haojing , Feng Yao , Situ Jiejin , Chen Yiling , Du Junxi , Qin Jin , Lv Pengcheng , Chen Kun
Published: April 2023

This study investigates the synthesis of a new compound, PYR26, and the multi-target mechanism of PYR26 inhibiting the proliferation of HepG2 human hepatocellular carcinoma cells. PYR26 significantly inhibits the growth of HepG2 cells (p < 0.0001) and this inhibition has a concentration effect. There was no significant change in ROS release from HepG2 cells after PYR26 treatment. The mRNA expressions of CDK4, c-Met and Bak genes in HepG2 cells were significantly inhibited (p < 0.05), while mRNA expression of pro-apoptotic factors such as caspase-3 and Cyt c was significantly increased (p < 0.01). The expression of PI3K, CDK4 and pERK proteins decreased. The expression level of caspase-3 protein was increased. PI3K is a kind of intracellular phosphatidylinositol kinase. PI3K signaling pathway is involved in signal transduction of a variety of growth factors, cytokines and extracellular matrix and plays an important role in preventing cell apoptosis, promoting cell survival and influencing cell glucose metabolism. CDK4 is a catalytic subunit of the protein kinase complex and is important for G1 phase progression of the cell cycle. PERK refers to phosphorylated activated ERK, which is translocated from cytoplasm to the nucleus after activation, and then participates in various biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell canceration. Compared with the model group and the positive control group, the tumor volume of the nude mice in the low-concentration PYR26 group, the medium-concentration group and the high-concentration group was smaller, and the organ volume was smaller than that in the model group and the positive control group. The tumor inhibition rates of low-concentration group PYR26, medium-concentration group and high-concentration group reached 50.46%, 80.66% and 74.59%, respectively. The results showed that PYR26 inhibited the proliferation of HepG2 cells and induced apoptosis of HepG2 cells by down-regulating c-Met, CDK4 and Bak, up-regulating the mRNA expression of caspase-3 and Cyt c genes, down-regulating PI3K, pERK and CDK4 proteins and up-regulating the protein level of caspase-3. In a certain range, with the increase in PYR26 concentration, the tumor growth was slower and the tumor volume was smaller. Preliminary results showed that PYR26 also had an inhibitory effect on the tumors of Hepa1-6 tumor-bearing mice. These results suggest that PYR26 has an inhibitory effect on the growth of liver cancer cells, therefore it has potential to be developed into a new anti-liver cancer drug.
Genetic Research Progress: Heat Tolerance in Rice
Authors: Liu Huaqing , Zeng Bohong , Zhao Jialiang , Yan Song , Wan Jianlin , Cao Zhibin
Published: April 2023

Heat stress (HS) caused by high-temperature weather seriously threatens international food security. Indeed, as an important food crop in the world, the yield and quality of rice are frequently affected by HS. Therefore, clarifying the molecular mechanism of heat tolerance and cultivating heat-tolerant rice varieties is urgent. Here, we summarized the identified quantitative trait loci (Quantitative Trait Loci, QTL) and cloned rice heat tolerance genes in recent years. We described the plasma membrane (PM) response mechanisms, protein homeostasis, reactive oxygen species (ROS) accumulation, and photosynthesis under HS in rice. We also explained some regulatory mechanisms related to heat tolerance genes. Taken together, we put forward ways to improve heat tolerance in rice, thereby providing new ideas and insights for future research.
Bioactive Constituents of Verbena officinalis Alleviate Inflammation and Enhance Killing Efficiency of Natural Killer Cells
Authors: Dai Xiangdong , Zhou Xiangda , Shao Rui , Zhao Renping , Yanamandra Archana K. , Xing Zhimei , Ding Mingyu , Wang Junhong , Liu Tao , Zheng Qi , Zhang Peng , Zhang Han , Wang Yi , Qu Bin , Wang Yu
Published: April 2023

Natural killer (NK) cells play key roles in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine for its anti-tumor and anti-inflammatory activities, but its effects on immune responses remain largely elusive. This study aimed to investigate the potential of V. officinalis extract (VO extract) to regulate inflammation and NK cell functions. We examined the effects of VO extract on lung injury in a mouse model of influenza virus infection. We also investigated the impact of five bioactive components of VO extract on NK killing functions using primary human NK cells. Our results showed that oral administration of VO extract reduced lung injury, promoted the maturation and activation of NK cells in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF-α and IL-1β) in the serum. Among five bioactive components of VO extract, Verbenalin significantly enhanced NK killing efficiency in vitro, as determined by real-time killing assays based on plate-reader or high-content live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated the killing process by reducing the contact time of NK cells with their target cells without affecting NK cell proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings suggest that VO extract has a satisfactory anti-inflammatory effect against viral infection in vivo, and regulates the activation, maturation, and killing functions of NK cells. Verbenalin from V. officinalis enhances NK killing efficiency, suggesting its potential as a promising therapeutic to fight viral infection.
ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives
Authors: Damiani Daniela , Tiribelli Mario
Published: April 2023

Despite recent advances, prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to poor response to therapy or relapse. Among causes of resistance, over-expression of multidrug resistance (MDR) proteins represents a pivotal mechanism. ABCG2 is an efflux transporter responsible for inducing MDR in leukemic cells; through its ability to extrude many antineoplastic drugs, it leads to AML resistance and/or relapse, even if conflicting data have been reported to date. Moreover, ABCG2 may be co-expressed with other MDR-related proteins and is finely regulated by epigenetic mechanisms. Here, we review the main issues regarding ABCG2 activity and regulation in the AML clinical scenario, focusing on its expression and the role of polymorphisms, as well as on the potential ways to inhibit its function to counteract drug resistance to, eventually, improve outcomes in AML patients.
Cytotoxic Steroidal Saponins Containing a Rare Fructosyl from the Rhizomes of Paris polyphylla var. latifolia
Authors: Li Tian-Yi , Du Yang , Wang Min-Chang , Liu Ke , Liu Yang , Cao Yu , Wang Yuan-Yuan , Chen Wen-Wen , Qian Xiao-Ying , Qiu Peng-Cheng , Tang Hai-Feng , Lu Yun-Yang
Published: April 2023

A phytochemical investigation of the steroidal saponins from the rhizomes of Paris polyohylla var. latifolia led to the discovery and characterization of three new spirostanol saponins, papolatiosides A–C (1–3), and nine known compounds (4–12). Their structures were established via extensive spectroscopic data analysis and chemical methods. Interestingly, compounds 1 and 2 possessed a fructosyl in their oligosaccharide moiety, which is rare in natural product and was firstly reported in family Melanthiaceae. The cytotoxicity of these saponins against several human cancer cell lines was evaluated by a CCK-8 experiment. As a result, compound 1 exhibited a significant cytotoxic effect on LN229, U251, Capan-2, HeLa, and HepG2 cancer cells with IC50 values of 4.18 ± 0.31, 3.85 ± 0.44, 3.26 ± 0.34, 3.30 ± 0.38 and 4.32 ± 0.51 μM, respectively. In addition, the result of flow cytometry analysis indicated that compound 1 could induce apoptosis of glioma cells LN229. The underlying mechanism was explored by network pharmacology and western bolt experiments, which indicated that compound 1 could induce glioma cells LN229 apoptosis by regulating the EGFR/PI3K/Akt/mTOR pathway.
SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling
Authors: Wang Weida , Wang Mingjin , Du Tingting , Hou Zhenyan , You Shen , Zhang Sen , Ji Ming , Xue Nina , Chen Xiaoguang
Published: April 2023

The metabolic enzymes involved in one-carbon metabolism are closely associated with tumor progression and could be potential targets for cancer therapy. Recent studies showed that serine hydroxymethyltransferase 2 (SHMT2), a crucial enzyme in the one-carbon metabolic pathway, plays a key role in tumor proliferation and development. However, the precise role and function of SHMT2 in gastric cancer (GC) remain poorly understood. In this study, we presented evidence that SHMT2 was necessary for hypoxia-inducible factor-1α (HIF1α) stability and contributed to GC cells’ hypoxic adaptation. The analysis of datasets retrieved from The Cancer Genome Atlas and the experimentation with human cell lines revealed a marked increase in SHMT2 expression in GC. The SHMT2 knockdown in MGC803, SGC7901, and HGC27 cell lines inhibited cell proliferation, colony formation, invasion, and migration. Notably, SHMT2 depletion disrupted redox homeostasis and caused glycolytic function loss in GC cells under hypoxic circumstances. Mechanistically, we discovered SHMT2 modulated HIF1α stability, which acted as a master regulator of hypoxia-inducible genes under hypoxic conditions. This, in turn, regulated the downstream VEGF and STAT3 pathways. The in vivo xenograft experiments showed that SHMT2 knockdown markedly reduced GC growth. Our results elucidate the novel function of SHMT2 in stabilizing HIF1α under hypoxic conditions, thus providing a potential therapeutic strategy for GC treatment.
Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet
Authors: Weber Sarah L. , Hustedt Karin , Schnepel Nadine , Visscher Christian , Muscher-Banse Alexandra S.
Published: April 2023

Mammals respond to amino acid (AA) deficiency by initiating an AA response pathway (AAR) that involves the activation of general control nonderepressible 2 (GCN2), phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and activation of transcription factor 4 (ATF4). In this study, the effects of protein (N) and/or phosphorus (P) restriction on the GCN2/eIF2α/ATF4 pathway in the liver and the induction of fibroblast growth factor 21 (FGF21) in young goats were investigated. An N-reduced diet resulted in a decrease in circulating essential AA (EAA) and an increase in non-essential AA (NEAA), as well as an increase in hepatic mRNA expression of GCN2 and ATF4 and protein expression of GCN2. Dietary N restriction robustly increased both hepatic FGF21 mRNA expression and circulating FGF21 levels. Accordingly, numerous significant correlations demonstrated the effects of the AA profile on the AAR pathway and confirmed an association. Furthermore, activation of the AAR pathway depended on the sufficient availability of P. When dietary P was restricted, the GCN2/eIF2α/ATF4 pathway was not initiated, and no increase in FGF21 was observed. These results illustrate how the AAR pathway responds to N- and/or P-reduced diets in ruminants, thus demonstrating the complexity of dietary component changes.
Influence of Fasting until Noon (Extended Postabsorptive State) on Clock Gene mRNA Expression and Regulation of Body Weight and Glucose Metabolism
Authors: Jakubowicz Daniela , Rosenblum Rachel Chava , Wainstein Julio , Twito Orit
Published: April 2023

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state”, has the potential to cause a deleterious effect on clock gene expression and to disrupt regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, and appetite, and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases and the consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantages of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.
A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement
Authors: Schneider Holm , Schweikl Christine , Faschingbauer Florian , Hadj-Rabia Smail , Schneider Pascal
Published: April 2023

X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by a genetic deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of ectodermal derivatives such as hair, sweat glands, and teeth. The absence of sweat glands and perspiration can evoke life-threatening hyperthermia. As molecular genetic findings are not always conclusive, the concentrations of circulating EDA1 may help to distinguish between total and partial EDA1 deficiencies. We previously treated nine male patients with obvious signs of XLHED with a recombinant EDA1 replacement protein, Fc-EDA, either shortly after birth (n = 3) or by prenatal administration in gestational week 26 and beyond (n = 6). Here, we present the long-term follow-up for up to six years. In patients who had received Fc-EDA after birth, neither sweat glands nor sweating ability were detected at the age of 12–60 months. In contrast, prenatal EDA1 replacement resulted in ample sweat gland development and pilocarpine-inducible sweating in all treated subjects, who also attained more permanent teeth than their untreated affected relatives. Normal perspiration has persisted for six years in the two oldest boys treated repeatedly with Fc-EDA in utero. When they had a sauna, adequate thermoregulation was evidenced. Lower sweat production after single prenatal dosing may indicate a dose–response relationship. The absence of circulating EDA1 in five prenatally treated subjects proved that these children would have been unable to perspire if they had been left untreated. The sixth infant was shown to produce an EDA1 molecule that, albeit interacting with its cognate receptor, cannot activate EDA1 signaling. In conclusion, a causal treatment of XLHED before birth is feasible.
Triaging HPV-Positive Cervical Samples with p16 and Ki-67 Dual Stained Cytology within an Organized Screening Program—A Prospective Observational Study from Western Norway
Authors: Øvestad Irene Tveiterås , Dalen Ingvild , Andersland Marie S. , Vintermyr Olav K. , Moltu Pia , Berland Jannicke M. , Janssen Emilius A. M. , Haugland Hans Kristian
Published: April 2023

The implementation of high-risk human papillomavirus testing (hrHPV testing) as a screening method in substitute for cytology has evoked the need for more sensitive and less objective tests for the triage of HPV-positive women. In a cohort of 1763 HPV-positive women, the potential of immunocytochemical p16 and Ki-67 dual staining as compared to cytology, alone or in combination with HPV partial genotyping, was tested for triage of women attending a cervical cancer screening program. Performance was measured using sensitivity, specificity, and positive and negative predictive values. Comparisons were assessed using logistic regression models and the McNemar test. Dual staining was evaluated in a prospectively collected study cohort of 1763 HPV-screened women. For triage of CIN2+ and CIN3+, NPV and sensitivity, 91.8% and 94.2% versus 87.9% and 89.7%, respectively, were significantly higher using dual staining together with HPV 16/18 positive, as compared to cytology (p < 0.001). The specificities, however, were lower for dual staining as compared to cytology. Conclusions: Dual staining is safer for decision-making regarding HPV-positive women’s need for follow-up with colposcopy and biopsy, as compared to cytology.
Secreted Amyloid Precursor Protein Alpha (sAPPα) Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes
Authors: Peppercorn Katie , Kleffmann Torsten , Hughes Stephanie M. , Tate Warren P.
Published: April 2023

Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer’s disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation.
Magnoflorine from Berberis vulgaris Roots—Impact on Hippocampal Neurons in Mice after Short-Term Exposure
Authors: Szalak Radosław , Matysek Małgorzata , Koval Maryna , Dziedzic Marcin , Kowalczuk-Vasilev Edyta , Kruk-Slomka Marta , Koch Wojciech , Arciszewski Marcin B. , Kukula-Koch Wirginia
Published: April 2023

In search of novel potential drug candidates that could be used as treatments or prophylactics for memory impairment, an aporphine alkaloid magnoflorine (MAG) isolated from the root of Berberis vulgaris was proven to exhibit beneficial anti-amnestic properties. Its effects on immunoreactivity to parvalbumin in the mouse hippocampus were assessed together with a study on its safety and concentration in the brain and plasma. For this purpose, four experimental groups were created: the MAG10 group—treated with 10 mg MAG/kg b.w. i.p., the MAG20 group—treated with 20 mg MAG/kg b.w. i.p., the MAG50 group—treated with 50 mg MAG/kg b.w. i.p., and a control group—injected with saline i.p. at a volume corresponding to their weight. Our results indicated that the hippocampal fields CA1–CA3 were characterized by an elevated number of parvalbumin-immunoreactive neurons (PV-IR) and nerve fibers in mice at the doses of 10 and 20 mg/kg b.w. (i.p.). No significant changes to the levels of IL-1β, IL-6 or TNF-α were observed for the above two doses; however, the administration of 50 mg/kg b.w. i.p. caused a statistically significant elevation of IL-6, IL-1beta plasma levels and an insignificant raise in the TNF-alpha value. The HPLC–MS analysis showed that the alkaloid’s content in the brain structures in the group treated with 50 mg/kg b.w. did not increase proportionally with the administered dose. The obtained results show that MAG is able to influence the immunoreactivity to PV-IR in hippocampal neurons and might act as a neuroprotective compound.