bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Analysis of the Growth-Regulating Factor (GRF) Family in Aquatic Plants and Their Roles in the ABA-Induced Turion Formation of Spirodela polyrhiza
Authors: Li Gaojie , Chen Yan , Zhao Xuyao , Yang Jingjing , Wang Xiaoyu , Li Xiaozhe , Hu Shiqi , Hou Hongwei
Published: September 2022

Growth-regulating factors (GRFs) are plant-specific transcription factors that play essential roles in regulating plant growth and stress response. The GRF gene families have been described in several terrestrial plants, but a comprehensive analysis of these genes in diverse aquatic species has not been reported yet. In this study, we identified 130 GRF genes in 13 aquatic plants, including floating plants (Azolla filiculoides, Wolffia australiana, Lemna minuta, Spirodela intermedia, and Spirodela polyrhiza), floating-leaved plants (Nymphaea colorata and Euryale ferox), submersed plants (Zostera marina, Ceratophyllum demersum, Aldrovanda vesiculosa, and Utricularia gibba), an emergent plant (Nelumbo nucifera), and an amphibious plant (Cladopus chinensis). The gene structures, motifs, and cis-acting regulatory elements of these genes were analyzed. Phylogenetic analysis divided these GRFs into five clusters, and ABRE cis-elements were highly enriched in the promoter region of the GRFs in floating plants. We found that abscisic acid (ABA) is efficient at inducing the turion of Spirodela polyrhiza (giant duckweed), accompanied by the fluctuated expression of SpGRF genes in their fronds. Our results provide information about the GRF gene family in aquatic species and lay the foundation for future studies on the functions of these genes.
Coevolution of Rumen Epithelial circRNAs with Their Microbiota and Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep
Authors: Guo Xinyu , Sha Yuzhu , Pu Xiaoning , Xu Ying , Yao Liangwei , Liu Xiu , He Yanyu , Hu Jiang , Wang Jiqing , Li Shaobin , Chen Guoshun
Published: September 2022

This study explores the effects of the coevolution of the host genome (the first genome) and gut microbiome (the second genome) on nutrition stress in Tibetan sheep during the cold season. The rumen epithelial tissue of six Tibetan sheep (Oula-type) was collected as experimental samples during the cold and warm seasons and the study lasted for half a year. The cDNA library was constructed and subjected to high-throughput sequencing. The circRNAs with significant differential expression were identified through bioinformatics analysis and functional prediction, and verified by real-time quantitative PCR (qRT-PCR). The results showed that a total of 56 differentially expressed (DE) circRNAs of rumen epithelial tissue were identified using RNA-seq technology, among which 29 were significantly upregulated in the cold season. The circRNA-miRNA regulatory network showed that DE circRNAs promoted the adaptation of Tibetan sheep in the cold season by targeting miR-150 and oar-miR-370-3p. The results of correlation analysis among circRNAs, microbiota, and metabolites showed that the circRNA NC_040275.1:28680890|28683112 had a very significant positive correlation with acetate, propionate, butyrate, and total volatile fatty acid (VFA) (p < 0.01), and had a significant positive correlation with Ruminococcus-1 (p < 0.05). In addition, circRNA NC_040256.1:78451819|78454934 and metabolites were enriched in the same KEGG pathway biosynthesis of amino acids (ko01230). In conclusion, the host genome and rumen microbiome of Tibetan sheep co-encoded a certain glycoside hydrolase (β-glucosidase) and coevolved efficient VFA transport functions and amino acid anabolic processes; thus, helping Tibetan sheep adapt to nutrient stress in the cold season in high-altitude areas.
Interaction between Alzheimer’s Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers
Authors: Kim Si Eun , Kim Hee Jin , Jang Hyemin , Weiner Michael W. , DeCarli Charles , Na Duk L. , Seo Sang Won
Published: September 2022

Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) and tau, and subcortical vascular cognitive impairment (SVCI) is characterized by cerebral small vessel disease (CSVD). They are the most common causes of cognitive impairment in the elderly population. Concurrent CSVD burden is more commonly observed in AD-type dementia than in other neurodegenerative diseases. Recent developments in Aβ and tau positron emission tomography (PET) have enabled the investigation of the relationship between AD biomarkers and CSVD in vivo. In this review, we focus on the interaction between AD and CSVD markers and the clinical effects of these two markers based on molecular imaging studies. First, we cover the frequency of AD imaging markers, including Aβ and tau, in patients with SVCI. Second, we discuss the relationship between AD and CSVD markers and the potential distinct pathobiology of AD markers in SVCI compared to AD-type dementia. Next, we discuss the clinical effects of AD and CSVD markers in SVCI, and hemorrhagic markers in cerebral amyloid angiopathy. Finally, this review provides both the current challenges and future perspectives for SVCI.
Transgenerationally Transmitted DNA Demethylation of a Spontaneous Epialleles Using CRISPR/dCas9-TET1cd Targeted Epigenetic Editing in Arabidopsis
Authors: Wang Min , He Li , Chen Bowei , Wang Yanwei , Wang Lishan , Zhou Wei , Zhang Tianxu , Cao Lesheng , Zhang Peng , Xie Linan , Zhang Qingzhu
Published: September 2022

CRISPR/dCas9 is an important DNA modification tool in which a disarmed Cas9 protein with no nuclease activity is fused with a specific DNA modifying enzyme. A previous study reported that overexpression of the TET1 catalytic domain (TET1cd) reduces genome-wide methylation in Arabidopsis. A spontaneous naturally occurring methylation region (NMR19-4) was identified in the promoter region of the PPH (Pheophytin Pheophorbide Hydrolase) gene, which encodes an enzyme that can degrade chlorophyll and accelerate leaf senescence. The methylation status of NMR19-4 is associated with PPH expression and leaf senescence in Arabidopsis natural accessions. In this study, we show that the CRISPR/dCas9-TET1cd system can be used to target the methylation of hypermethylated NMR19-4 region to reduce the level of methylation, thereby increasing the expression of PPH and accelerating leaf senescence. Furthermore, hybridization between transgenic demethylated plants and hypermethylated ecotypes showed that the demethylation status of edited NMR19-4, along with the enhanced PPH expression and accelerated leaf senescence, showed Mendelian inheritance in F1 and F2 progeny, indicating that spontaneous epialleles are stably transmitted trans-generationally after demethylation editing. Our results provide a rational approach for future editing of spontaneously mutated epialleles and provide insights into the epigenetic mechanisms that control plant leaf senescence.
Role of Circular RNAs in Pulmonary Fibrosis
Authors: Zhou Jian , Chen Yali , He Menglin , Li Xuehan , Wang Rurong
Published: September 2022

Pulmonary fibrosis is a chronic progressive form of interstitial lung disease, characterized by the histopathological pattern of usual interstitial pneumonia. Apart from aberrant alterations of protein-coding genes, dysregulation of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs (circRNAs), is crucial to the initiation and progression of pulmonary fibrosis. CircRNAs are single-stranded RNAs that form covalently closed loops without 5′ caps and 3′ tails. Different from canonical splicing of mRNA, they are produced from the back-splicing of precursor mRNAs and have unique biological functions, as well as potential biomedical implications. They function as important gene regulators through multiple actions, including sponging microRNAs and proteins, regulating transcription, and splicing, as well as protein-coding and translation in a cap-independent manner. This review comprehensively summarizes the alteration and functional role of circRNAs in pulmonary fibrosis, with a focus on the involvement of the circRNA in the context of cell-specific pathophysiology. In addition, we discuss the diagnostic and therapeutic potential of targeting circRNA and their regulatory pathway mediators, which may facilitate the translation of recent advances from bench to bedside in the future.
Development and Molecular Cytogenetic Characterization of a Novel Wheat-Rye T6RS.6AL Translocation Line from Secale cereale L. Qinling with Resistance to Stripe Rust and Powdery Mildew
Authors: Ren Tianheng , Sun Zixin , Ren Zhenglong , Tan Feiquan , Luo Peigao , Li Zhi
Published: September 2022

In this study, a novel T6RS.6AL translocation line, 117-6, was selected from a cross between common Chuannong25 (CN25) wheat and Qinling rye. The results of nondenaturing fluorescence in situ hybridization (ND-FISH) and PCR showed that 117-6 contained two T6RS.6AL translocation chromosomes. The distal region of the 6RS chromosome in 117-6 was mutant and showed different FISH signal patterns. When inoculated with different stripe rust races and powdery mildew races in seedlings, 117-6 expressed high resistance to them. The 117-6 line also exhibited high resistance to stripe rust and powdery mildew in the field under natural Puccinia striiformis f. sp. tritici (Pst) and Blumeria graminis f. sp. tritici (Bgt) infection. The cytogenetic analysis indicated that the introduction of 6RS conferred resistance ability. Compared with wheat parent CN25, 117-6 exhibited excellent agronomic traits in the field. The present study indicated that Qinling rye may carry favorite genes as a potential source for wheat genetic improvement, and 117-6 could be a useful germplasm for wheat breeding programs in the future.
TTYH3 Modulates Bladder Cancer Proliferation and Metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK Pathway
Authors: Biswas Polash Kumar , Kwak Yeonjoo , Kim Aram , Seok Jaekwon , Kwak Hee Jeong , Lee Moonjung , Dayem Ahmed Abdal , Song Kwonwoo , Park Jae-Yong , Park Kyoung Sik , Shin Hyun Jin , Cho Ssang-Goo
Published: September 2022

Tweety family member 3 (TTYH3) is a calcium-activated chloride channel with a non-pore-forming structure that controls cell volume and signal transduction. We investigated the role of TTYH3 as a cancer-promoting factor in bladder cancer. The mRNA expression of TTYH3 in bladder cancer patients was investigated using various bioinformatics databases. The results demonstrated that the increasingly greater expression of TTYH3 increasingly worsened the prognosis of patients with bladder cancer. TTYH3 knockdown bladder cancer cell lines were constructed by their various cancer properties measured. TTYH3 knockdown significantly reduced cell proliferation and sphere formation. Cell migration and invasion were also significantly reduced in knockdown bladder cancer cells, compared to normal bladder cancer cells. The knockdown of TTYH3 led to the downregulation of H-Ras/A-Raf/MEK/ERK signaling by inhibiting fibroblast growth factor receptor 1 (FGFR1) phosphorylation. This signaling pathway also attenuated the expression of c-Jun and c-Fos. The findings implicate TTYH3 as a potential factor regulating the properties of bladder cancer and as a therapeutic target.
Lysophosphatidic Acid Promotes Epithelial–Mesenchymal Transition in Kidney Epithelial Cells via the LPAR1/MAPK-AKT/KLF5 Signaling Pathway in Diabetic Nephropathy
Authors: Lee Geon-Ho , Cheon Jayeon , Kim Donghee , Jun Hee-Sook
Published: September 2022

The epithelial–mesenchymal transition (EMT) is a differentiation process associated with fibrogenesis in diabetic nephropathy (DN). Lysophosphatidic acid (LPA) is a small, naturally occurring glycerophospholipid implicated in the pathogenesis of DN. In this study, we investigated the role of LPA/LPAR1 signaling in the EMT of tubular cells as well as the underlying mechanisms. We observed a decrease in E-cadherin and an increase in vimentin expression levels in the kidney tubules of diabetic db/db mice, and treatment with ki16425 (LPAR1/3 inhibitor) inhibited the expression of these EMT markers. Ki16425 treatment also decreased the expression levels of the fibrotic factors fibronectin and alpha-smooth muscle actin (α-SMA) in db/db mice. Similarly, we found that LPA decreased E-cadherin expression and increased vimentin expression in HK-2 cells, which was reversed by treatment with ki16425 or AM095 (LPAR1 inhibitor). In addition, the expression levels of fibronectin and α-SMA were increased by LPA, and this effect was reversed by treatment with ki16425 and AM095 or by LPAR1 knockdown. Moreover, LPA induced the expression of the transcription factor, Krüppel-like factor 5 (KLF5), which was decreased by AM095 treatment or LPAR1 knockdown. The expression levels of EMT markers and fibrotic factors induced by LPA were decreased upon KLF5 knockdown in HK-2 cells. Inhibition of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and serine-threonine kinase (AKT) pathways decreased LPA-induced expression of KLF5 and EMT markers. In conclusion, these data suggest that LPA contributes to the pathogenesis of diabetic nephropathy by inducing EMT and renal tubular fibrosis via regulation of KLF5 through the LPAR1.
Valorization of Biomasses from Energy Crops for the Discovery of Novel Thermophilic Glycoside Hydrolases through Metagenomic Analysis
Authors: Iacono Roberta , Strazzulli Andrea , Giglio Rosa , Bitetti Federica , Cobucci-Ponzano Beatrice , Moracci Marco
Published: September 2022

The increasing interest for environmentally friendly technologies is driving the transition from fossil-based economy to bioeconomy. A key enabler for circular bioeconomy is to valorize renewable biomasses as feedstock to extract high value-added chemicals. Within this transition the discovery and the use of robust biocatalysts to replace toxic chemical catalysts play a significant role as technology drivers. To meet both the demands, we performed microbial enrichments on two energy crops, used as low-cost feed for extremophilic consortia. A culture-dependent approach coupled to metagenomic analysis led to the discovery of more than 300 glycoside hydrolases and to characterize a new α-glucosidase from an unknown hyperthermophilic archaeon. Aglu1 demonstrated to be the most active archaeal GH31 on 4Np-α-Glc and it showed unexpected specificity vs. kojibiose, revealing to be a promising candidate for biotechnological applications such as the liquefaction/saccharification of starch.
Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment
Authors: Song Kena , Yu Zhangqing , Zu Xiangyang , Li Guoqiang , Hu Zhigang , Xue Yun
Published: September 2022

The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of the ECM, are greatly remodeled alongside cancer development. More and more studies have confirmed that collagens changed from a barrier to providing assistance in cancer development. In this course, collagens cause remodeling alongside cancer progression, which in turn, promotes cancer development. The interaction between collagens and tumor cells is complex with biochemical and mechanical signals intervention through activating diverse signal pathways. As the mechanism gradually clears, it becomes a new target to find opportunities to diagnose and treat cancer. In this review, we investigated the process of collagen remodeling in cancer progression and discussed the interaction between collagens and cancer cells. Several typical effects associated with collagens were highlighted in the review, such as fibrillation in precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, and guiding invasion. Then, the values of cancer diagnosis and prognosis were focused on. It is worth noting that several generated fragments in serum were reported to be able to be biomarkers for cancer diagnosis and prognosis, which is beneficial for clinic detection. At a glance, a variety of reported biomarkers were summarized. Many collagen-associated targets and drugs have been reported for cancer treatment in recent years. The new targets and related drugs were discussed in the review. The mass data were collected and classified by mechanism. Overall, the interaction of collagens and tumor cells is complicated, in which the mechanisms are not completely clear. A lot of collagen-associated biomarkers are excavated for cancer diagnosis. However, new therapeutic targets and related drugs are almost in clinical trials, with merely a few in clinical applications. So, more efforts are needed in collagens-associated studies and drug development for cancer research and treatment.
Reaction-Diffusion Systems: Self-Balancing Diffusion and the Use of the Extent of Reaction as a Descriptor of Reaction Kinetics
Authors: Pekař Miloslav
Published: September 2022

Self-balancing diffusion is a theoretical concept that restricts the introduction of extents of reactions. This concept is analyzed in detail for general mass- and molar-based balances of reaction-diffusion mixtures, in relation to non-self-balancing cases, and with respect to its practical consequences. Self-balancing is a mathematical restriction on the divergences of diffusion fluxes. Fulfilling this condition enables the proper introduction of the extents of (independent) reactions that reduce the number of independent variables in thermodynamic descriptions. A note on a recent generalization of the concept of reaction and diffusion extents is also included. Even in the case of self-balancing diffusion, such extents do not directly replace reaction rates. Concentration changes caused by reactions (not by diffusion) are properly described by rates of independent reactions, which are instantaneous descriptors. If an overall descriptor is needed, the traditional extents of reactions can be used, bearing in mind that they include diffusion-caused changes. On the other hand, rates of independent reactions integrated with respect to time provide another overall, but reaction-only-related descriptor.
RPE65 c.353G>A, p.(Arg118Lys): A Novel Point Mutation Associated with Retinitis Pigmentosa and Macular Atrophy
Authors: Bjeloš Mirjana , Bušić Mladen , Ćurić Ana , Šarić Borna , Bosnar Damir , Marković Leon , Kuzmanović Elabjer Biljana , Rak Benedict
Published: September 2022

Precise genetic diagnosis in RPE65-mediated retinitis pigmentosa (RP) is necessary to establish eligibility for genetic treatment with voretigene neparvovec: a recombinant adeno-associated viral vector providing a functional RPE65 gene. This case report aims to report a novel RP-related point mutation RPE65 c.353G>A, p.(Arg118Lys), a variant of uncertain significance associated with a severe clinical presentation and the striking phenotypic feature of complete macular atrophy. We report the case of a 40-year-old male with inherited retinal dystrophy, all features typical for the RPE65-associated RP, and marked macular atrophy. Genetic testing identified that the patient was a compound heterozygote in trans form with two heterozygous variants: RPE65 c.499G>T, p.(Asp167Tyr) and RPE65 c.353G>A, p.(Arg118Lys). Furthermore, short-wavelength and near-infrared autofluorescence patterns exhibited deficiencies specific to mutations in the visual cycle genes. To the best of our knowledge, RPE65 c.353G>A, p.(Arg118Lys) is the first described point mutation on this locus, among all other reported insertional mutations, currently classified as likely benign and of uncertain significance. We concluded that this variant contributed to the pathological phenotype, demonstrating its significance clearly to be reclassified as likely pathogenic. This being the case, patients with this specific variant in homozygous or compound heterozygous form would be likely candidates for genetic treatment with voretigene neparvovec.
Development of Palladium and Platinum Decorated Granulated Carbon Nanocomposites for Catalytic Chlorate Elimination
Authors: Sikora Emőke , Muránszky Gábor , Kristály Ferenc , Fiser Béla , Farkas László , Viskolcz Béla , Vanyorek László
Published: September 2022

Granulated carbon nanotube-supported palladium and platinum-containing catalysts were developed. By using these, remarkable catalytic activity was achieved in chlorate ion hydrogenation. Nitrogen-doped bamboo-like carbon nanotubes (N-BCNTs) loaded gel beads were prepared by using Ca2+, Ni2+ or Fe3+ ions as precursors for cross-linking of sodium alginate. The gel beads were carbonized at 800 °C, and these granulated carbon nanocomposites (GCNC) were used as supports to prepare palladium and platinum-containing catalysts. All in all, three catalysts were developed and, in each case, >99 n/n% chlorate conversion was reached in the aqueous phase by using the Pd-Pt containing GCNCs, moreover, these systems retained their catalytic activity even after repeated use.
Addition of Synthetic Biomaterials to Deproteinized Bovine Bone Mineral (DBBM) for Bone Augmentation—A Preclinical In Vivo Study
Authors: Fujioka-Kobayashi Masako , Katagiri Hiroki , Lang Niklaus P. , Imber Jean-Claude , Schaller Benoit , Saulacic Nikola
Published: September 2022

(1) Aim: To investigate the effect of synthetic bone substitutes, α-tricalcium phosphate (α-TCP) or bi-layered biphasic calcium-phosphate (BBCP) combined with deproteinized bovine bone mineral (DBBM), on bone formation. (2) Methods: Thirty critical size defects were randomly treated with the following five different treatment modalities: (1) negative control (NC, empty), (2) DBBM, (3) α-TCP + DBBM (1:1), (4) BBCP 3%HA/97%α-TCP + DBBM (1:1), and (5) BBCP 6%HA/94%α-TCP + DBBM (1:1). The samples, at four weeks post-surgery, were investigated by micro-CT and histological analysis. (3) Results: A similar level of new bone formation was demonstrated in the DBBM with α-TCP bone substitute groups when compared to the negative control by histomorphometry. DBBM alone showed significantly lower new bone area than the negative control (p = 0.0252). In contrast to DBBM, the micro-CT analysis revealed resorption of the α-TCP + DBBM, BBCP 3%HA/97%α-TCP + DBBM and BBCP 6%HA/94%α-TCP + DBBM, as evidenced by a decrease of material density (p = 0.0083, p = 0.0050 and p = 0.0191, respectively), without changing their volume. (4) Conclusions: New bone formation was evident in all defects augmented with biomaterials, proving the osteoconductive properties of the tested material combinations. There was little impact of the HA coating degree on α-TCP in bone augmentation potential and material resorption for four weeks when mixed with DBBM.
Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture
Authors: Farzamfar Saeed , Elia Elissa , Chabaud Stéphane , Naji Mohammad , Bolduc Stéphane
Published: September 2022

Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells’ niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed.
Shrimp Lipid Droplet Protein Perilipin Involves in the Pathogenesis of AHPND-Causing Vibrio parahaemolyticus
Authors: Wang Chuanqi , Yao Defu , Zhao Mingming , Lu Kaiyu , Lin Zhongyang , Chen Xiuli , Zhao Yongzhen , Zhang Yueling
Published: September 2022

Acute hepatopancreatic necrosis disease (AHPND), caused by a unique strain of Vibrio parahaemolyticus (Vp (AHPND)), has become the world’s most severe debilitating disease in cultured shrimp. Thus far, the pathogenesis of AHPND remains largely unknow. Herein, in Litopenaeus vannamei, we found that a Vp (AHPND) infection significantly increased the expression of lipid droplets (LDs) protein LvPerilipin, as well as promoted the formation of LDs. In addition, the knockdown of LvPerilipin increased the shrimp survival rate in response to the Vp (AHPND) infection, and inhibited the proliferation of Vp (AHPND). Furthermore, we demonstrated that LvPerilipin depletion could increase the production of reactive oxygen species (ROS), which may be responsible for the decreased Vp (AHPND) proliferation. Taken together, our current data for the first time reveal that the shrimp lipid droplets protein Perilipin is involved in the pathogenesis of Vp (AHPND) via promoting LDs accumulation and decreasing ROS production.
Genome-Wide Identification of Laminin Family Related to Follicular Pseudoplacenta Development in Black Rockfish (Sebastes schlegelii)
Authors: Zhao Ning , Wang Xueying , Wang Tao , Xu Xiaojie , Liu Qinghua , Li Jun
Published: September 2022

As major elements of the basement membrane, laminins play a significant role in angiogenesis, migration, and adhesion of various cells. Sebastes schlegelii is a marine viviparous teleost of commercial importance. Previous research has reported abundant blood vessels and connective tissue in the ovary during gestation. In this study, 14 laminin genes of the α, β, and γ subfamilies from genomic data were identified based on zebrafish and human laminins, distributed on 9 chromosomes in S. schlegelii. Analysis of structural domains showed that coiled-coil regions and EGF domains existed in all laminin genes. Moreover, via qPCR, we found that the expression of laminin genes, including lama4, lama5, lamb4, lamc1, and lamc3, gradually increased from the phase III ovary stage and peaked in the early stage of gestation, especially lama4 and lama5 which showed dramatically increased expression at the blastula stage. Accordingly, in situ hybridization of lama4 was conducted. The results revealed that signals became stronger following the phase IV ovary stage, and the strongest signals were located on the follicular pseudoplacenta at the blastula stage. These results suggest that the high expression of laminin genes, especially lama4 after fertilization, may drive cell proliferation, migration, and tissue expansion in the S. schlegelii ovary and ultimately promote follicular pseudoplacenta formation.
Monitoring Therapeutic Responses to Silicified Cancer Cell Immunotherapy Using PET/MRI in a Mouse Model of Disseminated Ovarian Cancer
Authors: Taylor Erik N. , Wilson Colin M. , Franco Stefan , De May Henning , Medina Lorél Y. , Yang Yirong , Flores Erica B. , Bartee Eric , Selwyn Reed G. , Serda Rita E.
Published: September 2022

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [18F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer. Tumor progression was validated by bioluminescence imaging of luciferase expressing tumor cells, flow cytometric analysis of immune cells in the tumor microenvironment, and histopathology. While PET demonstrated the presence of metabolically active cancer cells through [18F]FDG uptake, MRI confirmed cancer-related accumulation of ascites and tissue anatomy. This approach provides complementary information on disease status without a confounding signal from treatment-induced inflammation. This work provides a possible roadmap to facilitate accurate monitoring of therapeutic responses to cancer immunotherapies.
Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)3-Functionalized PEG-PLGA Biopolymer Encapsulating Simvastatin for the Treatment of Osteoporosis in Rat Models
Authors: Lin Che-Wei , Lee Chih-Yun , Lin Sung-Yen , Kang Lin , Fu Yin-Chih , Chen Chung-Hwan , Wang Chih-Kuang
Published: September 2022

Simvastatin (SIM) is a lipid-lowering drug that also promotes bone formation, but its high liver specificity may cause muscle damage, and the low solubility of lipophilic drugs limits the systemic administration of SIM, especially in osteoporosis (OP) studies. In this study, we utilized the bone-targeting moiety of dendritic oligopeptides consisting of three aspartic acid moieties (dAsp3) and amphiphilic polymers (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid); PEG-PLGA) to create dAsp3-PEG-PLGA (APP) nanoparticles (NPs), which can carry SIM to treat OP. An in vivo imaging system showed that gold nanocluster (GNC)-PLGA/APP NPs had a significantly higher accumulation rate in representative bone tissues. In vivo experiments comparing low-dose SIM treatment (0.25 mg/kg per time, 2 times per week) showed that bone-targeting SIM/APP NPs could increase the bone formation effect compared with non-bone-targeting SIM/PP NPs in a local bone loss of hindlimb suspension (disuse) model, but did not demonstrate good bone formation in a postmenopausal (ovariectomized) model of systemic bone loss. The APP NPs could effectively target high mineral levels in bone tissue and were expected to reduce side effects in other organs affected by SIM. However, in vivo OP model testing showed that the same lower dose could not be used to treat different types of OP.
Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer
Authors: Li Chung-Liang , Moi Sin-Hua , Lin Huei-Shan , Hou Ming-Feng , Chen Fang-Ming , Shih Shen-Liang , Kan Jung-Yu , Kao Chieh-Ni , Wu Yi-Chia , Kao Li-Chun , Chen Ying-Hsuan , Lee Yi-Chen , Chiang Chih-Po
Published: September 2022

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.
Sparking Nano-Metals on a Surface of Polyethylene Terephthalate and Its Application: Anti-Coronavirus and Anti-Fogging Properties
Authors: Jantanasakulwong Kittisak , Thanakkasaranee Sarinthip , Seesuriyachan Phisit , Singjai Pisith , Saenjaiban Aphisit , Photphroet Siriphan , Pratinthong Kanticha , Phimolsiripol Yuthana , Leksawasdi Noppol , Chaiyaso Thanongsak , Sommano Sarana Rose , Jantrawut Pensak , Chomdej Siriwadee , Chotinan Suwit , Barba Francisco J. , Regenstein Joe M. , Reungsang Alissara , Rachtanapun Pornchai
Published: September 2022

The nano-metal-treated PET films with anti-virus and anti-fogging ability were developed using sparking nano-metal particles of Ag, Zn, and Ti wires on polyethylene terephthalate (PET) films. Ag nanoparticles were detected on the PET surface, while a continuous aggregate morphology was observed with Zn and Ti sparking. The color of the Ag-PET films changed to brown with increasing repeat sparking times, but not with the Zn-PET and Ti-PET films. The water contact angle of the nano-metal-treated PET films decreased with increasing repeat sparking times. The RT-PCR anti-virus test confirmed the high anti-virus efficiency of the nano-metal-treated PET films due to the fine particle distribution, high polarity, and binding of the nano-metal ions to the coronavirus, which was destroyed by heat after UV irradiation. A highly transparent, anti-fogging, and anti-virus face shield was prepared using the Zn-PET film. Sparking was an effective technique to prepare the alternative anti-virus and anti-fogging films for medical biomaterial applications because of their low cost, convenience, and fast processing.
Effects of Tetracycline on Scenedesmus obliquus Microalgae Photosynthetic Processes
Authors: Chen Zhehua , Gu Gan , Wang Ziyun , Ou Dong , Liang Xianrui , Hu Changwei , Li Xi
Published: September 2022

Tetracycline (TC) antibiotics can be detected worldwide in the aquatic environment due to their extensive use and low utilization efficiency, and they may affect the physiological processes of non-target organisms. In this study, the acute and sub-acute toxicities of TC on the freshwater microalga Scenedesmus obliquus were investigated with an emphasis on algal photosynthesis and transcription alterations during an 8 d TC exposure. The results showed that the IC10, IC30 and IC50 values were 1.8, 4.1 and 6.9 mg/L, respectively. During sub-acute exposure, the microalgae of the IC10 treatment was able to recover comparable growth to that of the control by day 7, while significantly lower cell densities were observed in the IC30 and IC50 treatments at the end of the exposure. The photosynthetic efficiency Fv/FM of S. obliquus first decreased as the TC concentration increased and then returned to a level close to that of the control on day 8, accompanied by an increase in photosynthetic activities, including light harvesting, electron transport and energy dissipation. Transcriptomic analysis of the IC10 treatment (1.8 mg/L TC) revealed that 2157 differentially expressed genes were up-regulated and 1629 were down-regulated compared with the control. KEGG and GO enrichments demonstrated that 28 photosynthesis-related genes involving light-harvesting chlorophyll protein complex, photosystem I, photosystem II, photosynthetic electron transport and enzymes were up-regulated, which may be the factor responsible for the enhanced photosynthesis and recovery of the microalgae. Our work may be helpful not only for gaining a better understanding of the environmental risk of TC at concentrations close to the real levels in natural waters, but also for explaining photosynthesis and related gene transcription induced by antibiotics.
The Role of Matrix Metalloproteinase in Inflammation with a Focus on Infectious Diseases
Authors: Lee Han Sol , Kim Woo Joo
Published: September 2022

Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases. Therefore, numerous studies have been conducted to understand the role of MMPs in disease pathogenesis. MMPs are involved in the pathogenesis of infectious diseases through a dysregulation of the activity and expression of MMPs. In this review, we discuss the role of MMPs in infectious diseases and inflammatory responses. Furthermore, we present the potential of MMPs as therapeutic targets in infectious diseases.
Plants in Microgravity: Molecular and Technological Perspectives
Authors: Baba Abu Imran , Mir Mohd Yaqub , Riyazuddin Riyazuddin , Cséplő Ágnes , Rigó Gábor , Fehér Attila
Published: September 2022

Plants are vital components of our ecosystem for a balanced life here on Earth, as a source of both food and oxygen for survival. Recent space exploration has extended the field of plant biology, allowing for future studies on life support farming on distant planets. This exploration will utilize life support technologies for long-term human space flights and settlements. Such longer space missions will depend on the supply of clean air, food, and proper waste management. The ubiquitous force of gravity is known to impact plant growth and development. Despite this, we still have limited knowledge about how plants can sense and adapt to microgravity in space. Thus, the ability of plants to survive in microgravity in space settings becomes an intriguing topic to be investigated in detail. The new knowledge could be applied to provide food for astronaut missions to space and could also teach us more about how plants can adapt to unique environments. Here, we briefly review and discuss the current knowledge about plant gravity-sensing mechanisms and the experimental possibilities to research microgravity-effects on plants either on the Earth or in orbit.
The Effect of the BCO2 Genotype on the Expression of Genes Related to Carotenoid, Retinol, and α-Tocopherol Metabolism in Rabbits Fed a Diet with Aztec Marigold Flower Extract
Authors: Strychalski Janusz , Gugołek Andrzej , Antoszkiewicz Zofia , Fopp-Bayat Dorota , Kaczorek-Łukowska Edyta , Snarska Anna , Zwierzchowski Grzegorz , Król-Grzymała Angelika , Matusevičius Paulius
Published: September 2022

This study investigated the effect of the BCO2 genotype and the addition of Aztec marigold flower extract to rabbit diets on the expression of BCO1, BCO2, LRAT, and TTPA genes in the liver. The levels of lutein, zeaxanthin, β-carotene, retinol, and α-tocopherol in the liver and blood serum of rabbits, as well as plasma biochemical parameters and serum antioxidant enzyme activities were also determined. Sixty male Termond White growing rabbits were divided into three groups based on their genotype at codon 248 of the BCO2 gene (ins/ins, ins/del and del/del); each group was divided into two subgroups: one subgroup received a standard diet, and the other subgroup was fed a diet supplemented with 6 g/kg of marigold flower extract. The obtained results indicate that the BCO2 genotype may affect the expression levels of BCO1 and BCO2 genes in rabbits. Moreover, the addition of marigold extract to the diet of BCO2 del/del rabbits may increase the expression level of the BCO2 gene. Finally, an increase in the amount of lutein in the diet of rabbits with the BCO2 del/del genotype contributes to its increased accumulation in the liver and blood of animals without compromising their health status or liver function.
Cyt-C Mediated Mitochondrial Pathway Plays an Important Role in Oocyte Apoptosis in Ricefield Eel (Monopterus albus)
Authors: He Zhi , Chen Qiqi , He Liang , Xiong Jinxin , Gao Kuo , Lai Bolin , Zheng Li , Pu Yong , Jiao Yuanyuan , Ma Zhijun , Tang Ziting , Zhang Mingwang , Yang Deying , Yan Taiming
Published: September 2022

Apoptosis plays a key role in the effective removal of excessive and defective germ cells, which is essential for sequential hermaphroditism and sex change in vertebrates. The ricefield eel, Monopterus albus is a protogynous hermaphroditic fish that undergoes a sequential sex change from female to male. Previous studies have demonstrated that apoptosis is involved in sex change in M. albus. However, the apoptotic signaling pathway is unclear. In the current study, we explored the underlying mechanism of apoptosis during gonadal development and focused on the role of the mitochondrial apoptosis signaling pathway in sex change in M. albus. Flow cytometry was performed to detect apoptosis in gonads at five sexual stages and ovary tissues exposed to hydrogen peroxide (H2O2) in vitro. Then the expression patterns of key genes and proteins in the mitochondrial pathway, death receptor pathway and endoplasmic reticulum (ER) pathway were examined. The results showed that the apoptosis rate was significantly increased in the early intersexual stage and then decreased with the natural sex change from female to male. Quantitative real-time PCR revealed that bax, tnfr1, and calpain were mainly expressed in the five stages. ELISA demonstrated that the relative content of cytochrome-c (cyt-c) in the mitochondrial pathway was significantly higher than that of caspase8 and caspase12, with a peak in the early intersexual stage, while the levels of caspase8 and caspase12 peaked in the late intersexual stage. Interestingly, the Pearson’s coefficient between cyt-c and the apoptosis rate was 0.705, which suggests that these factors are closely related during the gonadal development of M. albus. Furthermore, the cyt-c signal was found to be increased in the intersexual stage by immunohistochemistry. After incubation with H2O2, the mRNA expression of mitochondrial pathway molecules such as bax, apaf-1, and caspase3 increased in ovary tissues. In conclusion, the present results suggest that the mitochondrial apoptotic pathway may play a more important role than the other apoptotic pathways in sex change in M. albus.
Comparison between Immunocytochemistry, FISH and NGS for ALK and ROS1 Rearrangement Detection in Cytological Samples
Authors: Frankel Diane , Nanni Isabelle , Ouafik L’Houcine , Camilla Clara , Pellegrino Eric , Beaufils Nathalie , Greillier Laurent , Dutau Hervé , Astoul Philippe , Kaspi Elise , Roll Patrice
Published: September 2022

The detection of ROS1 and ALK rearrangements is performed for advanced-stage non-small cell lung cancer. Several techniques can be used on cytological samples, such as immunocytochemistry (ICC), fluorescence in situ hybridization (FISH) and, more recently, next-generation sequencing (NGS), which is gradually becoming the gold standard. We performed a retrospective study to compare ALK and ROS1 rearrangement results from immunocytochemistry, FISH and NGS methods from 131 cytological samples. Compared to NGS, the sensitivity and specificity of ICC were 0.79 and 0.91, respectively, for ALK, and 1 and 0.87 for ROS1. Regarding FISH, the sensitivity and specificity were both at 1 for ALK and ROS1 probes. False-positive cases obtained by ICC were systematically corrected by FISH. When using ICC and FISH techniques, results are very close to NGS. The false-positive cases obtained by ICC are corrected by FISH, and the true-positive cases are confirmed. NGS has the potential to improve the detection of ALK and ROS1 rearrangements in cytological samples; however, the cost of this technique is still much higher than the sequential use of ICC and FISH.
Biophysical Characterization of LTX-315 Anticancer Peptide Interactions with Model Membrane Platforms: Effect of Membrane Surface Charge
Authors: Koo Dong Jun , Sut Tun Naw , Tan Sue Woon , Yoon Bo Kyeong , Jackman Joshua A.
Published: September 2022

LTX-315 is a clinical-stage, anticancer peptide therapeutic that disrupts cancer cell membranes. Existing mechanistic knowledge about LTX-315 has been obtained from cell-based biological assays, and there is an outstanding need to directly characterize the corresponding membrane-peptide interactions from a biophysical perspective. Herein, we investigated the membrane-disruptive properties of the LTX-315 peptide using three cell-membrane-mimicking membrane platforms on solid supports, namely the supported lipid bilayer, intact vesicle adlayer, and tethered lipid bilayer, in combination with quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) measurements. The results showed that the cationic LTX-315 peptide selectively disrupted negatively charged phospholipid membranes to a greater extent than zwitterionic or positively charged phospholipid membranes, whereby electrostatic interactions were the main factor to influence peptide attachment and membrane curvature was a secondary factor. Of note, the EIS measurements showed that the LTX-315 peptide extensively and irreversibly permeabilized negatively charged, tethered lipid bilayers that contained high phosphatidylserine lipid levels representative of the outer leaflet of cancer cell membranes, while circular dichroism (CD) spectroscopy experiments indicated that the LTX-315 peptide was structureless and the corresponding membrane-disruptive interactions did not involve peptide conformational changes. Dynamic light scattering (DLS) measurements further verified that the LTX-315 peptide selectively caused irreversible disruption of negatively charged lipid vesicles. Together, our findings demonstrate that the LTX-315 peptide preferentially disrupts negatively charged phospholipid membranes in an irreversible manner, which reinforces its potential as an emerging cancer immunotherapy and offers a biophysical framework to guide future peptide engineering efforts.
HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression
Authors: Li Ruixiao , Meng Shan , Ji Mengting , Rong Xiaoyin , You Ziwei , Cai Chunbo , Guo Xiaohong , Lu Chang , Liang Guoming , Cao Guoqing , Li Bugao , Yang Yang
Published: September 2022

Obesity and its associated metabolic disease do serious harm to human health. The transcriptional cascade network with transcription factors as the core is the focus of current research on adipogenesis and its mechanism. Previous studies have found that HMG domain protein 20A (HMG20A) is highly expressed in the early stage of adipogenic differentiation of porcine intramuscular fat (IMF), which may be involved in regulating adipogenesis. In this study, HMG20A was found to play a key negative regulatory role in adipogenesis. Gain- and loss-of-function studies revealed that HMG20A inhibited the differentiation of SVF cells and C3H10T1/2 cells into mature adipocytes. RNA-seq was used to screen differentially expressed genes after HMG20A knockdown. qRT-PCR and ChIP-PCR confirmed that MEF2C was the real target of HMG20A, and HMG20A played a negative regulatory role through MEF2C. HMG20A binding protein LSD1 was found to alleviate the inhibitory effect of HMG20A on adipogenesis. Further studies showed that HMG20A could cooperate with LSD1 to increase the H3K4me2 of the MEF2C promoter and then increase the expression of MEF2C. Collectively, these findings highlight a role for HMG20A-dependent transcriptional and epigenetic regulation in adipogenesis.