bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular, Physiological and Hematological Responses of Crossbred Dairy Cattle in a Tropical Savanna Climate
Authors: Velayudhan Silpa Mullakkalparambil , Brügemann Kerstin , Alam Shahin , Yin Tong , Devaraj Chinnasamy , Sejian Veerasamy , Schlecht Eva , König Sven
Published: December 2022

A comprehensive study was conducted to assess the effects of seasonal transition and temperature humidity index (THI) on the adaptive responses in crossbred dairy cows reared in a tropical savanna region. A total of 40 lactating dairy cattle reared by small-scale dairy farmers in Bengaluru, India, were selected for this study. The research period comprised the transitioning season of summer to monsoon, wherein all traits were recorded at two points, one representing late summer (June) and the other early monsoon (July). A set of extensive variables representing physiological responses (pulse rate, respiration rate, rectal temperature, skin surface temperature), hematological responses (hematological profile), production (test day milk yield, milk composition) and molecular patterns (PBMC mRNA relative expression of selective stress response genes) were assessed. A significant effect of seasonal transition was identified on respiration rate (RR), skin surface temperature, mean platelet volume (MPV), platelet distribution width (PDWc), test day milk yield and on milk composition variables (milk density, lactose, solids-not-fat (SNF) and salts). The THI had a significant effect on RR, skin surface temperature, platelet count (PLT), plateletcrit (PCT) and PDWc. Lastly, THI and/or seasonal transition significantly affected the relative PBMC mRNA expression of heat shock protein 70 (HSP70), interferon beta (IFNβ), IFNγ, tumor necrosis factor alpha (TNFα), growth hormone (GH) and insulin-like growth factor-1 (IGF-1) genes. The results from this study reveal environmental sensitivity of novel physiological traits and gene expressions to climatic stressors, highlighting their potential as THI-independent heat stress biomarkers.
NRF2 in the Epidermal Pigmentary System
Authors: Ogawa Tatsuya , Ishitsuka Yosuke
Published: December 2022

Melanogenesis is a major part of the environmental responses and tissue development of the integumentary system. The balance between reduction and oxidation (redox) governs pigmentary responses, for which coordination among epidermal resident cells is indispensable. Here, we review the current understanding of melanocyte biology with a particular focus on the “master regulator” of oxidative stress responses (i.e., the Kelch-like erythroid cell-derived protein with cap‘n’collar homology-associated protein 1-nuclear factor erythroid-2-related factor 2 system) and the autoimmune pigment disorder vitiligo. Our investigation revealed that the former is essential in pigmentogenesis, whereas the latter results from unbalanced redox homeostasis and/or defective intercellular communication in the interfollicular epidermis (IFE). Finally, we propose a model in which keratinocytes provide a “niche” for differentiated melanocytes and may “imprint” IFE pigmentation.
Defining Two Chemosensory Arrays in Shewanella oneidensis
Authors: Fortier Emma M. , Bouillet Sophie , Infossi Pascale , Ali Chaouche Amine , Espinosa Leon , Giudici-Orticoni Marie-Thérèse , Mauriello Emilia M. F. , Iobbi-Nivol Chantal
Published: December 2022

Shewanella oneidensis has 2 functional chemosensory systems named Che1 and Che3, and 27 chemoreceptors. Che3 is dedicated to chemotaxis while Che1 could be involved in RpoS post-translational regulation. In this study, we have shown that two chemoreceptors Aer2so and McpAso, genetically related to the Che1 system, form distinct core-signaling units and signal to Che1 and Che3, respectively. Moreover, we observed that Aer2so is a cytoplasmic dynamic chemoreceptor that, when in complex with CheA1 and CheW1, localizes at the two poles and the centre of the cells. Altogether, the results obtained indicate that Che1 and Che3 systems are interconnected by these two chemoreceptors allowing a global response for bacterial survival.
Stereological Evidence of Non-Selective Hippocampal Neurodegeneration, IGF-1 Depletion, and Behavioral Deficit following Short Term Bilateral Adrenalectomy in Wistar Rats
Authors: Hamadi Naserddine , Deniz Ömür Gülsüm , Issa Ahlam Said Abi , Islam Azim Ullah Shamsul , Amir Naheed , Minhas Saeed Tariq , Madjid Nather , Khelifi-Touhami Fatima , Kaplan Süleyman , Adem Abdu
Published: December 2022

The development of animal models to study cell death in the brain is a delicate task. One of the models, that was discovered in the late eighties, is the induction of neurodegeneration through glucocorticoid withdrawal by adrenalectomy in albino rats. Such a model is one of the few noninvasive models for studying neurodegeneration. In the present study, using stereological technique and ultrastructural examination, we aimed to investigate the impact of short-term adrenalectomy (2 weeks) on different hippocampal neuronal populations in Wistar rats. In addition, the underlying mechanism(s) of degeneration in these neurons were investigated by measuring the levels of insulin-like growth factor-1 (IGF-1) and β-nerve growth factor (β-NGF). Moreover, we examined whether the biochemical and histological changes in the hippocampus, after short-term adrenalectomy, have an impact on the cognitive behavior of Wistar rats. Stereological counting in the hippocampus revealed significant neuronal deaths in the dentate gyrus and CA4/CA3, but not in the CA2 and CA1 areas, 7 and 14 days post adrenalectomy. The ultrastructural examinations revealed degenerated and degenerating neurons in the dentate, as well as CA4, and CA3 areas, over the course of 3, 7 and 14 days. The levels of IGF-1 were significantly decreased in the hippocampus of ADX rats 24 h post adrenalectomy, and lasted over the course of two weeks. However, β-NGF was not affected in rats. Using a passive avoidance task, we found a cognitive deficit in the ADX compared to the SHAM operated rats over time (3, 7, and 14 days). In conclusion, both granule and pyramidal cells were degenerated in the hippocampus following short-term adrenalectomy. The early depletion of IGF-1 might play a role in hippocampal neuronal degeneration. Consequently, the loss of the hippocampal neurons after adrenalectomy leads to cognitive deficits.
Platform Design and Preliminary Test Result of an Insect-like Flapping MAV with Direct Motor-Driven Resonant Wings Utilizing Extension Springs
Authors: Jeong Seung-hee , Kim Jeong-hwan , Choi Seung-ik , Park Jung-keun , Kang Tae-sam
Published: December 2022

In this paper, we propose a platform for an insect-like flapping winged micro aerial vehicle with a resonant wing-driving system using extension springs (FMAVRES). The resonant wing-driving system is constructed using an extension spring instead of the conventional helical or torsion spring. The extension spring can be mounted more easily, compared with a torsion spring. Furthermore, the proposed resonant driving system has better endurance compared with systems with torsion springs. Using a prototype FMAVRES, it was found that torques generated for roll, pitch, and yaw control are linear to control input signals. Considering transient responses, each torque response as an actuator is modelled as a simple first-order system. Roll, pitch, and yaw control commands affect each other. They should be compensated in a closed loop controller design. Total weight of the prototype FMAVRES is 17.92 g while the lift force of it is 21.3 gf with 80% throttle input. Thus, it is expected that the new platform of FMAVRES could be used effectively to develop simple and robust flapping MAVs.
Peptide Nanosheet-Inspired Biomimetic Synthesis of CuS Nanoparticles on Ti3C2 Nanosheets for Electrochemical Biosensing of Hydrogen Peroxide
Authors: Zhu Danzhu , Kong Hao , Yang Guozheng , He Peng , Luan Xin , Guo Lei , Wei Gang
Published: December 2022

Hydrogen peroxide (H2O2) is one of the intermediates or final products of biological metabolism and participates in many important biological processes of life activities. The detection of H2O2 is of great significance in clinical disease monitoring, environmental protection, and bioanalysis. In this study, Ti3C2-based nanohybrids are prepared by the biological modification and self-assembled peptide nanosheets (PNSs)-based biomimetic synthesis of copper sulfide nanoparticles (CuS NPs), which show potential application in the fabrication of low-cost and high-performance electrochemical H2O2 biosensors. The synthesized CuS-PNSs/Ti3C2 nanohybrids exhibit excellent electrochemical performance towards H2O2, in which CuS NPs can catalyze the decomposition of H2O2 and realize the transformation from a chemical signal to an electrical signal to achieve the purpose of H2O2 detection. The prepared CuS-PNSs/Ti3C2-based electrochemical biosensor platform exhibits a wide detection range (5 μM–15 mM) and a low detection limit (0.226 μM). In addition, it reveals good selectivity and stability and can realize the monitoring of H2O2 in a complex environment. The successful biomimetic synthesis of CuS-PNSs/Ti3C2 hybrid nanomaterials provides a green and friendly strategy for the design and synthesis of functional nanomaterials and also provides a new inspiration for the construction of highly effective electrochemical biosensors for practical detection of H2O2 in various environments.
The Relationship between Working Memory and Arithmetic in Primary School Children: A Meta-Analysis
Authors: Zhang Yuxin , Tolmie Andrew , Gordon Rebecca
Published: December 2022

Working memory (WM) plays a crucial role in the development of arithmetic ability. However, research findings related to which factors influence the relationship between WM and arithmetic skills are inconsistent. The present meta-analysis aimed to examine the links between WM and arithmetic in primary school children and investigate whether this is dependent on WM domains (i.e., verbal, visual, spatial), child age, arithmetic operation type, and arithmetic task type. A total of 11,224 participants with an age range of 6- to 12 years, from 55 independent samples were included in the meta-analysis. Analysis of 46 studies with 187 effect sizes revealed an overall significant and medium correlation between WM and arithmetic. Heterogeneity analyses indicated that verbal WM showed a stronger correlation with arithmetic than visuospatial WM, and that correlations between verbal WM and arithmetic declined with age, whereas correlations between spatial-sequential, and spatial-simultaneous WM and arithmetic remained stable throughout development. Addition and subtraction were more involved in verbal WM than multiplication and division. Moreover, mental and written arithmetic showed comparable correlations with WM in all domains. These findings suggest moderation effects of WM domains, age, and operation types in the WM-arithmetic relationship and highlight the significant role of verbal WM in arithmetic ability in primary school children.
Risk Factors for Delirium after Deep Brain Stimulation Surgery under Total Intravenous Anesthesia in Parkinson’s Disease Patients
Authors: Lu Wenbin , Chang Xinning , Bo Lulong , Qiu Yiqing , Zhang Mingyang , Wang Jiali , Wu Xi , Yu Xiya
Published: December 2022

Background: Postoperative delirium (POD) is associated with perioperative complications and mortality. Data on the risk factors for delirium after subthalamic nucleus deep brain stimulation (STN-DBS) surgery is not clarified in Parkinson’s disease (PD) patients receiving total intravenous anesthesia. We aimed to investigate the risk factors for delirium after STN-DBS surgery in PD patients. Methods:The retrospective cohort study was conducted, including 131 PD patients who underwent STN-DBS for the first time under total intravenous anesthesia from January to December 2021. Delirium assessments were performed twice daily for 7 days after surgery or until hospital discharge using the confusion assessment method for the intensive care unit. Multivariate logistic regression analysis was used to determine the risk factor of POD. Results: In total, 22 (16.8%) of 131 patients were in the POD group, while the other 109 patients were in the Non-POD group. Multivariate logistic regression analysis showed that preoperative Mini-mental State Examination score [odds ratio = 0.855, 95% confidence interval = 0.768–0.951, p = 0.004] and unified Parkinson’s disease rating scale part 3 (on state) score (odds ratio = 1.061, 95% confidence interval = 1.02–1.104, p = 0.003) were independently associated with delirium after surgery. Conclusions: In this retrospective cohort study of PD patients, a lower Mini-mental State Examination score and a higher unified Parkinson’s disease rating scale part 3 (on state) score were the independent risk factors for delirium after STN-DBS surgery in PD patients under total intravenous anesthesia.
Poor Internal Jugular Venous Outflow Is Associated with Poor Cortical Venous Outflow and Outcomes after Successful Endovascular Reperfusion Therapy
Authors: Shang Wenjin , Zhong Kaiyi , Shu Liming , Li Zhuhao , Hong Hua
Published: December 2022

Many patients show poor outcomes following endovascular reperfusion therapy (ERT), and poor cortical venous outflow is a risk factor for these poor outcomes. We investigated the association between the outflow of the internal jugular vein (IJV) and baseline cortical venous outflow and the outcomes after ERT. We retrospectively enrolled 78 patients diagnosed with an acute anterior circulation stroke and successful ERT. Poor IJV outflow on the affected side was defined as stenosis ≥50% or occlusion of ipsilateral IJV, and poor outflow of bilateral IJVs was defined as stenosis ≥50% or occlusion of both IJVs. Poor cortical venous outflow was defined as a cortical vein opacification score (COVES) of 0 on admission. Multivariate analysis showed that poor outflow of IJV on the affected side was an independent predictor for hemorrhagic transformation. The poor outflow of bilateral IJVs was an independent risk factor for poor clinical outcomes. These patients also had numerical trends of a higher incidence of symptomatic intracranial hemorrhage, midline shift >10 mm, and in-hospital mortality; however, statistical significance was not observed. Additionally, poor IJV outflow was an independent determinant of poor cortical venous outflow. For acute large vessel occlusion patients, poor IJV outflow is associated with poor baseline cortical venous outflow and outcomes after successful ERT.
Deep Learning-Driven Automated Fault Detection and Diagnostics Based on a Contextual Environment: A Case Study of HVAC System
Authors: Haruehansapong Kanjana , Roungprom Wisit , Kliangkhlao Mallika , Yeranee Kirttayoth , Sahoh Bukhoree
Published: December 2022

Indoor thermal comfort affects occupants’ daily activities and health. HVAC systems are necessary to control thermal comfort quality. Tracking and monitoring the effectiveness of HVAC system engines are critical activities because they ensure that the system can produce suitable indoor thermal comfort. However, the operation of such systems depends on practitioners and engineers, which is time-consuming and labor-intensive. Moreover, installing physical sensors into the system engine may keep track of the problem but may also require costs and maintenance. This research addressed this concern by presenting deep learning (DL)-driven automated fault detection and diagnostics (AFDD) for HVAC systems. It employed contextual factors as an indirect measurement to avoid modifying HVAC system engines (e.g., according to standard building appliance warranties) but was still able to effectively detect issues. The design and development of the DL model are proposed to encode complex behaviors of an HVAC system using contextual factors. The experimental results show that the predictive performance of our model achieved an average F-measure of over 97%, which was outstanding compared with the standard ML models. This proposed model will be a natural fit for AFDD for HVAC systems and is ready for future real-world applications as required by building engineering.
A Translational Approach to Spinal Neurofibromatosis: Clinical and Molecular Insights from a Wide Italian Cohort
Authors: Paterra Rosina , Bettinaglio Paola , Borghi Arianna , Mangano Eleonora , Tritto Viviana , Cesaretti Claudia , Schettino Carla , Bordoni Roberta , Santoro Claudia , Avignone Sabrina , Moscatelli Marco , Melone Mariarosa Anna Beatrice , Saletti Veronica , Piluso Giulio , Natacci Federica , Riva Paola , Eoli Marica
Published: December 2022

Spinal neurofibromatosis (SNF), a phenotypic subclass of neurofibromatosis 1 (NF1), is characterized by bilateral neurofibromas involving all spinal roots. In order to deepen the understanding of SNF’s clinical and genetic features, we identified 81 patients with SNF, 55 from unrelated families, and 26 belonging to 19 families with at least 1 member affected by SNF, and 106 NF1 patients aged >30 years without spinal tumors. A comprehensive NF1 mutation screening was performed using NGS panels, including NF1 and several RAS pathway genes. The main features of the SNF subjects were a higher number of internal neurofibromas (p < 0.001), nerve root swelling (p < 0.001), and subcutaneous neurofibromas (p = 0.03), while hyperpigmentation signs were significantly less frequent compared with the classical NF1-affected cohorts (p = 0.012). Fifteen patients underwent neurosurgical intervention. The histological findings revealed neurofibromas in 13 patients and ganglioneuromas in 2 patients. Phenotypic variability within SNF families was observed. The proportion of missense mutations was higher in the SNF cases than in the classical NF1 group (21.40% vs. 7.5%, p = 0.007), conferring an odds ratio (OR) of 3.34 (CI = 1.33–10.78). Two unrelated familial SNF cases harbored in trans double NF1 mutations that seemed to have a subclinical worsening effect on the clinical phenotype. Our study, with the largest series of SNF patients reported to date, better defines the clinical and genetic features of SNF, which could improve the management and genetic counseling of NF1.
The Effect of Oxidative Phosphorylation on Cancer Drug Resistance
Authors: Zhao Ziyi , Mei Yong , Wang Ziyang , He Weiling
Published: December 2022

Recent studies have shown that oxidative phosphorylation (OXPHOS) is a target for the effective attenuation of cancer drug resistance. OXPHOS inhibitors can improve treatment responses to anticancer therapy in certain cancers, such as melanomas, lymphomas, colon cancers, leukemias and pancreatic ductal adenocarcinoma (PDAC). However, the effect of OXPHOS on cancer drug resistance is complex and associated with cell types in the tumor microenvironment (TME). Cancer cells universally promote OXPHOS activity through the activation of various signaling pathways, and this activity is required for resistance to cancer therapy. Resistant cancer cells are prevalent among cancer stem cells (CSCs), for which the main metabolic phenotype is increased OXPHOS. CSCs depend on OXPHOS to survive targeting by anticancer drugs and can be selectively eradicated by OXPHOS inhibitors. In contrast to that in cancer cells, mitochondrial OXPHOS is significantly downregulated in tumor-infiltrating T cells, impairing antitumor immunity. In this review, we summarize novel research showing the effect of OXPHOS on cancer drug resistance, thereby explaining how this metabolic process plays a dual role in cancer progression. We highlight the underlying mechanisms of metabolic reprogramming in cancer cells, as it is vital for discovering new drug targets.
RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines
Authors: Albanell-Fernández Marta , Oltra Sara S. , Orts-Arroyo Marta , Ibarrola-Villava Maider , Carrasco Fany , Jiménez-Martí Elena , Cervantes Andrés , Castro Isabel , Martínez-Lillo José , Ribas Gloria
Published: December 2022

Ruthenium compounds have demonstrated promising activity in different cancer types, overcoming several limitations of platinum-based drugs, yet their global structure–activity is still under debate. We analyzed the activity of Runat-BI, a racemic Ru(III) compound, and of one of its isomers in eight tumor cell lines of breast, colon and gastric cancer as well as in a non-tumoral control. Runat-BI was prepared with 2,2’-biimidazole and dissolved in polyethylene glycol. We performed assays of time- and dose-dependent viability, migration, proliferation, and expression of pro- and antiapoptotic genes. Moreover, we studied the growth rate and cell doubling time to correlate it with the apoptotic effect of Runat-BI. As a racemic mixture, Runat-BI caused a significant reduction in the viability and migration of three cancer cell lines from colon, gastric and breast cancer, all of which displayed fast proliferation rates. This compound also demonstrated selectivity between tumor and non-tumor lines and increased proapoptotic gene expression. However, the isolated isomer did not show any effect. Racemic Runat-BI is a potential drug candidate for treatment of highly aggressive tumors. Further studies should be addressed at evaluating the role of the other isomer, for a more precise understanding of its antitumoral potential and mechanism of action.
Identifying Borderline Ovarian Tumor Recurrence Using Routine Ultrasound Follow-Up
Authors: Lazurko Caitlin , Feigenberg Tomer , Murphy Joan , Pulman Kate , Lennox Genevieve , Dube Valerie , Zigras Tiffany
Published: December 2022

Borderline ovarian tumors (BOTs) are non-invasive tumors frequently diagnosed in young patients. Surgical removal of the uterus, fallopian tubes, ovaries, and omentum is considered definitive management, however fertility-sparing approach is a recognized option. Surveillance is important due to known recurrence, but there is controversy over the effectiveness of follow-up modalities. The objective is to determine the efficacy of ultrasound screening in identifying tumor recurrence. This retrospective chart review evaluated all patients consulted and/or treated surgically at our institution from January 2015 to June 2020 diagnosed with BOT. Patients were excluded if concurrently diagnosed with another gynecologic malignancy, did not have yearly ultrasound follow-up, or were lost to follow-up. This study included 56 patients, 17 of whom underwent fertility preserving surgery. The overall rate of recurrence was 10.7%; with recurrence rates of 23.5% for the fertility preserving surgery population and 5.1% for the definitive surgery population. Ultrasound first identified 5 of the 6 (83.3%) recurrences. Overall time to recurrence was 51.5 months. In conclusion, recurrences were identified on routine ultrasound screening prior to symptom onset or detection via physical exam in 83.3% of cases. While the best modality of follow-up remains controversial, this review provides evidence supporting the use of routine ultrasound follow-up for early detection of BOT recurrence.
The Reaction Mechanism of the Cu(I) Catalyzed Alkylation of Heterosubstituted Alkynes
Authors: Silva Pedro J.
Published: December 2022

Alkynes may be regioselectively alkylated to alkenes by organocopper reagents in a reaction known as “carbocupration”, where an alkylCu(I) binds to the alkyne and transfers its organic moiety to one of the alkyne carbon atoms. Alkynes hetero-substituted with third-row elements yield alkenes with a regiochemistry opposite to that obtained when using alkynes hetero-substituted with second-row elements. Early computational investigations of his reaction mechanism have identified the importance of the organocopper counter-cation (Li+) to the achievement of good reaction rates, but in the subsequent two decades no further progress has been reported regarding the exploration of the mechanism or the explanation of the experimental regiochemistry. In this work, density-functional theory is used to investigate the mechanism used and to describe a model that correctly explains both the reaction rates at sub-zero temperatures and the regiochemistry profiles obtained with each of the heteroalkynes. The rate-determining step is shown to vary depending on the heterosubstituent, and the alkyl transfer is consistently shown to occur, somewhat counter-intuitively, to the alkyne carbon that is complexed by Cu rather than to the “free” alkyne carbon atom, which instead interacts with the counter-cation that stabilizes the developing electronic charge distribution.
Rescue of Misfolded Organic Cation Transporter 3 Variants
Authors: Angenoorth Thomas J. F. , Maier Julian , Stankovic Stevan , Bhat Shreyas , Sucic Sonja , Freissmuth Michael , Sitte Harald H. , Yang Jae-Won
Published: December 2022

Organic cation transporters (OCTs) are membrane proteins that take up monoamines, cationic drugs and xenobiotics. We previously reported novel missense mutations of organic cation transporter 3 (OCT3, SLC22A3), some with drastically impacted transport capabilities compared to wildtype. For some variants, this was due to ER retention and subsequent degradation of the misfolded transporter. For other transporter families, it was previously shown that treatment of misfolded variants with pharmacological and chemical chaperones could restore transport function to a certain degree. To investigate two potentially ER-bound, misfolded variants (D340G and R348W), we employed confocal and biochemical analyses. In addition, radiotracer uptake assays were conducted to assess whether pre-treatment with chaperones could restore transporter function. We show that pre-treatment of cells with the chemical chaperone 4-PBA (4-phenyl butyric acid) leads to increased membrane expression of misfolded variants and is associated with increased transport capacity of D340G (8-fold) and R348W (1.5 times) compared to untreated variants. We herein present proof of principle that folding-deficient SLC22 transporter variants, in particular those of OCT3, are amenable to rescue by chaperones. These findings need to be extended to other SLC22 members with corroborated disease associations.
Human Health during Space Travel: State-of-the-Art Review
Authors: Krittanawong Chayakrit , Singh Nitin Kumar , Scheuring Richard A. , Urquieta Emmanuel , Bershad Eric M. , Macaulay Timothy R. , Kaplin Scott , Dunn Carly , Kry Stephen F. , Russomano Thais , Shepanek Marc , Stowe Raymond P. , Kirkpatrick Andrew W. , Broderick Timothy J. , Sibonga Jean D. , Lee Andrew G. , Crucian Brian E.
Published: December 2022

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans’ natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.
Exploring the Nerve Regenerative Capacity of Compounds with Differing Affinity for PPARγ In Vitro and In Vivo
Authors: Rayner Melissa L. D. , Kellaway Simon C. , Kingston Isabel , Guillemot-Legris Owein , Gregory Holly , Healy Jess , Phillips James B.
Published: December 2022

Damage to peripheral nerves can cause debilitating consequences for patients such as lifelong pain and disability. At present, no drug treatments are routinely given in the clinic following a peripheral nerve injury (PNI) to improve regeneration and remyelination of damaged nerves. Appropriately targeted therapeutic agents have the potential to be used at different stages following nerve damage, e.g., to maintain Schwann cell viability, induce and sustain a repair phenotype to support axonal growth, or promote remyelination. The development of therapies to promote nerve regeneration is currently of high interest to researchers, however, translation to the clinic of drug therapies for PNI is still lacking. Studying the effect of PPARγ agonists for treatment of peripheral nerve injures has demonstrated significant benefits. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), has reproducibly demonstrated benefits in vitro and in vivo, suggested to be due to its agonist action on PPARγ. Other NSAIDs have demonstrated differing levels of PPARγ activation based upon their affinity. Therefore, it was of interest to determine whether affinity for PPARγ of selected drugs corresponded to an increase in regeneration. A 3D co-culture in vitro model identified some correlation between these two properties. However, when the drug treatments were screened in vivo, in a crush injury model in a rat sciatic nerve, the same correlation was not apparent. Further differences were observed between capacity to increase axon number and improvement in functional recovery. Despite there not being a clear correlation between affinity and size of effect on regeneration, all selected PPARγ agonists improved regeneration, providing a panel of compounds that could be explored for use in the treatment of PNI.
Antioxidants Prevent the Effects of Physical Exercise on Visual Cortical Plasticity
Authors: Sansevero Gabriele , Consorti Alan , Di Marco Irene , Terzibasi Tozzini Eva , Cellerino Alessandro , Sale Alessandro
Published: December 2022

Background: Physical activity has been recently shown to enhance adult visual cortical plasticity, both in human subjects and animal models. While physical activity activates mitochondrial oxidative metabolism leading to a transient production of reactive oxygen species, it remains unknown whether this process is involved in the plasticizing effects elicited at the visual cortical level. Results: Here, we investigated whether counteracting oxidative stress through a dietary intervention with antioxidants (vitamins E and C) interferes with the impact of physical exercise on visual cortex plasticity in adult rats. Antioxidant supplementation beyond the closure of the critical period blocked ocular dominance plasticity in response to eye deprivation induced by physical activity in adult rats. Conclusions: Antioxidants exerted their action through a mithormetic effect that involved dampening of oxidative stress and insulin-like growth factor 1 (IGF-1) signaling in the brain.
Natural Infection of Pomegranate (Punica Granatum) by Apple Dimple Fruit Viroid
Authors: Ruiz-García Ana Belén , Olmos Antonio , Marais Armelle , Faure Chantal , Candresse Thierry
Published: December 2022

The analysis by high throughput sequencing (HTS) and RT-PCR of Spanish pomegranate fruits showing yellow rings revealed the presence of viroid isolates closely related to fig isolates of apple dimple fruit viroid (ADFVd). The analysis of pomegranate public RNASeq data (Sequence Reads Archives, SRAs) from Israel provided evidence for the presence of similar ADFVd isolates in pomegranate trees in this country. In addition, reads or contigs of plum viroid I (PVd-I) isolates were also identified in two of the analyzed SRA datasets from Israel, suggesting the presence of this second viroid in pomegranate. Full length ADFVd genomic sequences have been recovered, increasing knowledge on the diversity of this viroid and on the pomegranate virome in which only four viruses and one viroid had previously been reported.
The Multiple Roles of Periostin in Non-Neoplastic Disease
Authors: Yang Lina , Guo Tongtong , Chen Yuanyuan , Bian Ka
Published: December 2022

Periostin, identified as a matricellular protein and an ECM protein, plays a central role in non-neoplastic diseases. Periostin and its variants have been considered to be normally involved in the progression of most non-neoplastic diseases, including brain injury, ocular diseases, chronic rhinosinusitis, allergic rhinitis, dental diseases, atopic dermatitis, scleroderma, eosinophilic esophagitis, asthma, cardiovascular diseases, lung diseases, liver diseases, chronic kidney diseases, inflammatory bowel disease, and osteoarthrosis. Periostin interacts with protein receptors and transduces signals primarily through the PI3K/Akt and FAK two channels as well as other pathways to elicit tissue remodeling, fibrosis, inflammation, wound healing, repair, angiogenesis, tissue regeneration, bone formation, barrier, and vascular calcification. This review comprehensively integrates the multiple roles of periostin and its variants in non-neoplastic diseases, proposes the utility of periostin as a biological biomarker, and provides potential drug-developing strategies for targeting periostin.
Bone Tissue and the Nervous System: What Do They Have in Common?
Authors: Minoia Arianna , Dalle Carbonare Luca , Schwamborn Jens Christian , Bolognin Silvia , Valenti Maria Teresa
Published: December 2022

Degenerative diseases affecting bone tissues and the brain represent important problems with high socio-economic impact. Certain bone diseases, such as osteoporosis, are considered risk factors for the progression of neurological disorders. Often, patients with neurodegenerative diseases have bone fractures or reduced mobility linked to osteoarthritis. The bone is a dynamic tissue involved not only in movement but also in the maintenance of mineral metabolism. Bone is also associated with the generation of both hematopoietic stem cells (HSCs), and thus the generation of the immune system, and mesenchymal stem cells (MSCs). Bone marrow is a lymphoid organ and contains MSCs and HSCs, both of which are involved in brain health via the production of cytokines with endocrine functions. Hence, it seems clear that bone is involved in the regulation of the neuronal system and vice versa. This review summarizes the recent knowledge on the interactions between the nervous system and bone and highlights the importance of the interaction between nerve and bone cells. In addition, experimental models that study the interaction between nerve and skeletal cells are discussed, and innovative models are suggested to better evaluate the molecular interactions between these two cell types.
CLPP Depletion Causes Diplotene Arrest; Underlying Testis Mitochondrial Dysfunction Occurs with Accumulation of Perrault Proteins ERAL1, PEO1, and HARS2
Authors: Key Jana , Gispert Suzana , Koornneef Lieke , Sleddens-Linkels Esther , Kohli Aneesha , Torres-Odio Sylvia , Koepf Gabriele , Amr Shady , Reichlmeir Marina , Harter Patrick N. , West Andrew Phillip , Münch Christian , Baarends Willy M. , Auburger Georg
Published: December 2022

Human Perrault syndrome (PRLTS) is autosomal, recessively inherited, and characterized by ovarian insufficiency with hearing loss. Among the genetic causes are mutations of matrix peptidase CLPP, which trigger additional azoospermia. Here, we analyzed the impact of CLPP deficiency on male mouse meiosis stages. Histology, immunocytology, different OMICS and biochemical approaches, and RT-qPCR were employed in CLPP-null mouse testis. Meiotic chromosome pairing and synapsis proceeded normally. However, the foci number of the crossover marker MLH1 was slightly reduced, and foci persisted in diplotene, most likely due to premature desynapsis, associated with an accumulation of the DNA damage marker γH2AX. No meiotic M-phase cells were detected. Proteome profiles identified strong deficits of proteins involved in male meiotic prophase (HSPA2, SHCBP1L, DMRT7, and HSF5), versus an accumulation of AURKAIP1. Histone H3 cleavage, mtDNA extrusion, and cGAMP increase suggested innate immunity activation. However, the deletion of downstream STING/IFNAR failed to alleviate pathology. As markers of underlying mitochondrial pathology, we observed an accumulation of PRLTS proteins ERAL1, PEO1, and HARS2. We propose that the loss of CLPP leads to the extrusion of mitochondrial nucleotide-binding proteins to cytosol and nucleus, affecting late meiotic prophase progression, and causing cell death prior to M-phase entry. This phenotype is more severe than in mito-mice or mutator-mice.
Mechanism Underlying Light Intensity-Induced Melanin Synthesis of Auricularia heimuer Revealed by Transcriptome Analysis
Authors: Qiu Zhiheng , Gao Yanliang , Wang Shuang , Wang Jun , Wang Xinyi , Cai Nuo , Zhao Jiazhi , Li Tingshu , Li Hongpeng , Li Tianlai , Shu Lili
Published: December 2022

Auricularia heimuer is a traditional edible and medicinal mushroom, which is widely used in biochemical research and is regarded as a good dietary supplement. The color of the ear-like fruiting body is an important indicator of its commercial quality. However, the mechanism by which light intensity influences the melanin synthesis of A. heimuer remains unclear. Here, we show that fruiting body color is significantly affected by light intensity. Transcriptional profiles of the fruiting bodies of A. heimuer grown in different light intensities were further analyzed. More differentially expressed genes (DEGs) were identified with a greater light intensity difference. A total of 1388 DEGs were identified from six comparisons, including 503 up-regulated genes and 885 down-regulated genes. The up-regulated genes were mainly associated with light sensing via photoreceptors, signal transduction via the mitogen-activated protein kinase (MAPK) signaling pathway, and melanin synthesis via the tyrosine metabolic pathway. Therefore, the genes involved in these processes may participate in regulating melanin synthesis under high light intensity. This insight into the transcriptional regulation of A. heimuer to light intensity should help to further comprehensively elucidate the underlying mechanism of light-induced melanin synthesis.
Pharmacodynamic Modeling to Evaluate the Impact of Cimetidine, an OCT2 Inhibitor, on the Anticancer Effects of Cisplatin
Authors: Mody Hardik , Vaidya Tanaya R. , Lesko Lawrence J. , Ait-Oudhia Sihem
Published: December 2022

Despite potent anticancer activity, the clinical utilization of cisplatin is limited due to nephrotoxicity. As Organic Cation Transporter 2 (OCT2) has been shown to be one of the key transporters involved in the uptake of cisplatin into renal proximal tubules, OCT2 inhibitors such as cimetidine have been explored to suppress cisplatin-induced nephrotoxicity. Nonetheless, the impact of OCT2 inhibition or cimetidine on the anti-cancer effects of cisplatin has not been extensively examined. The main objective of the present study was to quantitatively characterize the anticancer effects of cisplatin and cimetidine and determine their nature of interactions in two cancer cell lines, OCT2-negative hepatocellular carcinoma (HCC) cell line, Huh7, and OCT2-positive breast cancer cell line, MDA-MB-468. First, we determined the static concentration-response curves of cisplatin and cimetidine as single agents. Next, with the help of three-dimensional (3D) response surface analyses and a competitive interaction model, we determined their nature of interactions at static concentrations to be modestly synergistic or additive in Huh7 and antagonistic in MDA-MB-468. These results were consistent with the cell-level pharmacodynamic (PD) modeling analysis which leveraged the time-course effects of drugs as single agents and drug combinations. Our developed PD model can be further used to design future preclinical studies to further investigate the cisplatin and cimetidine combinations in different in vitro and in vivo cancer models.
Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome
Authors: Ramos-Martinez Espiridión , Vega-Sánchez Angel E. , Pérez-Rubio Gloria , Mejia Mayra , Buendía-Roldán Ivette , González-Pérez Montserrat I. , Mateos-Toledo Heidegger N. , Andrade Warrison A. , Falfán-Valencia Ramcés , Rojas-Serrano Jorge
Published: December 2022

Anti-synthetase syndrome (ASSD) is an autoimmune disorder characterized by inflammatory interstitial lung disease (ILD). The main objective of this work was to quantify the concentrations of cytokines and molecules associated with inflammasome activation in bronchoalveolar lavage (BAL) of patients with ASSD and a comparison group of systemic sclerosis (SSc) patients. Cytokines and lactate dehydrogenase (LDH) were determined using the concentrated BAL protein. The activity of caspase-1 and concentration of NLRP3 with the protein purified from the cell pellet in each group of patients. We found higher caspase-1 levels in ASSD vs. SSc, 1.25 RFU vs. 0.75 RFU p = 0.003, and LDH levels at 0.15 OD vs. 0.09 OD p < 0.001. A significant difference was observed in molecules associated with inflammasome activation, IL-18: 1.42 pg/mL vs. 0.87 pg/mL p = 0.02 and IFN-γ: 0.9 pg/mL vs. 0.86 pg/mL, p = 0.01. A positive correlation was found between caspase-1 and LDH in the patients with ASSD Rho 0.58 (p = 0.008) but not in the SSc group. In patients with ASSD, greater caspase-1 and higher LDH activity were observed in BAL, suggesting cell death due to pyroptosis and activation of the inflammasome pathway.
Accuracy of 3D Corrective Osteotomy for Pediatric Malunited Both-Bone Forearm Fractures
Authors: Roth Kasper , van Es Eline , Kraan Gerald , Eygendaal Denise , Colaris Joost , Stockmans Filip
Published: December 2022

Re-displacement of a pediatric diaphyseal forearm fracture can lead to a malunion with symptomatic impairment in forearm rotation, which may require a corrective osteotomy. Corrective osteotomy with two-dimensional (2D) radiographic planning for malunited pediatric forearm fractures can be a complex procedure due to multiplanar deformities. Three-dimensional (3D) corrective osteotomy can aid the surgeon in planning and obtaining a more accurate correction and better forearm rotation. This prospective study aimed to assess the accuracy of correction after 3D corrective osteotomy for pediatric forearm malunion and if anatomic correction influences the functional outcome. Our primary outcome measures were the residual maximum deformity angle (MDA) and malrotation after 3D corrective osteotomy. Post-operative MDA > 5° or residual malrotation > 15° were defined as non-anatomic corrections. Our secondary outcome measure was the gain in pro-supination. Between 2016–2018, fifteen patients underwent 3D corrective osteotomies for pediatric malunited diaphyseal both-bone fractures. Three-dimensional corrective osteotomies provided anatomic correction in 10 out of 15 patients. Anatomic corrections resulted in a greater gain in pro-supination than non-anatomic corrections: 70° versus 46° (p = 0.04, ANOVA). Residual malrotation of the radius was associated with inferior gain in pro-supination (p = 0.03, multi-variate linear regression). Three-dimensional corrective osteotomy for pediatric forearm malunion reliably provided an accurate correction, which led to a close-to-normal forearm rotation. Non-anatomic correction, especially residual malrotation of the radius, leads to inferior functional outcomes.
Restoring Force Model of Precast Segmental Reinforced Concrete Piers after Seawater Freeze–Thaw Cycles
Authors: Teng Fei , Zhang Yueying , Yan Weidong , Wang Xiaolei , Zhang Kexin
Published: December 2022

Precast segmental reinforced concrete (RC) piers have been widely used in the construction of offshore bridges to speed up construction. Offshore bridges in cold regions are inevitably affected by the seawater freeze–thaw cycles under the periodic movement of tides, which could reduce the mechanical property of RC piers. Based on the low cyclic loading test on 12 specimens with different seawater freeze–thaw cycles, axial compression ratio, diameters of longitudinal reinforcement, and stirrup spacing, the hysteresis characteristics of precast segmental RC piers were analyzed. The test results show that the peak load decreased by 11%, while the peak displacement increased by 40% after 125 seawater freeze–thaw cycles. The hysteresis curves became fuller and the residual displacement became smaller with the accumulation of freeze–thaw damage. In the same 125 freeze–thaw cycles, the peak load increased by 15% and 27% while increasing the axial compression ratio and the longitudinal reinforcement diameter. Combined with the regression analysis of the experimental results, the restoring force model of RC piers considering the seawater freeze–thaw damage and design parameters was established, and the calculation method of each characteristic point in the model was given. The deviation values of flexural capacity are not more than 6.5%, and the deviation values of peak displacement are not more than 12%. The restoring force model determined in this paper could provide a reference for seismic response analysis of offshore bridges in cold regions.
Steel Surface Defect Recognition: A Survey
Authors: Wen Xin , Shan Jvran , He Yu , Song Kechen
Published: December 2022

Steel surface defect recognition is an important part of industrial product surface defect detection, which has attracted more and more attention in recent years. In the development of steel surface defect recognition technology, there has been a development process from manual detection to automatic detection based on the traditional machine learning algorithm, and subsequently to automatic detection based on the deep learning algorithm. In this paper, we discuss the key hardware of steel surface defect detection systems and offer suggestions for related options; second, we present a literature review of the algorithms related to steel surface defect recognition, which includes traditional machine learning algorithms based on texture features and shape features as well as supervised, unsupervised, and weakly supervised deep learning algorithms (Incomplete supervision, inexact supervision, imprecise supervision). In addition, some common datasets and algorithm performance evaluation metrics in the field of steel surface defect recognition are summarized. Finally, we discuss the challenges of the current steel surface defect recognition algorithms and the corresponding solutions, and our future work focus is explained.