bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Mortality of Hospitalized Adult Patients with COVID-19 Pneumonia: A Two-Year Cohort Study in a Private Tertiary Care Center in Mexico
Authors: López-Pérez Carlos Axel , Santa Cruz-Pavlovich Francisco J. , Montiel-Cortés Juan Eduardo , Núñez-Muratalla Adriana , Morán-González Ruth Bibani , Villanueva-Gaona Ricardo , Franco-Mojica Xochitl , Moreno-Sandoval Denisse Gabriela , González-Bañuelos Joselyn Anacaren , López-Pérez Alan Ulises , Flores-González Marily , Grijalva-Ruiz Cristina , Valdez-Mendoza Edna Daniela , González-Lucano Luis Renee , López-Zendejas Martín
Published: March 2023

During the COVID-19 pandemic, the high prevalence of comorbidities and the disparities between the public and private health subsystems in Mexico substantially contributed to the severe impact of the disease. The objective of this study was to evaluate and compare the risk factors at admission for in-hospital mortality of patients with COVID-19. A 2-year retrospective cohort study of hospitalized adult patients with COVID-19 pneumonia was conducted at a private tertiary care center. The study population consisted of 1258 patients with a median age of 56 ± 16.5 years, of whom 1093 recovered (86.8%) and 165 died (13.1%). In the univariate analysis, older age (p < 0.001), comorbidities such as hypertension (p < 0.001) and diabetes (p < 0.001), signs and symptoms of respiratory distress, and markers of acute inflammatory response were significantly more frequent in non-survivors. The multivariate analysis showed that older age (p < 0.001), the presence of cyanosis (p = 0.005), and previous myocardial infarction (p = 0.032) were independent predictors of mortality. In the studied cohort, the risk factors present at admission associated with increased mortality were older age, cyanosis, and a previous myocardial infarction, which can be used as valuable predictors for patients’ outcomes. To our knowledge, this is the first study analyzing predictors of mortality in COVID-19 patients attended in a private tertiary hospital in Mexico.
When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases
Authors: Boi Dalila , Rubini Elisabetta , Breccia Sara , Guarguaglini Giulia , Paiardini Alessandro
Published: March 2023

Myc transcription factors are key regulators of many cellular processes, with Myc target genes crucially implicated in the management of cell proliferation and stem pluripotency, energy metabolism, protein synthesis, angiogenesis, DNA damage response, and apoptosis. Given the wide involvement of Myc in cellular dynamics, it is not surprising that its overexpression is frequently associated with cancer. Noteworthy, in cancer cells where high Myc levels are maintained, the overexpression of Myc-associated kinases is often observed and required to foster tumour cells’ proliferation. A mutual interplay exists between Myc and kinases: the latter, which are Myc transcriptional targets, phosphorylate Myc, allowing its transcriptional activity, highlighting a clear regulatory loop. At the protein level, Myc activity and turnover is also tightly regulated by kinases, with a finely tuned balance between translation and rapid protein degradation. In this perspective, we focus on the cross-regulation of Myc and its associated protein kinases underlying similar and redundant mechanisms of regulation at different levels, from transcriptional to post-translational events. Furthermore, a review of the indirect effects of known kinase inhibitors on Myc provides an opportunity to identify alternative and combined therapeutic approaches for cancer treatment.
Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma
Authors: Cadamuro Massimiliano , Sarcognato Samantha , Camerotto Riccardo , Girardi Noemi , Lasagni Alberto , Zanus Giacomo , Cillo Umberto , Gringeri Enrico , Morana Giovanni , Strazzabosco Mario , Campello Elena , Simioni Paolo , Guido Maria , Fabris Luca
Published: March 2023

Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.
ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma
Authors: Chua Kenon , Sim Arthur Yi Loong , Yeo Eric Yew Meng , Bin Masroni Muhammad Sufyan , Naw Wah Wah , Leong Sai Mun , Lee Kee Wah , Lim Huey Jin , Virshup David M. , Lee Victor Kwan Min
Published: March 2023

There is an increasing urgency in the search for new drugs to target high-grade cancers such as osteosarcomas (OS), as these have limited therapeutic options and poor prognostic outlook. Even though key molecular events leading to tumorigenesis are not well understood, it is widely agreed that OS tumours are Wnt-driven. ETC-159, a PORCN inhibitor that inhibits the extracellular secretion of Wnt, has recently progressed on to clinical trials. In vitro and in vivo murine and chick chorioallantoic membrane xenograft models were established to examine the effect of ETC-159 on OS. Consistent with our hypothesis, we noted that ETC-159 treatment not only resulted in markedly decreased β-catenin staining in xenografts, but also increased tumour necrosis and a significant reduction in vascularity—a hereby yet undescribed phenotype following ETC-159 treatment. Through further understanding the mechanism of this new window of vulnerability, therapies can be developed to potentiate and maximize the effectiveness of ETC-159, further increasing its clinical utility for the treatment of OS.
Structural Diversity among Edwardsiellaceae Core Oligosaccharides
Authors: Jordán Maria , Wojtys-Tekiel Sylwia , Merino Susana , Tomás Juan M. , Kaszowska Marta
Published: March 2023

The Edwardsiella genus presents five different pathogenic species: Edwardsiella tarda, E. anguillarum, E. piscicida, E. hoshinae and E. ictaluri. These species cause infections mainly in fish, but they can also infect reptiles, birds or humans. Lipopolysaccharide (endotoxin) plays an important role in the pathogenesis of these bacteria. For the first time, the chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharides of E. piscicida, E. anguillarum, E. hoshinae and E. ictaluri were studied. The complete gene assignments for all core biosynthesis gene functions were acquired. The structure of core oligosaccharides was investigated by ¹H and 13C nuclear magnetic resonance (NMR) spectroscopy. The structures of E. piscicida and E. anguillarum core oligosaccharides show the presence of →3,4)-L-glycero-α-D-manno-Hepp, two terminal β-D-Glcp, →2,3,7)-L-glycero-α-D-manno-Hepp, →7)-L-glycero-α-D-manno-Hepp, terminal α-D-GlcpN, two →4)-α-D-GalpA, → 3)-α-D-GlcpNAc, terminal β-D-Galp and →5-substituted Kdo. E. hoshinare core oligosaccharide shows only one terminal β-D-Glcp, and instead of terminal β-D-Galp a terminal α-D-GlcpNAc. E. ictaluri core oligosaccharide shows only one terminal β-D-Glcp, one →4)-α-D-GalpA and do not have terminal α-D-GlcpN (see complementary figure).
Effects of Different Gene Editing Modes of CRISPR/Cas9 on Soybean Fatty Acid Anabolic Metabolism Based on GmFAD2 Family
Authors: Zhou Junming , Li Zeyuan , Li Yue , Zhao Qiuzhu , Luan Xinchao , Wang Lixue , Liu Yixuan , Liu Huijing , Zhang Jun , Yao Dan
Published: March 2023

Δ12-fatty acid dehydrogenase (FAD2) is the essential enzyme responsible for catalyzing the formation of linoleic acid from oleic acid. CRISPR/Cas9 gene editing technology has been an essential tool for molecular breeding in soybeans. To evaluate the most suitable type of gene editing in soybean fatty acid synthesis metabolism, this study selected five crucial enzyme genes of the soybean FAD2 gene family—GmFAD2-1A, GmFAD2-1B, GmFAD2-2A, GmFAD2-2B, and GmFAD2-2C—and created a CRISPR/Cas9-mediated single gene editing vector system. The results of Sanger sequencing showed that 72 transformed plants positive for T1 generation were obtained using Agrobacterium-mediated transformation, of which 43 were correctly edited plants, with the highest editing efficiency of 88% for GmFAD2-2A. The phenotypic analysis revealed that the oleic acid content of the progeny of GmFAD2-1A gene-edited plants had a higher increase of 91.49% when compared to the control JN18, and the rest of the gene-edited plants in order were GmFAD2-2A, GmFAD2-1B, GmFAD2-2C, and GmFAD2-2B. The analysis of gene editing type has indicated that base deletions greater than 2bp were the predominant editing type in all editing events. This study provides ideas for the optimization of CRISPR/Cas9 gene editing technology and the development of new tools for precise base editing in the future.
Proteomic Markers for Mechanobiological Properties of Metastatic Cancer Cells
Authors: Leonov Sergey , Inyang Olumide , Achkasov Konstantin , Bogdan Elizaveta , Kontareva Elizaveta , Chen Yongheng , Fu Ying , Osipov Andreyan N. , Pustovalova Margarita , Merkher Yulia
Published: March 2023

The major cause (more than 90%) of all cancer-related deaths is metastasis, thus its prediction can critically affect the survival rate. Metastases are currently predicted by lymph-node status, tumor size, histopathology and genetic testing; however, all these are not infallible, and obtaining results may require weeks. The identification of new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies. Recently, the new mechanobiology-related techniques, independent of genetics, based on the mechanical invasiveness of cancer cells (microfluidic, gel indentation assays, migration assays etc.), demonstrated a high success rate for the detection of tumor cell metastasis propensity. However, they are still far away from clinical implementation due to complexity. Hence, the exploration of novel markers related to the mechanobiological properties of tumor cells may have a direct impact on the prognosis of metastasis. Our concise review deepens our knowledge of the factors that regulate cancer cell mechanotype and invasion, and incites further studies to develop therapeutics that target multiple mechanisms of invasion for improved clinical benefit. It may open a new clinical dimension that will improve cancer prognosis and increase the effectiveness of tumor therapies.
Toward the Development of Epigenome Editing-Based Therapeutics: Potentials and Challenges
Authors: Ueda Jun , Yamazaki Taiga , Funakoshi Hiroshi
Published: March 2023

The advancement in epigenetics research over the past several decades has led to the potential application of epigenome-editing technologies for the treatment of various diseases. In particular, epigenome editing is potentially useful in the treatment of genetic and other related diseases, including rare imprinted diseases, as it can regulate the expression of the epigenome of the target region, and thereby the causative gene, with minimal or no modification of the genomic DNA. Various efforts are underway to successfully apply epigenome editing in vivo, such as improving target specificity, enzymatic activity, and drug delivery for the development of reliable therapeutics. In this review, we introduce the latest findings, summarize the current limitations and future challenges in the practical application of epigenome editing for disease therapy, and introduce important factors to consider, such as chromatin plasticity, for a more effective epigenome editing-based therapy.
Red LED Light Improves Pepper (Capsicum annuum L.) Seed Radicle Emergence and Growth through the Modulation of Aquaporins, Hormone Homeostasis, and Metabolite Remobilization
Authors: Zaghdoud Chokri , Ollio Irene , Solano Cristóbal J. , Ochoa Jesús , Suardiaz Juan , Fernández Juan A. , Martínez Ballesta María del Carmen
Published: March 2023

Red LED light (R LED) is an efficient tool to improve seed germination and plant growth under controlled environments since it is more readily absorbed by photoreceptors’ phytochromes compared to other wavelengths of the spectrum. In this work, the effect of R LED on the radicle emergence and growth (Phase III of germination) of pepper seeds was evaluated. Thus, the impact of R LED on water transport through different intrinsic membrane proteins, via aquaporin (AQP) isoforms, was determined. In addition, the remobilization of distinct metabolites such as amino acids, sugars, organic acids, and hormones was analysed. R LED induced a higher germination speed index, regulated by an increased water uptake. PIP2;3 and PIP2;5 aquaporin isoforms were highly expressed and could contribute to a faster and more effective hydration of embryo tissues, leading to a reduction of the germination time. By contrast, TIP1;7, TIP1;8, TIP3;1 and TIP3;2 gene expressions were reduced in R LED-treated seeds, pointing to a lower need for protein remobilization. NIP4;5 and XIP1;1 were also involved in radicle growth but their role needs to be elucidated. In addition, R LED induced changes in amino acids and organic acids as well as sugars. Therefore, an advanced metabolome oriented to a higher energetic metabolism was observed, conditioning better seed germination performance together with a rapid water flux.
Quercetin 3-O-(6″-O-E-caffeoyl)-β-D-glucopyranoside, a Flavonoid Compound, Promotes Melanogenesis through the Upregulation of MAPKs and Akt/GSK3β/β-Catenin Signaling Pathways
Authors: Liu Changhai , Nueraihemaiti Mayire , Zang Deng , Edirs Salamet , Zou Guoan , Aisa Haji Akber
Published: March 2023

Quercetin 3-O-(6″-O-E-caffeoyl)-β-D-glucopyranoside is a flavonoid compound produced by various plants with reported antiprotozoal potential against E. histolytica and G. lamblia; however, its effects on skin pigment regulation have not been studied in detail. In this investigation, we discovered that quercetin 3-O-(6″-O-E-caffeoyl)—D-glucopyranoside (coded as CC7) demonstrated a more increased melanogenesis effect in B16 cells. CC7 exhibited no cytotoxicity or effective stimulating melanin content or intracellular tyrosinase activity. This melanogenic-promoting effect was accompanied by activated expression levels of microphthalmia-associated transcription factor (MITF), a key melanogenic regulatory factor, melanogenic enzymes, and tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) and 2 (TRP-2) in the CC7-treated cells. Mechanistically, we found that CC7 exerted melanogenic effects by upregulating the phosphorylation of stress-regulated protein kinase (p38) and c-Jun N-terminal kinase (JNK). Moreover, the CC7 upregulation of phosphor-protein kinase B (Akt) and Glycogen synthase kinase-3 beta (GSK-3β) increased the content of β-catenin in the cell cytoplasm, and subsequently, it translocated into the nucleus, resulting in melanogenesis. Specific inhibitors of P38, JNK, and Akt validated that CC7 promotes melanin synthesis and tyrosinase activity by regulating the GSK3β/β-catenin signaling pathways. Our results support that the CC7 regulation of melanogenesis involves MAPKs and Akt/GSK3β/β-catenin signaling pathways.
Oxidative Status of Medicago truncatula Seedlings after Inoculation with Rhizobacteria of the Genus Pseudomonas, Paenibacillus and Sinorhizobium
Authors: Kisiel Anna , Miller Tymoteusz
Published: March 2023

An increasing number of scientists working to raise agricultural productivity see the potential in the roots and the soil adjacent to them, together with a wealth of micro-organisms. The first mechanisms activated in the plant during any abiotic or biotic stress concern changes in the oxidative status of the plant. With this in mind, for the first time, an attempt was made to check whether the inoculation of seedlings of the model plant Medicago truncatula with rhizobacteria belonging to the genus Pseudomonas (P. brassicacearum KK5, P. corrugata KK7), Paenibacillus borealis KK4 and a symbiotic strain Sinorhizobium meliloti KK13 would change the oxidative status in the days following inoculation. Initially, an increase in H2O2 synthesis was observed, which led to an increase in the activity of antioxidant enzymes responsible for regulating hydrogen peroxide levels. The main enzyme involved in the reduction of H2O2 content in the roots was catalase. The observed changes indicate the possibility of using the applied rhizobacteria to induce processes related to plant resistance and thus to ensure protection against environmental stress factors. In the next stages, it seems reasonable to check whether the initial changes in the oxidative state affect the activation of other pathways related to plant immunity.
Metformin, Empagliflozin, and Their Combination Modulate Ex-Vivo Macrophage Inflammatory Gene Expression
Authors: Arefin Adittya , Gage Matthew C.
Published: March 2023

Type-2 Diabetes Mellitus is a complex, chronic illness characterized by persistent high blood glucose levels. Patients can be prescribed anti-diabetes drugs as single agents or in combination depending on the severity of their condition. Metformin and empagliflozin are two commonly prescribed anti-diabetes drugs which reduce hyperglycemia, however their direct effects on macrophage inflammatory responses alone or in combination are unreported. Here, we show that metformin and empagliflozin elicit proinflammatory responses on mouse bone-marrow-derived macrophages with single agent challenge, which are modulated when added in combination. In silico docking experiments suggested that empagliflozin can interact with both TLR2 and DECTIN1 receptors, and we observed that both empagliflozin and metformin increase expression of Tlr2 and Clec7a. Thus, findings from this study suggest that metformin and empagliflozin as single agents or in combination can directly modulate inflammatory gene expression in macrophages and upregulate the expression of their receptors.
Inhibition of Transglutaminase 2 as a Therapeutic Strategy in Celiac Disease—In Vitro Studies in Intestinal Cells and Duodenal Biopsies
Authors: Stricker Sebastian , de Laffolie Jan , Zimmer Klaus-Peter , Rudloff Silvia
Published: March 2023

Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a key mechanism in the pathogenesis of celiac disease (CD) and represents a potential therapeutic target. Recently, we have identified the small oxidative molecule PX-12 as an effective inhibitor of TG2 in vitro. In this study, we further investigated the effect of PX-12 and the established active-site directed inhibitor ERW1041 on TG2 activity and epithelial transport of gliadin peptides. We analyzed TG2 activity using immobilized TG2, Caco-2 cell lysates, confluent Caco-2 cell monolayers and duodenal biopsies from CD patients. TG2-mediated cross-linking of pepsin-/trypsin-digested gliadin (PTG) and 5BP (5-biotinamidopentylamine) was quantified by colorimetry, fluorometry and confocal microscopy. Cell viability was tested with a resazurin-based fluorometric assay. Epithelial transport of promofluor-conjugated gliadin peptides P31-43 and P56-88 was analyzed by fluorometry and confocal microscopy. PX-12 reduced TG2-mediated cross-linking of PTG and was significantly more effective than ERW1041 (10 µM, 15 ± 3 vs. 48 ± 8%, p < 0.001). In addition, PX-12 inhibited TG2 in cell lysates obtained from Caco-2 cells more than ERW1041 (10 µM; 12 ± 7% vs. 45 ± 19%, p < 0.05). Both substances inhibited TG2 comparably in the intestinal lamina propria of duodenal biopsies (100 µM, 25 ± 13% vs. 22 ± 11%). However, PX-12 did not inhibit TG2 in confluent Caco-2 cells, whereas ERW1041 showed a dose-dependent effect. Similarly, epithelial transport of P56-88 was inhibited by ERW1041, but not by PX-12. Cell viability was not negatively affected by either substance at concentrations up to 100 µM. PX-12 did not reduce TG2 activity or gliadin peptide transport in confluent Caco-2 cells. This could be caused by rapid inactivation or degradation of the substance in the Caco-2 cell culture. Still, our in vitro data underline the potential of the oxidative inhibition of TG2. The fact that the TG2-specific inhibitor ERW1041 reduced the epithelial uptake of P56-88 in Caco-2 cells further strengthens the therapeutic potential of TG2 inhibitors in CD.
Pan-Cancer Analysis Reveals Functional Similarity of Three lncRNAs across Multiple Tumors
Authors: Khazaal Abir , Zandavi Seid Miad , Smolnikov Andrei , Fatima Shadma , Vafaee Fatemeh
Published: March 2023

Long non-coding RNAs (lncRNAs) are emerging as key regulators in many biological processes. The dysregulation of lncRNA expression has been associated with many diseases, including cancer. Mounting evidence suggests lncRNAs to be involved in cancer initiation, progression, and metastasis. Thus, understanding the functional implications of lncRNAs in tumorigenesis can aid in developing novel biomarkers and therapeutic targets. Rich cancer datasets, documenting genomic and transcriptomic alterations together with advancement in bioinformatics tools, have presented an opportunity to perform pan-cancer analyses across different cancer types. This study is aimed at conducting a pan-cancer analysis of lncRNAs by performing differential expression and functional analyses between tumor and non-neoplastic adjacent samples across eight cancer types. Among dysregulated lncRNAs, seven were shared across all cancer types. We focused on three lncRNAs, found to be consistently dysregulated among tumors. It has been observed that these three lncRNAs of interest are interacting with a wide range of genes across different tissues, yet enriching substantially similar biological processes, found to be implicated in cancer progression and proliferation.
Cellular FXIII in Human Macrophage-Derived Foam Cells
Authors: Somodi Laura , Horváth Emőke , Bárdos Helga , Baráth Barbara , Pethő Dávid , Katona Éva , Balla József , Mutch Nicola J. , Muszbek László
Published: March 2023

Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.
Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities
Authors: Navarrete Cristian , Riquelme Alejandro , Baksai Natalia , Pérez Romina , González Claudia , Michea María , von Mühlenbrock Hans , Cafferata Emilio A. , Vernal Rolando
Published: March 2023

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.
Combined Metabolome and Transcriptome Analysis Elucidates Sugar Accumulation in Wucai (Brassica campestris L.)
Authors: Wang Chenggang , Zhou Jiajie , Zhang Shengnan , Gao Xun , Yang Yitao , Hou Jinfeng , Chen Guohu , Tang Xiaoyan , Wu Jianqiang , Yuan Lingyun
Published: March 2023

Wucai (Brassica campestris L.) is a leafy vegetable that originated in China, its soluble sugars accumulate significantly to improve taste quality during maturation, and it is widely accepted by consumers. In this study, we investigated the soluble sugar content at different developmental stages. Two periods including 34 days after planting (DAP) and 46 DAP, which represent the period prior to and after sugar accumulation, respectively, were selected for metabolomic and transcriptomic profiling. Differentially accumulated metabolites (DAMs) were mainly enriched in the pentose phosphate pathway, galactose metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and fructose and mannose metabolism. By orthogonal projection to latent structures-discriminant s-plot (OPLS-DA S-plot) and MetaboAnalyst analyses, D-galactose and β-D-glucose were identified as the major components of sugar accumulation in wucai. Combined with the transcriptome, the pathway of sugar accumulation and the interact network between 26 DEGs and the two sugars were mapped. CWINV4, CEL1, BGLU16, and BraA03g023380.3C had positive correlations with the accumulation of sugar accumulation in wucai. The lower expression of BraA06g003260.3C, BraA08g002960.3C, BraA05g019040.3C, and BraA05g027230.3C promoted sugar accumulation during the ripening of wucai. These findings provide insights into the mechanisms underlying sugar accumulation during commodity maturity, providing a basis for the breeding of sugar-rich wucai cultivars.
Zinc: From Biological Functions to Therapeutic Potential
Authors: Costa Maria Inês , Sarmento-Ribeiro Ana Bela , Gonçalves Ana Cristina
Published: March 2023

The trace element zinc (Zn) displays a wide range of biological functions. Zn ions control intercellular communication and intracellular events that maintain normal physiological processes. These effects are achieved through the modulation of several Zn-dependent proteins, including transcription factors and enzymes of key cell signaling pathways, namely those involved in proliferation, apoptosis, and antioxidant defenses. Efficient homeostatic systems carefully regulate intracellular Zn concentrations. However, perturbed Zn homeostasis has been implicated in the pathogenesis of several chronic human diseases, such as cancer, diabetes, depression, Wilson’s disease, Alzheimer’s disease, and other age-related diseases. This review focuses on Zn’s roles in cell proliferation, survival/death, and DNA repair mechanisms, outlines some biological Zn targets, and addresses the therapeutic potential of Zn supplementation in some human diseases.
The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications
Authors: Wirth Ulrich , Jiang Tianxiao , Schardey Josefine , Kratz Katharina , Li Mingming , Schirren Malte , Kühn Florian , Bazhin Alexandr , Werner Jens , Guba Markus , Schulz Christian , Andrassy Joachim
Published: March 2023

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.
Blocking the Hormone Receptors Modulates NLRP3 in LPS-Primed Breast Cancer Cells
Authors: Hamza Shaimaa , Garanina Ekaterina E. , Alsaadi Mohammad , Khaiboullina Svetlana F. , Tezcan Gulcin
Published: March 2023

NOD-like receptor protein 3 (NLRP3) may contribute to the growth and propagation of breast cancer (BC). The effect of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) on NLRP3 activation in BC remains unknown. Additionally, our knowledge of the effect of blocking these receptors on NLRP3 expression is limited. We used GEPIA, UALCAN, and the Human Protein Atlas for transcriptomic profiling of NLRP3 in BC. Lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP) were used to activate NLRP3 in luminal A MCF-7 and in TNBC MDA-MB-231 and HCC1806 cells. Tamoxifen (Tx), mifepristone (mife), and trastuzumab (Tmab) were used to block ER-α, PR, and HER2, respectively, on inflammasome activation in LPS-primed MCF7 cells. The transcript level of NLRP3 was correlated with ER-ɑ encoding gene ESR1 in luminal A (ER-α+, PR+) and TNBC tumors. NLRP3 protein expression was higher in untreated and LPS/ATP-treated MDA-MB-231 cells than in MCF7 cells. LPS/ATP-mediated NLRP3 activation reduced cell proliferation and recovery of wound healing in both BC cell lines. LPS/ATP treatment prevented spheroid formation in MDA-MB-231 cells but did not affect MCF7. HGF, IL-3, IL-8, M-CSF, MCP-1, and SCGF-b cytokines were secreted in both MDA-MB-231 and MCF7 cells in response to LPS/ATP treatment. Tx (ER-α inhibition) promoted NLRP3 activation and increased migration and sphere formation after LPS treatment of MCF7 cells. Tx-mediated activation of NLRP3 was associated with increased secretion of IL-8 and SCGF-b compared to LPS-only-treated MCF7 cells. In contrast, Tmab (Her2 inhibition) had a limited effect on NLRP3 activation in LPS-treated MCF7 cells. Mife (PR inhibition) opposed NLRP3 activation in LPS-primed MCF7 cells. We have found that Tx increased the expression of NLRP3 in LPS-primed MCF7. These data suggest a link between blocking ER-α and activation of NLRP3, which was associated with increased aggressiveness of the ER-α+ BC cells.
A Roadside and Cloud-Based Vehicular Communications Framework for the Provision of C-ITS Services
Authors: Vieira Emanuel , Almeida João , Ferreira Joaquim , Dias Tiago , Vieira Silva Ana , Moura Lara
Published: March 2023

Road infrastructure plays a critical role in the support and development of the Cooperative Intelligent Transport Systems (C-ITS) paradigm. Roadside Units (RSUs), equipped with vehicular communication capabilities, traffic radars, cameras, and other sensors, can provide a multitude of vehicular services and enhance the cooperative perception of vehicles on the road, leading to increased road safety and traffic efficiency. Moreover, the central C-ITS system responsible for overseeing the road traffic and infrastructure, such as the RSUs, needs an efficient way of collecting and disseminating important information to road users. Warnings of accidents or other dangers, and other types of vehicular services such as Electronic Toll Collection (ETC), are examples of the types of information that the central C-ITS system is responsible for disseminating. To remedy these issues, we present the design of an implemented roadside and cloud architecture for the support of C-ITS services. With the main objectives of managing Vehicle-to-Everything (V2X) communication units and network messages of a public authority or motorway operator acting as a central C-ITS system, the proposed architecture was developed for different mobility testbeds in Portugal, under the scope of the STEROID research project and the pan-European Connected Roads (C-Roads) initiative. RSUs, equipped with ETSI ITS-G5 communications, are deployed with a cellular link or fiber optics connection for remote control and configuration. These are connected to a cloud Message Queuing Telemetry Transport (MQTT) broker where communication is based on a geographical tiling scheme, which allows the selection of the appropriate coverage areas for the dissemination of C-ITS messages. The architecture is deployed in the field, on several Portuguese motorways, where road traffic and infrastructure are monitored through a C-ITS platform with visualization and event reporting capabilities. The provided architecture is independent of the underlying communication technology and can be easily adapted in the future to support Cellular-V2X (PC5 interface) or 5G RSUs. Performance results of the deployed architecture are provided.
Ex-Vivo Preservation of Heart Allografts—An Overview of the Current State
Authors: Kothari Perin
Published: March 2023

As heart transplantation continues to be the gold-standard therapy for end-stage heart failure, the supply-demand imbalance of available organs worsens. Until recently, there have been no advances in increasing the donor pool, as prolonged cold ischemic time excludes the use of certain donors. The TransMedics Organ Care System (OCS) allows for ex-vivo normothermic perfusion, which allows for a reduction of cold ischemic time and allows for long-distance procurements. Furthermore, the OCS allows for real-time monitoring and assessment of allograft quality, which can be crucial for extended-criteria donors or donation after cardiac death (DCD) donors. Conversely, the XVIVO device allows for hypothermic perfusion to preserve allografts. Despite their limitations, these devices have the potential to alleviate the supply-demand imbalance in donor availability.
Mechanical and Tribological Performance of HDPE Matrix Reinforced by Hybrid Gr/TiO2 NPs for Hip Joint Replacement
Authors: Nabhan Ahmed , Sherif Galal , Abouzeid Ragab , Taha Mohamed
Published: March 2023

Hip joint collapse is a very common health problem. Many cases need a joint replacement, so nano-polymeric composites are an ideal alternative solution. Due to its mechanical properties and wear resistance, HDPE might be considered a suitable alternative to frictional materials. The current research focuses on using hybrid nanofiller TiO2 NPs and nano-graphene with various loading compositions to evaluate the best loading amount. The compressive strength, modules of elasticity, and hardness were examined via experiments. The COF and wear resistance were evaluated via a pin-on-disk tribometer. The worn surfaces were analyzed based on 3D topography and SEM images. The HDPE samples with various compositions of 0.5%, 1.0%, 1.5%, and 2.0 wt.% filling content of TiO2 NPs and Gr (with a ratio of 1:1) were analyzed. Results revealed that hybrid nanofiller with a composition of 1.5 wt.% exhibits superior mechanical properties compared to other filling compositions. Moreover, the COF and wear rate decreased by 27.5% and 36.3%, respectively.
Identifying Financial Crises Using Machine Learning on Textual Data
Authors: Chen Mary , DeHaven Matthew , Kitschelt Isabel , Lee Seung Jung , Sicilian Martin J.
Published: March 2023

We use machine learning techniques on textual data to identify financial crises. The onset of a crisis and its duration have implications for real economic activity, and as such can be valuable inputs into macroprudential, monetary, and fiscal policy. The academic literature and the policy realm rely mostly on expert judgment to determine crises, often with a lag. Consequently, crisis durations and the buildup phases of vulnerabilities are usually determined only with the benefit of hindsight. Although we can identify and forecast a portion of crises worldwide to various degrees with traditional econometric techniques and using readily available market data, we find that textual data helps in reducing false positives and false negatives in out-of-sample testing of such models, especially when the crises are considered more severe. Building a framework that is consistent across countries and in real time can benefit policymakers around the world, especially when international coordination is required across different government policies.
Influence of Underutilization of Production Capacities on the Dynamics of Russian GDP: An Assessment on the Basis of Production Functions
Authors: Baranov Sergey , Skufina Tatiana , Samarina Vera
Published: March 2023

Sustainable development of the state implies a proportional change in the key macroeconomic indicators described by standard models, one of which is the exponential production function (a special case of the Cobb-Douglas function), where the number of employees (labor) and the value of fixed assets (capital) acts as factor inputs, and GDP becomes the output, and output elasticities of production factors are estimated. This function is successfully used to analyze and predict macroeconomic processes in both developed and developing economies. The purpose of the study is to use econometric modeling—applying the exponential Cobb-Douglas production function—to identify the presence or absence of dependencies of production factors (labor, capital, etc.) on the final product output in Russia. The study shows that in Russia, GDP does not significantly depend on fixed assets. The authors hypothesized that this discrepancy is due to underutilization of production capacities and proved that to reveal the real dependence of Russian GDP production on the value of fixed assets it is necessary to adjust the indicators published by Rosstat for utilization of production capacities, which made it possible to fully use the methodological capabilities of production functions for the analysis and forecasting of macroeconomic processes in Russia.
Comparing Predictors and Outcomes of Higher Allostatic Load across Zoo-Housed African Great Apes
Authors: Edes Ashley N. , Edwards Katie L. , Zimmerman Dawn , Jourdan Balbine , Crews Douglas E. , Wolfe Barbara A. , Neiffer Donald L. , Brown Janine L.
Published: March 2023

Stressors over the lifespan can contribute to physiological dysregulation, or allostatic load. Allostatic load has been studied in humans using allostatic load indices (ALIs) for over 25 years, but the same methods are rarely applied to other species. We constructed an ALI for zoo-housed western lowland gorillas, chimpanzees, and bonobos and tested potential predictors of and health outcomes associated with allostatic load. Allostatic load scores ranged from 0–6 for gorillas and chimpanzees and 0–7 for bonobos. Age was significantly associated with allostatic load in gorillas and chimpanzees but not bonobos. Cumulative stressful events were positively associated with allostatic load in chimpanzees. Wild-caught gorillas had higher allostatic load than zoo-born conspecifics, but rearing differences between zoo-born animals were not significant for any species. Age may affect associations of allostatic load with stressful events and birthplace as results change when it is included as a covariate. Allostatic load was not retained in best-fit models for risk of all-cause morbidity, cardiac disease, or mortality risk. Some analyses herein were limited by the use of retrospective data, such as reason for sample collection and length of records provided for individual animals. Nevertheless, these data indicate additional research is needed to optimize ALIs for non-human primates.
Physical, Thermal, and Chemical Properties of Fly Ash Cenospheres Obtained from Different Sources
Authors: Shishkin Andrei , Abramovskis Vitalijs , Zalite Ilmars , Singh Ashish Kumar , Mezinskis Gundars , Popov Vladimir , Ozolins Jurijs
Published: March 2023

Cenospheres are hollow particles in fly ash, a by-product of coal burning, and are widely used as a reinforcement when developing low-density composites called syntactic foams. This study has investigated the physical, chemical, and thermal properties of cenospheres obtained from three different sources, designated as CS1, CS2, and CS3, for the development of syntactic foams. Cenospheres with particle sizes ranging from 40 to 500 μm were studied. Different particle distribution by size was observed, and the most uniform distribution of CS particles was in the case of CS2: above 74% with dimensions from 100 to 150 μm. The CS bulk had a similar density for all samples and amounted to around 0.4 g·cm−3, with a particle shell material density of 2.1 g·cm−3. Post-heat-treatment samples showed the development of a SiO2 phase in the cenospheres, which was not present in the as-received product. CS3 had the highest quantity of Si compared to the other two, showing the difference in source quality. Energy-dispersive X-ray spectrometry and a chemical analysis of the CS revealed that the main components of the studied CS were SiO2 and Al2O3. In the case of CS1 and CS2, the sum of these components was on average from 93 to 95%. In the case of CS3, the sum of SiO2 and Al2O3 did not exceed 86%, and Fe2O3 and K2O were present in appreciable quantities in CS3. Cenospheres CS1 and CS2 did not sinter during heat treatment up to 1200 °C, while sample CS3 was already subjected to sintering at 1100 °C because of the presence of a quartz phase, Fe2O3 and K2O. For the application of a metallic layer and subsequent consolidation via spark plasma sintering, CS2 can be deemed the most physically, thermally, and chemically suitable.
Spatio-Temporal Dynamics of Diffusion-Associated Deformations of Biological Tissues and Polyacrylamide Gels Observed with Optical Coherence Elastography
Authors: Alexandrovskaya Yulia M. , Kasianenko Ekaterina M. , Sovetsky Alexander A. , Matveyev Alexander L. , Zaitsev Vladimir Y.
Published: March 2023

In this work, we use the method of optical coherence elastography (OCE) to enable quantitative, spatially resolved visualization of diffusion-associated deformations in the areas of maximum concentration gradients during diffusion of hyperosmotic substances in cartilaginous tissue and polyacrylamide gels. At high concentration gradients, alternating sign, near-surface deformations in porous moisture-saturated materials are observed in the first minutes of diffusion. For cartilage, the kinetics of osmotic deformations visualized by OCE, as well as the optical transmittance variations caused by the diffusion, were comparatively analyzed for several substances that are often used as optical clearing agents, i.e., glycerol, polypropylene, PEG-400 and iohexol, for which the effective diffusion coefficients were found to be 7.4 ± 1.8, 5.0 ± 0.8, 4.4 ± 0.8 and 4.6 ± 0.9 × 10−6 cm2/s, respectively. For the osmotically induced shrinkage amplitude, the influence of the organic alcohol concentration appears to be more significant than the influence of its molecular weight. The rate and amplitude of osmotically induced shrinkage and dilatation in polyacrylamide gels is found to clearly depend on the degree of their crosslinking. The obtained results show that observation of osmotic strains with the developed OCE technique can be applied for structural characterization of a wide range of porous materials, including biopolymers. In addition, it may be promising for revealing alterations in the diffusivity/permeability of biological tissues that are potentially associated with various diseases.
Study on Ag(I) Loaded ZIF-8 and Ag(I) Ion Release in Artificial Seawater
Authors: Tsai Shang-Tien , Tang Wei-Cheng , Wei Yeu-Kuen , Wu Kevin C.-W.
Published: March 2023

From a porous structure perspective, the one-stage de novo synthesis method and impregnation method were applied to synthesize Ag(I) ion-containing ZIF-8 samples. With the de novo synthesis method, Ag(I) ions could be located inside micropores or adsorbed on the external surface of the ZIF-8 by selecting AgNO3 in water or Ag2CO3 in ammonia solution as precursors, respectively. The ZIF-8 confining Ag(I) ion exhibited a much lower constant releasing rate than the Ag(I) ion adsorbed on the ZIF-8 surface in artificial seawater. As such, strong diffusion resistance in association with the confinement effect is contributed by ZIF-8’s micropore. On the other hand, the release of Ag(I) ions adsorbed on the external surface was diffusion limited. Therefore, the releasing rate would reach a maximum not increasing with Ag(I) loading in the ZIF-8 sample.