bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Thylakoid Lipids in Protochlorophyllide Oxidoreductase Activation: Allosteric Mechanism Elucidated by a Computational Study
Authors: Liu Ruiyuan , Wang Leng , Meng Yue , Li Fang , Nie Haiyu , Lu Huizhe
Published: December 2022

Light-dependent protochlorophyllide oxidoreductase (LPOR) is a chlorophyll synthetase that catalyzes the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide) with indispensable roles in regulating photosynthesis processes. A recent study confirmed that thylakoid lipids (TL) were able to allosterically enhance modulator-induced LPOR activation. However, the allosteric modulation mechanism of LPOR by these compounds remains unclear. Herein, we integrated multiple computational approaches to explore the potential cavities in the Arabidopsis thaliana LPOR and an allosteric site around the helix-G region where high affinity for phosphatidyl glycerol (PG) was identified. Adopting accelerated molecular dynamics simulation for different LPOR states, we rigorously analyzed binary LPOR/PG and ternary LPOR/NADPH/PG complexes in terms of their dynamics, energetics, and attainable allosteric regulation. Our findings clarify the experimental observation of increased NADPH binding affinity for LPOR with PGs. Moreover, the simulations indicated that allosteric regulators targeting LPOR favor a mechanism involving lid opening upon binding to an allosteric hinge pocket mechanism. This understanding paves the way for designing novel LPOR activators and expanding the applications of LPOR.
Polθ Inhibition: An Anticancer Therapy for HR-Deficient Tumours
Authors: Barszczewska-Pietraszek Gabriela , Drzewiecka Małgorzata , Czarny Piotr , Skorski Tomasz , Śliwiński Tomasz
Published: December 2022

DNA polymerase theta (Polθ)-mediated end joining (TMEJ) is, along with homologous recombination (HR) and non-homologous end-joining (NHEJ), one of the most important mechanisms repairing potentially lethal DNA double-strand breaks (DSBs). Polθ is becoming a new target in cancer research because it demonstrates numerous synthetically lethal interactions with other DNA repair mechanisms, e.g., those involving PARP1, BRCA1/2, DNA-PK, ATR. Inhibition of Polθ could be achieved with different methods, such as RNA interference (RNAi), CRISPR/Cas9 technology, or using small molecule inhibitors. In the context of this topic, RNAi and CRISPR/Cas9 are still more often applied in the research itself rather than clinical usage, different than small molecule inhibitors. Several Polθ inhibitors have been already generated, and two of them, novobiocin (NVB) and ART812 derivative, are being tested in clinical trials against HR-deficient tumors. In this review, we describe the significance of Polθ and the Polθ-mediated TMEJ pathway. In addition, we summarize the current state of knowledge about Polθ inhibitors and emphasize the promising role of Polθ as a therapeutic target.
Salicylate Sodium Suppresses Monocyte Chemoattractant Protein-1 Production by Directly Inhibiting Phosphodiesterase 3B in TNF-α-Stimulated Adipocytes
Authors: Zhang Xiaoyu , Gao Yuan , Liu Zhuangzhuang , Li Wenjing , Kang Yuan , Li Ximeng , Xu Zhenlu , Peng Cheng , Qi Yun
Published: December 2022

As a worldwide health issue, obesity is associated with the infiltration of monocytes/macrophages into the adipose tissue causing unresolved inflammation. Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on obesity-related monocytes/macrophages infiltration. Clinically, aspirin and salsalate are beneficial for the treatment of metabolic diseases in which adipose tissue inflammation plays an essential role. Herein, we investigated the effect and precise mechanism of their active metabolite salicylate on TNF-α-elevated MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could lower the level of MCP-1 in TNF-α-stimulated adipocytes, which resulted from a previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than its known targets IKKβ and AMPK. The SAS directly bound to the PDE3B to inactivate it, thus elevating the intracellular cAMP level and activating PKA. Subsequently, the expression of MKP-1 was increased, which led to the decrease in p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of cAMP/PKA compromised the suppressive effect of SAS on MCP-1. In addition to PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings identify a previously unrecognized pathway through which SAS is capable of attenuating the inflammation of adipocytes.
Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction
Authors: Lim Xiong Chang , Huang Chenyuan , Yatim Siti Maryam J. M. , Chong Suet Yen , Tan Sock Hwee , Yang Xiaoxun , Heldt Caryn L. , Pedersen Jodi , Talanker Michael , Modh Harshvardhan , Wacker Matthias G. , Pastorin Giorgia , Chan Siew Pang , Richards A. Mark , Charles Chris J. , Chan Mark Y. , Wang Jiong-Wei
Published: December 2022

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.
Antibacterial and Antibiofilm Properties of Self-Assembled Dipeptide Nanotubes
Authors: Soares Iris , Rodrigues Inês , da Costa Paulo Martins , Gales Luís
Published: December 2022

Over recent decades, multidrug-resistant pathogens have become a global concern, with WHO even considering it one of the biggest threats to global health, food security, and development today, which led to the search for alternative antibacterial agents. A special class is formed by peptides composed by the diphenylalanine motif whose antibacterial properties result from their supramolecular arrangement into nanotubes. However, several other dipeptides that also form nanotubes have been largely overlooked. Here, we present the antibacterial activity of four dipeptide nanotubes. The results point to diverse mechanisms through which dipeptide nanotubes exert their effect against bacteria. Antibacterial activity was similar for dipeptide nanotubes sufficiently wide to allow water flux while dipeptides displaying smaller channels were inactive. This suggests that two of the tested dipeptides, L-Phe-L-Phe (FF, diphenylalanine) and L-Leu-L-Ser (LS), are pore forming structures able to induce membrane permeation and affect cellular hydration and integrity. Of these two dipeptides, only FF demonstrated potential to inhibit biofilm formation. The amyloid-like nature and hydrophobicity of diphenylalanine assemblies are probably responsible for their adhesion to cell surfaces preventing biofilm formation and bacteria attachment.
Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers
Authors: Kim Eunbin , Ham Seoyoon , Jung Bok Ki , Park Jin-Woo , Kim Jihee , Lee Ju Hee
Published: December 2022

One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I/R pressure load. In this model, topically applied baicalin (100 mg/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1β), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-β, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.
Recent Advances in Synthesis, Characterization and Applications of Innovative Materials in Removal of Water Contaminants
Authors: Dippong Thomas
Published: December 2022

Water is a scarce resource with a close and intricate nexus with energy [...]
Nanomaterials-Functionalized Hydrogels for the Treatment of Cutaneous Wounds
Authors: Liu Yangkun , Su Gongmeiyue , Zhang Ruoyao , Dai Rongji , Li Zhao
Published: December 2022

Hydrogels have been utilized extensively in the field of cutaneous wound treatment. The introduction of nanomaterials (NMs), which are a big category of materials with diverse functionalities, can endow the hydrogels with additional and multiple functions to meet the demand for a comprehensive performance in wound dressings. Therefore, NMs-functionalized hydrogels (NMFHs) as wound dressings have drawn intensive attention recently. Herein, an overview of reports about NMFHs for the treatment of cutaneous wounds in the past five years is provided. Firstly, fabrication strategies, which are mainly divided into physical embedding and chemical synthesis of the NMFHs, are summarized and illustrated. Then, functions of the NMFHs brought by the NMs are reviewed, including hemostasis, antimicrobial activity, conductivity, regulation of reactive oxygen species (ROS) level, and stimulus responsiveness (pH responsiveness, photo-responsiveness, and magnetic responsiveness). Finally, current challenges and future perspectives in this field are discussed with the hope of inspiring additional ideas.
GSK3β Inhibition by Phosphorylation at Ser389 Controls Neuroinflammation
Authors: Calvo Belen , Fernandez Miriam , Rincon Mercedes , Tranque Pedro
Published: December 2022

The inhibition of Glycogen Synthase Kinase 3 β (GSK3β) by Ser9 phosphorylation affects many physiological processes, including the immune response. However, the consequences of GSK3β inhibition by alternative Ser389 phosphorylation remain poorly characterized. Here we have examined neuroinflammation in GSK3β Ser389 knock-in (KI) mice, in which the phosphorylation of Ser389 GSK3β is impaired. The number of activated microglia/infiltrated macrophages, astrocytes, and infiltrated neutrophils was significantly higher in these animals compared to C57BL/6J wild-type (WT) counterparts, which suggests that the failure to inactivate GSK3β by Ser389 phosphorylation results in sustained low-grade neuroinflammation. Moreover, glial cell activation and brain infiltration of immune cells in response to lipopolysaccharide (LPS) failed in GSK3β Ser389 KI mice. Such effects were brain-specific, as peripheral immunity was not similarly affected. Additionally, phosphorylation of the IkB kinase complex (IKK) in response to LPS failed in GSK3β Ser389 KI mice, while STAT3 phosphorylation was fully conserved, suggesting that the NF-κB signaling pathway is specifically affected by this GSK3β regulatory pathway. Overall, our findings indicate that GSK3β inactivation by Ser389 phosphorylation controls the brain inflammatory response, raising the need to evaluate its role in the progression of neuroinflammatory pathologies.
Role of Adenylyl Cyclase Type 7 in Functions of BV-2 Microglia
Authors: Hu Yawen , Hill Rebecca A. , Yoshimura Masami
Published: December 2022

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was inhibited in the presence of PGE1; AC7 KO BV-2 cells showed lower and PGE1-insensitive phagocytic activity. Innate immune activities of the parental BV-2 cells, including bacterial killing, nitric oxide synthesis, and expression of arginase 1 and interleukin 10 were activated as expected with small effects of ethanol. However, the innate immune activities of AC7 KO cells were either drastically diminished or not detected. The data presented suggest that AC7 has an important role in the innate immune functions of microglial cells. AC7’s involvement in ethanol’s effects on immune functions remains unclear. Further studies are needed.
The Active Site of the Enzyme 10-Formyl-THFDH in the Honey Bee Apis mellifera—A Key Player in Formic Acid Detoxification
Authors: Mating Moritz , Zou Ye , Sharbati Soroush , Einspanier Ralf
Published: December 2022

Honey bees are important managed pollinators that fulfill important ecological and economic functions. In recent decades, the obligate ectoparasite Varroa destructor severely affected the survival of honey bees, as it weakened them by different means. A common treatment against V. destructor is formic acid fumigation, which has been used for decades by beekeepers across the world. This treatment is known to be effective, but many beekeepers report adverse effects of formic acid on bees, which include damage to the brood, worker bee mortality, and queen loss. Little is known about the molecular mechanisms of formic acid detoxification in honey bees. Recently, we reported upregulation of the bee enzyme, 10-formyl-THFDH, under formic acid fumigation. Here, the active site of this enzyme is characterized by an interdisciplinary approach combining homology modeling and protein mutagenesis. In addition, the limitations of the 3D protein structure prediction program AlphaFold2 are shown in regard to docking studies. This study provides a more thorough understanding of the molecular detoxification mechanisms of formic acid in Apis mellifera.
Dextran Sulfate Nanocarriers: Design, Strategies and Biomedical Applications
Authors: Ramasundaram Subramaniyan , Saravanakumar Gurusamy , Sobha Sivasangu , Oh Tae Hwan
Published: December 2022

Dextran sulfate (DXS) is a hydrophilic, non-toxic, biodegradable, biocompatible and safe biopolymer. These biomedically relevant characteristics make DXS a promising building block in the development of nanocarrier systems for several biomedical applications, including imaging and drug delivery. DXS polyanion can bind with metal oxide nanomaterials, biological receptors and therapeutic drug molecules. By taking advantage of these intriguing properties, DXS is used to functionalize or construct nanocarriers for specific applications. In particular, the diagnostic or therapeutic active agent-loaded DXS nanoparticles are prepared by simple coating, formation of polyelectrolyte complexes with other positively charged polymers or through self-assembly of amphiphilic DXS derivatives. These nanoparticles show a potential to localize the active agents at the pathological site and minimize undesired side effects. As DXS can recognize and be taken up by macrophage surface receptors, it is also used as a targeting ligand for drug delivery. Besides as a nanocarrier scaffold material, DXS has intrinsic therapeutic potential. DXS binds to thrombin, acts as an anticoagulant and exhibits an inhibitory effect against coagulation, retrovirus, scrapie virus and human immunodeficiency virus (HIV). Herein, biomedical applications involving the use of DXS as nanocarriers for drugs, biomolecules, and imaging agents have been reviewed. A special focus has been made on strategies used for loading and delivering of drugs and biomolecules meant for treating several diseases, including cancer, inflammatory diseases and ocular disease.
The Flavonoid Biosynthesis and Regulation in Brassica napus: A Review
Authors: Chen Yuan-Yuan , Lu Hai-Qin , Jiang Kai-Xuan , Wang Yi-Ran , Wang You-Ping , Jiang Jin-Jin
Published: December 2022

Brassica napus is an important crop for edible oil, vegetables, biofuel, and animal food. It is also an ornamental crop for its various petal colors. Flavonoids are a group of secondary metabolites with antioxidant activities and medicinal values, and are important to plant pigmentation, disease resistance, and abiotic stress responses. The yellow seed coat, purple leaf and inflorescence, and colorful petals of B. napus have been bred for improved nutritional value, tourism and city ornamentation. The putative loci and genes regulating flavonoid biosynthesis in B. napus have been identified using germplasms with various seed, petal, leaf, and stem colors, or different flavonoid contents under stress conditions. This review introduces the advances of flavonoid profiling, biosynthesis, and regulation during development and stress responses of B. napus, and hopes to help with the breeding of B. napus with better quality, ornamental value, and stress resistances.
Effect of Gene Silencing of Translation Initiation Factors eIF(iso)4G and eIF(iso)4E on Sour Cherry Rootstock Resistance to Sharka Disease
Authors: Mourenets Lilia , Pushin Alexander , Timerbaev Vadim , Khmelnitskaya Tatyana , Gribkov Eduard , Andreev Nikita , Dolgov Sergey
Published: December 2022

Sharka disease, caused by the Plum pox virus (PPV), is one of the most harmful, quarantine viral diseases that affect stone fruit crops. The absence of natural resistance to the virus in stone fruits has become a decisive factor for the use of genetic transformation methods to obtain stable forms. The eIF(iso)4G and eIF(iso)4E genes encode translation initiation factors used in the PPV life cycle. In the presented study, the effect of silencing these genes using the RNA interference method on the resistance of sour cherry rootstock 146-2 plants (Prunus pumila L. x Prunus tomentosa Thunb) to the sharka disease was studied. Two vectors have been created for the genetic transformation of plants, with self-complementary sequences of the eIF(iso)4G and eIF(iso)4E gene fragments. The hairpin expression cassette contains a strong promoter of the peach ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) gene, as well as an intron and terminator of the same gene. We used the pMF1 vector containing recombinase R and a codA-nptII gene which makes it possible to obtain intragenic marker-free plants. A successful genetic transformation was carried out by the AGL0 strain of A. tumefaciens. Whole leaves of shoots cultivated in vitro were used as a source of explants. Eight independent transgenic lines of rootstock 146-2 were obtained in experiments (sixlines with a hairpin to the eIF(iso)4G gene and two lines with a hairpin to the eIF(iso)4E gene). Their status was confirmed by the PCR and Southern blotting. The obtained plants were acclimatized in a greenhouse. The silencing of the eIF(iso)4G and eIF(iso)4E genes in transgenic plants was confirmed by the quantitative PCR. The presence of specific small interfering (si) RNAs was confirmed by the method of Northern blotting. Plants of all transgenic rootstock lines were infected with PPV by the method of grafting with infected buds. Resistance to the PPV infection of the obtained transgenic plants was carried out by using an enzyme immunoassay. The ELISA results showed that silencing the eIF(iso)4G gene did not lead to increased resistance while silencing the eIF(iso)4E factor gene led to increased resistance to the PPV, and the one line’s plants showed no signs of infection for two years after infecting. The work demonstrates a (promising) approach in which the creation of stone cultures resistant to the plum pox virus can be achieved by suppressing the genes of translation initiation factors in clonal rootstocks.
The Diagnostic Performance of Ultrasonography in the Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis
Authors: Issa Peter P. , Albuck Aaron L. , Hossam Eslam , Hussein Mohammad , Aboueisha Mohamed , Attia Abdallah S. , Omar Mahmoud , Abdelrahman Seif , Naser Gehad , Clark Robert D. E. , Toraih Eman , Kandil Emad
Published: December 2022

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74–78%). The specificity of ETE detection was 51% (95%CI = 49–54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54–11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered.
IL-33 and IL-37: A Possible Axis in Skin and Allergic Diseases
Authors: Borgia Francesco , Custurone Paolo , Li Pomi Federica , Vaccaro Mario , Alessandrello Clara , Gangemi Sebastiano
Published: December 2022

Interleukin (IL)-37 and IL-33 are among the latest cytokines identified, playing a role in several inflammatory conditions, spanning from systemic conditions to tumors to localized diseases. As newly discovered interleukins, their role is still scarcely understood, but their potential role as therapeutic targets or disease activity markers suggests the need to reorganize the current data for a better interpretation. The aim of this review is to collect and organize data produced by several studies to create a complete picture. The research was conducted on the PubMed database, and the resulting articles were sorted by title, abstract, English language, and content. Several studies have been assessed, mostly related to atopic dermatitis and immunologic pathways. Collective data demonstrates a pro-inflammatory role of IL-33 and an anti-inflammatory one for IL-37, possibly related to each other in an IL-33/IL-37 axis. Although further studies are needed to assess the safety and plausibility of targeting these two interleukins for patients affected by skin conditions, the early results indicate that both IL-33 and IL-37 represent markers of disease activity.
Synergistic Antioxidant Effect of Prebiotic Ginseng Berries Extract and Probiotic Strains on Healthy and Tumoral Colorectal Cell Lines
Authors: De Giani Alessandra , Oldani Monica , Forcella Matilde , Lasagni Marina , Fusi Paola , Di Gennaro Patrizia
Published: December 2022

Oxidative stress caused by reactive oxygen species (ROS, O2•−, HO•, and H2O2) affects the aging process and the development of several diseases. A new frontier on its prevention includes functional foods with both specific probiotics and natural extracts as antioxidants. In this work, Panax ginseng C.A. Meyer berries extract was characterized for the presence of beneficial molecules (54.3% pectin-based polysaccharides and 12% ginsenosides), able to specifically support probiotics growth (OD600nm > 5) with a prebiotic index of 0.49. The administration of the extract to a probiotic consortium induced the production of short-chain fatty acids (lactic, butyric, and propionic acids) and other secondary metabolites derived from the biotransformation of Ginseng components. Healthy and tumoral colorectal cell lines (CCD841 and HT-29) were then challenged with these metabolites at concentrations of 0.1, 0.5, and 1 mg/mL. The cell viability of HT-29 decreased in a dose-dependent manner after the exposition to the metabolites, while CCD841 vitality was not affected. Regarding ROS production, the metabolites protected CCD841 cells, while ROS levels were increased in HT-29 cells, potentially correlating with the less functionality of glutathione S-transferase, catalase, and total superoxide dismutase enzymes, and a significant increase in oxidized glutathione.
Construction of a Hierarchical Gene Regulatory Network to Reveal the Drought Tolerance Mechanism of Shanxin Poplar
Authors: Wang Pengyu , Wang Jingxin , Sun Xiaomeng , Yang Xue , Sun Shilin , Han Xue , Li Dandan , Wang Yucheng
Published: December 2022

Drought stress is a common adverse environment that plants encounter, and many drought-tolerant genes have been characterized. The gene regulatory network (GRN) is important in revealing the drought tolerance mechanism. Here, to investigate the regulatory mechanism of Shanxin poplar (Populus davidiana × P. bolleana) responding to drought stress, a three-layered GRN was built, and the regulatory relationship between genes in the GRN were predicted from expression correlation using a partial correlation coefficient-based algorithm. The GRN contains 1869 regulatory relationships, and includes 11 and 19 transcription factors (TFs) in the first and second layers, respectively, and 158 structural genes in the bottom layers involved in eight enriched biological processes. ChIP-PCR and qRT-PCR based on transient transformation were performed to validate the reliability of the GRN. About 88.0% of predicted interactions between the first and second layers, and 82.0% of predicted interactions between the second and third layers were correct, suggesting that the GRN is reliable. Six TFs were randomly selected from the top layer for characterizing their function in drought, and all of these TFs can confer drought tolerance. The important biological processes related to drought tolerance were identified, including “response to jasmonic acid”, “response to oxidative stress”, and “response to osmotic stress”. In this GRN, PdbERF3 is predicted to play an important role in drought tolerance. Our data revealed the key regulators, TF-DNA interactions, and the main biological processes involved in adaption of drought stress in Shanxin poplar.
Effects of Different Freezing Methods on Physicochemical Properties of Sweet Corn during Storage
Authors: Wang Mingying , Jin Siyuan , Ding Zhaoyang , Xie Jing
Published: December 2022

Fresh sweet corn has a series of physiological and biochemical reactions after picking due to the high moisture content, leading to damaged nutritional value. Rapid freezing of sweet corn after harvest can minimize tissue damage and quality deterioration. In this study, freshly harvested sweet corn was frozen by ultrasound-assisted freezing, brine freezing, strong wind freezing, and refrigerator freezing. The effects of different freezing methods on hardness, water loss, color, epidermal structure, soluble solids content, soluble sugars content, peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activities of frozen sweet corn during storage were investigated. The results showed that brine freezing and strong wind freezing could effectively reduce the quality loss of sweet corn, keep the color, soluble sugars, and soluble solids content of the sweet corn, delay the decrease in antioxidant enzyme activity, and maintain the quality of sweet corn during long term storage.
Differential Plasma Metabolites between High- and Low-Grade Meningioma Cases
Authors: Kurokawa Gabriel A. , Hamamoto Filho Pedro T. , Delafiori Jeany , Galvani Aline F. , de Oliveira Arthur N. , Dias-Audibert Flávia L. , Catharino Rodrigo R. , Pardini Maria Inês M. C. , Zanini Marco A. , Lima Estela de O. , Ferrasi Adriana C.
Published: December 2022

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.
The Role of Cancer Stem Cells and Their Extracellular Vesicles in the Modulation of the Antitumor Immunity
Authors: Chulpanova Daria S. , Rizvanov Albert A. , Solovyeva Valeriya V.
Published: December 2022

Cancer stem cells (CSCs) are a population of tumor cells that share similar properties to normal stem cells. CSCs are able to promote tumor progression and recurrence due to their resistance to chemotherapy and ability to stimulate angiogenesis and differentiate into non-CSCs. Cancer stem cells can also create a significant immunosuppressive environment around themselves by suppressing the activity of effector immune cells and recruiting cells that support tumor escape from immune response. The immunosuppressive effect of CSCs can be mediated by receptors located on their surface, as well as by secreted molecules, which transfer immunosuppressive signals to the cells of tumor microenvironment. In this article, the ability of CSCs to regulate the antitumor immune response and a contribution of CSC-derived EVs into the avoidance of the immune response are discussed.
Low-Intensity Pulsed Ultrasound Alleviates Human Testicular Leydig Cell Senescence In Vitro
Authors: Han Sha , Luo Jiaqiang , Xu Shuai , Zhao Liangyu , Yao Chencheng , Xu Junwei , Tian Ruhui , Zhi Erlei , Huang Yuhua , Xia Shujie , Li Zheng , Li Peng
Published: December 2022

Aging has a significant negative impact on human testicular function; steroidogenesis is gradually impaired, and testosterone replacement therapy still has many risks. Low-intensity pulsed ultrasound (LIPUS) has been used as a novel non-invasive treatment for male erectile dysfunction and other fields, and has been shown to increase testosterone levels in animal models. Testosterone is synthesized and secreted by Leydig cells (LCs), and the serum testosterone level decreases after aging due to the LCs senescence. However, the effect of LIPUS on human senescent LCs has not been reported. In this study, human senescent LCs were isolated and stimulated with different energy intensities in vitro, and cell morphology, cell apoptosis, cell proliferation, cell senescence levels, lipid droplet number, testosterone and INSL3 secretion levels were tested and analyzed. Quantitative Polymerase Chain Reaction (QPCR) and Western Blot were performed to compare cell senescence characteristics and the expression profile of key pathways of testosterone secretion, and transcriptome analysis was performed to explore the signaling pathways of LCs alteration after LIPUS stimulation. It was safe and effective to stimulate LCs with the 75 mW/cm2 energy of LIPUS in vitro, which not only improved the senescence phenotype, but also effectively enhanced the secretory function of LCs in vitro, and increased the expression of key pathways of the testosterone synthesis pathway. These results suggest that LIPUS could be used as a novel treatment to human senescent LCs with decreased testosterone secretion levels in vitro.
A Novel Anti-TRPV6 Antibody and Its Application in Cancer Diagnosis In Vitro
Authors: Haustrate Aurélien , Mihalache Adriana , Cordier Clément , Gosset Pierre , Prevarskaya Natalia , Lehen’kyi V’yacheslav
Published: December 2022

Though the first discovery of TRPV6 channel expression in various tissues took place in the early 2000s, reliable tools for its protein detection in various cells and tissues are still missing. Here we show the generation and validation of rabbit polyclonal anti-TRPV6 channel antibodies (rb79–82) against four epitopes of 15 amino acids. Among them, only one antibody, rb79, was capable of detecting the full-length glycosylated form of the TRPV6 channel at around 100 kDa. The generated antibody was shown to be suitable for all in vitro applications, such as immunoblotting, immunoprecipitation, immunocytochemistry, immunofluorescence, etc. One of the most important applications is immunohistochemistry using the paraffin-embedded sections from cancer resection specimens. Using prostate cancer resection specimens, we have confirmed the absence of the TRPV6 protein in both healthy and benign hyperplasia, as well as its expression and correlation to the prostate cancer grades. Thus, the generated rabbit polyclonal anti-TRPV6 channel antibody rb79 is suitable for all in vitro diagnostic applications and particularly for the diagnosis in clinics using paraffin-embedded sections from patients suffering from various diseases and disorders involving the TRPV6 channel.
Overexpression of Mtr-miR319a Contributes to Leaf Curl and Salt Stress Adaptation in Arabidopsis thaliana and Medicago truncatula
Authors: Li Mingna , Xu Lei , Zhang Lixia , Li Xiao , Cao Chunyu , Chen Lin , Kang Junmei , Yang Qingchuan , Liu Yajiao , Sod Bilig , Long Ruicai
Published: December 2022

Salt stress is a worldwide agronomic issue that limits crop yield and quality. Improving salt stress tolerance via genetic modification is the most efficient method to conquer soil salinization problems in crops. Crop miRNAs have been declared to be tightly associated with responding and adapting to salt stress and are advantageous for salt tolerance modification. However, very few studies have validated vital salt tolerance miRNAs and coupled potent target genes in Medicago species, the most economically important forage legume species. In this study, Mtr-miR319a, a miRNA that was identified from the previous next-generation sequencing assay of salt-treated Medicago truncatula, was overexpressed in M. truncatula and Arabidopsis thaliana, inducing the curly leaves and salt stress tolerance phenotypes. Combining the elevated expression level of Mtr-miR319a in the M. truncatula overexpression lines under normal and salt-treatment conditions, the regulatory roles of Mtr-miR319a in leaf development and salt stress adaptation were demonstrated. Several predicted target genes of Mtr-miR319a were also regulated by Mtr-miR319a and were associated with the aforementioned phenotypes in M. truncatula plants, most notably MtTCP4. Our study clarified the functional role of Mtr-miR319a and its target genes in regulating leaf development and defending salt stress, which can help to inform crop breeding efforts for improving salt tolerance via genetic engineering.
Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress
Authors: Ceccatelli Berti Camilla , Gihaz Shalev , Figuccia Sonia , Choi Jae-Yeon , Pal Anasuya C. , Goffrini Paola , Ben Mamoun Choukri
Published: December 2022

Human PANK1, PANK2, and PANK3 genes encode several pantothenate kinase isoforms that catalyze the phosphorylation of vitamin B5 (pantothenic acid) to phosphopantothenate, a critical step in the biosynthesis of the major cellular cofactor, Coenzyme A (CoA). Mutations in the PANK2 gene, which encodes the mitochondrial pantothenate kinase (PanK) isoform, have been linked to pantothenate-kinase associated neurodegeneration (PKAN), a debilitating and often fatal progressive neurodegeneration of children and young adults. While the biochemical properties of these enzymes have been well-characterized in vitro, their expression in a model organism such as yeast in order to probe their function under cellular conditions have never been achieved. Here we used three yeast mutants carrying missense mutations in the yeast PanK gene, CAB1, which are associated with defective growth at high temperature and iron, mitochondrial dysfunction, increased iron content, and oxidative stress, to assess the cellular function of human PANK genes and functional conservation of the CoA-controlled processes between humans and yeast. Overexpression of human PANK1 and PANK3 in these mutants restored normal cellular activity whereas complementation with PANK2 was partial and could only be achieved with an isoform, PanK2mtmΔ, lacking the mitochondrial transit peptide. These data, which demonstrate functional conservation of PanK activity between humans and yeast, set the stage for the use of yeast as a model system to investigate the impact of PKAN-associated mutations on the metabolic pathways altered in this disease.
Clonal Micropropagation of Cymbidium erythrostylum Rolfe
Authors: Hussien Muthab , Kryuchkova Viktoriya , Raeva-Bogoslovskaya Ekaterina , Molkanova Olga
Published: December 2022

Cymbidium erythrostylum Rolfe is one of the most beautiful species of the genus cymbidium which is used as a cut flower or indoor plant. However, it was registered as a rare species even in its original habitat. This study was carried out to develop a protocol for in vitro propagation of C. erythrostilum. We used protosomes obtained by the asymbiotic germination of seed on 1/2 of Murashige and Skoog nutrient medium (MS) supplemented with 1 mg/L 2-Isopentenyl adenine (2iP) as objects of study. During the multiplication stage, the number of formed protosomes on a culture medium containing 0.8 mg/L 6-Benzylaminopurine (6-BAP) was higher (3.8 ± 0.2 protosomes). During the subsequent cultivation on ½ MS medium supplemented with 2 mg/L 6-BAP and 0.5 mg/L a-naphthaleneacetic acid (NAA), the highest numbers of shoots (4.00 ± 0.19 shoots/plantlet) and leaves (4.50 ± 0.14 leaves/plantlet) were obtained. At the rooting stage under in vitro conditions, the most effective was the use of ½ MS nutrient medium with the addition of 0.5 mg/L of indolyl-3-butyric acid IBA, 1 g/l charcoal, and 50 g/l banana puree. The obtained plants were successfully adapted to a substrate consisting of bark, perlite, and peat in a ratio of 1:1:1.
Analyzing Public Opinions Regarding Virtual Tourism in the Context of COVID-19: Unidirectional vs. 360-Degree Videos
Authors: Huynh Thai Hoc , Silhavy Petr , Dey Sandeep Kumar , Hoang Sinh Duc , Prokopova Zdenka , Silhavy Radek
Published: December 2022

Over the last few years, more and more people have been using YouTube videos to experience virtual reality travel. Many individuals utilize comments to voice their ideas or criticize a subject on YouTube. The number of replies to 360-degree and unidirectional videos is enormous and might differ between the two kinds of videos. This presents the problem of efficiently evaluating user opinions with respect to which type of video will be more appealing to viewers, positive comments, or interest. This paper aims to study SentiStrength-SE and SenticNet7 techniques for sentiment analysis. The findings demonstrate that the sentiment analysis obtained from SenticNet7 outperforms that from SentiStrength-SE. It is revealed through the sentiment analysis that sentiment disparity among the viewers of 360-degree and unidirectional videos is low and insignificant. Furthermore, the study shows that unidirectional videos garnered the most traffic during COVID-19 induced global travel bans. The study elaborates on the capacity of unidirectional videos on travel and the implications for industry and academia. The second aim of this paper also employs a Convolutional Neural Network and Random Forest for sentiment analysis of YouTube viewers’ comments, where the sentiment analysis output by SenticNet7 is used as actual values. Cross-validation with 10-folds is employed in the proposed models. The findings demonstrate that the max-voting technique outperforms compared with an individual fold.
First Identification and Investigation of piRNAs in the Larval Gut of the Asian Honeybee, Apis cerana
Authors: Long Qi , Sun Ming-Hui , Fan Xiao-Xue , Cai Zong-Bing , Zhang Kai-Yao , Wang Si-Yi , Zhang Jia-Xin , Gu Xiao-Yu , Song Yu-Xuan , Chen Da-Fu , Fu Zhong-Min , Guo Rui , Niu Qing-Sheng
Published: December 2022

Piwi-interacting RNAs (piRNAs), a class of small non-coding RNAs (ncRNAs), play pivotal roles in maintaining the genomic stability and modulating biological processes such as growth and development via the regulation of gene expression. However, the piRNAs in the Asian honeybee (Apis cerana) are still largely unknown at present. In this current work, on the basis of previously gained high-quality small RNA-seq datasets, piRNAs in the larval gut of Apis cerana cerana, the nominated species of A. cerana, were identified for the first time, followed by an in-depth investigation of the regulatory roles of differentially expressed piRNAs (DEpiRNAs) in the developmental process of the A. c. cerana. Here, a total of 621 piRNAs were identified in A. c. cerana larval guts, among which 499 piRNAs were shared by 4-(Ac4 group), 5-(Ac5 group), and 6-day-old (Ac6 group) larval guts, while the numbers of unique ones equaled 79, 37, and 11, respectively. The piRNAs in each group ranged from 24 nucleotides (nt) to 33 nt in length, and the first base of the piRNAs had a cytosine (C) bias. Additionally, five up-regulated and five down-regulated piRNAs were identified in the Ac4 vs. Ac5 comparison group, nine of which could target 9011 mRNAs; these targets were involved in 41 GO terms and 137 pathways. Comparatively, 22 up-regulated piRNAs were detected in the Ac5 vs. Ac6 comparison group, 21 of which could target 28,969 mRNAs; these targets were engaged in 46 functional terms and 164 pathways. The results suggested an overall alteration of the expression pattern of piRNAs during the developmental process of A. c. cerana larvae. The regulatory network analysis showed that piR-ace-748815 and piR-ace-512574 in the Ac4 vs. Ac5 comparison group as well as piR-ace-716466 and piR-ace-828146 in the Ac5 vs. Ac6 comparison group were linked to the highest number of targets. Further investigation indicated that targets of DEpiRNAs in the abovementioned two comparison groups could be annotated to several growth and development-associated pathways, such as the Jak/STAT, TGF-β, and Wnt signaling pathways, indicating the involvement of DEpiRNAs in modulating larval gut development via these crucial pathways. Moreover, the expression trends of six randomly selected DEpiRNAs were verified using a combination of stem-loop RT-PCR and RT-qPCR. These results not only provide a novel insight into the development of the A. c. cerana larval gut, but also lay a foundation for uncovering the epigenetic mechanism underlying larval gut development.
Discriminative Evaluation of Sarcopenic Dysphagia Using Handgrip Strength or Calf Circumference in Patients with Dysphagia Using the Area under the Receiver Operating Characteristic Curve
Authors: Kishimoto Hiroshi , Wakabayashi Hidetaka , Nishioka Shinta , Momosaki Ryo
Published: December 2022

This multicenter cross-sectional study aimed to evaluate the discriminative ability of sarcopenic dysphagia (SD) using handgrip strength (HGS) or calf circumference (CC) in patients with dysphagia. Patients aged 20 years or older who were registered in a database at acute, rehabilitation, long-term care hospitals and home health care facilities were included. Logistic regression analysis was performed using SD as the outcome and HGS, CC, and other confounding factors as covariates, separately by sex. Algorithm-based SD diagnosis and HGS or CC were used as the reference and index tests, respectively. Their accuracy was evaluated using the area under the receiver operating characteristic curve (AUC), and cutoff values were calculated. Of the 460 patients, 285 (126 males) were diagnosed with SD. Logistic regression analysis showed that HGS (odds ratio [OR], 0.909; 95% confidence interval [CI], 0.873–0.947) in males and CC (OR, 0.767; 95% CI, 0.668–0.880) in females were independently associated with SD. The AUC for HGS in males was 0.735 (p < 0.001) and CC in females was 0.681 (p < 0.001). The cutoff values were 19.7 kg for HGS in males (sensitivity, 0.75; specificity, 0.63) and 29.5 cm for CC in females (sensitivity, 0.86; specificity, 0.48). HGS in males and CC in females provided statistically significant information to discriminate SD from dysphagia.
Diagnosis and Treatment for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma
Authors: Nakamura Shotaro , Hojo Mariko
Published: December 2022

Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first reported in 1984, shows an indolent clinical course. However, the detailed clinicopathological characteristics of gastric MALT lymphoma have not been fully elucidated. We performed a literature search concerning the clinical features and treatment for gastric MALT lymphoma using PubMED. MALT lymphomas develop in single or multiple extranodal organs, of which the stomach is one of the most frequent sites; gastric MALT lymphoma accounts for 7% to 9% of all B-cell lymphomas, and 40% to 50% of primary gastric lymphomas. The eradication of Helicobacter pylori (H. pylori) is the first-line treatment for patients with gastric MALT lymphoma, regardless of the clinical stage. Approximately 60–90% of cases with stage I/II1 disease only achieve a complete histological response via H. pylori eradication. In patients who do not respond to H. pylori eradication therapy, second-line treatments such as watch-and-wait, radiotherapy, chemotherapy, rituximab immunotherapy, and/or a combination of these are recommended. Thus, H. pylori plays a causative role in the pathogenesis of gastric MALT lymphoma, and H. pylori eradication leads to complete histological remission in the majority of cases.