bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Adenine Nucleotide Metabolism by Adenylate Kinase Isozymes: Physiological Roles and Diseases
Authors: Fujisawa Koichi
Published: March 2023

Adenylate kinase (AK) regulates adenine nucleotide metabolism and catalyzes the ATP + AMP ⇌ 2ADP reaction in a wide range of organisms and bacteria. AKs regulate adenine nucleotide ratios in different intracellular compartments and maintain the homeostasis of the intracellular nucleotide metabolism necessary for growth, differentiation, and motility. To date, nine isozymes have been identified and their functions have been analyzed. Moreover, the dynamics of the intracellular energy metabolism, diseases caused by AK mutations, the relationship with carcinogenesis, and circadian rhythms have recently been reported. This article summarizes the current knowledge regarding the physiological roles of AK isozymes in different diseases. In particular, this review focused on the symptoms caused by mutated AK isozymes in humans and phenotypic changes arising from altered gene expression in animal models. The future analysis of intracellular, extracellular, and intercellular energy metabolism with a focus on AK will aid in a wide range of new therapeutic approaches for various diseases, including cancer, lifestyle-related diseases, and aging.
Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight
Authors: Waseem Mohammad , Wang Bi-Dar
Published: March 2023

Cancer has been progressively a major global health concern. With this developing global concern, cancer determent is one of the most significant public health challenges of this era. To date, the scientific community undoubtedly highlights mitochondrial dysfunction as a hallmark of cancer cells. Permeabilization of the mitochondrial membranes has been implicated as the most considerable footprint in apoptosis-mediated cancer cell death. Under the condition of mitochondrial calcium overload, exclusively mediated by oxidative stress, an opening of a nonspecific channel with a well-defined diameter in mitochondrial membrane allows free exchange between the mitochondrial matrix and the extra mitochondrial cytosol of solutes and proteins up to 1.5 kDa. Such a channel/nonspecific pore is recognized as the mitochondrial permeability transition pore (mPTP). mPTP has been established for regulating apoptosis-mediated cancer cell death. It has been evident that mPTP is critically linked with the glycolytic enzyme hexokinase II to defend cellular death and reduce cytochrome c release. However, elevated mitochondrial Ca2+ loading, oxidative stress, and mitochondrial depolarization are critical factors leading to mPTP opening/activation. Although the exact mechanism underlying mPTP-mediated cell death remains elusive, mPTP-mediated apoptosis machinery has been considered as an important clamp and plays a critical role in the pathogenesis of several types of cancers. In this review, we focus on structure and regulation of the mPTP complex-mediated apoptosis mechanisms and follow with a comprehensive discussion addressing the development of novel mPTP-targeting drugs/molecules in cancer treatment.
Generation of a p21 Reporter Mouse and Its Use to Identify and Eliminate p21high Cells In Vivo
Authors: Yi Zimei , Ren Le , Wei Yu , Chen Siyi , Zhao Jiechen , Zhu Jiayu , Wu Junhua
Published: March 2023

P21 and p16 have been identified as inducers of senescence. Many transgenic mouse models have been developed to target cells expressing high levels of p16Ink4a (p16high) and investigate their potential contribution to tissue dysfunction in aging, obesity, and other pathological conditions. However, the specific roles of p21 in various senescence-driven processes remain unclear. To gain a deeper understanding of p21, we built a p21-3MR mouse model containing a p21 promoter-driven module that allowed us to target cells with high p21Chip expression (p21high). Using this transgenic mouse, we monitored, imaged, and eliminated p21high cells in vivo. We also applied this system to chemically induced weakness and found that the clearance of p21high cells improved doxorubicin (DOXO)-induced multi-organ toxicity in mice. By recognizing p21 transcriptional activation spatially and temporally, the p21-3MR mouse model can be a valuable and powerful tool for studying p21high cells to further understand senescence biology.
Denervation Drives YAP/TAZ Activation in Muscular Fibro/Adipogenic Progenitors
Authors: Gallardo Felipe S. , Córdova-Casanova Adriana , Bock-Pereda Alexia , Rebolledo Daniela L. , Ravasio Andrea , Casar Juan Carlos , Brandan Enrique
Published: March 2023

Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to the activation and expansion of resident fibro/adipogenic progenitors (FAPs), i.e., multipotent stromal cells with myofibroblast potential. Using in vivo and in silico approaches, we revealed FAPs as a novel cell population that activates the transcriptional coregulators YAP/TAZ in response to skeletal muscle denervation. Here, we found that denervation induces the expression and transcriptional activity of YAP/TAZ in whole muscle lysates. Using the PdgfraH2B:EGFP/+ transgenic reporter mice to trace FAPs, we demonstrated that denervation leads to increased YAP expression that accumulates within FAPs nuclei. Consistently, re-analysis of published single-nucleus RNA sequencing (snRNA-seq) data indicates that FAPs from denervated muscles have a higher YAP/TAZ signature level than control FAPs. Thus, our work provides the foundations to address the functional role of YAP/TAZ in FAPs in a neurogenic pathological context, which could be applied to develop novel therapeutic approaches for the treatment of muscle disorders triggered by motoneuron degeneration.
Impact of Obesity on the IL-6 Immune Marker and Th17 Immune Cells in C57BL/6 Mice Models with Imiquimod-Induced Psoriasis
Authors: Park So Hee , Lee Kyung Ah , Choi Jae-Hyeog , Park SaeGwang , Kim Dae-Wook , Jung So Young
Published: March 2023

Obese psoriatic patients experience higher disease severity and exhibit poorer treatment responses and clinical outcomes. It has been proposed that proinflammatory cytokines produced by adipose tissue exacerbate psoriasis; however, the role of obesity in psoriasis remains unclear. This study aimed to elucidate the role of obesity in the pathogenesis of psoriasis, focusing on immunological changes. To induce obesity, mice were fed a high-fat diet for 20 weeks. We then applied imiquimod to the skin on a mouse’s back for seven consecutive days to induce psoriasis and scored lesion severity every day for seven days. Cytokine levels in serum and the Th17 cell population in the spleen and draining lymph nodes were studied to identify immunological differences. The clinical severity was more remarkable, and histologically the epidermis was also significantly thicker in the obese group. Increased levels of IL-6 and TNF-α were observed in serum after psoriasis. They were elevated to a greater degree, with greater expansion of the functional Th17 cell population in the obese group. It is concluded that obesity could exacerbate psoriasis through mechanisms that involve elevated proinflammatory cytokine secretion and an expanded Th17 cell population.
Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening
Authors: Pivetta Thais P. , Vieira Tânia , Silva Jorge C. , Ribeiro Paulo A. , Raposo Maria
Published: March 2023

Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC50 values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC50 of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC50 values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated.
Genetic Obesity in Pregnant Ay Mice Does Not Affect Susceptibility to Obesity and Food Choice in Offspring
Authors: Makarova Elena , Dubinina Anastasia , Denisova Elena , Kazantseva Antonina
Published: March 2023

Maternal diet and obesity (MO) may influence taste preferences and increase the susceptibility to obesity in offspring, but the impact of MO per se to these influences is poorly understood. We evaluated the influence of MO on food choice and susceptibility to obesity in offspring when mothers consumed a standard diet (SD). Mice with the Lethal yellow mutation (Ay/a) develop obesity consuming an SD. Metabolic parameters were assessed in pregnant and lactating Ay/a (obesity) and a/a (control) mothers. Metabolic response to the consumption of a sweet–fat diet (SFD: SD, lard, and sweet biscuits) and the choice of components of this diet were evaluated in their male and female offspring. Compared to control mothers, pregnant obese mothers had higher levels of insulin, leptin, and FGF21. MO increased food intake and liver expression of lipogenesis genes in male offspring consuming the SD. SFD consumption caused obesity development and insulin resistance, increased liver expression of glycolytic and lipogenesis genes, and affected hypothalamic expression of anorexigenic and orexigenic genes. In offspring of both sexes, MO had no effect on food choice and metabolic response to SFD intake. Therefore, when obese mothers consume a balanced diet, MO does not affect food choice and development of diet-induced obesity in offspring.
Nanodiamond Particles Reduce Oxidative Stress Induced by Methyl Viologen and High Light in the Green Alga Chlamydomonas reinhardtii
Authors: Antal Taras K. , Volgusheva Alena A. , Baizhumanov Adil A. , Kukarskikh Galina P. , Mezzi Alessio , Caschera Daniela , Ciasca Gabriele , Lambreva Maya D.
Published: March 2023

Widely used in biomedical and bioanalytical applications, the detonation nanodiamonds (NDs) are generally considered to be biocompatible and non-toxic to a wide range of eukaryotic cells. Due to their high susceptibility to chemical modifications, surface functionalisation is often used to tune the biocompatibility and antioxidant activity of the NDs. The response of photosynthetic microorganisms to redox-active NDs is still poorly understood and is the focus of the present study. The green microalga Chlamydomonas reinhardtii was used to assess the potential phytotoxicity and antioxidant activity of NDs hosting hydroxyl functional groups at concentrations of 5–80 μg NDs/mL. The photosynthetic capacity of microalgae was assessed by measuring the maximum quantum yield of PSII photochemistry and the light-saturated oxygen evolution rate, while oxidative stress was assessed by lipid peroxidation and ferric-reducing antioxidant capacity. We demonstrated that hydroxylated NDs might reduce cellular levels of oxidative stress, protect PSII photochemistry and facilitate the PSII repair under methyl viologen and high light associated stress conditions. Factors involved in this protection may include the low phytotoxicity of hydroxylated NDs in microalgae and their ability to accumulate in cells and scavenge reactive oxygen species. Our findings could pave the way for using hydroxylated NDs as antioxidants to improve cellular stability in algae-based biotechnological applications or semi-artificial photosynthetic systems.
B. abortus Infection Promotes an Imbalance in the Adipocyte–Osteoblast Crosstalk Favoring Bone Resorption
Authors: Freiberger Rosa Nicole , López Cinthya Alicia Marcela , Sviercz Franco Agustín , Cevallos Cintia , Guano Alex David , Jarmoluk Patricio , Quarleri Jorge , Delpino María Victoria
Published: March 2023

Osteoarticular injury is the most common presentation of active brucellosis in humans. Osteoblasts and adipocytes originate from mesenchymal stem cells (MSC). Since those osteoblasts are bone-forming cells, the predilection of MSC to differentiate into adipocytes or osteoblasts is a potential factor involved in bone loss. In addition, osteoblasts and adipocytes can be converted into each other according to the surrounding microenvironment. Here, we study the incumbency of B. abortus infection in the crosstalk between adipocytes and osteoblasts during differentiation from its precursors. Our results indicate that soluble mediators present in culture supernatants from B. abotus-infected adipocytes inhibit osteoblast mineral matrix deposition in a mechanism dependent on the presence of IL-6 with the concomitant reduction of Runt-related transcription factor 2 (RUNX-2) transcription, but without altering organic matrix deposition and inducing nuclear receptor activator ligand kβ (RANKL) expression. Secondly, B. abortus-infected osteoblasts stimulate adipocyte differentiation with the induction of peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT enhancer binding protein β (C/EBP-β). We conclude that adipocyte–osteoblast crosstalk during B. abortus infection could modulate mutual differentiation from its precursor cells, contributing to bone resorption.
Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19
Authors: Mancini Maria , Natoli Silvia , Gardoni Fabrizio , Di Luca Monica , Pisani Antonio
Published: March 2023

Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson’s disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.
Integrated ATAC-Seq and RNA-Seq Data Analysis to Reveal OsbZIP14 Function in Rice in Response to Heat Stress
Authors: Qiu Fuxiang , Zheng Yingjie , Lin Yao , Woldegiorgis Samuel Tareke , Xu Shichang , Feng Changqing , Huang Guanpeng , Shen Huiling , Xu Yinying , Kabore Manegdebwaoga Arthur Fabrice , Ai Yufang , Liu Wei , He Huaqin
Published: March 2023

Transcription factors (TFs) play critical roles in mediating the plant response to various abiotic stresses, particularly heat stress. Plants respond to elevated temperatures by modulating the expression of genes involved in diverse metabolic pathways, a regulatory process primarily governed by multiple TFs in a networked configuration. Many TFs, such as WRKY, MYB, NAC, bZIP, zinc finger protein, AP2/ERF, DREB, ERF, bHLH, and brassinosteroids, are associated with heat shock factor (Hsf) families, and are involved in heat stress tolerance. These TFs hold the potential to control multiple genes, which makes them ideal targets for enhancing the heat stress tolerance of crop plants. Despite their immense importance, only a small number of heat-stress-responsive TFs have been identified in rice. The molecular mechanisms underpinning the role of TFs in rice adaptation to heat stress still need to be researched. This study identified three TF genes, including OsbZIP14, OsMYB2, and OsHSF7, by integrating transcriptomic and epigenetic sequencing data analysis of rice in response to heat stress. Through comprehensive bioinformatics analysis, we demonstrated that OsbZIP14, one of the key heat-responsive TF genes, contained a basic-leucine zipper domain and primarily functioned as a nuclear TF with transcriptional activation capability. By knocking out the OsbZIP14 gene in the rice cultivar Zhonghua 11, we observed that the knockout mutant OsbZIP14 exhibited dwarfism with reduced tiller during the grain-filling stage. Under high-temperature treatment, it was also demonstrated that in the OsbZIP14 mutant, the expression of the OsbZIP58 gene, a key regulator of rice seed storage protein (SSP) accumulation, was upregulated. Furthermore, bimolecular fluorescence complementation (BiFC) experiments uncovered a direct interaction between OsbZIP14 and OsbZIP58. Our results suggested that OsbZIP14 acts as a key TF gene through the concerted action of OsbZIP58 and OsbZIP14 during rice filling under heat stress. These findings provide good candidate genes for genetic improvement of rice but also offer valuable scientific insights into the mechanism of heat tolerance stress in rice.
The Origins of the Dark—Hyperactivity and Negative Peer Relationships, an Objectively Lower Sleep Efficiency, and a Longer Sleep Onset Latency at Age Five Were Associated with Callous-Unemotional Traits and Low Empathy at Age 14
Authors: Eisenhut Larina , Sadeghi-Bahmani Dena , Ngo Vinh Tong , Mikoteit Thorsten , Brühl Annette Beatrix , Stadler Christina , Dürsteler Kenneth M. , Hatzinger Martin , Brand Serge
Published: March 2023

Background: Within the spectrum of emotional competencies, callous-unemotional traits are socially discouraged, while empathy is considered a socially much more accepted emotional trait. This holds particularly true for adolescents, who are still building up their social and emotional competencies. The aims of the present study were two-fold: First, longitudinally, to identify traits of behavioral problems and objective sleep dimensions at the age of 5 years to predict callous-unemotional traits and empathy at the age of 14 years. Second, cross-sectionally, to associate callous-unemotional traits and empathy with current insomnia, stress, and mental toughness. Methods: Preschoolers at the age of 5 years were contacted nine years later at the age of 14 years. At 5 years, parents rated their children’s behavior (Strength and Difficulties Questionnaire, SDQ); in parallel, children underwent a one-night sleep-EEG assessment. At the age of 14 years, adolescents completed a series of questionnaires covering callous-unemotional traits, insomnia, empathy, stress, and mental toughness. Results: A total of 77 adolescents (38.1% females) took part in the present study. Longitudinally, higher scores for hyperactivity at age 5 significantly predicted higher callous-unemotional traits at age 14. A higher score for negative peer relationships at age 5 significantly predicted lower scores for cognitive empathy at age 14. Further, objective sleep-EEG measures showed that a higher sleep efficiency and a shorter sleep latency was associated with lower scores for callousness. Cross-sectionally, higher scores for callous-unemotional traits were associated with higher insomnia and stress, while lower insomnia was associated with higher empathy. Mental toughness was unrelated to callous-unemotional traits and empathy. Conclusions: It appears that hyperactivity traits and negative peer relationships and more unfavorable objective sleep patterns at 5 years predicted socially discouraged callous-unemotional traits and low empathy during adolescence. Further, cross-sectionally at the age of 14, callous-unemotional traits, subjective poor sleep, and higher stress were associated.
The Effects of SGLT2 Inhibitors on Liver Cirrhosis Patients with Refractory Ascites: A Literature Review
Authors: Miyamoto Yasunori , Honda Akira , Yokose Seiji , Nagata Mariko , Miyamoto Jiro
Published: March 2023

Decompensated liver cirrhosis is often complicated by refractory ascites, and intractable ascites are a predictor of poor prognosis in patients with liver cirrhosis. The treatment of ascites in patients with cirrhosis is based on the use of aldosterone blockers and loop diuretics, and occasionally vasopressin receptor antagonists are also used. Recent reports suggest that sodium–glucose cotransporter 2 (SGLT2) inhibitors may be a new treatment for refractory ascites with a different mechanism with respect to conventional agents. The main mechanisms of ascites reduction with SGLT2 inhibitors appear to be natriuresis and osmotic diuresis. However, other mechanisms, including improvements in glucose metabolism and nutritional status, hepatoprotection by ketone bodies and adiponectin, amelioration of the sympathetic nervous system, and inhibition of the renin–angiotensin–aldosterone system, may also contribute to the reduction of ascites. This literature review describes previously reported cases in which SGLT2 inhibitors were used to effectively treat ascites caused by liver cirrhosis. The discussion of the mechanisms involved is expected to contribute to establishing SGLT2 therapy for ascites in the future.
Cognitive Dysfunctions Measured with the MCCB in Deficit and Non-Deficit Schizophrenia
Authors: Plichta Piotr , Tyburski Ernest , Bielecki Maksymilian , Mak Monika , Kucharska-Mazur Jolanta , Podwalski Piotr , Rek-Owodziń Katarzyna , Waszczuk Katarzyna , Sagan Leszek , Michalczyk Anna , Misiak Błażej , Samochowiec Jerzy
Published: March 2023

This study compared cognitive domains between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), analyzing relationships between psychopathological dimensions and cognitive domains. A total of 29 DS patients, 45 NDS patients, and 39 HC subjects participated. Cognitive domains were measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale. Clinical groups performed poorer than HC groups in regards to speed of processing, attention/vigilance, working memory, verbal and visual learning and memory, reasoning and problem solving, and social cognition. DS patients scored poorer than NDS patients in terms of all cognitive domains and the overall score, except for reasoning and problem solving. Positive, negative, disorganization, and resistance symptoms were related to cognitive functions only in NDS patients. Our findings suggest that the MCCB battery is sensitive to detecting cognitive dysfunctions in both deficit and non-deficit schizophrenia.
Artificial Liver Support with CytoSorb and MARS in Liver Failure: A Retrospective Propensity Matched Analysis
Authors: Popescu Mihai , David Corina , Marcu Alexandra , Olita Mihaela Roxana , Mihaila Mariana , Tomescu Dana
Published: March 2023

Background: Liver failure represents a life-threatening organ dysfunction with liver transplantation as the only proven curable therapy to date. Liver assist devices have been extensively researched to either bridge such patients to transplantation or promote spontaneous recovery. The aim of our study was to compare two such devices, the Molecular Adsorbent Recirculating System (MARS) and CytoSorb, in patients with liver failure. Methods: We retrospectively included 15 patients who underwent MARS during their intensive care unit stay and matched them to 15 patients who underwent hemoadsorption using CytoSorb. Clinical and paraclinical data obtained after each individual session, after the course of treatment, as well as at the end of the intensive care unit stay were compared between the two groups. Results: Single sessions of CytoSorb and MARS were both associated with a significant decrease in bilirubin (p = 0.04 and p = 0.04, respectively) and ammonia levels (p = 0.04 and p = 0.04, respectively), but only CytoSorb therapy was associated with a decrease in lactate dehydrogenase levels (p = 0.04) and in platelet count (p = 0.04). After the course of treatment, only CytoSorb was associated with a significant decrease in lactate (p = 0.01), bilirubin (p = 0.01), ammonia (p = 0.02), and lactate dehydrogenase levels (p = 0.01), while patients treated with MARS did not show any improvement in paraclinical liver tests. In addition, only CytoSorb treatment was associated with a significant improvement in the Model for End-Stage Liver Disease Score (p = 0.04). Conclusion: In conclusion, our results show a potential benefit of CytoSorb in rebalancing liver functional tests in patients with liver failure compared to MARS but the exact effects on patient outcome, including hospital length of stay and survival, should be further investigated in randomized control trials.
Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies
Authors: Wu Chieh-Chen , Liao Mao-Hung , Kung Woon-Man , Wang Yao-Chin
Published: March 2023

Previous epidemiological studies have raised the concern that the use of proton pump inhibitors (PPIs) is associated with an increased risk of kidney diseases. To date, no comprehensive meta-analysis has been conducted to assess the association between PPIs and the risk of chronic kidney disease (CKD). Therefore, we conducted a systematic review and meta-analysis to address the association between PPIs and CKD. The primary search was conducted in the most popular databases, such as PubMed, Scopus, and Web of Science. All observational studies evaluated the risk of CKD among PPI users, and non-users were considered for inclusion. Two reviewers conducted data extraction and assessed the risk of bias. Random-effect models were used to calculate pooled effect sizes. A total of 6,829,905 participants from 10 observational studies were included. Compared with non-PPI use, PPI use was significantly associated with an increased risk of CKD (RR 1.72, 95% CI: 1.02–2.87, p = 0.03). This updated meta-analysis showed that PPI was significantly associated with an increased risk of CKD. Association was observed in the same among moderate-quality studies. Until further randomized control trials (RCTs) and biological studies confirm these results, PPI therapy should not stop patients with gastroesophageal reflux disease (GERD). However, caution should be used when prescribing to patients with high-risk kidney disease.
Promising Perinatal Outcome after Using a Simplified Low-Cost IVF Culture System Specifically Designed for Resource-Poor Countries
Authors: Ombelet Willem , Van Blerkom Jonathan , Bruckers Liesbeth , Dhont Nathalie , Nargund Geeta , Campo Rudi
Published: March 2023

Background: Assisted reproductive techniques services are often not accessible to the majority of infertile couples in Low and Middle Income Countries (LMIC) due to high costs. Lowering IVF laboratory costs is a crucial step to make IVF affordable for a larger part of the world population. We developed a simplified culture system (SCS) which has proven to be effective, and the next step is to prove its safety.Methods: Preterm birth (PTB) and low birthweight (LBW) of 176 singletons born after using the SCS, 105 after fresh embryo transfer (fresh ET), and 71 after frozen embryo transfer (frozen ET) were compared with all IVF/ICSI singletons born in Belgium between 2013 and 2018. When comparing our 105 SCS babies born after fresh ET with all Belgian babies born after conventional IVF only, we also adjusted for 7 risk factors known to influence perinatal outcome, namelythe mother’s age, day of transfer, pituitary inhibition protocol, rank of cycles, number of oocytes retrieved, number of embryos transferred, and gender of the baby.Findings: Before adjustment, we found a significantly higher PTB (10.2% vs. 3.8%, OR 2.852, 95% CI [1.042–7.803], p-value 0.0413) and LBW (9.8% vs. 2.9%, OR 3.692, 95% CI [1.163–11.721], p-value 0.0267) in the conventional IVF group versus SCS after fresh ET. After adjusting for seven risk parameters, these differences remained significant (PTB: OR 2.627, 95% CI [1.013–6.816], p-value 0.0471) and LBW: OR 3.267, 95% CI [1.118–9.549], p-value 0.0305). PTB and LBW between both groups was not significantly different for singletons born after frozen ET. Interpretation: Taking into account the small series, PTB and LBW rates in SCS singletons in FRET cycles are very reassuring and significantly lower compared to babies born after conventional IVF in Belgium. Being aware of its effectiveness, our results offer a good perspective for SCS to become an important tool to implement low-cost IVF in LMIC.
Safety and Immunogenicity of Anti-SARS-CoV-2 Booster Dose in Patients with Chronic Liver Disease
Authors: Cossiga Valentina , Capasso Mario , Guarino Maria , Loperto Ilaria , Brusa Stefano , Cutolo Francesco Maria , Attanasio Maria Rosaria , Lieto Raffaele , Portella Giuseppe , Morisco Filomena
Published: March 2023

The low response to vaccines is a well-known problem in cirrhosis. We evaluated the safety and immunogenicity of booster doses in patients with chronic liver disease (CLD), comparing the humoral response in cirrhotic vs. non-cirrhotic patients, and the impact of different factors on immune response. From September 2021 to April 2022, outpatients with CLD who completed the primary vaccination course and the booster dose against SARS-CoV-2 were enrolled. Blood samples were collected after second and third doses for detecting anti-spike protein IgG. We enrolled 340 patients; among them, 91 subjects were cirrhotic. After primary vaccination course, 60 (17.6%) patients did not develop a positive antibody titer, without significant differences between cirrhotic and non-cirrhotic patients (p = 0.076); most of them (88.3%) developed it after booster dose. At multivariable analysis, factors associated with higher humoral response after booster dose were only porto-sinusoidal vascular disorder (p = 0.007) as an etiology of CLD and the use of the mRNA-1273 vaccine (p = 0.001). In conclusion, in patients with CLD, a booster dose against SARS-CoV-2 induces an excellent immunogenicity and leads to an adequate antibody response. Cirrhosis is not associated with a worse humoral response, compared to patients with non-cirrhotic CLD.
Clinical Advances in the Diagnosis and Treatment of Biliary Tract Diseases
Authors: Matsubara Saburo
Published: March 2023

Although the biliary tract is a small organ, it is diverse in location (intrahepatic bile ducts, extrahepatic bile ducts, gallbladder, and ampulla) and disease (including benign and malignant), thus a multidisciplinary approach involving endoscopists, surgeons, oncologists, radiologists, and infectious disease specialists is often required to treat biliary tract disease [...]
Bovine Grafting: An Effective Alternative after Curettage of Benign Bone Tumors
Authors: Montanhini Priscilla , Antunes Bruno P. , Pestilho Julie Francine Cerutti , Galia Carlos Roberto , Guedes Alex , Becker Ricardo Gehrke
Published: March 2023

We retrospectively reviewed 28 patients (15 women and 13 men) with benign bone tumors or pseudotumors treated with curettage and filling with freeze-dried bovine bone graft Orthogen (Baumer S/A, São Paulo, Brazil). The aim of the study was to evaluate the rate of incorporation of Orthogen into the host bone, as well as to describe the outcomes of bone healing (quality, time, and complications). General characteristics, tumor volume, size, site, complications, percent filled, and healing quality at 6 and 12 months were assessed through radiographs. Mean patient age was 20.5 (range 4.7–75.1) years. The most common lesion type was simple bone cyst (12/28), and the most common sites were the tibia (7/28) and humerus (7/28). There were no postoperative pathologic fractures. Two cases (7.1%) of serous fluid leakage through the wound occurred. Mean cavity volume was 20.1 (range 2.7–101.4) cm3. At 6 and 12 months, 75% and 77.8% of cavities, respectively, showed complete bone healing. At 12 months, 81% of cavities filled >90% with graft showed complete bone healing vs. only 19% of those filled <90%. Filling with bovine bone graft resulted in few complications and excellent healing after curettage of benign bone tumors or pseudotumors. Complete healing occurred in most cases by 12 months. Cavities with a higher percentage of filling had a higher rate of complete radiographic incorporation.
Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods
Authors: Ren Jingxin , Zhang Yuhang , Guo Wei , Feng Kaiyan , Yuan Ye , Huang Tao , Cai Yu-Dong
Published: March 2023

The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20–85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These symptoms are not life-threatening but severely affect patients’ quality of life and increase the risk of depression and anxiety. The pathological mechanisms of these symptoms have not been fully identified. In the current study, we aimed to identify the important biomarkers at the expression level associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated loss of taste or olfactory ability, and we have suggested the potential pathogenetic mechanisms of COVID-19 complications. We designed a machine-learning-based approach to analyze the transcriptome of 577 COVID-19 patient samples, including 84 COVID-19 samples with a decreased ability to taste or smell and 493 COVID-19 samples without impairment. Each sample was represented by 58,929 gene expression levels. The features were analyzed and sorted by three feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, and Monte Carlo feature selection). The optimal feature sets were obtained through incremental feature selection using two classification algorithms: decision tree (DT) and random forest (RF). The top genes identified by these multiple methods (H3-5, NUDT5, and AOC1) are involved in olfactory and gustatory impairments. Meanwhile, a high-performance RF classifier was developed in this study, and three sets of quantitative rules that describe the impairment of olfactory and gustatory functions were obtained based on the optimal DT classifiers. In summary, this study provides a new computation analysis and suggests the latent biomarkers (genes and rules) for predicting olfactory and gustatory impairment caused by COVID-19 complications.
Deformation Inhomogeneities of a Hypoeutectic Aluminum-Silicon Alloy Modified by Electron Beam Treatment
Authors: Ustinov Artem , Klopotov Anatoly , Ivanov Yuri , Zagulyaev Dmitry , Teresov Anton , Petrikova Elizaveta , Gurianov Denis , Chumaevskii Andrey
Published: March 2023

This paper presents the results of uniaxial tensile tests on specimens of the hypoeutectic aluminum-silicon alloy A319. According to the results, the influence of surface treatment by pulsed electron beam on the mechanical properties of the material was determined. The peculiarities of deformation localization in the material caused by grinding of the surface layer material structure due to rapid crystallization during electron beam treatment were revealed. The surface treatment up to the depth of 100 µm leads to the formation of a fine dendritic columnar structure of silumin and to an increase in the plasticity of the samples. The influence of the surface treatment affects the increase in the deformation localization in the region of the stable concentrator before failure. The greatest increase in ductility and localization of deformation occurs during treatment with an energy density of 15 J/cm2. In the process of specimen deformation, unstable, metastable, and stable areas of plastic deformation localization are formed and replaced, and the formation of stable areas of localized plastic deformation, in which the specimen fails at the end of the test, can be detected at the initial stages of testing. In specimens, during the test in the zone of localized plastic deformation, bands are formed which pass through the entire surface of the specimen at an angle of 35 to 55 degrees to the tensile axis, and their development leads to the formation of stable zones of localized plastic deformation and to the failure of the specimen.
Chitins from Seafood Waste as Sustainable Porous Carbon Precursors for the Development of Eco-Friendly Supercapacitors
Authors: Brandão Ana T. S. C. , Costa Renata , State Sabrina , Potorac Pavel , Dias Catarina , Vázquez José A. , Valcarcel Jesus , Silva A. Fernando , Enachescu Marius , Pereira Carlos M.
Published: March 2023

Carbon materials derived from marine waste have been drawing attention for supercapacitor applications. In this work, chitins from squid and prawn marine wastes were used as carbon precursors for further application as electrodes for energy storage devices. Chitins were obtained through a deproteinization method based on enzymatic hydrolysis as an alternative to chemical hydrolysis as commonly presented in the literature. The obtained porous carbons were characterized using a BET surface area analyzer to determine the specific surface area and pore size, as well as scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), Raman spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), to characterize their morphology, composition, and structure. The electrochemical characterization was performed using a glassy carbon (GC) electrode modified with marine waste-based porous carbons as the working electrode through cyclic voltammetry and galvanostatic charge/discharge using ethaline, a choline chloride-based deep eutectic solvent (DES), as an eco-friendly and sustainable electrolyte. Squid and prawn chitin-based carbons presented a surface area of 149.3 m2 g−1 and 85.0 m2 g−1, pore volume of 0.053 cm3 g−1 and 0.029 cm3 g−1, and an associated specific capacitance of 20 and 15 F g−1 at 1 A g−1, respectively. Preliminary studies were performed to understand the effect of -OH groups on the chitin-based carbon surface with DES as an electrolyte, as well as the effect of aqueous electrolytes (1 mol L−1 sulphuric acid (H2SO4) and 1 mol L−1 potassium hydroxide (KOH)) on the capacitance and retention of the half-cell set up. It is provided, for the first time, the use of chitin-based carbon materials obtained through a one-step carbonization process combined with an eco-friendly DES electrolyte for potential application in energy storage devices.
Fully Integrated Silicon Photonic Erbium-Doped Nanodiode for Few Photon Emission at Telecom Wavelengths
Authors: Tavani Giulio , Barri Chiara , Mafakheri Erfan , Franzò Giorgia , Celebrano Michele , Castriotta Michele , Di Giancamillo Matteo , Ferrari Giorgio , Picciariello Francesco , Foletto Giulio , Agnesi Costantino , Vallone Giuseppe , Villoresi Paolo , Sorianello Vito , Rotta Davide , Finazzi Marco , Bollani Monica , Prati Enrico
Published: March 2023

Recent advancements in quantum key distribution (QKD) protocols opened the chance to exploit nonlaser sources for their implementation. A possible solution might consist in erbium-doped light emitting diodes (LEDs), which are able to produce photons in the third communication window, with a wavelength around 1550 nm. Here, we present silicon LEDs based on the electroluminescence of Er:O complexes in Si. Such sources are fabricated with a fully-compatible CMOS process on a 220 nm-thick silicon-on-insulator (SOI) wafer, the common standard in silicon photonics. The implantation depth is tuned to match the center of the silicon layer. The erbium and oxygen co-doping ratio is tuned to optimize the electroluminescence signal. We fabricate a batch of Er:O diodes with surface areas ranging from 1 µm × 1 µm to 50 µm × 50 µm emitting 1550 nm photons at room temperature. We demonstrate emission rates around 5 × 106 photons/s for a 1 µm × 1 µm device at room temperature using superconducting nanowire detectors cooled at 0.8 K. The demonstration of Er:O diodes integrated in the 220 nm SOI platform paves the way towards the creation of integrated silicon photon sources suitable for arbitrary-statistic-tolerant QKD protocols.
Enhanced Electrorheological Polishing Efficiency of Alumina-Doped Titanium Dioxide Particles
Authors: Hu Xufeng , Sun Han , Zhao Xiaopeng , Yin Jianbo
Published: March 2023

Electrorheological (ER) polishing is a novel polishing technology having flexible and tunable characteristics. At present, ER polishing uses ER particles to drive abrasive particles to polish the material surface. Under the action of high-speed centrifugation, the abrasive particles are easily separated from ER particles due to their significantly different ER effect, and this can easily cause the degradation of polishing ability. In this work, alumina-doped titanium dioxide ER polishing particles were developed via a sol-gel method. As a classical abrasive, alumina has higher hardness and can improve the ER effect of titanium dioxide by doping. Thus, alumina-doped titanium dioxide particles simultaneously possess high ER effect and high hardness. No phase separation appears in the polishing process and the result shows that alumina-doped titanium dioxide has a good polishing efficiency for materials with Mohs hardness of 3 and below.
Relevance of Environmental Factors in the Steel Life Cycle for a Transition toward Circular Sustainable Production and Consumption Systems: A Joint Bibliometric and Bibliographic Analysis
Authors: Casazza Marco , Barone Fabrizio
Published: March 2023

The design of steel structures has evolved thanks to the increased ability to model the behavior of more complex structures. However, further constraints arise from the need for a transition toward more sustainable production and consumption systems. In particular, the assessment of the economic benefits and efficiency of existing production systems should be integrated with assessment of environmental, economic and social sustainability. In the case of steel, and limited to the environmental dimension, the literature covers various study areas, ranging from the analysis of resource flows to the assessment of steel’s environmental impacts. However, an integrated view of existing peer-reviewed studies is currently missing. The purpose of this work is to overcome this shortcoming with a review that considers and integrates research on the steel life cycle from various perspectives: analysis of material flows; quantification of emissions; environmental monitoring and indicators; and circular economy aspects, including reuse and recycling. This study is based on a deep bibliometric and bibliographical analysis of the above-cited aspects, including the key topics, authors and journals, to single out some potential research directions that have previously been neglected. The results of the analyses indicate that, even though discussed in the literature, the redesign of products is still lacking adequate consideration. The same gap was also evidenced when it came to studies on the management of waste materials and recommissioning. There is also still a lack of knowledge on the possible meaningful indicators of environmental sustainability in the case of steel. Moreover, while digital technologies that enable sustainability are being intensely developed and widely implemented, the design, testing and application of sensors for the environmental monitoring of steel production is under-studied and the interaction of environmental factors with steel structures is poorly addressed. Finally, this work evidenced poor attention with respect to water and soil pollution generated in different phases of the steel life cycle. All these aspects should be considered in future research, which would also have a beneficial effect in the implementation of informed policies for a transition toward a circular and sustainable steel life cycle.
Metabolomic Changes in Patients Affected by Multiple Sclerosis and Treated with Fingolimod
Authors: Murgia Federica , Lorefice Lorena , Noto Antonio , Spada Martina , Frau Jessica , Fenu Giuseppe , Coghe Giancarlo , Gagliano Antonella , Atzori Luigi , Cocco Eleonora
Published: March 2023

Current treatment for Multiple Sclerosis (MS) consists of a multidisciplinary approach including disease-modifying therapies. The response to treatment is heterogeneous, representing a crucial challenge in the classification of patients. Metabolomics is an innovative tool that can identifies biomarkers/predictors of treatment response. We aimed to evaluate plasma metabolic changes in a group of naïve Relapsing-Remitting MS patients starting Fingolimod treatment, to find specific metabolomic features that predict the therapeutic response as well as the possible side effects. The study included 42 Relapsing-Remitting MS blood samples, of which 30 were classified as responders after two years of FINGO treatment, whereas 12 patients were Not-Responders. For fifteen patients, samples were collected at four time points: before starting the therapy; at six months after the initiation; at twelve months after; and at twenty-four months after initiation. The serum was analysed through Nuclear Magnetic Resonance and multivariate and univariate statistical analysis. Considering the single comparison between each time point, it was possible to identify a set of metabolites changing their concentrations based on the drug intake. FINGO influences aminoacidic and energy metabolisms and reduces oxidative stress and the activity of the immune system, both typical features of MS.