bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood
Authors: Alouini Souhail , Guinard Jerôme , Belin Olivier , Mesnard Louis , Werner Evelyne , Prazuck Thierry , Pichon Chantal
Published: February 2022

Objective: There are few data on the maternal–fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns’ samples and search antibodies in cord blood. Methods: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers’ blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. Results: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers’ samples. IgM was negative in the 23 cord blood samples. Conclusions: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.
Association between the Physical Activity Behavioral Profile and Sedentary Time with Subjective Well-Being and Mental Health in Chilean University Students during the COVID-19 Pandemic
Authors: Reyes-Molina Daniel , Alonso-Cabrera Jesús , Nazar Gabriela , Parra-Rizo Maria Antonia , Zapata-Lamana Rafael , Sanhueza-Campos Cristian , Cigarroa Igor
Published: February 2022

Objective: To analyze the association between the behavioral profile of physical activity and sedentary time with subjective well-being and mental health in university students during the COVID-19 pandemic in Chile. Methods: Cross-sectional study in a voluntary sample of 469 university students (22.4 ± 0.19 years; 66% women). According to students’ self-reports of physical activity and sedentary time, four behavioral profiles were created to investigate their association with subjective well-being and mental health using one-factor ANOVA that was adjusted to a multifactorial model. Results: The physically inactive and sedentary behavior profile presents the lowest levels of subjective well-being (p < 0.001), positive affective experiences (p < 0.001) and general mental health (p = 0.001). When adjusting for confounding variables, it was observed that the physically active and non-sedentary profile was associated with better general mental health (p < 0.01) in contrast to those who are physically active and sedentary. Conclusions: Chilean university students with a physically inactive and sedentary profile during the pandemic presented worse well-being and mental health, with a sedentary lifestyle being one of the variables that most affects the mental health of these students. Therefore, measures should be implemented to encourage this population to maintain adequate levels of physical activity and reduce sedentary times.
Self-Assessment of the Pelvic Floor by Women Practicing Recreational Horseback Riding
Authors: Urbowicz Monika , Saulicz Mariola , Saulicz Aleksandra , Saulicz Edward
Published: February 2022

The aim of this study was to compare the condition of the pelvic floor in women who are involved in regular recreational horseback riding, with both physically active women as well as women not undertaking any recreational physical activity. Taking into account horseback riding and physical activity, 140 healthy women aged 17 to 61 were divided into three groups: women practicing horseback riding (WPHR) (46 persons), physically active women (PAW) (47 persons) and women not physically active (WNPA) (47 persons). The Australian Pelvic Floor Questionnaire (APFQ) was used to measure the extent of pelvic floor dysfunctions in women from all three groups. The lowest average values were found in the group of women practicing recreational horseback riding, and the highest in the group of women not physically active (95% CI: 0.61–1.15 vs. 0.87–1.44 —bladder scores; 0.82–1.32 vs. 1.24–1.8—bowel scores; 0.07–0.33 vs. 0.08–0.35—prolapse of reproductive organs scores; 0.4–1.07 vs. 0.49–1.3—sexual function). Statistically significant intergroup differences were recorded only for the bowel function rate (p = 0.021). The overall pelvic floor dysfunction rate in the WPHR group was lower when compared with both control groups (95% CI: 2.15–3.62 vs. 2.34–3.54 in women from PAW group and vs. 3.0–4.56 in women from WNPA group). Based on this study, it can be concluded that all of the pelvic floor related symptoms, their frequency, and severity levels do not qualify recreational horseback riding as being a risk factor for developing pelvic floor dysfunction in women.
Correction: Beristain Iraola et al. User Centered Virtual Coaching for Older Adults at Home Using SMART Goal Plans and I-Change Model. Int. J. Environ. Res. Public Health 2021, 18, 6868
Authors: Beristain Iraola Andoni , Álvarez Sánchez Roberto , Hors-Fraile Santiago , Petsani Despoina , Timoleon Michail , Díaz-Orueta Unai , Carroll Joanne , Hopper Louise , Epelde Gorka , Kerexeta Jon , Bamidis Panagiotis D. , Konstantinidis Evdokimos I.
Published: February 2022

The author would like to change the authorship in the previous publication [...]
How Well Are Manufacturing Companies in Transylvania, Romania Adapting to the Low-Carbon Economy in Order to Become Sustainable?
Authors: Dragomir Mihai , Blagu Diana Alina , Popescu Sorin , Fulea Mircea , Neamțu Călin
Published: February 2022

This paper addresses the degree of readiness of manufacturing companies in the well-defined area of Transylvania, Romania for tackling the challenges of the low-carbon economy (LCE) in view of the ambitious goals of the European Union. The presented survey aims to provide a better understanding about the management and reduction in the carbon footprint among production companies in Romania, as this sector is not usually included official strategies or studies. One hundred and three companies, selected based on voluntary sampling responses, were investigated using a 40-item questionnaire. The survey was applied to the manufacturing sector, including automotive, furniture production, and metal processing domains, which are locally representative and a good approximation of what small- and medium-sized firms look like across the EU, thus furnishing a good view of what takes place in other countries as well. The results obtained were analyzed using univariate descriptive statistics, multi-variate item analysis, and hypothesis testing to arrive at conclusions with a high degree of applicability. The purpose was to obtain an accurate overview about the actual situation and help companies find solutions in order to reduce the carbon footprint in the production field and achieve sustainable manufacturing. We arrive at the conclusion that manufacturing firms have a high degree of interest in decarbonization, but understand the efforts required to the same degree they understand the opportunities it brings. For example, 55% of respondents are interested in the benefits of LCE, while 90% of them observe at least one environmental standard, and ca. 70% implement at least common decarbonization measures, such as electricity savings or process optimization. While raising awareness and improving technological processes are accepted and embraced, other issues (i.e., involvement in RDI and CSR, change management, as well as financing investment efforts) should be addressed by proper policies.
Association of Dietary Calcium Intake with Dental, Skeletal and Non-Skeletal Fluorosis among Women in the Ethiopian Rift Valley
Authors: Mulualem Demmelash , Hailu Dejene , Tessema Masresha , Whiting Susan Joyce
Published: February 2022

Fluorosis is a major public health problem in the Rift Valley of Ethiopia. Low calcium (Ca) intake may worsen fluorosis symptoms. We assessed the occurrence of fluorosis symptoms among women living in high-fluoride (F) communities in South Ethiopia and their associations with dietary Ca intake. Women (n = 270) from two villages provided clinical and questionnaire data. Dental fluorosis examination was done using Dean’s Index, and skeletal and non-skeletal fluorosis assessment was carried out using physical tests and clinical symptoms. Daily Ca intake was estimated by a food frequency questionnaire. Food, drinking water and beverage samples were analyzed for F level. Many subjects (56.3%) exhibited dental fluorosis. One-third of the women were unable to perform the physical exercises indicative of skeletal fluorosis; about half had ≥2 symptoms of skeletal/non-skeletal fluorosis. The average F level in drinking water sources was ~5 mg/L. The F content in staple food samples varied from 0.8–13.6 mg/kg. Average Ca intake was 406 ± 97 mg/day. Women having ≤400 mg/day Ca intake had ~3 times greater odds of developing skeletal rigidity with joint pains [AOR = 2.8, 95%CI: 1.6, 5.0] and muscular weakness [AOR = 2.9, 95%CI: 1.3, 6.3] compared to those with higher intakes. No association of calcium intake was seen with dental fluorosis. As low dietary Ca intake was associated with symptoms related to skeletal and non-skeletal fluorosis, this warrants nutritional intervention on calcium intakes in this setting.
Carbon-Emission Characteristics and Influencing Factors in Growing and Shrinking Cities: Evidence from 280 Chinese Cities
Authors: Tong Xinhua , Guo Shurui , Duan Haiyan , Duan Zhiyuan , Gao Chang , Chen Wu
Published: February 2022

The CO2 emission-mitigation policies adopted in different Chinese cities are important for achieving national emission-mitigation targets. China faces enormous inequalities in terms of regional economic development and urbanization, with some cities growing rapidly, while others are shrinking. This study selects 280 cities in China and divides them into two groups of growing cities and two groups of shrinking cities. This is achieved using an index called “urban development degree,” which is calculated based on economic, demographic, social, and land-use indicators. Then, the 280 cities’ CO2 emission characteristics are examined, and extended STIRPAT (stochastic impacts by regression on population, affluence, and technology) is used to verify the influencing factors. We find that rapidly growing cities (RGCs) present a trend of fluctuating growth in CO2 emissions, rapidly shrinking cities (RSCs) show an inverted U-shaped trend, and slightly growing (SGCs) and slightly shrinking cities (SSCs) show a trend of rising first, followed by steady development. Moreover, for growing cities, the population, economy, and proportion of tertiary industry have positive effects on carbon emissions, while technology has negative effects. For shrinking cities, the population and economy have significant positive effects on carbon emissions, while technology and the proportion of tertiary industry have negative effects.
Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review
Authors: Tiecco Giorgio , Storti Samuele , Degli Antoni Melania , Focà Emanuele , Castelli Francesco , Quiros-Roldan Eugenia
Published: February 2022

The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.
Unexpected Enhancement of Cytotoxicity of Cisplatin in a Rat Kidney Proximal Tubular Cell Line Overexpressing Mitochondrial Glutathione Transport Activity
Authors: Lash Lawrence H.
Published: February 2022

In previous studies, we identified the two principal transporters that mediate the uptake of glutathione (GSH) from cytoplasm into the mitochondrial matrix of rat kidney proximal tubular cells. We hypothesized that genetic modulation of transporter expression could markedly alter susceptibility of renal proximal tubular cells to a broad array of oxidants and mitochondrial toxicants. Indeed, we previously showed that overexpression of either of these transporters resulted in diminished susceptibility to several chemicals. In the present work, we investigated the influence of overexpression of the mitochondrial 2-oxoglutarate carrier (OGC) in NRK-52E cells on the cytotoxicity of the antineoplastic drug cisplatin. In contrast to previous results showing that overexpression of the mitochondrial OGC provided substantial protection of NRK-52E cells from injury due to several toxicants, we found a remarkable enhancement of cellular injury from exposure to cisplatin as compared to wild-type NRK-52E cells. Despite the oxidative stress that cisplatin is known to cause in the renal proximal tubule, the increased concentrations of mitochondrial GSH associated with OGC overexpression likely resulted in increased delivery of cisplatin to molecular targets and increased cellular injury rather than the typical protection observed in the previous work.
Innate Immunity in Mucopolysaccharide Diseases
Authors: Mandolfo Oriana , Parker Helen , Bigger Brian
Published: February 2022

Mucopolysaccharidoses are rare paediatric lysosomal storage disorders, characterised by accumulation of glycosaminoglycans within lysosomes. This is caused by deficiencies in lysosomal enzymes involved in degradation of these molecules. Dependent on disease, progressive build-up of sugars may lead to musculoskeletal abnormalities and multi-organ failure, and in others, to cognitive decline, which is still a challenge for current therapies. The worsening of neuropathology, observed in patients following recovery from flu-like infections, suggests that inflammation is highly implicated in disease progression. This review provides an overview of the pathological features associated with the mucopolysaccharidoses and summarises current knowledge regarding the inflammatory responses observed in the central nervous system and periphery. We propose a model whereby progressive accumulation of glycosaminoglycans elicits an innate immune response, initiated by the Toll-like receptor 4 pathway, but also precipitated by secondary storage components. Its activation induces cells of the immune system to release pro-inflammatory cytokines, such as TNF-α and IL-1, which induce progression through chronic neuroinflammation. While TNF-α is mostly associated with bone and joint disease in mucopolysaccharidoses, increasing evidence implicates IL-1 as a main effector of innate immunity in the central nervous system. The (NOD)-like receptor protein 3 inflammasome is therefore implicated in chronic neuroinflammation and should be investigated further to identify novel anti-inflammatory treatments.
The Different Temozolomide Effects on Tumorigenesis Mechanisms of Pediatric Glioblastoma PBT24 and SF8628 Cell Tumor in CAM Model and on Cells In Vitro
Authors: Damanskienė Eligija , Balnytė Ingrida , Valančiūtė Angelija , Alonso Marta Maria , Preikšaitis Aidanas , Stakišaitis Donatas
Published: February 2022

It is necessary to elucidate the individual effects of temozolomide (TMZ) on carcinogenesis and tumor resistance to chemotherapy mechanisms. The study aimed to investigate the TMZ 50 and 100 μM dose effect difference between PBT24 and SF8628 cell line high-grade pediatric glioblastoma (phGBM) xenografts in a chicken chorioallantoic membrane (CAM) model, on PCNA and EZH2 immunohistochemical expression in the tumor and on the expression of NKCC1, KCC2, E- and N-cadherin genes in TMZ-treated and control cell groups in vitro. TMZ at a 100 μg dose reduced the incidence of PBT24 xenograft invasion into the CAM, CAM thickening and the number of blood vessels in the CAM (p < 0.05), but did not affect the SF8628 tumor in the CAM model. The TMZ impact on PBT24 and SF8628 tumor PCNA expression was similarly significantly effective but did not alter EZH2 expression in the studied tumors. The TMZ at 50 μM caused significantly increased RNA expression of the NKCC1 gene in both studied cell types compared with controls (p < 0.05). The expression of the KCC2 gene was increased in PBT24 TMZ-treated cells (p < 0.05), and no TMZ effect was found in SF8628-treated cells. The study supports the suggestion that individual sensitivity to TMZ should be assessed when starting treatment.
The Association of Rpb4 with RNA Polymerase II Depends on CTD Ser5P Phosphatase Rtr1 and Influences mRNA Decay in Saccharomyces cerevisiae
Authors: Garrido-Godino Ana I. , Cuevas-Bermúdez Abel , Gutiérrez-Santiago Francisco , Mota-Trujillo Maria del Carmen , Navarro Francisco
Published: February 2022

Rtr1 is an RNA polymerase II (RNA pol II) CTD-phosphatase that influences gene expression during the transition from transcription initiation to elongation and during transcription termination. Rtr1 interacts with the RNA pol II and this interaction depends on the phosphorylation state of the CTD of Rpb1, which may influence dissociation of the heterodimer Rpb4/7 during transcription. In addition, Rtr1 was proposed as an RNA pol II import factor in RNA pol II biogenesis and participates in mRNA decay by autoregulating the turnover of its own mRNA. Our work shows that Rtr1 acts in RNA pol II assembly by mediating the Rpb4/7 association with the rest of the enzyme. RTR1 deletion alters RNA pol II assembly and increases the amount of RNA pol II associated with the chromatin that lacks Rpb4, decreasing Rpb4-mRNA imprinting and, consequently, increasing mRNA stability. Thus, Rtr1 interplays RNA pol II biogenesis and mRNA decay regulation. Our data also indicate that Rtr1 mediates mRNA decay regulation more broadly than previously proposed by cooperating with Rpb4. Interestingly, our data include new layers in the mechanisms of gene regulation and in the crosstalk between mRNA synthesis and decay by demonstrating how the association of Rpb4/7 to the RNA pol II influences mRNA decay.
Effects of Cell Density and Microenvironment on Stem Cell Mitochondria Transfer among Human Adipose-Derived Stem Cells and HEK293 Tumorigenic Cells
Authors: Burch Shalise A. , Luna Lopez Carlos
Published: February 2022

Stem cells (SC) are largely known for their potential to restore damaged tissue through various known mechanisms. Among these mechanisms is their ability to transfer healthy mitochondria to injured cells to rescue them. This mitochondrial transfer plays a critical role in the healing process. To determine the optimal parameters for inducing mitochondrial transfer between cells, we assessed mitochondrial transfer as a function of seeding density and in two-dimensional (2D) and semi three-dimensional (2.5D) culture models. Since mitochondrial transfer can occur through direct contact or secretion, the 2.5D culture model utilizes collagen to provide cells with a more physiologically relevant extracellular matrix and offers a more realistic representation of cell attachment and movement. Results demonstrate the dependence of mitochondrial transfer on cell density and the distance between donor and recipient cell. Furthermore, the differences found between the transfer of mitochondria in 2D and 2.5D microenvironments suggest an optimal mode of mitochondria transport. Using these parameters, we explored the effects on mitochondrial transfer between SCs and tumorigenic cells. HEK293 (HEK) is an immortalized cell line derived from human embryonic kidney cells which grow rapidly and form tumors in culture. Consequently, HEKs have been deemed tumorigenic and are widely used in cancer research. We observed mitochondrial transfer from SCs to HEK cells at significantly higher transfer rates when compared to a SC–SC co-culture system. Interestingly, our results also revealed an increase in the migratory ability of HEK cells when cultured with SCs. As more researchers find co-localization of stem cells and tumors in the human body, these results could be used to better understand their biological relationship and lead to enhanced therapeutic applications.
Aducanumab and Its Effects on Tau Pathology: Is This the Turning Point of Amyloid Hypothesis?
Authors: Silvestro Serena , Valeri Andrea , Mazzon Emanuela
Published: February 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting millions of people around the world. The two main pathological mechanisms underlying the disease are beta-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of Tau proteins in the brain. Their reduction has been associated with slowing of cognitive decline and disease progression. Several antibodies aimed to target Aβ or Tau in order to represent hope for millions of patients, but only a small number managed to be selected to participate in clinical trials. Aducanumab is a monoclonal antibody recently approved by the Food and Drug Administration (FDA), which, targeting (Aβ) oligomers and fibrils, was able to reduce Aβ accumulation and slow the progression of cognitive impairment. It was also claimed to have an effect on the second hallmark of AD, decreasing the level of phospho-Tau evaluated in cerebrospinal fluid (CSF) and by positron emission tomography (PET). This evidence may represent a turning point in the development of AD-efficient drugs.
The Contribution of TSLP Activation to Hyperalgesia in Dorsal Root Ganglia Neurons of a Rat
Authors: Lu Chun-Ching , Lu Ying-Yi , Tsai Hung-Pei , Wu Chieh-Hsin
Published: February 2022

Peripheral nerve injury involves divergent alterations within dorsal root ganglia (DRG) neurons sensitized by persistent inflammation. Thymic stromal lymphopoietin (TSLP) production is crucial in the development of chronic inflammatory responses. Herein, we investigate the changes of TSLP expression in rats’ DRG neurons between injured and uninjured sides in the same rat. Linalyl acetate (LA) was served as a TSLP inhibitor and given intraperitoneally. Rats were assigned to be group of chronic constriction injury (CCI) of the sciatic nerve and the group of CCI of the sciatic nerve administrated with LA. Over 14 days, the rats were measured for paw withdrawal thresholds. DRGs were collected to assess morphological changes via immunofluorescence study. After receiving CCI, the rats rapidly developed mechanical hyperalgesia. TSLP expression at DRG, on the ipsilateral injured side, was consistent with changes in pain behaviors. TSLP appeared in nerve fibers with both small diameters and large diameters. Additionally, TSLP was expressed mostly in transient receptor potential vanilloid-1 (TRPV1)-positive nociceptive neurons. Administration with LA can attenuate the pain behaviors and expression of TSLP in DRG neurons, and in apoptotic neurons at the injured side, but not in the contra-lateral uninjured side. Overall, these results imply that altered expressions of TSLP in nociceptive DRG neurons contributed to mechanical hyperalgesia in a CCI rat model.
Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R
Authors: Wang Jixiu , Sun Qianhui , Zhang Jian , Wang Huanling , Liu Hong
Published: February 2022

Interleukin-6 (IL-6) is a multipotent cytokine. IL-6 plays a dual role in inflammation through both classical signaling (IL-6 binds membrane IL-6 receptor/IL-6R) and trans-signaling (IL-6 binds soluble IL-6R). However, the regulation of IL-6 activity, especially the regulation of signaling pathways and downstream genes mediated by IL-6 trans-signaling, remains largely unclear in teleost. Grass carp (Ctenopharyngodon idellus) hepatic (L8824) cells, kidney (CIK) cells, and primary hepatocytes were used as test models in this study. First, the biological activity of recombinant blunt snout bream (Megalobrama amblycephala) IL-6 (rmaIL-6) and sIL-6R (rmasIL-6R) was verified by quantitative PCR (qPCR) and western blot. The western blot results showed that rmaIL-6 significantly upregulated signal transducer and activator of transcription 3 (STAT3) phosphorylation in L8824 cells and primary hepatocytes, while rmaIL-6 in combination with rmasIL-6R (rmaIL-6+rmasIL-6R) significantly upregulated STAT3 phosphorylation in all types of cells. Furthermore, maIL-6 and maIL-6+rmasIL-6R could only induce extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation in L8824 cells and CIK cells, respectively. Therefore, IL-6 mainly acts by activating the janus kinase (JAK)/STAT3 pathway rather than the mitogen-activated protein kinase (MEK)/ERK pathway. Finally, the activation of the JAK2/STAT3 pathway was shown to be essential for the generation of socs3a and socs3b induced by IL-6 trans-signaling after treatment by JAK2/STAT3 pathway inhibitors (c188-9 and TG101348). These findings provide functional insights into IL-6 classical signaling and trans-signaling regulatory mechanisms in teleost, enriching our knowledge of fish immunology.
New Function of Cholesterol Oxidation Products Involved in Osteoporosis Pathogenesis
Authors: Che Yanting , Yang Jingzhi , Tang Fen , Wei Ziheng , Chao Yufan , Li Na , Li Henghui , Wu Si , Dong Xin
Published: February 2022

Osteoporosis (OP) is a systemic bone disease characterized by decreased bone strength, microarchitectural changes in bone tissues, and increased risk of fracture. Its occurrence is closely related to various factors such as aging, genetic factors, living habits, and nutritional deficiencies as well as the disturbance of bone homeostasis. The dysregulation of bone metabolism is regarded as one of the key influencing factors causing OP. Cholesterol oxidation products (COPs) are important compounds in the maintenance of bone metabolic homeostasis by participating in several important biological processes such as the differentiation of mesenchymal stem cells, bone formation in osteoblasts, and bone resorption in osteoclasts. The effects of specific COPs on mesenchymal stem cells are mainly manifested by promoting osteoblast genesis and inhibiting adipocyte genesis. This review aims to elucidate the biological roles of COPs in OP development, starting from the molecular mechanisms of OP, pointing out opportunities and challenges in current research, and providing new ideas and perspectives for further studies of OP pathogenesis.
The Influence of the Material Structure on the Mechanical Properties of Geopolymer Composites Reinforced with Short Fibers Obtained with Additive Technologies
Authors: Korniejenko Kinga , Kejzlar Pavel , Louda Petr
Published: February 2022

Additive manufacturing technologies have a lot of potential advantages for construction application, including increasing geometrical construction flexibility, reducing labor costs, and improving efficiency and safety, and they are in line with the sustainable development policy. However, the full exploitation of additive manufacturing technology for ceramic materials is currently limited. A promising solution in these ranges seems to be geopolymers reinforced by short fibers, but their application requires a better understanding of the behavior of this group of materials. The main objective of the article is to investigate the influence of the microstructure of the material on the mechanical properties of the two types of geopolymer composites (flax and carbon-reinforced) and to compare two methods of production of geopolymer composites (casting and 3D printing). As raw material for the matrix, fly ash from the Skawina coal power plant (located at: Skawina, Lesser Poland, Poland) was used. The provided research includes mechanical properties, microstructure investigations with the use of scanning electron microscope (SEM), confocal microscopy, and atomic force microscope (AFM), chemical and mineralogical (XRD-X-ray diffraction, and XRF-X-ray fluorescence), analysis of bonding in the materials (FT-IR), and nuclear magnetic resonance spectroscopy analysis (NMR). The best mechanical properties were reached for the sample made by simulating 3D printing process for the composite reinforced by flax fibers (48.7 MPa for the compressive strength and 9.4 MPa for flexural strength). The FT-IR, XRF and XRD results show similar composition of all investigated materials. NMR confirms the presence of SiO4 and AlO4 tetrahedrons in a three-dimensional structure that is crucial for geopolymer structure. The microscopy observations show a better coherence of the geopolymer made in additive technology to the reinforcement and equal fiber distribution for all investigated materials. The results show the samples made by the additive technology had comparable, or better, properties with those made by a traditional casting method.
Effect of Air Exposure-Induced Hypoxia on Neurotransmitters and Neurotransmission Enzymes in Ganglia of the Scallop Azumapecten farreri
Authors: Kotsyuba Elena , Dyachuk Vyacheslav
Published: February 2022

The nervous system expresses neuromolecules that play a crucial role in regulating physiological processes. Neuromolecule synthesis can be regulated by oxygen-dependent enzymes. Bivalves are a convenient model for studying air exposure-induced hypoxia. Here, we studied the effects of hypoxia on the expression and dynamics of neurotransmitters, and on neurotransmitter enzyme distribution, in the central nervous system (CNS) of the scallop Azumapecten farreri. We analyzed the expression of the neurotransmitters FMRFamide and serotonin (5-HT) and the choline acetyltransferase (CHAT) and universal NO-synthase (uNOS) enzymes during air exposure-induced hypoxia. We found that, in early-stage hypoxia, total serotonin content decreased in some CNS regions but increased in others. CHAT-lir cell numbers increased in all ganglia after hypoxia; CHAT probably appears de novo in accessory ganglia. Short-term hypoxia caused increased uNOS-lir cell numbers, while long-term exposure led to a reduction in their number. Thus, hypoxia weakly influences the number of FMRFamide-lir neurons in the visceral ganglion and does not affect peptide expression in the pedal ganglion. Ultimately, we found that the localization and level of synthesis of neuromolecules, and the numbers of cells expressing these molecules, vary in the scallop CNS during hypoxia exposure. This indicates their possible involvement in hypoxia resistance mechanisms.
Numerical Simulation of S-Shaped Current–Voltage Curves Induced by Electron Traps in Inverted Organic Photovoltaics
Authors: Luo Shanglin , Huo Mingfang , Xue Qin , Xie Guohua
Published: February 2022

Organic photovoltaics (OPVs) differ from their inorganic counterparts because of inevitable electronic disorders and structural heterogeneity. Charge carrier traps are inevitable in organic semiconductors. A common failure mechanism of OPVs is the development of an S-shaped current density–voltage characteristic (J-V curve). Herein, we focus on investigating the underlying physical mechanism of S-shaped deformation of J-V curve of the inverted organic photovoltaic devices with bulk-heterojunction, proven by experiments with the n-doped electron extraction layer and numerical simulations assuming electron traps (0.1 eV deeper) in the electron extraction layer. The numerical simulations are quite consistent with the experimental results. In addition, the open circuit voltage induced by S-kink is exemplified to be enhanced after removing the electron traps in the interlayer by introducing a dopant of cesium carbonate.
Immature Testicular Tissue Engineered from Weaned Mice to Adults for Prepubertal Fertility Preservation—An In Vivo Translational Study
Authors: Tseng How , Liu Yung-Liang , Lu Buo-Jia , Chen Chi-Huang
Published: February 2022

Male pediatric survivors of cancers and bone marrow transplantation often require adjuvant chemoradiation therapy that may be gonadotoxic. The optimal methods to preserve fertility in these prepubertal males are still under investigation. This manuscript presents an in vivo experiment which involved transplantation of immature testicular tissues (ITT) from transgenic donor, to wild-type recipient mice. Donors and recipients were age-mismatched (from 20-week-old donors to 3-week-old recipients, and vice versa) and the transplantation sites involved the abdomen, skin of the head, back muscle, and scrotum. The application of poly-l-lactic acid (PLLA) scaffold was also evaluated in age-matched donors and recipients (both 3-weeks-old). To quantitively evaluate the process of spermatogenesis after ITT transplantation and scaffold application, bioluminescence imaging (BLI) was employed. Our result showed that ITT from 3-week-old mice had the best potential for spermatogenesis, and the optimal transplantation site was in the scrotum. Spermatogenesis was observed in recipient mice up to 51 days after transplantation, and up to the 85th day if scaffold was used. The peak of spermatogenesis occurred between the 42nd and 55th days in the scaffold group. This animal model may serve as a framework for further studies in prepubertal male fertility preservation.
Circadian Gene cry Controls Tumorigenesis through Modulation of Myc Accumulation in Glioblastoma Cells
Authors: Jarabo Patricia , de Pablo Carmen , González-Blanco Amanda , Casas-Tintó Sergio
Published: February 2022

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. This aggressive tumor grows fast and spreads through the brain causing death in 15 months. GB cells display a high mutation rate and generate a heterogeneous population of tumoral cells that are genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We used a Drosophila model of GB that reproduces the features of human GB and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We studied the contribution of cry to the expansion of GB cells and the neurodegeneration and premature death caused by GB, and we determined that cry is required for GB progression. Moreover, we determined that the PI3K pathway regulates cry expression in GB cells, and in turn, cry is necessary and sufficient to promote Myc accumulation in GB. These results contribute to understanding the mechanisms underlying GB malignancy and lethality, and describe a novel role of Cry in GB cells.
Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease
Authors: Abu-Rumeileh Samir , Barschke Peggy , Oeckl Patrick , Baiardi Simone , Mammana Angela , Mastrangelo Andrea , Al Shweiki Mhd Rami , Steinacker Petra , Ladogana Anna , Capellari Sabina , Otto Markus , Parchi Piero
Published: February 2022

Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.
SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance
Authors: Sun Boshu , Xu Liangliang , Bi Wenhui , Ou Wen-Bin
Published: February 2022

SALL4, a member of the SALL family, is an embryonic stem cell regulator involved in self-renewal and pluripotency. Recently, SALL4 overexpression was found in malignant cancers, including lung cancer, hepatocellular carcinoma, breast cancer, gastric cancer, colorectal cancer, osteosarcoma, acute myeloid leukemia, ovarian cancer, and glioma. This review updates recent advances of our knowledge of the biology of SALL4 with a focus on its mechanisms and regulatory functions in tumors and human hematopoiesis. SALL4 overexpression promotes proliferation, development, invasion, and migration in cancers through activation of the Wnt/β-catenin, PI3K/AKT, and Notch signaling pathways; expression of mitochondrial oxidative phosphorylation genes; and inhibition of the expression of the Bcl-2 family, caspase-related proteins, and death receptors. Additionally, SALL4 regulates tumor progression correlated with the immune microenvironment involved in the TNF family and gene expression through epigenetic mechanisms, consequently affecting hematopoiesis. Therefore, SALL4 plays a critical oncogenic role in gene transcription and tumor growth. However, there are still some scientific hypotheses to be tested regarding whether SALL4 is a therapeutic target, such as different tumor microenvironments and drug resistance. Thus, an in-depth understanding and study of the functions and mechanisms of SALL4 in cancer may help develop novel strategies for cancer therapy.
Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy
Authors: McCarty Mark F.
Published: February 2022

Macroautophagy is a “cell cleansing” process that rids cells of protein aggregates and damaged organelles that may contribute to disease pathogenesis and the dysfunctions associated with aging. Measures which boost longevity and health span in rodents typically up-regulate macroautophagy, and it has often been suggested that safe strategies which can promote this process in humans may contribute to healthful aging. The kinase ULK1 serves as a trigger for autophagy initiation, and the transcription factors TFEB, FOXO1, ATF4 and CHOP promote expression of a number of proteins which mediate macroautophagy. Nutraceutical or dietary measures which stimulate AMPK, SIRT1, eIF5A, and that diminish the activities of AKT and mTORC1, can be expected to boost the activities of these pro-autophagic factors. The activity of AMPK can be stimulated with the phytochemical berberine. SIRT1 activation may be achieved with a range of agents, including ferulic acid, melatonin, urolithin A, N1-methylnicotinamide, nicotinamide riboside, and glucosamine; correction of ubiquinone deficiency may also be useful in this regard, as may dietary strategies such as time-restricted feeding or intermittent fasting. In the context of an age-related decrease in cellular polyamine levels, provision of exogenous spermidine can boost the hypusination reaction required for the appropriate post-translational modification of eIF5A. Low-protein plant-based diets could be expected to increase ATF4 and CHOP expression, while diminishing IGF-I-mediated activation of AKT and mTORC1. Hence, practical strategies for protecting health by up-regulating macroautophagy may be feasible.
The Effects of Antioxidants from Natural Products on Obesity, Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism
Authors: Khutami Chindiana , Sumiwi Sri Adi , Khairul Ikram Nur Kusaira , Muchtaridi Muchtaridi
Published: February 2022

Obesity is a risk factor that leads to the development of other diseases such as dyslipidemia and diabetes. These three metabolic disorders can occur simultaneously, hence, the treatment requires many drugs. Antioxidant compounds have been reported to have activities against obesity, dyslipidemia and diabetes via several mechanisms. This review aims to discuss the antioxidant compounds that have activity against obesity, dyslipidemia and diabetes together with their molecular signaling mechanism. The literature discussed in this review was obtained from the PUBMED database. Based on the collection of literature obtained, antioxidant compounds having activity against the three disorders (obesity, dyslipidemia and diabetes) were identified. The activity is supported by various molecular signaling pathways that are influenced by these antioxidant compounds, further study of which would be useful in predicting drug targets for a more optimal effect. This review provides insights on utilizing one of these antioxidant compounds as opposed to several drugs. It is hoped that in the future, the number of drugs in treating obesity, dyslipidemia and diabetes altogether can be minimized consequently reducing the risk of side effects.
Real-Time Fluorescence Microscopy on Living E. coli Sheds New Light on the Antibacterial Effects of the King Penguin β-Defensin AvBD103b
Authors: Landon Céline , Zhu Yanyu , Mustafi Mainak , Madinier Jean-Baptiste , Lelièvre Dominique , Aucagne Vincent , Delmas Agnes F. , Weisshaar James C.
Published: February 2022

(1) Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Among AMPs, the disulfide-rich β-defensin AvBD103b, whose antibacterial activities are not inhibited by salts contrary to most other β-defensins, is particularly appealing. Information about the mechanisms of action is mandatory for the development and approval of new drugs. However, data for non-membrane-disruptive AMPs such as β-defensins are scarce, thus they still remain poorly understood. (2) We used single-cell fluorescence imaging to monitor the effects of a β-defensin (namely AvBD103b) in real time, on living E. coli, and at the physiological concentration of salts. (3) We obtained key parameters to dissect the mechanism of action. The cascade of events, inferred from our precise timing of membrane permeabilization effects, associated with the timing of bacterial growth arrest, differs significantly from the other antimicrobial compounds that we previously studied in the same physiological conditions. Moreover, the AvBD103b mechanism does not involve significant stereo-selective interaction with any chiral partner, at any step of the process. (4) The results are consistent with the suggestion that after penetrating the outer membrane and the cytoplasmic membrane, AvBD103b interacts non-specifically with a variety of polyanionic targets, leading indirectly to cell death.
Investigating Glioblastoma Multiforme Sub-Proteomes: A Computational Study of CUSA Fluid Proteomic Data
Authors: Moresi Fabiana , Rossetti Diana Valeria , Vincenzoni Federica , Simboli Giorgia Antonia , La Rocca Giuseppe , Olivi Alessandro , Urbani Andrea , Sabatino Giovanni , Desiderio Claudia
Published: February 2022

Based on our previous proteomic study on Cavitating Ultrasound Aspirator (CUSA) fluid pools of Newly Diagnosed (ND) and Recurrent (R) glioblastomas (GBMs) of tumor core and periphery, as defined by 5-aminolevulinc acid (5-ALA) metabolite fluorescence, this work aims to apply a bioinformatic approach to investigate specifically into three sub-proteomes, i.e., Not Detected in Brain (NB), Cancer Related (CR) and Extracellular Vesicles (EVs) proteins following selected database classification. The study of these yet unexplored specific datasets aims to understand the high infiltration capability and relapse rate that characterizes this aggressive brain cancer. Out of the 587 proteins highly confidently identified in GBM CUSA pools, 53 proteins were classified as NB. Their gene ontology (GO) analysis showed the over-representation of blood coagulation and plasminogen activating cascade pathways, possibly compatible with Blood Brain Barrier damage in tumor disease and surgery bleeding. However, the NB group also included non-blood proteins and, specifically, histones correlated with oncogenesis. Concerning CR proteins, 159 proteins were found in the characterized GBM proteome. Their GO analysis highlighted the over-representation of many pathways, primarily glycolysis. Interestingly, while CR proteins were identified in ND-GBM exclusively in the tumor zones (fluorescence positive core and periphery zones) as predictable, conversely, in R-GBM they were unexpectedly characterized prevalently in the healthy zone (fluorescence negative tumor periphery). Relative to EVs protein classification, 60 proteins were found. EVs are over-released in tumor disease and are important in the transport of biological macromolecules. Furthermore, the presence of EVs in numerous body fluids makes them a possible low-invasive source of brain tumor biomarkers to be investigated. These results give new hints on the molecular features of GBM in trying to understand its aggressive behavior and open to more in-depth investigations to disclose potential disease biomarkers.