bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Dimensional Comparison of the Impact Mechanism of the Self-Rated Health Status of Urban and Rural Residents in Chinese Social Environments
Authors: Yu Chao , Zhang Xinyi , Gao Junbo
Published: August 2022

Self-rated health status (SRHS) reflects individuals’ social environment, and the difference between urban and rural areas in China further highlights the impact of social environment on health. This paper aimed to systematically analyze and compare the impact mechanism of the SRHS of urban and rural residents from multiple dimensions, i.e., time, space, and scale. Drawing on data from the Chinese General Social Survey (CGSS) and China Statistical Yearbook, we used spatial, cross, and HLM analyses. Results indicate that: (1) From 2010 to 2017, the overall SRHS level of Chinese residents gradually declined; the gradient pattern of east, middle, and west became more marked, and the health level in rural areas generally fell behind that of urban areas. (2) The focus of SRHS moved toward mental health, and people’s perceptions of the social environment gradually became a key factor affecting health. (3) In the long term, the gradient allocation of medical service resources could narrow the gap between urban and rural areas to comprehensively improve regional health levels.
The Influence of Protective Headgear on the Visual Field of Recreational-Level Skiers
Authors: Očić Mateja , Bon Ivan , Ružić Lana , Cigrovski Vjekoslav , Rupčić Tomislav
Published: August 2022

The benefit of protective headgear for recreational skiers is an ongoing debate in the snow sports industry, and there are a lot of opposing opinions. Due to the dynamic conditions in which winter sports are performed, athletes demand rapid and constant processing of visual information. A sufficient level of anticipation helps athletes to properly position themselves to reduce the forces transferred to the head or even move to avoid a collision. To objectively identify the impact of protective headgear on the visual field when skiing, it is necessary to conduct suitable measurements. The sample consisted of 43 recreational-level skiers (27 M, 16 F; age 31.6 ± 8.23 years). A predefined testing protocol on an ortoreter was used to assess the visual field for three conditions of wearing protective headgear. Differences in perceived visual stimuli between the three conditions were evaluated by repeated measures analysis of variance (ANOVA). Based on the observed results, it can be concluded that the combination of wearing a ski helmet and ski goggles significantly negatively influences visual performance in a way that the visual field is narrowed, for both helmet users and non-users, only when comparing the tested conditions. When comparing helmet users and non-users, there are no differences in the amount of visual impairment; therefore, the habit of wearing a helmet does not influence the ability of perceiving visual stimuli.
Geochemical Characteristics and Environmental Implications of Surface Sediments from Different Types of Sand Dunes in the Dinggye Area, Southern Tibet
Authors: Pan Meihui , Chen Yougui , Hao Zewen , Li Chenlu , Zhao Huimin , Wang Jinyu , Gong Yifu
Published: August 2022

Geochemical characteristics of aeolian sand are beneficial for understanding sand dune formation and evolution. Few studies in the Dinggye area, Southern Tibet, have focused on the geochemical characteristics of aeolian sand. Thus, we present new geochemical data that provide insights into the geochemical characteristics and environmental implications of aeolian sands in the Dinggye area. The results show that mobile dunes, climbing sand sheets, and nebkhas show heterogeneity in elemental concentrations and UCC-normalized distribution; MgO, TiO2, Ni, Pb, and Nb are higher in mobile dunes; SiO2, CaO, K2O, Na2O, P2O5, V, Cr, Co, Cu, Ba, and Ce are higher in climbing sand sheets; and Al2O3, Fe2O3, La, Zn, As, Sr, Y, Zr, Rb, and Ga are higher in nebkhas. Principal component analysis (PCA) and correlation analysis indicate that the main factor affecting elemental content is grain size sorting, followed by provenance, while chemical weathering and regional precipitation are less influential. The CIA and A-CN-K triangle indicate that the different dune types are at a lower chemical weathering stage, with plagioclase weathering and decomposition first. The combination of grain size characteristics, elemental ratios, multidimensional scale (MDS), PCA, and geomorphological conditions suggest that the flood plain and the lakeshore are the main sand sources of aeolian sands in the Dinggye area.
Economic Growth and Environmental Quality: Analysis of Government Expenditure and the Causal Effect
Authors: Donkor Mary , Kong Yusheng , Manu Emmanuel Kwaku , Ntarmah Albert Henry , Appiah-Twum Florence
Published: August 2022

Environmental expenditures (EX) are made by the government and industries which are either long-term or short-term investments. The principal target of EX is to eliminate environmental hazards, promote sustainable natural resources, and improve environmental quality (EQ). Thus, this study looks at the impact of economic growth (EG), and government finance expenditure (GEX) on EQ in Northern Africa and Southern Africa (NASA) republics from 2000–2016. The panel quantile regression (PQR) and panel vector autoregressive (PVAR) model in a generalized method of moment framework (GMM) were employed as a framework. The PQR results show that; (i) In Northern republics, GEX had a significant positive effect on EQ at 25%, 50%, and 75% quantiles levels. (ii) In the Southern republics, GEX had a significant negative impact on EQ at 25%. Moreover, the PVAR through the GMM established that EG and GEX are significantly positive while the parameter for CO2 is insignificant and negative in the North. However, in the South, GEX and CO2 were statistically significant, while EG positively impacts EQ. Lastly, the granger causality report in North indicates uni-directional causation running from LNGEX → LNGDPpc, LNCO2 → LNGDPpc, LNFF → LNGEX, and LNFDI → LNGEX. Similarly, there is uni-directional causation in South republics from LNGEX → LNGDPpc, LNCO2 → LNGEX, and LNFDI → LNGEX.
The Role of E3 Ubiquitin Ligases in Chloroplast Function
Authors: Hand Katherine A. , Shabek Nitzan
Published: August 2022

Chloroplasts are ancient organelles responsible for photosynthesis and various biosynthetic functions essential to most life on Earth. Many of these functions require tightly controlled regulatory processes to maintain homeostasis at the protein level. One such regulatory mechanism is the ubiquitin-proteasome system whose fundamental role is increasingly emerging in chloroplasts. In particular, the role of E3 ubiquitin ligases as determinants in the ubiquitination and degradation of specific intra-chloroplast proteins. Here, we highlight recent advances in understanding the roles of plant E3 ubiquitin ligases SP1, COP1, PUB4, CHIP, and TT3.1 as well as the ubiquitin-dependent segregase CDC48 in chloroplast function.
Pathogenesis, Murine Models, and Clinical Implications of Metabolically Healthy Obesity
Authors: Cho Yun Kyung , Lee Yoo La , Jung Chang Hee
Published: August 2022

Although obesity is commonly associated with numerous cardiometabolic pathologies, some people with obesity are resistant to detrimental effects of excess body fat, which constitutes a condition called “metabolically healthy obesity” (MHO). Metabolic features of MHO that distinguish it from metabolically unhealthy obesity (MUO) include differences in the fat distribution, adipokine types, and levels of chronic inflammation. Murine models are available that mimic the phenotype of human MHO, with increased adiposity but preserved insulin sensitivity. Clinically, there is no established definition of MHO yet. Despite the lack of a uniform definition, most studies describe MHO as a particular case of obesity with no or only one metabolic syndrome components and lower levels of insulin resistance or inflammatory markers. Another clinical viewpoint is the dynamic and changing nature of MHO, which substantially impacts the clinical outcome. In this review, we explore the pathophysiology and some murine models of MHO. The definition, variability, and clinical implications of the MHO phenotype are also discussed. Understanding the characteristics that differentiate people with MHO from those with MUO can lead to new insights into the mechanisms behind obesity-related metabolic derangements and diseases.
Molecular Research and Treatment of Breast Cancer
Authors: Kawiak Anna
Published: August 2022

Breast cancer is the leading cause of cancer-related deaths in the female population [...]
Magnetofluoro-Immunosensing Platform Based on Binary Nanoparticle-Decorated Graphene for Detection of Cancer Cell-Derived Exosomes
Authors: Lee Jaewook , Lee Ji-Heon , Mondal Jagannath , Hwang Joon , Kim Han Sang , Kumar Vinoth , Raj Akhil , Hwang Seung Rim , Lee Yong-Kyu
Published: August 2022

Multi-functionalized carbon nanomaterials have attracted interest owing to their excellent synergic properties, such as plasmon resonance energy transfer and surface-enhanced Raman scattering. Particularly, nanoparticle (NP)-decorated graphene (GRP) has been applied in various fields. In this study, silver NP (AgNP)- and magnetic iron oxide NP (IONP)-decorated GRP were prepared and utilized as biosensing platforms. In this case, AgNPs and GRP exhibit plasmonic properties, whereas IONPs exhibit magnetic properties; therefore, this hybrid nanomaterial could function as a magnetoplasmonic substrate for the magnetofluoro-immunosensing (MFI) system. Conversely, exosomes were recently considered high-potential biomarkers for the diagnosis of diseases. However, exosome diagnostic use requires complex isolation and purification methods. Nevertheless, we successfully detected a prostate-cancer-cell-derived exosome (PC-exosome) from non-purified exosomes in a culture media sample using Ag/IO-GRP and dye-tetraspanin antibodies (Ab). First, the anti-prostate-specific antigen was immobilized on the Ag/IO-GRP and it could isolate the PC-exosome from the sample via an external magnetic force. Dye-tetraspanin Ab was added to the sample to induce the sandwich structure. Based on the number of exosomes, the fluorescence intensity from the dye varied and the system exhibited highly sensitive and selective performance. Consequently, these hybrid materials exhibited excellent potential for biosensing platforms.
Crystal Structures of the Clostridium botulinum Neurotoxin A6 Cell Binding Domain Alone and in Complex with GD1a Reveal Significant Conformational Flexibility
Authors: Gregory Kyle S. , Newell Anna R. , Mojanaga Otsile O. , Liu Sai Man , Acharya K. Ravi
Published: August 2022

Clostridium botulinum neurotoxin A (BoNT/A) targets the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, by cleaving synaptosomal-associated protein of 25 kDa size (SNAP-25). Cleavage of SNAP-25 results in flaccid paralysis due to repression of synaptic transmission at the neuromuscular junction. This activity has been exploited to treat a range of diseases associated with hypersecretion of neurotransmitters, with formulations of BoNT/A commercially available as therapeutics. Generally, BoNT activity is facilitated by three essential domains within the molecule, the cell binding domain (HC), the translocation domain (HN), and the catalytic domain (LC). The HC, which consists of an N-terminal (HCN) and a C-terminal (HCC) subdomain, is responsible for BoNT’s high target specificity where it forms a dual-receptor complex with synaptic vesicle protein 2 (SV2) and a ganglioside receptor on the surface of motor neurons. In this study, we have determined the crystal structure of botulinum neurotoxin A6 cell binding domain (HC/A6) in complex with GD1a and describe the interactions involved in ganglioside binding. We also present a new crystal form of wild type HC/A6 (crystal form II) where a large ‘hinge motion’ between the HCN and HCC subdomains is observed. These structures, along with a comparison to the previously determined wild type crystal structure of HC/A6 (crystal form I), reveals the degree of conformational flexibility exhibited by HC/A6.
Metal Ion Periplasmic-Binding Protein YfeA of Glaesserella parasuis Induces the Secretion of Pro-Inflammatory Cytokines of Macrophages via MAPK and NF-κB Signaling through TLR2 and TLR4
Authors: Yang Zhen , Tang Xinwei , Wang Kang , Dai Ke , Chang Yung-Fu , Du Senyan , Zhao Qin , Huang Xiaobo , Wu Rui , Yan Qigui , Cao Sanjie , Wen Yiping
Published: August 2022

The YfeA gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system Yfe, encodes the substrate-binding subunit of the iron, zinc, and manganese transport system in bacteria. As a potential vaccine candidate in Glaesserella parasuis, the functional mechanisms of YfeA in the infection process remain obscure. In this study, vaccination with YfeA effectively protected the C56BL6 mouse against the G. parasuis SC1401 challenge. Bioinformatics analysis suggests that YfeA is highly conserved in G. parasuis, and its metal-binding sites have been strictly conserved throughout evolution. Stimulation of RAW 264.7 macrophages with YfeA verified that toll-like receptors (TLR) 2 and 4 participated in the positive transcription and expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. The activation of TLR2 and TLR4 utilized the MyD88/MAL and TRIF/TRAM pairs to initiate TLRs signaling. Furthermore, YfeA was shown to stimulate nuclear translocation of NF-κB and activated diverse mitogen-activated protein (MAP) kinase signaling cascades, which are specific to the secretion of particular cytokine(s) in murine macrophages. Separate blocking TLR2, TLR4, MAPK, and RelA (p65) pathways significantly decreased YfeA-induced pro-inflammatory cytokine production. In addition, YfeA-stimulated RAW 264.7 produces the pro-inflammatory hallmark, reactive oxygen species (ROS). In conclusion, our findings indicate that YfeA is a novel pro-inflammatory mediator in G. parasuis and induces TLR2 and TLR4-dependent pro-inflammatory activity in RAW 264.7 macrophages through P38, JNK-MAPK, and NF-κB signaling pathways.
Glutamate Neurotoxicity and Destruction of the Blood–Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies
Authors: Gruenbaum Benjamin F. , Zlotnik Alexander , Fleidervish Ilya , Frenkel Amit , Boyko Matthew
Published: August 2022

Traumatic brain injury (TBI) is associated with significant cognitive and psychiatric conditions. Neuropsychiatric symptoms can persist for years following brain injury, causing major disruptions in patients’ lives. In this review, we examine the role of glutamate as an aftereffect of TBI that contributes to the development of neuropsychiatric conditions. We hypothesize that TBI causes long-term blood–brain barrier (BBB) dysfunction lasting many years and even decades. We propose that dysfunction in the BBB is the central factor that modulates increased glutamate after TBI and ultimately leads to neurodegenerative processes and subsequent manifestation of neuropsychiatric conditions. Here, we have identified factors that determine the upper and lower levels of glutamate concentration in the brain after TBI. Furthermore, we consider treatments of disruptions to BBB integrity, including repairing the BBB and controlling excess glutamate, as potential therapeutic modalities for the treatment of acute and chronic neuropsychiatric conditions and symptoms. By specifically focusing on the BBB, we hypothesize that restoring BBB integrity will alleviate neurotoxicity and related neurological sequelae.
Serum Levels of Vascular Endothelial Growth Factor, Platelet Activating Factor and Eosinophil-Derived Neurotoxin in Chronic Spontaneous Urticaria—A Pilot Study in Adult Patients
Authors: Gomułka Krzysztof , Mędrala Wojciech
Published: August 2022

Chronic spontaneous urticaria (CSU) is a skin disease characterized by the presence of wheals, angioedema, or both for at least 6 weeks. Although, CSU is often regarded as autoimmune in nature, its etiology is not fully explained and interactions between various small molecules are still taken under account. The aim of this research was to investigate the mean serum concentration of vascular endothelial growth factor (VEGF), platelet activating factor (PAF), and eosinophil-derived neurotoxin (EDN) in relation to the disease activity and pruritus intensity in adult patients with CSU. Fifteen patients with CSU and 15 healthy subjects participated in this pilot study. Blood samples were taken to examine the mean serum levels of VEGF, PAF, and EDN by the enzyme-linked immunosorbent assay test (ELISA). The Urticaria Activity Score (UAS7) and The Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that VEGF, PAF, and EDN concentrations were higher in patients with CSU compared with those of the control group, but only for VEGF it was statistically significant (p = 0.008). However, levels of all investigated cytokines were not significantly correlated neither with the disease activity nor with the pruritus intensity. Our results showed higher serum levels of VEGF, PAF, and EDN among CSU patients which may highlight a functional role of these cytokines in the disease’s pathogenesis. In contrast, VEGF, PAF, or EDN might not be useful to reflect the severity of symptoms.
A Longitudinal Study of the Association between the LEPR Polymorphism and Treatment Response in Patients with Bipolar Disorder
Authors: Chang Hui Hua , Hsueh Yuan-Shuo , Cheng Yung Wen , Tseng Huai-Hsuan
Published: August 2022

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.
Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines
Authors: Wróblewska-Łuczka Paula , Cabaj Justyna , Bąk Weronika , Bargieł Julia , Grabarska Aneta , Góralczyk Agnieszka , Łuszczki Jarogniew J.
Published: August 2022

The incidence of melanoma is steadily increasing worldwide. Melanoma is the most lethal skin cancer, and new therapeutic methods are being sought. Our research aimed to investigate the cytotoxic and antiproliferative effects of betulinic acid in vitro, used alone and in combination with taxanes (paclitaxel, docetaxel) in four melanoma cell lines. Isobolographic analysis allowed us to assess the interactions between these compounds. Betulinic acid had no cytotoxic effect on normal human keratinocyte HaCaT cells; the amount of LDH released by them was significantly lower compared to melanoma cell lines. The present study shows that betulinic acid significantly inhibits the growth of melanoma cell lines in vitro. The IC50 values of betulinic acid ranged from 2.21 µM to 15.94 µM against the four melanoma lines. Co-treatment of betulinic acid with paclitaxel or docetaxel generated desirable drug–drug interactions, such as an additive and additive with a tendency to synergy interactions.
Downregulation of miR-99b-5p and Upregulation of Nuclear mTOR Cooperatively Promotes the Tumor Aggressiveness and Drug Resistance in African American Prostate Cancer
Authors: Gujrati Himali , Ha Siyoung , Waseem Mohammad , Wang Bi-Dar
Published: August 2022

Mammalian target of rapamycin (mTOR) regulates various fundamental cellular events including cell proliferation, protein synthesis, metabolism, apoptosis, and autophagy. Tumor suppressive miR-99b-5p has been implicated in regulating PI3K/AKT/mTOR signaling in a variety of types of cancer. Our previous study suggested the reciprocal miR-99b-5p/MTOR (downregulated/upregulated) pairing as a key microRNA-mRNA regulatory component involved in the prostate cancer (PCa) disparities. In this study, we further validated the expression profiles of mTOR and miR-99b-5p in the PCa, colon, breast, and lung cancer specimens and cell lines. The immunohistochemistry (IHC), immunofluorescence, Western blot, and RT-qPCR assays have confirmed that mTOR is upregulated while miR-99b-5p is downregulated in different patient cohorts and a panel of cancer cell lines. Intriguingly, elevated nuclear mTOR expression was observed in African American PCa and other advanced cancers. Transfection of the miR-99b-5p mimic resulted in a significant reduction in nuclear mTOR and androgen receptor (AR), while a slight/moderate to no decrease in cytoplasmic mTOR and AR in PCa and other cancer cells, suggesting that miR-99b-5p inhibits mTOR and AR expression and their nuclear translocation. Moreover, overexpression of miR-99b-5p targets/inhibits AR-mTOR axis, subsequently initiating cell apoptosis and sensitizing docetaxel-induced cytotoxicity in various cancers. In conclusion, our data suggest that reciprocal miR-99b-5p/nuclear mTOR pairing may be a more precise diagnostic/prognostic biomarker for aggressive PCa, than miR-99b-5p/MTOR pairing or mTOR alone. Targeting the AR-mTOR axis using miR-99b-5p has also been suggested as a novel therapeutic strategy to induce apoptosis and overcome chemoresistance in aggressive PCa.
Current Knowledge on Interactions of Plant Materials Traditionally Used in Skin Diseases in Poland and Ukraine with Human Skin Microbiota
Authors: Melnyk Natalia , Vlasova Inna , Skowrońska Weronika , Bazylko Agnieszka , Piwowarski Jakub P. , Granica Sebastian
Published: August 2022

Skin disorders of different etiology, such as dermatitis, atopic dermatitis, eczema, psoriasis, wounds, burns, and others, are widely spread in the population. In severe cases, they require the topical application of drugs, such as antibiotics, steroids, and calcineurin inhibitors. With milder symptoms, which do not require acute pharmacological interventions, medications, dietary supplements, and cosmetic products of plant material origin are gaining greater popularity among professionals and patients. They are applied in various pharmaceutical forms, such as raw infusions, tinctures, creams, and ointments. Although plant-based formulations have been used by humankind since ancient times, it is often unclear what the mechanisms of the observed beneficial effects are. Recent advances in the contribution of the skin microbiota in maintaining skin homeostasis can shed new light on understanding the activity of topically applied plant-based products. Although the influence of various plants on skin-related ailments are well documented in vivo and in vitro, little is known about the interaction with the network of the skin microbial ecosystem. The review aims to summarize the hitherto scientific data on plant-based topical preparations used in Poland and Ukraine and indicate future directions of the studies respecting recent developments in understanding the etiology of skin diseases. The current knowledge on investigations of interactions of plant materials/extracts with skin microbiome was reviewed for the first time.
Effects of Varying Glucose Concentrations on ACE2′s Hypothalamic Expression and Its Potential Relation to COVID-19-Associated Neurological Dysfunction
Authors: Srivastava Ankita , Mussa Bashair M.
Published: August 2022

The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted millions of lives, despite several vaccine interventions and strict precautionary measures. The main causative organism of this disease is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which infects the host via two key players: the angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2). Some reports revealed that patients with glycemic dysregulation could have increased susceptibility to developing COVID-19 and its related neurological complications. However, no previous studies have looked at the involvement of these key molecules within the hypothalamus, which is the central regulator of glucose in the brain. By exposing embryonic mouse hypothalamic neurons to varying glucose concentrations, we aimed to investigate the expression of ACE2 and TMPRSS2 using quantitative real time polymerase chain reaction and western blotting. A significant and time-dependent increase and decrease was observed on the viability of hypothalamic neurons with increasing and decreasing glucose concentrations, respectively (p < 0.01 and p < 0.001, respectively). Under the same increasing and decreasing glucose conditions, the expression of hypothalamic ACE2 also revealed a significant and time-dependent increase (p < 0.01). These findings suggest that SARS-CoV-2 invades the hypothalamic circuitry. In addition, it highlights the importance of strict glycemic control for COVID-19 in diabetic patients.
Biomolecular Fluorescence Complementation Profiling and Artificial Intelligence Structure Prediction of the Kaposi’s Sarcoma-Associated Herpesvirus ORF18 and ORF30 Interaction
Authors: Maeda Yoshiko , Watanabe Tadashi , Izumi Taisuke , Kuriyama Kazushi , Ohno Shinji , Fujimuro Masahiro
Published: August 2022

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the protein-protein interactions of the vPIC factors have not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral proteins has not been sufficiently revealed. In order to clarify these issues, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Glu36, His41, and Trp170) of ORF18 that were responsible for its interaction with ORF30. Pull-down assays also showed that these four residues were required for the ORF18-ORF30 interaction. The artificial intelligence (AI) system AlphaFold2 predicted that the identified four residues are localized on the surface of ORF18 and are in proximity to each other. Thus, our AI-predicted model supports the importance of the four residues for binding ORF18 to ORF30. These results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions.
Fatty Acid-Binding Proteins: Their Roles in Ischemic Stroke and Potential as Drug Targets
Authors: Guo Qingyun , Kawahata Ichiro , Cheng An , Jia Wenbin , Wang Haoyang , Fukunaga Kohji
Published: August 2022

Stroke is among the leading causes of death and disability worldwide. However, despite long-term research yielding numerous candidate neuroprotective drugs, there remains a lack of effective neuroprotective therapies for ischemic stroke patients. Among the factors contributing to this deficiency could be that single-target therapy is insufficient in addressing the complex and extensive mechanistic basis of ischemic brain injury. In this context, lipids serve as an essential component of multiple biological processes and play important roles in the pathogenesis of numerous common neurological diseases. Moreover, in recent years, fatty acid-binding proteins (FABPs), a family of lipid chaperone proteins, have been discovered to be involved in the onset or development of several neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. However, comparatively little attention has focused on the roles played by FABPs in ischemic stroke. We have recently demonstrated that neural tissue-associated FABPs are involved in the pathological mechanism of ischemic brain injury in mice. Here, we review the literature published in the past decade that has reported on the associations between FABPs and ischemia and summarize the relevant regulatory mechanisms of FABPs implicated in ischemic injury. We also propose candidate FABPs that could serve as potential therapeutic targets for ischemic stroke.
Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches
Authors: Arnedo María , Ascaso Ángela , Latorre-Pellicer Ana , Lucia-Campos Cristina , Gil-Salvador Marta , Ayerza-Casas Ariadna , Pablo María Jesús , Gómez-Puertas Paulino , Ramos Feliciano J. , Bueno-Lozano Gloria , Pié Juan , Puisac Beatriz
Published: August 2022

The Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins.
Functionalization of Graphite with Oxidative Plasma
Authors: Stelmachowski Paweł , Maj Dominik , Grzybek Gabriela , Kruczała Krzysztof , Kotarba Andrzej
Published: August 2022

Surface-modified graphite is studied as an electrode material, an adsorbent, and a membrane component, among other applications. Modifying the graphite with plasma can be used to create relevant surface functionalities, in particular, various oxygen groups. The application of surface-oxidized graphite often requires its use in an aqueous environment. The application in an aqueous environment is not an issue for acid-oxidized carbons, but a discrepancy in the structure–activity relationship may arise because plasma-oxidized carbons show a time-dependent decrease in the degree of functionalization and related properties. Moreover, plasma-oxidized materials are often characterized in terms of their chemical and physical properties, most notably their degree of functionalization after plasma treatment, without contact with water. In this study, we used low-temperature plasma oxidation with pure oxygen and carbon dioxide and sample-washing with concentrated nitric and sulfuric acids. To evaluate the electronic properties of modified graphite, the work function changes and surface oxygen content were measured just after plasma modification and after water immersion. We show that water immersion drastically decreases the work function of plasma-treated samples, which is accompanied by a decrease in the number of radicals introduced by plasma. Our results demonstrate that the increase in stable work function as a result of plasma treatment, brought about by an increase in the surface oxygen species concentration, can be realized most effectively for the acid-washed graphite.
Gut Microbiome and Metabolome Modulation by Maternal High-Fat Diet and Thermogenic Challenge
Authors: Paz Henry A. , Pilkington Anna-Claire , Zhong Ying , Chintapalli Sree V. , Sikes James , Lan Renny S. , Shankar Kartik , Wankhade Umesh D.
Published: August 2022

The gut microbiota plays a critical role in energy homeostasis and its dysbiosis is associated with obesity. Maternal high-fat diet (HFD) and β-adrenergic stimuli alter the gut microbiota independently; however, their collective regulation is not clear. To investigate the combined effect of these factors on offspring microbiota, 20-week-old offspring from control diet (17% fat)- or HFD (45% fat)-fed dams received an injection of either vehicle or β3-adrenergic agonist CL316,243 (CL) for 7 days and then cecal contents were collected for bacterial community profiling. In a follow-up study, a separate group of mice were exposed to either 8 °C or 30 °C temperature for 7 days and blood serum and cecal contents were used for metabolome profiling. Both maternal diet and CL modulated the gut bacterial community structure and predicted functional profiles. Particularly, maternal HFD and CL increased the Firmicutes/Bacteroidetes ratio. In mice exposed to different temperatures, the metabolome profiles clustered by treatment in both the cecum and serum. Identified metabolites were enriched in sphingolipid and amino acid metabolism in the cecum and in lipid and energy metabolism in the serum. In summary, maternal HFD altered offspring’s response to CL and altered microbial composition and function. An independent experiment supported the effect of thermogenic challenge on the bacterial function through metabolome change.
Antiviral Effect of pIFNLs against PEDV and VSV Infection in Different Cells
Authors: Chen Jing , Xu Wang , Li Peiheng , Song Lina , Jiang Yuhang , Hao Pengfei , Gao Zihan , Zou Wancheng , Jin Ningyi , Li Chang
Published: August 2022

Type III and type I interferon have similar mechanisms of action, and their different receptors lead to different distributions in tissue. On mucosal surfaces, type III interferon exhibits strong antiviral activity. Porcine epidemic diarrhea virus (PEDV) is an economically important enteropathogenic coronavirus, which can cause a high incidence rate and mortality in piglets. Here, we demonstrate that porcine interferon lambda 1 (pIFNL1) and porcine interferon lambda 3 (pIFNL3) can inhibit the proliferation of vesicular stomatitis virus with an enhanced green fluorescent protein (VSV-EGFP) in different cells, and also show strong antiviral activity when PEDV infects Vero cells. Both forms of pIFNLs were shown to be better than porcine interferon alpha (pIFNα), the antiviral activity of pIFNL1 is lower than that of pIFNL3. Therefore, our results provide experimental evidence for the inhibition of PEDV infection by pIFNLs, which may provide a promising treatment for the prevention and treatment of Porcine epidemic diarrhea (PED) in piglets.
Functions of Egg-Coating Substances Secreted by Female Accessory Glands in Alderflies, Fishflies and Dobsonflies (Megaloptera)
Authors: Yu Pei , Liu Xingyue , Hayashi Fumio
Published: August 2022

Eggs of insects are immobile and must endure harsh environmental conditions (e.g., low temperatures in winter and aridity in summer) and avoid attack by egg-eating predators, egg parasites, and microbes. Females of Megaloptera lay their eggs as a single- or multi-layered egg mass, which is coated with chemical substances secreted from the female reproductive accessory glands. In this study, we observed the egg masses laid by females of two species of Sialidae (alderflies), nine species of Chauliodinae (fishflies), and 23 species of Corydalinae (dobsonflies) belonging to the order Megaloptera and examined the functions of accessory gland substances coating the laid eggs. The female accessory gland is a single tube in alderflies and fishflies but a paired pouch in dobsonflies. The amount and color of the gland substances differ greatly among species. These substances prevent egg desiccation, inhibit egg feeding by ladybird beetles, and repel ants. Most characteristics of the egg mass structures and the effectiveness of accessory gland substances reflect the phylogeny of Megaloptera, although some differ among closely related taxa.
New Burmese Amber Rove Beetle Fossils Assigned to the Rare Extant Subfamily Coomaniinae (Coleoptera: Staphylinidae)
Authors: Jenkins Shaw Josh , Solodovnikov Alexey , Bai Ming , Żyła Dagmara
Published: August 2022

The Mesozoic, ca. 99-million-year-old Burmese amber is an incredible source of fossil beetles that have been very actively studied in recent times and have already significantly improved our knowledge about the evolution of the large family of Staphylinidae, the rove beetles. Nevertheless, new extinct taxa of high phylogenetic interest are being discovered, among which the following three rove beetle species are described here: Coomania megistos sp. nov., Coomania enkarsios sp. nov. and Coomania yini sp. nov. These fossils preserved enough morphological characters to be identified as members of the rove beetle lineage formed by Staphylininae and allied subfamilies. Based on the fragments of morphology available for observation, they are hypothesized to be the extinct members of the extant rare monobasic subfamily Coomaniinae, sister to the recently mega-diverse and abundant Staphylininae. Limitations of the available fossil material prompted us to place the new species in the extant, monobasic genus Coomania Cameron, 1939, pending a more refined generic placement when more characters become available via additional material or advanced examination techniques. The odd morphology and rarity of the extant members of Coomaniinae restricted to Southeast Asia and Northern Australia make them an enigmatic subfamily among the hyper-diverse Staphylinidae. The newly described fossils, albeit without sufficient details concealed by imperfect preservation, shed some light on the past diversity of Coomaniinae and its divergence from Staphylininae.
Integrated Pest Management of Wireworms (Coleoptera: Elateridae) and the Rhizosphere in Agroecosystems
Authors: Nikoukar Atoosa , Rashed Arash
Published: August 2022

The rhizosphere is where plant roots, physical soil, and subterranean organisms interact to contribute to soil fertility and plant growth. In agroecosystems, the nature of the ecological interactions within the rhizosphere is highly dynamic due to constant disruptions from agricultural practices. The concept of integrated pest management (IPM) was developed in order to promote an approach which is complementary to the environment and non-target organisms, including natural enemies, by reducing the sole reliance on synthetic pesticides to control pests. However, some of the implemented integrated cultural and biological control practices may impact the rhizosphere, especially when targeting subterranean pests. Wireworms, the larval stage of click beetles (Coleoptera: Elateridae), are generalist herbivores and a voracious group of pests that are difficult to control. This paper introduces some existing challenges in wireworm IPM, and discusses the potential impacts of various control methods on the rhizosphere. The awareness of the potential implications of different pest management approaches on the rhizosphere will assist in decision-making and the selection of the control tactics with the least long-term adverse effects on the rhizosphere.
Exercise Testing in Aortic Stenosis: Safety, Tolerability, Clinical Benefits and Prognostic Value
Authors: Saeed Sahrai , Chambers John B.
Published: August 2022

Background: Routine exercise testing in asymptomatic patients with valvular heart disease (VHD) better classifies the hemodynamic severity of valve stenosis or regurgitation, and describes the symptomatic status and functional capacity of the patient. This is crucial for planned surveillance and optimal timing of surgery, particularly for aortic stenosis (AS), because once symptoms occur, there is a sharp increase in the risk of sudden death unless valve intervention is performed. Purpose: To conduct a focused clinical review on the benefits of exercise testing in patients with AS. Methods: The electronic database PubMed was systematically searched for relevant retrospective and prospective cohort studies reporting on the safety, feasibility and tolerability of exercise testing in VHD, with a special focus on AS. Results and conclusions: In patients with significant AS, exercise testing is safe, feasible and reveals symptoms in a significant proportion of patients. In addition, serial testing has incremental prognostic value over a baseline test alone. Exercise testing in patients with AS is underused and should be performed routinely to refine the hemodynamic severity of AS.
Safe Performance of Track Dilation and Bile Aspiration with ERCP Catheter in EUS-Guided Hepaticogastrostomy with Plastic Stents: A Retrospective Multicenter Study
Authors: Kobori Ikuhiro , Hashimoto Yusuke , Shibuki Taro , Okumura Kei , Sekine Masanari , Miyagaki Aki , Sasaki Yoshihiro , Takano Yuichi , Katayama Yasumi , Kuwada Masaru , Gyotoku Yoshinori , Kusano Yumi , Tamano Masaya
Published: August 2022

Objectives: Endoscopic-ultrasound-guided hepaticogastrostomy (EUS-HGS) with plastic stent placement is associated with a high incidence of adverse events that may be reduced using an endoscopic retrograde cholangiopancreatography (ERCP) contrast catheter in the track dilation step. In this study, we evaluated the usefulness of track dilation and bile aspiration performed with an ERCP contrast catheter in EUS-HGS with plastic stent placement. Methods: In a multicenter setting, 22 EUS-HGS cases dilated with an ERCP contrast catheter were analyzed retrospectively and compared between a bile aspiration group and no bile aspiration group. Results: Overall, adverse events occurred in three (13.6%) cases of bile leakage, three (13.6%) cases of peritonitis, and one (4.5%) case of bleeding. Comparing patients with and without bile aspiration, 6 of the 11 patients (54.5%) with no bile aspiration had adverse events, whereas only 1 of the 11 patients (9.1%) who had bile aspiration, as much bile as possible, had an adverse event (bleeding). In univariate analysis, the only factor affecting the occurrence of adverse events was bile aspiration whenever possible (odds ratio, 12.0; 95%CI 1.12–128.84). Conclusions: In EUS-HGS with plastic stent placement, track dilation and bile aspiration with an ERCP contrast catheter may be useful in reducing adverse events.
Robot-Assisted Pedicle Screw Placement Led to Lower Screw Loosening Rate than Fluoroscopy-Guided Technique in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disease: A Single-Center Retrospective Study
Authors: Lai Yen-Po , Lin Yu-Hsien , Wu Yun-Che , Shih Cheng-Min , Chen Kun-Hui , Lee Cheng-Hung , Pan Chien-Chou
Published: August 2022

Robot-assisted pedicle screw placement for spine surgery has become popular in recent years. This study compares clinical, radiographic outcomes and the screw loosening rate between robot-assisted and fluoroscopy-guided pedicle screw placement in patients who underwent transforaminal lumbar interbody fusion (TLIF). We retrospectively examined 108 patients with the degenerative lumbar disease who underwent TLIF. According to whether the robotic system was used, patients were assigned to either the robot-assisted (Ro TLIF, n = 29) or fluoroscopy-guided TLIF (FG TLIF, n = 79) group. Radiographic parameters and patient-reported outcomes, including leg and back pain visual analog scale (VAS) and Oswestry Disability Index (ODI), were assessed. Loosening signs were noted in 48 out of 552 pedicle screws. The screw loosening rate was higher in the FG TLIF (10.2%) than Ro TLIF group (4.3%). A significant correlation was found between screw loosening and age, the number of level(s) fused, and the ratio of the average distance from the pedicle screw to the upper endplate to vertebral body height. VAS-leg, VAS-back, and ODI showed significant improvements in both groups postoperatively (all p < 0.05). These results indicated that robot-assisted pedicle screw placement in TLIF had a lower screw loosening rate and similar patient-reported outcomes compared with the fluoroscopy-guided technique.
Tubulointerstitial Nephritis and Uveitis Syndrome (TINU): A Case Series in a Tertiary Care Uveitis Setting
Authors: Paroli Maria Pia , Cappiello Daniele , Staccini Davide , Caccavale Rosalba , Paroli Marino
Published: August 2022

Background: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with tubulointerstitial nephritis (TIN). However, the prevalence and clinical features of TINU are still a matter of debate. To add information about TINU, we describe here the clinical features of a series of patients affected by TINU in a retrospective study. Methods: A total of 9358 clinical records of both adult and pediatric patients up to 21 years of age, referred to the Uveitis Center of the Sapienza University of Rome, were examined. The medical records covered a period from 1990 to 2020. Various demographic and clinical features were analyzed in patients who met the criteria for TINU. Results: Twenty-one patients with TINU were identified. TINU was classified as definite, possible, or probable by the currently recognized international criteria. The median age at diagnosis was 14 years (interquartile range 12–35). Females were predominant (15/21, 71.4%). In most cases (14/21, 66.6%), patients developed ocular disease concurrently with renal disease. The most frequent type of ocular involvement was bilateral anterior uveitis (9/21, 42.8%). In two cases, patients presented with bilateral intermediate uveitis; in three cases, they presented with bilateral or unilateral alternating posterior uveitis; and in four cases, they presented with bilateral panuveitis. In one case, the uveitis was anterior in the right eye (OD) and posterior in the left eye (OS), and two cases presented with bilateral asynchronous or unilateral alternating anterior uveitis. All patients received treatment with systemic corticosteroids and topical ocular therapy. At the end of the follow-up, a significant improvement in ocular signs and symptoms with a return to normal visual acuity was generally observed. In all patients, acute kidney injury (AKI) reverted completely and none progressed to chronic kidney disease (CKD). Conclusions: Patients with TINU may often present with atypical uveitis. We suggest that patients with sudden-onset uveitis, even if not bilateral anterior, should be referred to a nephologist for an assessment of the possible presence of renal disease.