bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Agricultural Production Efficiency of Yangtze River Economic Belt Based on a Three-Stage DEA Malmquist Model
Authors: Pan Zhiwei , Tang Decai , Kong Haojia , He Junxia
Published: January 2022

The Yangtze River Economic Belt (YREB) is a major national strategic development area in China, and the development of the YREB will greatly promote the development of the entirety China, so research on its agricultural production efficiency is also of great significance. This paper is committed to studying the agricultural production efficiency of 11 provinces in the YREB and adopts a combination of the Data Envelopment Analysis (DEA) model and the Malmquist index to make a dynamic and static analysis on the YREB’s agricultural production efficiency from 2010 to 2019. Then, a three-stage DEA Malmquist model that eliminates the factors of random interference and management inefficiency is compared to a model without elimination. The results show that the adjusted technological efficiency changes, technological progress, and total factor productivity increased by −0.1%, 0.24%, and 0.22%, respectively. When comparing these values to the pre-adjustment values, the results indicate that the effect of environmental variables cannot be ignored when studying the agricultural production efficiency of the YREB. At the same time, the differences in the agricultural production efficiency in the YREB are reasonably explained, and feasible suggestions are put forward.
What Happened in ‘The HERizon Project’?—Process Evaluation of a Multi-Arm Remote Physical Activity Intervention for Adolescent Girls
Authors: Cowley Emma S. , Foweather Lawrence , Watson Paula M. , Belton Sarahjane , Thompson Andrew , Thijssen Dick , Wagenmakers Anton J. M.
Published: January 2022

This mixed-methods process evaluation examines the reach, recruitment, fidelity, adherence, acceptability, mechanisms of impact, and context of remote 12-week physical activity (PA) interventions for adolescent girls named The HERizon Project. The study was comprised of four arms—a PA programme group, a behaviour change support group, a combined group, and a comparison group. Data sources included intervention deliverer and participant logbooks (100 and 71% respective response rates, respectively), exit surveys (72% response rate), and semi-structured focus groups/interviews conducted with a random subsample of participants from each of the intervention arms (n = 34). All intervention deliverers received standardised training and successfully completed pre-intervention competency tasks. Based on self-report logs, 99% of mentors adhered to the call guide, and 100% of calls and live workouts were offered. Participant adherence and intervention receipt were also high for all intervention arms. Participants were generally satisfied with the intervention components; however, improvements were recommended for the online social media community within the PA programme and combined intervention arms. Autonomy, sense of accomplishment, accountability, and routine were identified as factors facilitating participant willingness to adhere to the intervention across all intervention arms. Future remote interventions should consider structured group facilitation to encourage a genuine sense of community among participants.
Association of Dietary Patterns with MRI Markers of Hepatic Inflammation and Fibrosis in the MAST4HEALTH Study
Authors: Amanatidou Athina I. , Kaliora Andriana C. , Amerikanou Charalampia , Stojanoski Stefan , Milosevic Natasa , Vezou Chara , Beribaka Mirjana , Banerjee Rajarshi , Kalafati Ioanna-Panagiota , Smyrnioudis Ilias , Kurth Mary Jo , Kannt Aimo , Francino M. Pilar , Visvikis-Siest Sophie , Deloukas Panos , Llorens Carlos , Marascio Fernando , Milic Natasa , Medic-Stojanoska Milica , Gastaldelli Amalia , Trivella Maria Giovanna , Dedoussis George V.
Published: January 2022

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely “High-Sugar”, “Prudent”, “Western”, “High-Fat and Salt”, “Plant-Based”, and “Low-Fat Dairy and Poultry”. The “Western” pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the “Low-Fat Dairy and Poultry” pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a “Low-Fat Dairy and Poultry” dietary pattern were negatively associated with MRI parameters (cT1: beta: −0.052, p-value: 0.046, PDFF: beta: −0.448, p-value: 0.030, LIF: beta: −0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.
Trust in the Healthcare System and Physicians in Croatia: A Survey of the General Population
Authors: Nikodem Krunoslav , Ćurković Marko , Borovečki Ana
Published: January 2022

Trust in healthcare systems and physicians is considered important for the delivery of good healthcare. A cross-sectional survey was conducted on a random three-stage sample of the general population of Croatia (N = 1230), stratified by regions. Of respondents, 58.7% displayed a high or very high level of trust in the healthcare system, 65.6% in physicians, and 78.3% in their family physician. Respondents’ views regarding patients’ roles in the discussion of treatment options, confidence in physicians’ expertise, and underlying motives of physicians were mixed. Respondents with a lower level of education, those with low monthly incomes, and those from smaller settlements had lower levels of trust in physicians and the healthcare system. Trust in other institutions, religiosity and religious beliefs, tolerance of personal choice, and experience of caring for the seriously ill and dying were predictors of trust in healthcare and physicians. Our findings suggest that levels of healthcare-related trust in Croatia are increasing in comparison with previous research, but need improvement. Levels of trust are lowest in populations that are most vulnerable and most in need of care and protection.
Cost-Effectiveness Analysis of Improving Nurses’ Education Level in the Context of In-Hospital Mortality
Authors: Wieczorek-Wójcik Beata , Gaworska-Krzemińska Aleksandra , Szynkiewicz Piotr , Wójcik Michał , Orzechowska Monika , Kilańska Dorota
Published: January 2022

(1) Background: an assessment of the cost-effectiveness of employing an increased number of nurses with higher education from the perspective of the service provider. (2) Methods: Based on a year-long study results and data collected from a large hospital, we conducted of the costs of preventing one death. The study involved intervention by 10% increase in the percentage of nursing care hours provided by nurses with higher education. The measure of health effects was the cost of avoiding one death (CER). The cost-effectiveness analysis (CEA) was used as the evaluation method. (3) Results: The cost of employing a larger percentage of nurses with higher education amounts to a total of amounts to a USD 11,730.62 an increase of 3.02% as compared to the base costs. The estimated number of deaths that could be prevented was 44 deaths. Mortality per 1000 patient days was 9.42, mortality after intervention was 8.41. The cost of preventing one death by the 10% increase in BSN/MSN NCH percentage in non-surgical wards USD 263.92. (4) Conclusions: increasing the percentage of care hours provided by nurses with tertiary education is a cost-effective method of reducing in-hospital mortality.
Energy Poverty and Depression in Rural China: Evidence from the Quantile Regression Approach
Authors: Zhang Jun , He Yuang , Zhang Jing
Published: January 2022

Despite the growing awareness and interest in the impact of energy poverty on depression, studies in developing economies are relative limited, and there is a gap of knowledge of such impact among rural individuals in China. In this study, we investigate the impact of energy poverty on depression among rural Chinese individuals aged 16 and above, and our sample includes 13,784 individuals from 6103 households. With data from the 2018 China Family Panel Studies, we apply the instrumental variable (IV) quantile regression approach to address the potential endogeneity of energy poverty and allow for heterogeneous effects of energy poverty on depression across individuals with different levels of depression. Our estimates from the IV quantile regression suggest a strong positive impact of energy poverty on depression at the upper quantile of depression scores, but no impact at the middle and lower quantiles. The primary results are robust and consistent with alternative energy poverty measures, and we find that energy poverty does not affect depression of low-risk individuals (with low depression scores), but it does affect that of high-risk individuals. We also find individual socio-demographic factors of age, gender, household size, religious belief, education, marriage and employment status play roles in affecting depression. The findings of this study generate policy implications for energy poverty alleviation and mental health promotion.
Peripheral Nerve Injury Treatments and Advances: One Health Perspective
Authors: Lopes Bruna , Sousa Patrícia , Alvites Rui , Branquinho Mariana , Sousa Ana Catarina , Mendonça Carla , Atayde Luís Miguel , Luís Ana Lúcia , Varejão Artur S. P. , Maurício Ana Colette
Published: January 2022

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.
Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes
Authors: Perrin-Cocon Laure , Kundlacz Cindy , Jacquemin Clémence , Hanoulle Xavier , Aublin-Gex Anne , Figl Marianne , Manteca Jeremy , André Patrice , Vidalain Pierre-Olivier , Lotteau Vincent , Diaz Olivier
Published: January 2022

Hepatitis C virus (HCV) relies on cellular lipid metabolism for its replication, and actively modulates lipogenesis and lipid trafficking in infected hepatocytes. This translates into an intracellular accumulation of triglycerides leading to liver steatosis, cirrhosis and hepatocellular carcinoma, which are hallmarks of HCV pathogenesis. While the interaction of HCV with hepatocyte metabolic pathways is patent, how viral proteins are able to redirect central carbon metabolism towards lipogenesis is unclear. Here, we report that the HCV protein NS5A activates the glucokinase (GCK) isoenzyme of hexokinases through its D2 domain (NS5A-D2). GCK is the first rate-limiting enzyme of glycolysis in normal hepatocytes whose expression is replaced by the hexokinase 2 (HK2) isoenzyme in hepatocellular carcinoma cell lines. We took advantage of a unique cellular model specifically engineered to re-express GCK instead of HK2 in the Huh7 cell line to evaluate the consequences of NS5A-D2 expression on central carbon and lipid metabolism. NS5A-D2 increased glucose consumption but decreased glycogen storage. This was accompanied by an altered mitochondrial respiration, an accumulation of intracellular triglycerides and an increased production of very-low density lipoproteins. Altogether, our results show that NS5A-D2 can reprogram central carbon metabolism towards a more energetic and glycolytic phenotype compatible with HCV needs for replication.
Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice
Authors: Hutin David , Hagen Karoline Alvik , Shao Peng , Sugamori Kim , Grant Denis M. , Matthews Jason
Published: January 2022

Poly-ADP-ribose polymerases (PARPs) are important regulators of the immune system, including TCDD-inducible poly-ADP-ribose polymerase (TIPARP), also known as poly-ADP-ribose polymerase 7 (PARP7). PARP7 negatively regulates aryl hydrocarbon receptor (AHR) and type I interferon (IFN-I) signaling, both of which have been implicated in intestinal homeostasis and immunity. Since the loss of PARP7 expression increases AHR and IFN-I signaling, we used a murine dextran sulfate sodium (DSS)-induced colitis model to investigate the effect of PARP7 loss on DSS-induced intestinal inflammation. DSS-exposed Parp7−/− mice had less body weight loss, lower disease index scores, and reduced expression of several inflammation genes, including interleukin IL-6, C-x-c motif chemokine ligand 1 (Cxcl1), and lipocalin-2, when compared with wild-type mice. However, no significant difference was observed between genotypes in the colonic expression of the AHR target gene cytochrome P450 1A1 (Cyp1a1). Moreover, no significant differences in microbial composition were observed between the genotypes. Our findings demonstrate that the absence of PARP7 protein results in an impaired immune response to colonic inflammation and suggests that PARP7 may participate in the recruitment of immune cells to the inflammation site, which may be due to its role in IFN-I signaling rather than AHR signaling.
The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets
Authors: Dabravolski Siarhei A. , Khotina Victoria A. , Omelchenko Andrey V. , Kalmykov Vladislav A. , Orekhov Alexander N.
Published: January 2022

The vascular endothelial growth factor (VEGF) family, the crucial regulator of angiogenesis, lymphangiogenesis, lipid metabolism and inflammation, is involved in the development of atherosclerosis and further CVDs (cardiovascular diseases). This review discusses the general regulation and functions of VEGFs, their role in lipid metabolism and atherosclerosis development and progression. These functions present the great potential of applying the VEGF family as a target in the treatment of atherosclerosis and related CVDs. In addition, we discuss several modern anti-atherosclerosis VEGFs-targeted experimental procedures, drugs and natural compounds, which could significantly improve the efficiency of atherosclerosis and related CVDs’ treatment.
Cellular and Molecular Alterations Underlying Abnormal Bone Growth in X-Linked Hypophosphatemia
Authors: Fuente Rocío , García-Bengoa María , Fernández-Iglesias Ángela , Gil-Peña Helena , Santos Fernando , López José Manuel
Published: January 2022

X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is caused by inactivating mutations of the phosphate-regulating endopeptidase gene (PHEX). XLH is mainly characterized by short stature, bone deformities and rickets, while in hypophosphatemia, normal or low vitamin D levels and low renal phosphate reabsorption are the principal biochemical aspects. The cause of growth impairment in patients with XLH is not completely understood yet, thus making the study of the growth plate (GP) alterations necessary. New treatment strategies targeting FGF23 have shown promising results in normalizing the growth velocity and improving the skeletal effects of XLH patients. However, further studies are necessary to evaluate how this treatment affects the GP as well as its long-term effects and the impact on adult height.
Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?
Authors: Montaño Luis M. , Sommer Bettina , Solís-Chagoyán Héctor , Romero-Martínez Bianca S. , Aquino-Gálvez Arnoldo , Gomez-Verjan Juan C. , Calixto Eduardo , González-Avila Georgina , Flores-Soto Edgar
Published: January 2022

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection’s outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.
Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model
Authors: Ormazabal Valeska , Nova-Lampeti Estefanía , Rojas Daniela , Zúñiga Felipe A. , Escudero Carlos , Lagos Paola , Moreno Alexa , Pavez Yanara , Reyes Camila , Yáñez Milly , Vidal Mabel , Cabrera-Vives Guillermo , Oporto Katherine , Aguayo Claudio
Published: January 2022

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.
Towards an Ideal In Cell Hybridization-Based Strategy to Discover Protein Interactomes of Selected RNA Molecules
Authors: Spiniello Michele , Scalf Mark , Casamassimi Amelia , Abbondanza Ciro , Smith Lloyd M.
Published: January 2022

RNA-binding proteins are crucial to the function of coding and non-coding RNAs. The disruption of RNA–protein interactions is involved in many different pathological states. Several computational and experimental strategies have been developed to identify protein binders of selected RNA molecules. Amongst these, ‘in cell’ hybridization methods represent the gold standard in the field because they are designed to reveal the proteins bound to specific RNAs in a cellular context. Here, we compare the technical features of different ‘in cell’ hybridization approaches with a focus on their advantages, limitations, and current and potential future applications.
Chemerin Affects P4 and E2 Synthesis in the Porcine Endometrium during Early Pregnancy
Authors: Gudelska Marlena , Dobrzyn Kamil , Kiezun Marta , Kisielewska Katarzyna , Rytelewska Edyta , Kaminski Tadeusz , Smolinska Nina
Published: January 2022

Chemerin, belonging to the adipokine family, exhibits pleiotropic activity. We hypothesised that the adipokine could be involved in the regulation of steroidogenesis in the porcine endometrium. Thus, the aim of this study was to determine the effect of chemerin on the key steroidogenic enzyme proteins’ abundance (Western blot), as well as on P4 and E2 secretion (radioimmunoassay) by the porcine endometrium during early pregnancy and the mid-luteal phase of the oestrous cycle. Moreover, we investigated the hormone impact on Erk and Akt signalling pathway activation (Western blot). Chemerin stimulated E2 production on days 10 to 11 of pregnancy. On days 10 to 11 and 15 to 16 of gestation, and on days 10 to 11 of the cycle, chemerin enhanced the expression of StAR and all steroidogenic enzyme proteins. On days 12 to 13 of pregnancy, chemerin decreased StAR and most of the steroidogenic enzyme proteins’ abundance, whereas the P450C17 abundance was increased. On days 27 to 28 of pregnancy, chemerin increased StAR and P450C17 protein contents and decreased 3βHSD protein amounts. It was noted that the adipokine inhibited Erk1/2 and stimulated Akt phosphorylation. The obtained results indicate that chemerin affected P4 and E2 synthesis through the Erk1/2 and Akt signalling pathways.
Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
Authors: Codden Christina J. , Chin Michael T.
Published: January 2022

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has revealed alterations in communication between various cell types, but no direct and integrated comparison between the two HCM phenotypes has been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility, and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding, and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication, and in endothelial cell communication to other cell types, largely through changes in the expression of integrin-β1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for the personalized management of different HCM phenotypes.
The Peptide A-3302-B Isolated from a Marine Bacterium Micromonospora sp. Inhibits HSV-2 Infection by Preventing the Viral Egress from Host Cells
Authors: Sureram Sanya , Arduino Irene , Ueoka Reiko , Rittà Massimo , Francese Rachele , Srivibool Rattanaporn , Darshana Dhanushka , Piel Jörn , Ruchirawat Somsak , Muratori Luisa , Lembo David , Kittakoop Prasat , Donalisio Manuela
Published: January 2022

Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 μM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections.
Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?
Authors: Wójcik-Bojek Urszula , Różalska Barbara , Sadowska Beata
Published: January 2022

The main purpose of this review is to present justification for the urgent need to implement specific prophylaxis of invasive Staphylococcus aureus infections. We emphasize the difficulties in achieving this goal due to numerous S. aureus virulence factors important for the process of infection and the remarkable ability of these bacteria to avoid host defense mechanisms. We precede these considerations with a brief overview of the global necessitiy to intensify the use of vaccines against other pathogens as well, particularly in light of an impasse in antibiotic therapy. Finally, we point out global trends in research into modern technologies used in the field of molecular microbiology to develop new vaccines. We focus on the vaccines designed to fight the infections caused by S. aureus, which are often resistant to the majority of available therapeutic options.
Photochemical Synthesis of Silver Hydrosol Stabilized by Carbonate Ions and Study of Its Bactericidal Impact on Escherichia coli: Direct and Indirect Effects
Authors: Ershov Vadim , Tarasova Natalia , Abkhalimov Evgeny , Safonov Alexey , Sorokin Vladimir , Ershov Boris
Published: January 2022

The great attention paid to silver nanoparticles is largely related to their antibacterial and antiviral effects and their possible use as efficient biocidal agents. Silver nanoparticles are being widely introduced into various areas of life, including industry, medicine, and agriculture. This leads to their spreading and entering the environment, which generates the potential risk of toxic effect on humans and other biological organisms. Proposed paper describes the preparation of silver hydrosols containing spherical metal nanoparticles by photochemical reduction of Ag+ ions with oxalate ions. In deaerated solutions, this gives ~10 nm particles, while in aerated solutions, ~20 nm particles with inclusion of the oxide Ag2O are obtained. Nanoparticles inhibit the bacterium Escherichia coli and suppress the cell growth at concentrations of ~1 × 10−6–1 × 10−4 mol L−1. Silver particles cause the loss of pili and deformation and destruction of cell membranes. A mechanism of antibacterial action was proposed, taking into account indirect suppressing action of Ag+ ions released upon the oxidative metal dissolution and direct (contact) action of nanoparticles on bacterial cells, resulting in a change in the shape and destruction of the bacteria.
Time-Dependent Changes in Protein Composition of Medial Prefrontal Cortex in Rats with Neuropathic Pain
Authors: Ujcikova Hana , Robles Dagoberto , Yue Xu , Svoboda Petr , Lee Yeon Sun , Navratilova Edita
Published: January 2022

Chronic pain is associated with time-dependent structural and functional reorganization of the prefrontal cortex that may reflect adaptive pain compensatory and/or maladaptive pain-promoting mechanisms. However, the molecular underpinnings of these changes and whether there are time-dependent relationships to pain progression are not well characterized. In this study, we analyzed protein composition in the medial prefrontal cortex (mPFC) of rats at two timepoints after spinal nerve ligation (SNL) using two-dimensional gel electrophoresis (2D-ELFO) and liquid chromatography with tandem mass spectrometry (LC–MS/MS). SNL, but not sham-operated, rats developed persistent tactile allodynia and thermal hyperalgesia, confirming the presence of experimental neuropathic pain. Two weeks after SNL (early timepoint), we identified 11 proteins involved in signal transduction, protein transport, cell homeostasis, metabolism, and apoptosis, as well as heat-shock proteins and chaperones that were upregulated by more than 1.5-fold compared to the sham-operated rats. Interestingly, there were only four significantly altered proteins identified at 8 weeks after SNL (late timepoint). These findings demonstrate extensive time-dependent modifications of protein expression in the rat mPFC under a chronic neuropathic pain state that might underlie the evolution of chronic pain characterized by early pain-compensatory and later aberrant mechanisms.
Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production
Authors: Vokurka Martin , Lacina Lukáš , Brábek Jan , Kolář Michal , Ng Yi Zhen , Smetana Karel
Published: January 2022

Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.
Solvent- and Light-Sensitive AIEE-Active Azo Dye: From Spherical to 1D and 2D Assemblies
Authors: Han Mina , Abe Ikue , Oh Jihun , Jung Jaehoon , Son Young Ji , Noh Jaegeun , Hara Mitsuo , Seki Takahiro
Published: January 2022

Fluorescent molecular assembly systems provide an exciting platform for creating stimuli-responsive nano- and microstructured materials with optical, electronic, and sensing functions. To understand the relationship between (i) the plausible molecular structures preferentially adopted depending on the solvent polarity (such as N,N-dimethylformamide [DMF], tetrahydrofuran [THF], and toluene), (ii) the resulting spectroscopic features, and (iii) self-assembled nano-, micro-, and macrostructures, we chose a sterically crowded triangular azo dye (3Bu) composed of a polar molecular core and three peripheral biphenyl wings. The chromophore changed the solution color from yellow to pink-red depending on the solvent polarity. In a yellow DMF solution, a considerable amount of the twisted azo form could be kept stable with the help of favorable intermolecular interactions with the solvent molecules. By varying the concentration of the DMF solution, the morphology of self-assembled structures was transformed from nanoparticles to micrometer-sized one-dimensional (1D) structures such as sticks and fibers. In a pink-red toluene solution, the periphery of the central ring became more planar. The resulting significant amount of the keto-hydrazone tautomer grew into micro- and millimeter-sized 1D structures. Interestingly, when THF-H2O (1:1) mixtures were stored at a low temperature, elongated fibers were stacked sideways and eventually developed into anisotropic two-dimensional (2D) sheets. Notably, subsequent exposure of visible-light-irradiated sphere samples to solvent vapor resulted in reversible fluorescence off↔on switching accompanied by morphological restoration. These findings suggest that rational selection of organic dyes, solvents, and light is important for developing reusable fluorescent materials.
Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders
Authors: Trifonova Ekaterina A. , Mustafin Zakhar S. , Lashin Sergey A. , Kochetov Alex V.
Published: January 2022

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication and behavioral problems. ASD is highly heritable; however, environmental factors also play a considerable role in this disorder. A significant part of both syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.
Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone
Authors: Wągrodzki Michał , Tysarowski Andrzej , Seliga Katarzyna , Wojnowska Aneta , Stepaniuk Maria , Castañeda Wysocka Patrycja , Makuła Donata , Pieńkowski Andrzej , Szostakowski Bartłomiej , Zub Renata , Rutkowski Piotr
Published: January 2022

To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97–100%) and 100% (95% CI: 96.15–100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24–98.13%) and 100% (95% CI: 93.94–100.0%), respectively. P.G35 mutations were discovered in 2/9 (22.2%) secondary malignant GCTBs and 9/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.
Molecular Mechanisms Leading from Periodontal Disease to Cancer
Authors: Sobocki Bartosz Kamil , Basset Charbel A. , Bruhn-Olszewska Bożena , Olszewski Paweł , Szot Olga , Kaźmierczak-Siedlecka Karolina , Guziak Mateusz , Nibali Luigi , Leone Angelo
Published: January 2022

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL–RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.
TLCrys: Transfer Learning Based Method for Protein Crystallization Prediction
Authors: Jin Chen , Shi Zhuangwei , Kang Chuanze , Lin Ken , Zhang Han
Published: January 2022

X-ray diffraction technique is one of the most common methods of ascertaining protein structures, yet only 2–10% of proteins can produce diffraction-quality crystals. Several computational methods have been proposed so far to predict protein crystallization. Nevertheless, the current state-of-the-art computational methods are limited by the scarcity of experimental data. Thus, the prediction accuracy of existing models hasn’t reached the ideal level. To address the problems above, we propose a novel transfer-learning-based framework for protein crystallization prediction, named TLCrys. The framework proceeds in two steps: pre-training and fine-tuning. The pre-training step adopts attention mechanism to extract both global and local information of the protein sequences. The representation learned from the pre-training step is regarded as knowledge to be transferred and fine-tuned to enhance the performance of crystalization prediction. During pre-training, TLCrys adopts a multi-task learning method, which not only improves the learning ability of protein encoding, but also enhances the robustness and generalization of protein representation. The multi-head self-attention layer guarantees that different levels of the protein representation can be extracted by the fine-tuned step. During transfer learning, the fine-tuning strategy used by TLCrys improves the task-specialized learning ability of the network. Our method outperforms all previous predictors significantly in five crystallization stages of prediction. Furthermore, the proposed methodology can be well generalized to other protein sequence classification tasks.
Cold Response Transcriptome Analysis of the Alternative Splicing Events Induced by the Cold Stress in D. catenatum
Authors: Zheng Yan , Luo Landi , Chen Qian , Yang Danni , Gong Yuqiang , Yang Ya , Qin Xiangshi , Wang Yuhua , Kong Xiangxiang , Yang Yongping
Published: January 2022

Dendrobium catenatum Lindl is a valuable medicinal herb and gardening plant due to its ornamental value and special medical value. Low temperature is a major bottleneck restricting D. catenatum expansion towards the north, which influences the quality and yield of D. catenatum. In this study, we analysed the cold response of D. catenatum by RNA-Seq. A total of 4302 differentially expressed genes were detected under cold stress, which were mainly linked to protein kinase activity, membrane transport and the glycan biosynthesis and metabolism pathway. We also identified 4005 differential alternative events in 2319 genes significantly regulated by cold stress. Exon skipping and intron retention were the most common alternative splicing isoforms. Numerous genes were identified that differentially modulated under cold stress, including cold-induced transcription factors and splicing factors mediated by AS (alternative splicing). GO enrichment analysis found that differentially alternatively spliced genes without differential expression levels were related to RNA/mRNA processing and spliceosomes. DAS (differentially alternative splicing) genes with different expression levels were mainly enriched in protein kinase activity, plasma membrane and cellular response to stimulus. We further identified and cloned DcCBP20 in D. catenatum; we found that DcCBP20 promotes the generation of alternative splicing variants in cold-induced genes under cold stress via genetic experiments and RT–PCR. Taken together, our results identify the main cold-response pathways and alternative splicing events in D. catenatum responding to cold treatment and that DcCBP20 of D. catenatum get involved in regulating the AS and gene expression of cold-induced genes during this process. Our study will contribute to understanding the role of AS genes in regulating the cold stress response in D. catenatum.
Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function
Authors: Van Bergen Nicole J. , Hock Daniella H. , Spencer Lucy , Massey Sean , Stait Tegan , Stark Zornitza , Lunke Sebastian , Roesley Ain , Peters Heidi , Lee Joy Yaplito , Le Fevre Anna , Heath Oliver , Mignone Cristina , Yang Joseph Yuan-Mou , Ryan Monique M. , D’Arcy Colleen , Nash Margot , Smith Sile , Caruana Nikeisha J. , Thorburn David R. , Stroud David A. , White Susan M. , Christodoulou John , Brown Natasha J.
Published: January 2022

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein’s precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child’s clinical presentation.
Shigella Outer Membrane Vesicles as Promising Targets for Vaccination
Authors: Qasim Muhammad , Wrage Marius , Nüse Björn , Mattner Jochen
Published: January 2022

The clinical symptoms of shigellosis, a gastrointestinal infection caused by Shigella spp. range from watery diarrhea to fulminant dysentery. Endemic infections, particularly among children in developing countries, represent the majority of clinical cases. The situation is aggravated due to the high mortality rate of shigellosis, the rapid dissemination of multi-resistant Shigella strains and the induction of only serotype-specific immunity. Thus, infection prevention due to vaccination, encompassing as many of the circulating serotypes as possible, has become a topic of interest. However, vaccines have turned out to be ineffective so far. Outer membrane vesicles (OMVs) are promising novel targets for vaccination. OMVs are constitutively secreted by Gram-negative bacteria including Shigella during growth. They are composed of soluble luminal portions and an insoluble membrane and can contain toxins, bioactive periplasmic and cytoplasmic (lipo-) proteins, (phospho-) lipids, nucleic acids and/or lipopolysaccharides. Thus, OMVs play an important role in bacterial cell–cell communication, growth, survival and pathogenesis. Furthermore, they modulate the secretion and transport of biomolecules, the stress response, antibiotic resistance and immune responses of the host. Thus, OMVs serve as novel secretion machinery. Here, we discuss the current literature and highlight the properties of OMVs as potent vaccine candidates because of their immunomodulatory, antigenic and adjuvant properties.
Antioxidant and Anticancer Activities and Protein Interaction of the Oxidovanadium(IV) Naringin Complex
Authors: Restrepo-Guerrero Andrés Gonzalo , Goitia-Semenco Helen , Naso Luciana G. , Rey Marilin , Gonzalez Pablo J. , Ferrer Evelina G. , Williams Patricia A. M.
Published: January 2022

The complex of oxidovanadium(IV) with naringin (Narg) [VO(Narg)2] 8H2O (VONarg) was prepared according to the literature improving the synthetic procedure and physicochemical characterization. In addition, biological activities (cytotoxic, antioxidant, and BSA interaction) were determined. The metal coordinated through the 5-hydroxy and 4-carbonyl groups of rings A and C of naringin, respectively. The antioxidant activity of VONarg, determined in vitro, was higher than those of the flavonoid against superoxide and peroxyl reactive oxygen species (ROS) and DPPH radical. The cytotoxic properties were determined by a MTT assay on adenocarcinoma human alveolar basal epithelial cells (A549). VONarg exerted a 20% decrease in cancer cells viability at 24 h incubation, while naringin and oxidovanadium(IV) cation did not show cytotoxicity. Measurements with the normal HEK293 cell line showed that the inhibitory action of the complex is selective. VONarg generated intracellular reactive oxygen species (ROS), depletion of reduced glutathione and depolarization of mitochondrial membrane potential, typical for apoptotic pathway, producing cell death by oxidative stress mechanism. Moreover, naringin interacted with bovine serum albumin (BSA) through hydrophobic interactions in a spontaneous process, and VONarg showed greater affinity for the protein but can still be transported and delivered by it (Ka 104 L·mol−1 order).