bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Evaluation and Molecular Docking Studies of Novel 1,3,4-Oxadiazole Derivatives of 4,6-Dimethyl-2-sulfanylpyridine-3-carboxamide
Authors: Świątek Piotr , Glomb Teresa , Dobosz Agnieszka , Gębarowski Tomasz , Wojtkowiak Kamil , Jezierska Aneta , Panek Jarosław J. , Świątek Małgorzata , Strzelecka Małgorzata
Published: January 2022

To date, chronic inflammation is involved in most main human pathologies such as cancer, and autoimmune, cardiovascular or neurodegenerative disorders. Studies suggest that different prostanoids, especially prostaglandin E2, and their own synthase (cyclooxygenase enzyme-COX) can promote tumor growth by activating signaling pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are used, alongside corticosteroids, to treat inflammatory symptoms particularly in all chronic diseases. However, their toxicity from COX inhibition and the suppression of physiologically important prostaglandins limits their use. Therefore, in continuation of our efforts in the development of potent, safe, non-toxic chemopreventive compounds, we report herein the design, synthesis, biological evaluation of new series of Schiff base-type hybrid compounds containing differently substituted N-acyl hydrazone moieties, 1,3,4-oxadiazole ring, and 4,6-dimethylpyridine core. The anti-COX-1/COX-2, antioxidant and anticancer activities were studied. Schiff base 13, containing 2-bromobenzylidene residue inhibited the activity of both isoenzymes, COX-1 and COX-2 at a lower concentration than standard drugs, and its COX-2/COX-1 selectivity ratio was similar to meloxicam. Furthermore, the results of cytotoxicity assay indicated that all of the tested compounds exhibited potent anti-cancer activity against A549, MCF-7, LoVo, and LoVo/Dx cell lines, compared with piroxicam and meloxicam. Moreover, our experimental study was supported by density functional theory (DFT) and molecular docking to describe the binding mode of new structures to cyclooxygenase.
Insights into the Structure and Protein Composition of Moorella thermoacetica Spores Formed at Different Temperatures
Authors: Malleck Tiffany , Fekraoui Fatima , Bornard Isabelle , Henry Céline , Haudebourg Eloi , Planchon Stella , Broussolle Véronique
Published: January 2022

The bacterium Moorella thermoacetica produces the most heat-resistant spores of any spoilage-causing microorganism known in the food industry. Previous work by our group revealed that the resistance of these spores to wet heat and biocides was lower when spores were produced at a lower temperature than the optimal temperature. Here, we used electron microcopy to characterize the ultrastructure of the coat of the spores formed at different sporulation temperatures; we found that spores produced at 55 °C mainly exhibited a lamellar inner coat tightly associated with a diffuse outer coat, while spores produced at 45 °C showed an inner and an outer coat separated by a less electron-dense zone. Moreover, misarranged coat structures were more frequently observed when spores were produced at the lower temperature. We then analyzed the proteome of the spores obtained at either 45 °C or 55 °C with respect to proteins putatively involved in the spore coat, exosporium, or in spore resistance. Some putative spore coat proteins, such as CotSA, were only identified in spores produced at 55 °C; other putative exosporium and coat proteins were significantly less abundant in spores produced at 45 °C. Altogether, our results suggest that sporulation temperature affects the structure and protein composition of M. thermoacetica spores.
The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer’s Disease
Authors: Swingler Tracey E. , Niu Lingzi , Pontifex Matthew G. , Vauzour David , Clark Ian M.
Published: January 2022

The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.
IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis
Authors: Wang Xing , Kaiser Hannah , Kvist-Hansen Amanda , McCauley Benjamin D. , Skov Lone , Hansen Peter Riis , Becker Christine
Published: January 2022

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10−12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10−8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10−5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.
A NAC Transcription Factor TuNAC69 Contributes to ANK-NLR-WRKY NLR-Mediated Stripe Rust Resistance in the Diploid Wheat Triticum urartu
Authors: Xu Yang , Zou Shenghao , Zeng Hao , Wang Wei , Wang Bin , Wang Huan , Tang Dingzhong
Published: January 2022

Stripe rust is one of the most devastating diseases in wheat. Nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domain receptors (NLRs) recognize pathogenic effectors and trigger plant immunity. We previously identified a unique NLR protein YrU1 in the diploid wheat Triticum urartu, which contains an N-terminal ANK domain and a C-terminal WRKY domain and confers disease resistance to stripe rust fungus Puccinia striiformis f. sp. Tritici (Pst). However, how YrU1 functions in disease resistance is not clear. In this study, through the RNA-seq analysis, we found that the expression of a NAC member TuNAC69 was significantly up-regulated after inoculation with Pst in the presence of YrU1. TuNAC69 was mainly localized in the nucleus and showed transcriptional activation in yeast. Knockdown TuNAC69 in diploid wheat Triticum urartu PI428309 that contains YrU1 by virus-induced gene silencing reduced the resistance to stripe rust. In addition, overexpression of TuNAC69 in Arabidopsis enhanced the resistance to powdery mildew Golovinomyces cichoracearum. In summary, our study indicates that TuNAC69 participates in the immune response mediated by NLR protein YrU1, and likely plays an important role in disease resistance to other pathogens.
Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model
Authors: Chang Cheng-Chung , Tsou Hsi-Kai , Chang Hsu-Hsin , Chan Long Yi , Zhuo Guan-Yu , Maeda Tomoji , Lin Chin-Yu
Published: January 2022

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease’s progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.
Evaluating a Targeted Cancer Therapy Approach Mediated by RNA trans-Splicing In Vitro and in a Xenograft Model for Epidermolysis Bullosa-Associated Skin Cancer
Authors: Woess Katharina , Sun Yuchen , Morio Hanae , Stierschneider Anna , Kaufmann Anna , Hainzl Stefan , Trattner Lisa , Kocher Thomas , Tockner Birgit , Leb-Reichl Victoria , Steiner Markus , Brachtl Gabriele , South Andrew P. , Bauer Johann W. , Reichelt Julia , Furihata Tomomi , Wally Verena , Koller Ulrich , Piñón Hofbauer Josefina , Guttmann-Gruber Christina
Published: January 2022

Conventional anti-cancer therapies based on chemo- and/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In the present work, we expand the application of this approach, using the same RTM44 in aggressive skin cancer arising in the rare genetic skin disease recessive dystrophic epidermolysis bullosa (RDEB). Stable expression of RTM44, but not a splicing-deficient control (NC), in RDEB-SCC cells resulted in expression of the expected fusion product at the mRNA and protein level. Importantly, systemic GCV treatment of mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared with controls. Thus, our results demonstrate the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy.
Regulation of Heterogenous LexA Expression in Staphylococcus aureus by an Antisense RNA Originating from Transcriptional Read-Through upon Natural Mispairings in the sbrB Intrinsic Terminator
Authors: Bastet Laurène , Bustos-Sanmamed Pilar , Catalan-Moreno Arancha , Caballero Carlos J. , Cuesta Sergio , Matilla-Cuenca Leticia , Villanueva Maite , Valle Jaione , Lasa Iñigo , Toledo-Arana Alejandro
Published: January 2022

Bacterial genomes are pervasively transcribed, generating a wide variety of antisense RNAs (asRNAs). Many of them originate from transcriptional read-through events (TREs) during the transcription termination process. Previous transcriptome analyses revealed that the lexA gene from Staphylococcus aureus, which encodes the main SOS response regulator, is affected by the presence of an asRNA. Here, we show that the lexA antisense RNA (lexA-asRNA) is generated by a TRE on the intrinsic terminator (TTsbrB) of the sbrB gene, which is located downstream of lexA, in the opposite strand. Transcriptional read-through occurs by a natural mutation that destabilizes the TTsbrB structure and modifies the efficiency of the intrinsic terminator. Restoring the mispairing mutation in the hairpin of TTsbrB prevented lexA-asRNA transcription. The level of lexA-asRNA directly correlated with cellular stress since the expressions of sbrB and lexA-asRNA depend on the stress transcription factor SigB. Comparative analyses revealed strain-specific nucleotide polymorphisms within TTsbrB, suggesting that this TT could be prone to accumulating natural mutations. A genome-wide analysis of TREs suggested that mispairings in TT hairpins might provide wider transcriptional connections with downstream genes and, ultimately, transcriptomic variability among S. aureus strains.
High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations
Authors: Lee Dong Woo , Kim Jung Eun , Lee Ga-Haeng , Son Arang , Park Hee Chul , Oh Dongryul , Jo Kwanghyun , Choi Changhoon
Published: January 2022

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines—Fadu and Cal27—cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.
A Complexed Crystal Structure of a Single-Stranded DNA-Binding Protein with Quercetin and the Structural Basis of Flavonol Inhibition Specificity
Authors: Lin En-Shyh , Luo Ren-Hong , Huang Cheng-Yang
Published: January 2022

Single-stranded DNA (ssDNA)-binding protein (SSB) plays a crucial role in DNA replication, repair, and recombination as well as replication fork restarts. SSB is essential for cell survival and, thus, is an attractive target for potential antipathogen chemotherapy. Whether naturally occurring products can inhibit SSB remains unknown. In this study, the effect of the flavonols myricetin, quercetin, kaempferol, and galangin on the inhibition of Pseudomonas aeruginosa SSB (PaSSB) was investigated. Furthermore, SSB was identified as a novel quercetin-binding protein. Through an electrophoretic mobility shift analysis, myricetin could inhibit the ssDNA binding activity of PaSSB with an IC50 of 2.8 ± 0.4 μM. The effect of quercetin, kaempferol, and galangin was insignificant. To elucidate the flavonol inhibition specificity, the crystal structure of PaSSB complexed with the non-inhibitor quercetin was solved using the molecular replacement method at a resolution of 2.3 Å (PDB entry 7VUM) and compared with a structure with the inhibitor myricetin (PDB entry 5YUN). Although myricetin and quercetin bound PaSSB at a similar site, their binding poses were different. Compared with myricetin, the aromatic ring of quercetin shifted by a distance of 4.9 Å and an angle of 31o for hydrogen bonding to the side chain of Asn108 in PaSSB. In addition, myricetin occupied and interacted with the ssDNA binding sites Lys7 and Glu80 in PaSSB whereas quercetin did not. This result might explain why myricetin could, but quercetin could not, strongly inhibit PaSSB. This molecular evidence reveals the flavonol inhibition specificity and also extends the interactomes of the natural anticancer products myricetin and quercetin to include the OB-fold protein SSB.
XRCC4 and MRE11 Roles and Transcriptional Response to Repair of TALEN-Induced Double-Strand DNA Breaks
Authors: Benjamin Ronald , Banerjee Atoshi , Wu Xiaogang , Geurink Corey , Buczek Lindsay , Eames Danielle , Trimidal Sara G. , Pluth Janice M. , Schiller Martin R.
Published: January 2022

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 exonuclease activity), albeit with ~40% reduced efficiency compared to normal cells. Editing in the absence of XRCC4 or MRE11 exonuclease was robust, with little difference between the indel profiles amongst any of the groups. Reviewing the transcriptional profiles of the mirin-treated XRCC4 knockout cells showed 307 uniquely differentially expressed genes, a number far greater than for either of the other cell lines (the HeLa XRCC4 knockout sample had 83 genes, and the mirin-treated HeLa cells had 30 genes uniquely differentially expressed). Pathways unique to the XRCC4 knockout+mirin group included differential expression of p53 downstream pathways, and metabolic pathways indicating cell adaptation for energy regulation and stress response. In conclusion, our study showed that TALEN-induced DSBs are repaired, even when a key DSB repair protein or protein function is not operational, without a change in indel profiles. However, transcriptional profiles indicate the induction of unique cellular responses dependent upon the DNA repair protein(s) hampered.
Native and Engineered Probiotics: Promising Agents against Related Systemic and Intestinal Diseases
Authors: Shen Haokun , Zhao Zitong , Zhao Zengjue , Chen Yuyi , Zhang Linghua
Published: January 2022

Intestinal homeostasis is a dynamic balance involving the interaction between the host intestinal mucosa, immune barrier, intestinal microecology, nutrients, and metabolites. Once homeostasis is out of balance, it will increase the risk of intestinal diseases and is also closely associated with some systemic diseases. Probiotics (Escherichia coli Nissle 1917, Akkermansia muciniphila, Clostridium butyricum, lactic acid bacteria and Bifidobacterium spp.), maintaining the gut homeostasis through direct interaction with the intestine, can also exist as a specific agent to prevent, alleviate, or cure intestinal-related diseases. With genetic engineering technology advancing, probiotics can also show targeted therapeutic properties. The aims of this review are to summarize the roles of potential native and engineered probiotics in oncology, inflammatory bowel disease, and obesity, discussing the therapeutic applications of these probiotics.
Insulin Clearance in Obesity and Type 2 Diabetes
Authors: Koh Han-Chow E. , Cao Chao , Mittendorfer Bettina
Published: January 2022

Plasma insulin clearance is an important determinant of plasma insulin concentration. In this review, we provide an overview of the factors that regulate insulin removal from plasma and discuss the interrelationships among plasma insulin clearance, excess adiposity, insulin sensitivity, and type 2 diabetes (T2D). We conclude with the perspective that the commonly observed lower insulin clearance rate in people with obesity, compared with lean people, is not a compensatory response to insulin resistance but occurs because insulin sensitivity and insulin clearance are mechanistically, directly linked. Furthermore, insulin clearance decreases postprandially because of the marked increase in insulin delivery to tissues that clear insulin. The commonly observed high postprandial insulin clearance in people with obesity and T2D likely results from the relatively low insulin secretion rate, not an impaired adaptation of tissues that clear insulin.
Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes
Authors: Cliff Chelsy L. , Williams Bethany M. , Chadjichristos Christos E. , Mouritzen Ulrik , Squires Paul E. , Hills Claire E.
Published: January 2022

Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.
Potential Biomarkers for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Kim Ka Young , Shin Ki Young , Chang Keun-A
Published: January 2022

Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.
Immunomodulatory Properties and Osteogenic Activity of Polyetheretherketone Coated with Titanate Nanonetwork Structures
Authors: Yang Yuanyuan , Zhang Honghao , Komasa Satoshi , Kusumoto Tetsuji , Kuwamoto Shinsuke , Okunishi Tohru , Kobayashi Yasuyuki , Hashimoto Yoshiya , Sekino Tohru , Okazaki Joji
Published: January 2022

Polyetheretherketone (PEEK) is a potential substitute for conventional metallic biomedical implants owing to its superior mechanical and chemical properties, as well as biocompatibility. However, its inherent bio-inertness and poor osseointegration limit its use in clinical applications. Herein, thin titanium films were deposited on the PEEK substrate by plasma sputtering, and porous nanonetwork structures were incorporated on the PEEK surface by alkali treatment (PEEK-TNS). Changes in the physical and chemical characteristics of the PEEK surface were analyzed to establish the interactions with cell behaviors. The osteoimmunomodulatory properties were evaluated using macrophage cells and osteoblast lineage cells. The functionalized nanostructured surface of PEEK-TNS effectively promoted initial cell adhesion and proliferation, suppressed inflammatory responses, and induced macrophages to anti-inflammatory M2 polarization. Compared with PEEK, PEEK-TNS provided a more beneficial osteoimmune environment, including increased levels of osteogenic, angiogenic, and fibrogenic gene expression, and balanced osteoclast activities. Furthermore, the crosstalk between macrophages and osteoblast cells showed that PEEK-TNS could provide favorable osteoimmunodulatory environment for bone regeneration. PEEK-TNS exhibited high osteogenic activity, as indicated by alkaline phosphatase activity, osteogenic factor production, and the osteogenesis/osteoclastogenesis-related gene expression of osteoblasts. The study establishes that the fabrication of titanate nanonetwork structures on PEEK surfaces could extract an adequate immune response and favorable osteogenesis for functional bone regeneration. Furthermore, it indicates the potential of PEEK-TNS in implant applications.
Towards Tabula Gallus
Authors: Yamagata Masahito
Published: January 2022

The Tabula Gallus is a proposed project that aims to create a map of every cell type in the chicken body and chick embryos. Chickens (Gallus gallus) are one of the most recognized model animals that recapitulate the development and physiology of mammals. The Tabula Gallus will generate a compendium of single-cell transcriptome data from Gallus gallus, characterize each cell type, and provide tools for the study of the biology of this species, similar to other ongoing cell atlas projects (Tabula Muris and Tabula Sapiens/Human Cell Atlas for mice and humans, respectively). The Tabula Gallus will potentially become an international collaboration between many researchers. This project will be useful for the basic scientific study of Gallus gallus and other birds (e.g., cell biology, molecular biology, developmental biology, neuroscience, physiology, oncology, virology, behavior, ecology, and evolution). It will eventually be beneficial for a better understanding of human health and diseases.
Genome-Wide Identification and Characterization of the RCI2 Gene Family in Allotetraploid Brassica napus Compared with Its Diploid Progenitors
Authors: Sun Weiqi , Li Mengdi , Wang Jianbo
Published: January 2022

Brassica napus and its diploid progenitors (B. rapa and B. oleracea) are suitable for studying the problems associated with polyploidization. As an important anti-stress protein, RCI2 proteins widely exist in various tissues of plants, and are crucial to plant growth, development, and stress response. In this study, the RCI2 gene family was comprehensively identified and analyzed, and 9, 9, and 24 RCI2 genes were identified in B. rapa, B. oleracea, and B. napus, respectively. Phylogenetic analysis showed that all of the identified RCI2 genes were divided into two groups, and further divided into three subgroups. Ka/Ks analysis showed that most of the identified RCI2 genes underwent a purifying selection after the duplication events. Moreover, gene structure analysis showed that the structure of RCI2 genes is largely conserved during polyploidization. The promoters of the RCI2 genes in B. napus contained more cis-acting elements, which were mainly involved in plant development and growth, plant hormone response, and stress responses. Thus, B. napus might have potential advantages in some biological aspects. In addition, the changes of RCI2 genes during polyploidization were also discussed from the aspects of gene number, gene structure, gene relative location, and gene expression, which can provide reference for future polyploidization analysis.
Radiolabeled Gold Nanoseeds Decorated with Substance P Peptides: Synthesis, Characterization and In Vitro Evaluation in Glioblastoma Cellular Models
Authors: Silva Francisco , D’Onofrio Alice , Mendes Carolina , Pinto Catarina , Marques Ana , Campello Maria Paula Cabral , Oliveira Maria Cristina , Raposinho Paula , Belchior Ana , Di Maria Salvatore , Marques Fernanda , Cruz Carla , Carvalho Josué , Paulo António
Published: January 2022

Despite some progress, the overall survival of patients with glioblastoma (GBM) remains extremely poor. In this context, there is a pressing need to develop innovative therapy strategies for GBM, namely those based on nanomedicine approaches. Towards this goal, we have focused on nanoparticles (AuNP-SP and AuNP-SPTyr8) with a small gold core (ca. 4 nm), carrying DOTA chelators and substance P (SP) peptides. These new SP-containing AuNPs were characterized by a variety of analytical techniques, including TEM and DLS measurements and UV-vis and CD spectroscopy, which proved their high in vitro stability and poor tendency to interact with plasma proteins. Their labeling with diagnostic and therapeutic radionuclides was efficiently performed by DOTA complexation with the trivalent radiometals 67Ga and 177Lu or by electrophilic radioiodination with 125I of the tyrosyl residue in AuNP-SPTyr8. Cellular studies of the resulting radiolabeled AuNPs in NKR1-positive GBM cells (U87, T98G and U373) have shown that the presence of the SP peptides has a crucial and positive impact on their internalization by the tumor cells. Consistently, 177Lu-AuNP-SPTyr8 showed more pronounced radiobiological effects in U373 cells when compared with the non-targeted congener 177Lu-AuNP-TDOTA, as assessed by cell viability and clonogenic assays and corroborated by Monte Carlo microdosimetry simulations.
Self-Healing Materials for Electronics Applications
Authors: Mashkoor Fouzia , Lee Sun Jin , Yi Hoon , Noh Seung Man , Jeong Changyoon
Published: January 2022

Self-healing materials have been attracting the attention of the scientists over the past few decades because of their effectiveness in detecting damage and their autonomic healing response. Self-healing materials are an evolving and intriguing field of study that could lead to a substantial increase in the lifespan of materials, improve the reliability of materials, increase product safety, and lower product replacement costs. Within the past few years, various autonomic and non-autonomic self-healing systems have been developed using various approaches for a variety of applications. The inclusion of appropriate functionalities into these materials by various chemistries has enhanced their repair mechanisms activated by crack formation. This review article summarizes various self-healing techniques that are currently being explored and the associated chemistries that are involved in the preparation of self-healing composite materials. This paper further surveys the electronic applications of self-healing materials in the fields of energy harvesting devices, energy storage devices, and sensors. We expect this article to provide the reader with a far deeper understanding of self-healing materials and their healing mechanisms in various electronics applications.
Ectopic Expression of FVIII in HPCs and MSCs Derived from hiPSCs with Site-Specific Integration of ITGA2B Promoter-Driven BDDF8 Gene in Hemophilia A
Authors: Zhao Junya , Zhou Miaojin , Wang Zujia , Wu Lingqian , Hu Zhiqing , Liang Desheng
Published: January 2022

Hemophilia A (HA) is caused by mutations in the coagulation factor VIII (FVIII) gene (F8). Gene therapy is a hopeful cure for HA; however, FVIII inhibitors formation hinders its clinical application. Given that platelets promote coagulation via locally releasing α-granule, FVIII ectopically expressed in platelets has been attempted, with promising results for HA treatment. The B-domain-deleted F8 (BDDF8), driven by a truncated ITGA2B promoter, was targeted at the ribosomal DNA (rDNA) locus of HA patient-specific induced pluripotent stem cells (HA-iPSCs). The F8-modified, human induced pluripotent stem cells (2bF8-iPSCs) were differentiated into induced hematopoietic progenitor cells (iHPCs), induced megakaryocytes (iMKs), and mesenchymal stem cells (iMSCs), and the FVIII expression was detected. The ITGA2B promoter-driven BDDF8 was site-specifically integrated into the rDNA locus of HA-iPSCs. The 2bF8-iPSCs were efficiently differentiated into 2bF8-iHPCs, 2bF8-iMKs, and 2bF8-iMSCs. FVIII was 10.31 ng/106 cells in lysates of 2bF8-iHPCs, compared to 1.56 ng/106 cells in HA-iHPCs, and FVIII was 3.64 ng/106 cells in 2bF8-iMSCs lysates, while 1.31 ng/106 cells in iMSCs with CMV-driven BDDF8. Our results demonstrated a high expression of FVIII in iHPCs and iMSCs derived from hiPSCs with site-specific integration of ITGA2B promoter-driven BDDF8, indicating potential clinical prospects of this platelet-targeted strategy for HA gene therapy.
Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
Authors: Button Lucy , Rogers Bryony , Thomas Emily , Bradfield Alice , Alnafakh Rafah , Drury Josephine , Hapangama Dharani K.
Published: January 2022

Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.
Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases
Authors: Zhong Yajie , Zhang Xuan , Chong Waipo
Published: January 2022

Interleukin (IL)-24 belongs to the IL-10 family and signals through two receptor complexes, i.e., IL-20RA/IL-20RB and IL-20RB/IL22RA1. It is a multifunctional cytokine that can regulate immune response, tissue homeostasis, host defense, and oncogenesis. Elevation of IL-24 is associated with chronic inflammation and autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Its pathogenicity has been confirmed by inducing inflammation and immune cell infiltration for tissue damage. However, recent studies also revealed their suppressive functions in regulating immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. The tolerogenic properties of IL-24 were reported in various animal models of autoimmune diseases, suggesting the complex functions of IL-24 in regulating autoimmunity. In this review, we discuss the immunoregulatory functions of IL-24 and its roles in autoimmune diseases.
Towards a Bibliometric Mapping of Network Public Opinion Studies
Authors: Qiang Yujie , Tao Xuewen , Gou Xiaoqing , Lang Zhihui , Liu Hui
Published: January 2022

To grasp the current status of network public opinion (NPO) research and explore the knowledge base and hot trends from a quantitative perspective, we retrieved 1385 related papers and conducted a bibliometric mapping analysis on them. Co-occurrence analysis, cluster analysis, co-citation analysis and keyword burst analysis were performed using VOSviewer and CiteSpace software. The results show that the NPO is mainly distributed in the disciplinary fields associated with journalism and communication and public management. There are four main hotspots: analysis of public opinion, analysis of communication channels, technical means and challenges faced. The knowledge base in the field of NPO research includes social media, user influence, and user influence related to opinion dynamic modeling and sentiment analysis. With the advent of the era of big data, big data technology has been widely used in various fields and to some extent can be said to be the research frontier in the field. Transforming big data public opinion into early warning, realizing in-depth analysis and accurate prediction of public opinion as well as improving decision-making ability of public opinion are the future research directions of NPO.
Linguistic Mathematical Relationships Saved or Lost in Translating Texts: Extension of the Statistical Theory of Translation and Its Application to the New Testament
Authors: Matricciani Emilio
Published: January 2022

The purpose of the paper is to extend the general theory of translation to texts written in the same language and show some possible applications. The main result shows that the mutual mathematical relationships of texts in a language have been saved or lost in translating them into another language and consequently texts have been mathematically distorted. To make objective comparisons, we have defined a “likeness index”—based on probability and communication theory of noisy binary digital channels-and have shown that it can reveal similarities and differences of texts. We have applied the extended theory to the New Testament translations and have assessed how much the mutual mathematical relationships present in the original Greek texts have been saved or lost in 36 languages. To avoid the inaccuracy, due to the small sample size from which the input data (regression lines) are calculated, we have adopted a “renormalization” based on Monte Carlo simulations whose results we consider as “experimental”. In general, we have found that in many languages/translations the original linguistic relationships have been lost and texts mathematically distorted. The theory can be applied to texts translated by machines. Because the theory deals with linear regression lines, the concepts of signal-to-noise-ratio and likenss index can be applied any time a scientific/technical problem involves two or more linear regression lines, therefore it is not limited to linguistic variables but it is universal.
Latest Advances in Finite Element Modelling and Model Updating of Cable-Stayed Bridges
Authors: Sharry Thomas , Guan Hong , Nguyen Andy , Oh Erwin , Hoang Nam
Published: January 2022

As important links in the transport infrastructure system, cable-stayed bridges are among the most popular candidates for implementing structural health monitoring (SHM) technology. The primary aim of SHM for these bridges is to ensure their structural integrity and satisfactory performance by monitoring their behaviour over time. Finite element (FE) model updating is a well-recognised approach for SHM purposes, as an accurate model serves as a baseline reference for damage detection and long-term monitoring efforts. One of the many challenges is the development of the initial FE model that can accurately reflect the dynamic characteristics and the overall behaviour of a bridge. Given the size, slenderness, use of long cables, and high levels of structural redundancy, precise initial models of long-span cable-stayed bridges are desirable to better facilitate the model updating process and to improve the accuracy of the final updated model. To date, very few studies offer in-depth discussions on the modelling approaches for cable-stayed bridges and the methods used for model updating. As such, this article presents the latest advances in finite element modelling and model updating methods that have been widely adopted for cable-stayed bridges, through a critical literature review of existing research work. An overview of current SHM research is presented first, followed by a comprehensive review of finite element modelling of cable-stayed bridges, including modelling approaches of the deck girder and cables. A general overview of model updating methods is then given before reviewing the model updating applications to cable-stayed bridges. Finally, an evaluation of all available methods and assessment for future research outlook are presented to summarise the research achievements and current limitations in this field.
Effect of Organic Farming and Agricultural Abandonment on Beneficial Arthropod Communities Associated with Olive Groves in Western Spain: Implications for Bactrocera oleae Management
Authors: de Paz Víctor , Tobajas Estefanía , Rosas-Ramos Natalia , Tormos José , Asís Josep Daniel , Baños-Picón Laura
Published: January 2022

Agricultural abandonment and intensification are among the main land-use changes in Europe. Along with these processes, different proposals have been developed to counteract the negative effects derived from agricultural intensification, including organic management. In this context, we aimed to determine how organic management and farmland abandonment affect Bactrocera oleae and its main groups of natural enemies: hymenopteran parasitoids, spiders, ants, carabids, and staphylinids. Between May and October 2018, four samplings were carried out in nine olive groves (three under organic management, three under traditional management, and three abandoned) in a rural area on the border between Spain and Portugal (Salamanca, Western Spain). Our results suggested differences between the natural enemy community composition of abandoned and organic groves, with slightly higher levels of richness and abundance in abandoned groves. We found no differences between organic and traditional groves. The managed olive groves sustained a different natural enemy community but were similarly rich and diverse compared with the more complex abandoned groves, with the latter not acting as a reservoir of B. oleae in our study area. Both systems may provide complementary habitats; however, further abandonment could cause a reduction in heterogeneity at the landscape scale and, consequently, a biodiversity loss.
A Review of the Evolution of Termite Control: A Continuum of Alternatives to Termiticides in the United States with Emphasis on Efficacy Testing Requirements for Product Registration
Authors: Oi Faith
Published: January 2022

The global economic impact of termites is estimated to be approximately USD 40 billion annually, and subterranean termites are responsible for about 80% of the total impact. Twenty-eight species of termites have been described as invasive, and these termites are spreading, partially due to global trade, making effective control methods essential. Termite control is complex, as is the biology and behavior of this social insect group. In the U.S., termite prevention and control (with claims of structural protection) is regulated by more than one industry (pest control and building construction), and at the federal and state levels. Termite prevention has historically relied on building construction practices that do not create conducive conditions for termite infestations, but as soil termiticides developed, heavy reliance on pesticides became the standard for termite control. The concern for human and environmental health has driven the development of termite control alternatives and regulation for products claiming structural protection. Product development has also provided unprecedented opportunities to study the biology and behavior of cryptobiotic termites. Technological advances have allowed for the re-examination of questions about termite behavior. Advances in communications via social media provide unrestricted access to information, creating a conundrum for consumers and science educators alike.
Low Heat Availability Could Limit the Potential Spread of the Emerald Ash Borer to Northern Europe (Prognosis Based on Growing Degree Days per Year)
Authors: Orlova-Bienkowskaja Marina J. , Bieńkowski Andrzej O.
Published: January 2022

Emerald ash borer Agrilus planipennis (Coleoptera: Buprestidae) is one of 20 priority quarantine pests of the European Union. It is native to Asia and is established in the USA, Canada, European Russia, and Ukraine. We made the first prognosis of the potential range of A. planipennis in Europe based on heat availability. Mean annual growing degree days base 10 °C (AGDD10) was calculated for each grid square (0.25° × 0.25° latitude x longitude degrees) on the Earth’s surface. Minimal AGDD10 recorded in the grid squares currently occupied by A. planipennis was 714° in Asia, 705° in North America, and 711° in European Russia. Agrilus planipennis has never been recorded in localities with AGDD10 below 700°. If the phenotypic plasticity would not allow this species to overcome this threshold, cold regions of Europe would probably not be invaded by A. planipennis. Thus, Fraxinus excelsior could potentially escape from A. planipennis in some regions of Norway, Sweden, Finland, Ireland, and Great Britain.