bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity Analysis of Some Frequently Used Food Processing Chemicals Using Allium cepa Biomonitoring System
Authors: Bhuia Md. Shimul , Siam Md. Sajjad Hossain , Ahamed Md. Riat , Roy Uttam Kumar , Hossain Md. Imran , Rokonuzzman Md. , Islam Tawhida , Sharafat Rezoan , Bappi Mehedi Hasan , Mia Md. Nayem , Emamuzzaman Md. , de Almeida Ray Silva , Coutinho Henrique Douglas Melo , Raposo António , Alturki Hmidan A. , Islam Muhammad Torequl
Published: April 2023

Frequent use of various food processing chemical agents sometimes causes damage to our bodies by inducing cytotoxicity, genotoxicity, and mutagenesis. In Bangladesh, among various chemical agents, formalin, saccharin, and urea are vastly used for processing foodstuffs by industry and local people. This study is focused to assess the toxic effects of formalin, saccharin, and urea on the popularly used eukaryotic test model, Allium cepa L. The assay was carried out by exposing different concentrations of test samples to A. cepa at 24, 48, and 72 h, where distilled water and CuSO4·5H2O (0.6 µg/mL) were utilized as the vehicle and positive control, respectively. The root length of the onions was measured in mm, and the results propose that all the chemical agents demonstrated toxicity in onions in a concentration- and exposure-time-dependent manner. The highest root length was examined at the lower concentrations, and with the increase in the concentration of the test sample and exposure time, the RG (root growth) was inhibited due to the deposition of chemicals and hampering of cell division in the root meristematic region of A. cepa. All the chemical agents also revealed a concentration- and time-dependent adaptive effect up to 72 h inspection of 24 h and a depletion of % root growth at 72 h inspection of 48 h. Our study suggests that sufficient precautions should be confirmed during its industrial and traditional usage as a toxicological response to the chemical agents observed in the A. cepa assay.
Transcriptional Regulation Technology for Gene Perturbation in Fission Yeast
Authors: Ishikawa Ken , Saitoh Shigeaki
Published: April 2023

Isolation and introduction of genetic mutations is the primary approach to characterize gene functions in model yeasts. Although this approach has proven very powerful, it is not applicable to all genes in these organisms. For example, introducing defective mutations into essential genes causes lethality upon loss of function. To circumvent this difficulty, conditional and partial repression of target transcription is possible. While transcriptional regulation techniques, such as promoter replacement and 3′ untranslated region (3′UTR) disruption, are available for yeast systems, CRISPR–Cas-based technologies have provided additional options. This review summarizes these gene perturbation technologies, including recent advances in methods based on CRISPR–Cas systems for Schizosaccharomyces pombe. We discuss how biological resources afforded by CRISPRi can promote fission yeast genetics.
Bio-Based Valorization of Lignin-Derived Phenolic Compounds: A Review
Authors: Martínková Ludmila , Grulich Michal , Pátek Miroslav , Křístková Barbora , Winkler Margit
Published: April 2023

Lignins are the most abundant biopolymers that consist of aromatic units. Lignins are obtained by fractionation of lignocellulose in the form of “technical lignins”. The depolymerization (conversion) of lignin and the treatment of depolymerized lignin are challenging processes due to the complexity and resistance of lignins. Progress toward mild work-up of lignins has been discussed in numerous reviews. The next step in the valorization of lignin is the conversion of lignin-based monomers, which are limited in number, into a wider range of bulk and fine chemicals. These reactions may need chemicals, catalysts, solvents, or energy from fossil resources. This is counterintuitive to green, sustainable chemistry. Therefore, in this review, we focus on biocatalyzed reactions of lignin monomers, e.g., vanillin, vanillic acid, syringaldehyde, guaiacols, (iso)eugenol, ferulic acid, p-coumaric acid, and alkylphenols. For each monomer, its production from lignin or lignocellulose is summarized, and, mainly, its biotransformations that provide useful chemicals are discussed. The technological maturity of these processes is characterized based on, e.g., scale, volumetric productivities, or isolated yields. The biocatalyzed reactions are compared with their chemically catalyzed counterparts if the latter are available.
NMR and Patch-Clamp Characterization of Yeast Mitochondrial Pyruvate Carrier Complexes
Authors: Wang Zhen , Ding Wen , Ruan Maosen , Liu Yong , Yang Jing , Zhang Huiqin , Shen Bing , Wang Junfeng , Li Yunyan
Published: April 2023

The mitochondrial pyruvate carrier (Mpc) plays an indispensable role in the transport of pyruvates across the mitochondrial inner membrane. Despite the two distinct homologous proteins, Mpc1 and Mpc2, were identified in 2012, there are still controversies on the basic functional units and oligomeric state of Mpc complexes. In this study, yeast Mpc1 and Mpc2 proteins were expressed in a prokaryotic heterologous system. Both homo- and hetero-dimers were successfully reconstituted in mixed detergents. Interactions among Mpc monomers were recorded utilizing paramagnetic relaxation enhancement (PRE) nuclear magnetic resonance (NMR) methods. By single-channel patch-clamp assays, we discovered that both the Mpc1–Mpc2 hetero-dimer and Mpc1 homo-dimer are able to transport K+ ions. Furthermore, the Mpc1–Mpc2 hetero-dimer demonstrated the ability to transport pyruvates, at a rate significantly higher than that of the Mpc1 homo-dimer, indicating that it could be the basic functional unit of Mpc complexes. Our findings provide valuable insights for further structural determination and the study of the transport mechanism of Mpc complexes.
An Integrated View of Stressors as Causative Agents in OA Pathogenesis
Authors: Floramo Joseph S. , Molchanov Vladimir , Liu Huadie , Liu Ye , Craig Sonya E. L. , Yang Tao
Published: April 2023

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell’s response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage can be repaired, and sometimes, even worse, the stress response can overtax the system itself, further aggravating homeostasis and leading to its loss. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance. The consequence of the accumulation of stress on articular chondrocytes is aberrant mitogenesis and differentiation, defective extracellular matrix production and turnover, cellular senescence, and cell death. The most severe form of stress-induced chondrocyte dysfunction in the joints is osteoarthritis (OA). Here, we summarize studies on the cellular effects of stressors on articular chondrocytes and demonstrate that the molecular effectors of the stress pathways connect to amplify articular joint dysfunction and OA development.
SVM-Based Model Combining Patients’ Reported Outcomes and Lymphocyte Phenotypes of Depression in Systemic Lupus Erythematosus
Authors: Dong Chen , Yang Nengjie , Zhao Rui , Yang Ying , Gu Xixi , Fu Ting , Sun Chi , Gu Zhifeng
Published: April 2023

Background: The incidence of depression in patients with systemic lupus erythematosus (SLE) is high and leads to a lower quality of life than that in undepressed SLE patients and healthy individuals. The causes of SLE depression are still unclear. Methods: A total of 94 SLE patients were involved in this study. A series of questionnaires (Hospital Depression Scale, Social Support Rate Scale and so on) were applied. Flow cytometry was used to test the different stages and types of T cells and B cells in peripheral blood mononuclear cells. Univariate and multivariate analyses were conducted to explore the key contributors to depression in SLE. Support Vector Machine (SVM) learning was applied to form the prediction model. Results: Depressed SLE patients showed lower objective support, severer fatigue, worse sleep quality and higher percentages of ASC%PBMC, ASC%CD19+, MAIT, TEM%Th, TEMRA%Th, CD45RA+CD27-Th, TEMRA%CD8 than non-depressed patients. A learning-based SVM model combining objective and patient-reported variables showed that fatigue, objective support, ASC%CD19+, TEM%Th and TEMRA%CD8 were the main contributing factors to depression in SLE. With the SVM model, the weight of TEM%Th was 0.17, which is the highest among objective variables, and the weight of fatigue was 0.137, which was the highest among variables of patients’ reported outcomes. Conclusions: Both patient-reported factors and immunological factors could be involved in the occurrence and development of depression in SLE. Scientists can explore the mechanism of depression in SLE or other psychological diseases from the above perspective.
Distinct Effects of Familial Parkinson’s Disease-Associated Mutations on α-Synuclein Phase Separation and Amyloid Aggregation
Authors: Xu Bingkuan , Fan Fengshuo , Liu Yunpeng , Liu Yinghui , Zhou Lin , Yu Haijia
Published: April 2023

The Lewy bodies and Lewy neurites are key pathological hallmarks of Parkinson’s disease (PD). Single-point mutations associated with familial PD cause α-synuclein (α-Syn) aggregation, leading to the formation of Lewy bodies and Lewy neurites. Recent studies suggest α-Syn nucleates through liquid–liquid phase separation (LLPS) to form amyloid aggregates in a condensate pathway. How PD-associated mutations affect α-Syn LLPS and its correlation with amyloid aggregation remains incompletely understood. Here, we examined the effects of five mutations identified in PD, A30P, E46K, H50Q, A53T, and A53E, on the phase separation of α-Syn. All other α-Syn mutants behave LLPS similarly to wild-type (WT) α-Syn, except that the E46K mutation substantially promotes the formation of α-Syn condensates. The mutant α-Syn droplets fuse to WT α-Syn droplets and recruit α-Syn monomers into their droplets. Our studies showed that α-Syn A30P, E46K, H50Q, and A53T mutations accelerated the formation of amyloid aggregates in the condensates. In contrast, the α-Syn A53E mutant retarded the aggregation during the liquid-to-solid phase transition. Finally, we observed that WT and mutant α-Syn formed condensates in the cells, whereas the E46K mutation apparently promoted the formation of condensates. These findings reveal that familial PD-associated mutations have divergent effects on α-Syn LLPS and amyloid aggregation in the phase-separated condensates, providing new insights into the pathogenesis of PD-associated α-Syn mutations.
A Novel Longitudinal Phenotype–Genotype Association Study Based on Deep Feature Extraction and Hypergraph Models for Alzheimer’s Disease
Authors: Kong Wei , Xu Yufang , Wang Shuaiqun , Wei Kai , Wen Gen , Yu Yaling , Zhu Yuemin
Published: April 2023

Traditional image genetics primarily uses linear models to investigate the relationship between brain image data and genetic data for Alzheimer’s disease (AD) and does not take into account the dynamic changes in brain phenotype and connectivity data across time between different brain areas. In this work, we proposed a novel method that combined Deep Subspace reconstruction with Hypergraph-Based Temporally-constrained Group Sparse Canonical Correlation Analysis (DS-HBTGSCCA) to discover the deep association between longitudinal phenotypes and genotypes. The proposed method made full use of dynamic high-order correlation between brain regions. In this method, the deep subspace reconstruction technique was applied to retrieve the nonlinear properties of the original data, and hypergraphs were used to mine the high-order correlation between two types of rebuilt data. The molecular biological analysis of the experimental findings demonstrated that our algorithm was capable of extracting more valuable time series correlation from the real data obtained by the AD neuroimaging program and finding AD biomarkers across multiple time points. Additionally, we used regression analysis to verify the close relationship between the extracted top brain areas and top genes and found the deep subspace reconstruction approach with a multi-layer neural network was helpful in enhancing clustering performance.
Polymorphic Rearrangements of Human Chromosome 9 and Male Infertility: New Evidence and Impact on Spermatogenesis
Authors: Mottola Filomena , Santonastaso Marianna , Ronga Valentina , Finelli Renata , Rocco Lucia
Published: April 2023

Chromosomal polymorphisms are structural variations in chromosomes that define the genomic variance of a species. These alterations are recurrent in the general population, and some of them appear to be more recurrent in the infertile population. Human chromosome 9 is highly heteromorphic, and how its rearrangement affects male fertility remains to be fully investigated. In this study, we aimed to investigate the association between the polymorphic rearrangements of chromosome 9 and male infertility via an Italian cohort of male infertile patients. Cytogenetic analysis was carried out, along with Y microdeletion screening, semen analysis, fluorescence in situ hybridization, and TUNEL assays using spermatic cells. Chromosome 9 rearrangements were observed in six patients: three of them showed a pericentric inversion, while the others showed a polymorphic heterochromatin variant 9qh. Of these, four patients exhibited oligozoospermia associated with teratozoospermia, along with a percentage of aneuploidy in the sperm of above 9%, in particular, an increase in XY disomy. Additionally, high values for sperm DNA fragmentation (≥30%) were observed in two patients. None of them had microdeletions to the AZF loci on chromosome Y. Our results suggest that polymorphic rearrangements of chromosome 9 might be associated with abnormalities in sperm quality due to incorrect spermatogenesis regulation.
Plasmalogens: Free Radical Reactivity and Identification of Trans Isomers Relevant to Biological Membranes
Authors: Ferreri Carla , Ferocino Alessandra , Batani Gessica , Chatgilialoglu Chryssostomos , Randi Vanda , Riontino Maria Vittoria , Vetica Fabrizio , Sansone Anna
Published: April 2023

Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desaturase enzymatic activity and they are known to be involved in the peroxidation process, whereas the reactivity through cis-trans double bond isomerization has not yet been identified. Using 1-(1Z-octadecenyl)-2-arachidonoyl-sn-glycero-3-phosphocholine (C18 plasm-20:4 PC) as a representative molecule, we showed that the cis-trans isomerization can occur at both plasmalogen unsaturated moieties, and the product has characteristic analytical signatures useful for omics applications. Using plasmalogen-containing liposomes and red blood cell (RBC) ghosts under biomimetic Fenton-like conditions, in the presence or absence of thiols, peroxidation, and isomerization processes were found to occur with different reaction outcomes due to the particular liposome compositions. These results allow gaining a full scenario of plasmalogen reactivity under free radical conditions. Moreover, clarification of the plasmalogen reactivity under acidic and alkaline conditions was carried out, identifying the best protocol for RBC membrane fatty acid analysis due to their plasmalogen content of 15–20%. These results are important for lipidomic applications and for achieving a full scenario of radical stress in living organisms.
Tissue Factor Pathway Inhibitors as Potential Targets for Understanding the Pathophysiology of Preeclampsia
Authors: Kobayashi Hiroshi , Matsubara Sho , Yoshimoto Chiharu , Shigetomi Hiroshi , Imanaka Shogo
Published: April 2023

Background: Preeclampsia is a hypertensive disorder of pregnancy that causes maternal and perinatal morbidity and mortality worldwide. Preeclampsia is associated with complex abnormalities of the coagulation and fibrinolytic system. Tissue factor (TF) is involved in the hemostatic system during pregnancy, while the Tissue Factor Pathway Inhibitor (TFPI) is a major physiological inhibitor of the TF-initiated coagulation cascade. The imbalance in hemostatic mechanisms may lead to a hypercoagulable state, but prior research has not comprehensively investigated the roles of TFPI1 and TFPI2 in preeclamptic patients. In this review, we summarize our current understanding of the biological functions of TFPI1 and TFPI2 and discuss future directions in preeclampsia research. Methods: A literature search was performed from inception to 30 June 2022 in the PubMed and Google Scholar databases. Results: TFPI1 and TFPI2 are homologues with different protease inhibitory activities in the coagulation and fibrinolysis system. TFPI1 is an essential physiological inhibitor of the TF-initiated extrinsic pathway of coagulation. On the other hand, TFPI2 inhibits plasmin-mediated fibrinolysis and exerts antifibrinolytic activity. It also inhibits plasmin-mediated inactivation of clotting factors and maintains a hypercoagulable state. Furthermore, in contrast to TFPI1, TFPI2 suppresses trophoblast cell proliferation and invasion and promotes cell apoptosis. TFPI1 and TFPI2 may play important roles in regulating the coagulation and fibrinolytic system and trophoblast invasion to establish and maintain successful pregnancies. Concentrations of TF, TFPI1, and TFPI2 in maternal blood and placental tissue are significantly altered in preeclamptic women compared to normal pregnancies. Conclusions: TFPI protein family may affect both the anticoagulant (i.e., TFPI1) and antifibrinolytic/procoagulant (i.e., TFPI2) systems. TFPI1 and TFPI2 may function as new predictive biomarkers for preeclampsia and navigate precision therapy.
Gas Flow-Dependent Modification of Plasma Chemistry in μAPP Jet-Generated Cold Atmospheric Plasma and Its Impact on Human Skin Fibroblasts
Authors: Feibel Dennis , Golda Judith , Held Julian , Awakowicz Peter , Schulz-von der Gathen Volker , Suschek Christoph V. , Opländer Christian , Jansen Florian
Published: April 2023

The micro-scaled Atmospheric Pressure Plasma Jet (µAPPJ) is operated with low carrier gas flows (0.25–1.4 slm), preventing excessive dehydration and osmotic effects in the exposed area. A higher yield of reactive oxygen or nitrogen species (ROS or RNS) in the µAAPJ-generated plasmas (CAP) was achieved, due to atmospheric impurities in the working gas. With CAPs generated at different gas flows, we characterized their impact on physical/chemical changes of buffers and on biological parameters of human skin fibroblasts (hsFB). CAP treatments of buffer at 0.25 slm led to increased concentrations of nitrate (~352 µM), hydrogen peroxide (H2O2; ~124 µM) and nitrite (~161 µM). With 1.40 slm, significantly lower concentrations of nitrate (~10 µM) and nitrite (~44 µM) but a strongly increased H2O2 concentration (~1265 µM) was achieved. CAP-induced toxicity of hsFB cultures correlated with the accumulated H2O2 concentrations (20% at 0.25 slm vs. ~49% at 1.40 slm). Adverse biological consequences of CAP exposure could be reversed by exogenously applied catalase. Due to the possibility of being able to influence the plasma chemistry solely by modulating the gas flow, the therapeutic use of the µAPPJ represents an interesting option for clinical use.
A Pig Model to Assess Skin Lesions after Apomorphine Application
Authors: Martin Vera , Knecht Christian , Duerlinger Sophie , Richter Barbara , Ladinig Andrea
Published: April 2023

Owing to their similarities, pigs are often used as experimental models for humans. In particular, the similarity of the skin allows them to be a good dermatological model. The aim of the study was to develop an animal model in conventional domestic pigs to evaluate skin lesions macroscopically and histologically after a continuous subcutaneous apomorphine application. A total of 16 pigs from two different age groups were injected with four different apomorphine formulations for 12 h daily over a period of 28 days into the subcutis, which was then evaluated macroscopically for nodules and erythema, as well as histologically. Differences in skin lesions between the formulations were found, with formulation 1 leading to the fewest nodules, least skin lesions, no lymph follicles, least necrosis, and best skin tolerance. Older pigs were easier to handle and, because of the thicker skin and subcutis of these animals, drug application with the appropriate needle length was safer. The experimental setup worked well and an animal model to assess skin lesions after a continuous subcutaneous application of drugs could be successfully established.
SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel
Authors: Santoro Annapaola , Capri Andrea , Petrone Daniele , Colavita Francesca , Meschi Silvia , Matusali Giulia , Mizzoni Klizia , Notari Stefania , Agrati Chiara , Goletti Delia , Pezzotti Patrizio , Puro Vincenzo
Published: April 2023

Background: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. Methods: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. Results: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. Conclusions: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of ‘protective immunity’ from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.
Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland
Authors: Ludwikowska Kamila M. , Moksud Nafeesa , Tracewski Paweł , Sokolski Mateusz , Szenborn Leszek
Published: April 2023

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.
Correlation of Shear Bond Strength and Degree of Conversion in Conventional and Self-Adhesive Systems Used in Orthodontic Bonding Procedures
Authors: Perković Vjera , Šimunović Aničić Marina , Lughi Vanni , Pozzan Lucia , Meštrović Senka , Turco Gianluca
Published: April 2023

(1) Background: Self-adhesive systems have been proposed for the orthodontic bonding with the intention to reduce the traditional three-component system. (2) Methods: The sample consisted of 32 extracted intact permanent premolars randomly divided into two groups (n = 16). In Group I the metal brackets were bonded with Transbond XT Primer and Transbond XT Paste. In Group II the metal brackets were bonded with GC Ortho connect. The resin was polymerized for 20 s from two directions (mesial and occlusal) using a Bluephase light-curing unit. The shear bond strength (SBS) was measured using a universal testing machine. Immediately after SBS testing, Raman microspectrometry was performed for each sample to calculate the degree of conversion (DC). (3) Results: There was no statistically significant difference in the SBS between the two groups. A significantly higher DC (p < 0.001) value was recorded in Group II, in which the brackets were bonded with GC. Very weak or no correlation (0.01) was recorded between SBS and DC in Group I and moderate positive correlation was recorded in Group II (0.33). (4) Conclusions: No difference was found in SBS between the conventional and two-step systems used in orthodontics. The two-step system demonstrated higher DC compared to the conventional system. There is a very weak or moderate correlation between DC and SBS.
Dysuricemia—A New Concept Encompassing Hyperuricemia and Hypouricemia
Authors: Otani Naoyuki , Ouchi Motoshi , Mizuta Einosuke , Morita Asuka , Fujita Tomoe , Anzai Naohiko , Hisatome Ichiro
Published: April 2023

The importance of uric acid, the final metabolite of purines excreted by the kidneys and intestines, was not previously recognized, except for its role in forming crystals in the joints and causing gout. However, recent evidence implies that uric acid is not a biologically inactive substance and may exert a wide range of effects, including antioxidant, neurostimulatory, proinflammatory, and innate immune activities. Notably, uric acid has two contradictory properties: antioxidant and oxidative ones. In this review, we present the concept of “dysuricemia”, a condition in which deviation from the appropriate range of uric acid in the living body results in disease. This concept encompasses both hyperuricemia and hypouricemia. This review draws comparisons between the biologically biphasic positive and negative effects of uric acid and discusses the impact of such effects on various diseases.
Preeclampsia Susceptibility Assessment Based on Deep Learning Modeling and Single Nucleotide Polymorphism Analysis
Authors: Saadaty Aida , Parhoudeh Sara , Khashei Varnamkhasti Khalil , Moghanibashi Mehdi , Naeimi Sirous
Published: April 2023

The early diagnosis of preeclampsia, a key outlook in improving pregnancy outcomes, still remains elusive. The present study aimed to examine the interleukin-13 and interleukin-4 pathway potential in the early detection of preeclampsia as well as the relationship between interleukin-13 rs2069740(T/A) and rs34255686(C/A) polymorphisms and preeclampsia risk to present a combined model. This study utilized raw data from the GSE149440 microarray dataset, and an expression matrix was constructed using the RMA method and affy package. The genes related to the interleukin-13 and interleukin-4 pathway were extracted from the GSEA, and their expression levels were applied to design multilayer perceptron and PPI graph convolutional neural network models. Moreover, genotyping for the rs2069740(T/A) and rs34255686(C/A) polymorphisms of the interleukin-13 gene were tested using the amplification refractory mutation system PCR method. The outcomes revealed that the expression levels of interleukin-4 and interleukin-13 pathway genes could significantly differentiate early preeclampsia from normal pregnancy. Moreover, the present study’s data suggested significant differences in the genotype distribution, the allelic frequencies and some of the risk markers of the study, in the position of rs34255686 and rs2069740 polymorphisms between the case and control groups. A combined test of two single nucleotide polymorphisms and an expression-based deep learning model could be designed for future preeclampsia diagnostic purposes.
Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH
Authors: Wu Kefan , Chen Lili , Qiu Zhen , Zhao Bo , Hou Jiabao , Lei Shaoqin , Jiang Meng , Xia Zhongyuan
Published: April 2023

(1) SAH induces cellular stress and endoplasmic reticulum stress, activating the unfolded protein response (UPR) in nerve cells. IRE1 (inositol-requiring enzyme 1) is a protein that plays a critical role in cellular stress response. Its final product, Xbp1s, is essential for adapting to changes in the external environment. This process helps maintain proper cellular function in response to various stressors. O-GlcNAcylation, a means of protein modification, has been found to be involved in SAH pathophysiology. SAH can increase the acute O-GlcNAcylation level of nerve cells, which enhances the stress capacity of nerve cells. The GFAT1 enzyme regulates the level of O-GlcNAc modification in cells, which could be a potential target for neuroprotection in SAH. Investigating the IRE1/XBP1s/GFAT1 axis could offer a promising avenue for future research. (2) Methods: SAH was induced using a suture to perforate an artery in mice. HT22 cells with Xbp1 loss- and gain-of-function in neurons were generated. Thiamet-G was used to increase O-GlcNAcylation; (3) Results: Severe neuroinflammation caused by subarachnoid hemorrhage leads to extensive endoplasmic reticulum stress of nerve cells. Xbp1s, the final product of unfolded proteins induced by endoplasmic reticulum stress, can induce the expression of the hexosamine pathway rate limiting enzyme GFAT1, increase the level of O-GlcNAc modification of cells, and have a protective effect on neural cells; (4) Conclusions: The correlation between Xbp1s displayed by immunohistochemistry and O-GlcNAc modification suggests that the IRE1/XBP1 branch of unfolded protein reaction plays a key role in subarachnoid hemorrhage. IRE1/XBP1 branch is a new idea to regulate protein glycosylation modification, and provides a promising strategy for clinical perioperative prevention and treatment of subarachnoid hemorrhage.
Necessity of an Integrative Animal Model for a Comprehensive Study of Attention-Deficit/Hyperactivity Disorder
Authors: Lee Won-Seok , Yoon Bo-Eun
Published: April 2023

Animal models of attention-deficit/hyperactivity disorder (ADHD) have been used to study and understand the behavioral, neural, and physiological mechanisms underlying ADHD. These models allow researchers to conduct controlled experiments and manipulate specific brain regions or neurotransmitter systems to investigate the underlying causes of ADHD and test potential drug targets or treatments. However, it is essential to note that while these models can provide valuable insights, they do not ideally mimic the complex and heterogeneous nature of ADHD and should be interpreted cautiously. Additionally, since ADHD is a multifactorial disorder, environmental and epigenetic factors should be considered simultaneously. In this review, the animal models of ADHD reported thus far are classified into genetic, pharmacological, and environmental models, and the limitations of the representative models are discussed. Furthermore, we provide insights into a more reliable alternative model for the comprehensive study of ADHD.
Development of a Pneumatic-Driven Fiber-Shaped Robot Scaffold for Use as a Complex 3D Dynamic Culture System
Authors: Hoque Muh Amdadul , Mahmood Nasif , Ali Kiran M. , Sefat Eelya , Huang Yihan , Petersen Emily , Harrington Shane , Fang Xiaomeng , Gluck Jessica M.
Published: April 2023

Cells can sense and respond to different kinds of continuous mechanical strain in the human body. Mechanical stimulation needs to be included within the in vitro culture system to better mimic the existing complexity of in vivo biological systems. Existing commercial dynamic culture systems are generally two-dimensional (2D) which fail to mimic the three-dimensional (3D) native microenvironment. In this study, a pneumatically driven fiber robot has been developed as a platform for 3D dynamic cell culture. The fiber robot can generate tunable contractions upon stimulation. The surface of the fiber robot is formed by a braiding structure, which provides promising surface contact and adequate space for cell culture. An in-house dynamic stimulation using the fiber robot was set up to maintain NIH3T3 cells in a controlled environment. The biocompatibility of the developed dynamic culture systems was analyzed using LIVE/DEAD™ and alamarBlue™ assays. The results showed that the dynamic culture system was able to support cell proliferation with minimal cytotoxicity similar to static cultures. However, we observed a decrease in cell viability in the case of a high strain rate in dynamic cultures. Differences in cell arrangement and proliferation were observed between braided sleeves made of different materials (nylon and ultra-high molecular weight polyethylene). In summary, a simple and cost-effective 3D dynamic culture system has been proposed, which can be easily implemented to study complex biological phenomena in vitro.
Porphyrin-Based Covalent Organic Frameworks: Design, Synthesis, Photoelectric Conversion Mechanism, and Applications
Authors: Li Xiaoyu , Tang Chuanyin , Zhang Li , Song Mingyang , Zhang Yujie , Wang Shengjie
Published: April 2023

Photosynthesis occurs in high plants, and certain organisms show brilliant technology in converting solar light to chemical energy and producing carbohydrates from carbon dioxide (CO2). Mimicking the mechanism of natural photosynthesis is receiving wide-ranging attention for the development of novel materials capable of photo-to-electric, photo-to-chemical, and photocatalytic transformations. Porphyrin, possessing a similar highly conjugated core ring structure to chlorophyll and flexible physical and chemical properties, has become one of the most investigated photosensitizers. Chemical modification and self-assembly of molecules as well as constructing porphyrin-based metal (covalent) organic frameworks are often used to improve its solar light utilization and electron transfer rate. Especially porphyrin-based covalent organic frameworks (COFs) in which porphyrin molecules are connected by covalent bonds combine the structural advantages of organic frameworks with light-capturing properties of porphyrins and exhibit great potential in light-responsive materials. Porphyrin-based COFs are expected to have high solar light utilization, fast charge separation/transfer performance, excellent structural stability, and novel steric selectivity by special molecular design. In this paper, we reviewed the research progress of porphyrin-based COFs in the design, synthesis, properties, and applications. We focused on the intrinsic relationship between the structure and properties, especially the photoelectric conversion properties and charge transfer mechanism of porphyrin-based COFs, and tried to provide more valuable information for the design of advanced photosensitizers. The applications of porphyrin-based COFs in photocatalysis and phototherapy were emphasized based on their special structure design and light-to-electric (or light-to-heat) conversion control.
Site-Specific Bioinspired Architecture—A Case Study of the Allen–Lambe House by Frank Lloyd Wright: The Pragmatic versus the Naturalistic, Intent versus Realization
Authors: Hyde Richard
Published: April 2023

Research into biomimetics has focused on science and technology, often developing the innovative parts of buildings from nature, leading to a new field of bioinspired architecture. The work of Frank Lloyd Wright is presented as an early example of bioinspired architecture and explores how buildings might be more broadly integrated into their site and environment. Integrating architecture, biomimetics and eco-mimesis as a framework to look at the work of Frank Lloyd Wright, provides a new understanding of his architecture and directions for future research into the ecological design of buildings and cities.
The Be-Home Kids Program: An Integrated Approach for Delivering Behavioral Therapies to Adolescents with Episodic and Chronic Migraine
Authors: Grazzi Licia , Montisano Danilo Antonio , Raggi Alberto , Rizzoli Paul
Published: April 2023

Migraine disorders are common in populations of children and adolescents. There are different pharmacological treatments for migraine in young patients, but none have specific indications, and doubts about their efficacy exist. The feasibility and effectiveness of behavioral approaches have already been documented in clinical experiences, and they are generally associated with fewer or no unpleasant effects. Among them, mindfulness practice offers a suitable alternative to other adolescent treatments. We present the results of a pilot study, the Be-Home Kids program, performed during the COVID-19 emergency. It was delivered by web and included education on drug use, lifestyle issues, and six sessions of mindfulness-based behavioral practice. We assessed headache frequency, medication intake, and other psychological variables and followed twenty-one adolescents with chronic or high-frequency episodic migraine without aura for 12 months. Results indicated an overall clinical improvement, particularly a 64% reduction in headache frequency over 12 months. In conclusion, our results indicate that a combined treatment which includes patients’ education and six sessions of mindfulness-based practice delivered over the web, can be of great support in reducing headache frequency, medication intake, and the associated psychological burden disability in adolescent migraine patients.
Efficacy of Functional Remediation on Cognitive and Psychosocial Functioning in Patients with Bipolar Disorder: Study Protocol for a Randomized Controlled Study
Authors: Accardo Vivian , Barlati Stefano , Ceraso Anna , Nibbio Gabriele , Vieta Eduard , Vita Antonio
Published: April 2023

Background: Neurocognitive impairment is a prominent characteristic of bipolar disorder (BD), linked with poor psychosocial functioning. This study’s purpose is to evaluate the effectiveness of functional remediation (FR) in enhancing neurocognitive dysfunctions in a sample of remitted patients with diagnosis of BD in comparison to treatment as usual—TAU. To quantify the neurocognitive damage, the Brief Assessment of Cognition in Affective Disorders (BAC-A) will be used, and the overall psychosocial functioning will be measured with the Functioning Assessment Short Test—FAST. Methods: The randomized, rater-blinded, controlled study will include two arms (1:1) encompassing 54 outpatients with diagnosis of BD-I and BD-II, as defined by the DSM-5 criteria. In the experimental phase, remitted patients aged 18–55 years will be involved. At the baseline, at the end of intervention and at the 6-month follow-up, patients will be evaluated using clinical scales (Young Mania Rating Scale (Y-MRS) and Hamilton Depression Rating Scale (HAM-D)). Neurocognitive measurements and psychosocial functioning will be valued, respectively, with BAC-A and FAST. Discussion: The primary expected outcome is that following FR intervention, patients will exhibit improved cognitive abilities and psychosocial outcomes compared to the participants in the TAU group. It is now recognized that neurocognitive deficits are potential predictors of functional outcome in patients with BD. In recent years, there has been a growing interest in the implementation of interventions that, in addition to symptomatic remission, are also aimed at neurocognitive dysfunctions in order to achieve a recovery of psychosocial functioning.
High-Performance Fiber-Reinforced Composites: Latest Advances and Prospects
Authors: Wang Lei , Tang Shengwen
Published: April 2023

Fiber-reinforced composites (FRCs) have been extensively utilized in various fields of engineering throughout the world [...]
Adjustment of Matrix Effects in Analysis of 36 Secondary Metabolites of Microbial and Plant Origin in Indoor Floor Dust Using Liquid Chromatography-Tandem Mass Spectrometry
Authors: Rimayi Cornelius , Park Ju-Hyeong
Published: April 2023

Exposure to microbial agents in water-damaged buildings is a major public health concern. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become a primary tool for testing environmental samples for microbial secondary metabolites (SMs); however, matrix effects can lead to inaccurate results in exposure assessment. Applying a universal internal standard (ISTD) and a matrix-matched calibration can adjust for matrix effects, as shown by our previous study. However, there are only few isotope-labeled internal standards for SMs available on the market. In this study, we determined the best-performing ISTDs among ten candidates (nine 13C-labeled isotopes and one unlabeled analogue) for each of 36 SMs. We analyzed school floor dust spiked with the 36 SMs to identify the best-performing ISTDs (initial experiment) and examined reproducibility with the selected ISTDs and the same spiked dust (validation 1). We also tested applicability for the selected ISTDs using spiked dust collected from different schools (validation 2). The three experiments showed that 26, 17, and 19 SMs had recoveries within the range 100 ± 40%. 13C-ochratoxin A and 13C-citrinin were most frequently selected as the best ISTDs for the 36 SMs, followed by deepoxy-deoxynivalenol, 13C-sterigmatocystin, and 13C-deoxynivalenol. Our study shows that using the identified, best-performing analogous ISTDs for those metabolites may improve testing accuracy for indoor dust and help better estimate exposure effects on potential health.
An Overview of the Application of Fiber-Reinforced Cementitious Composites in Spray Repair of Drainage Pipes
Authors: Dong Shun , Wang Dianchang , Hui Erqing , Gao Chao , Zhang Han , Tan Yaosheng
Published: April 2023

The structural performance of buried drainage pipes is gradually deteriorating under the influence of external loads and chemical and microbial corrosion. It is crucial to reinforce them and improve their bearing capacity for safe use. One of the important technologies used to extend the service life of deteriorated pipes is the use of fiber-reinforced cementitious composites (FRCC) for spray repair. Combined with the current situation of drainage pipes, this article introduces the basic properties of FRCC, briefly describes the requirements for material performance for drainage pipe spraying rehabilitation, reviews the structural bearing capacity of drainage pipes repaired by spraying with FRCC, and discusses the relevant research and engineering applications of the spraying method. Studies show that FRCC has high strength and corrosion resistance, and excellent sprayability. The structural performance of the host pipe is significantly improved after repair, but measures should be taken to enhance the interfacial bonding performance during the repair. In the design of the liner wall thickness, there is no unified calculation theory, and the existing methods have not considered the influence of secondary load on the structure. It is recommended to combine the type of pipe defects and the degree of deterioration in further study.
The Effect of Fiber Volume Fraction on Fiber Distribution in Steel Fiber Reinforced Self-Compacting Concrete
Authors: Zhao Yun , Bi Jihong , Zhou Junlong , Liu Xiaomin , Li Xiaopeng , Geng Wenbin
Published: April 2023

This paper investigates the effect of fiber volume fraction on fiber distribution in steel fiber reinforced self-compacting concrete (SFRSCC) through experiments and numerical simulations. Three types of SFRSCC beam specimens with different fiber volume fractions (0.3%, 0.6%, and 0.9%) were cut to expose the steel fibers. The number and the orientation angle of the steel fibers on the beam sections were determined by image analysis techniques. Fiber density, fiber segregation coefficient, fiber dispersion coefficient and fiber orientation coefficient were applied to evaluate fiber distribution on the beam sections. Based on the experimental data, numerical models simulating the pouring process of fresh SFRSCC were established to analyze the overall fiber distribution in the specimens. The results show that the distribution state of the fibers on the beam sections is not random and uniform, which is correlated to the fiber volume fraction. Due to the variable rheological properties, a greater fiber volume fraction causes better fiber uniformity, lower fiber segregation and worse fiber alignment on the beam sections. Meanwhile, the numerical results show that the distribution law of fibers along the length direction of the specimens is almost independent of the fiber volume fraction. In addition, increasing the fiber volume fraction results in the increase of the average angle of the fiber orientation in the specimens. The results can provide a reference for optimizing the fiber distribution in the concrete matrix.
An Ontology to Represent the Prevention through Design (PtD) Concept in Integrated Project Delivery (IPD) in the Construction Industry from an Architectural Perspective
Authors: Samsudin Nor Syamimi , Khalil Natasha , Mohammad Mazlina Zaira , Md Ajis Azizah , Hamzah Helmi , Che Ibrahim Che Khairil Izam , Manu Patrick
Published: April 2023

The Prevention through Design (PtD) concept has been widely used to mitigate potential safety and health hazards and minimize residual risks during the early design phase. Integrated Project Delivery (IPD) prioritizes project-wide collaboration and coordination; therefore, the importance of PtD has been widely recognized. There are still neglected issues pertaining to the implementation of the PtD concept from the architectural perspective. Hence, to fill this research gap, this review was motivated to highlight the ontological framework of PtD practices in the construction industry from the architectural perspective. The study is a thematic review aimed to synthesize the literature from 2011 to 2022 on the PtD concept from an architectural perspective. The study, using ATLAST.ti 8, a keyword search, followed by a filter using inclusion criteria from Scopus, Science Direct, Web of Science databases, and the snowball method, identified and analyzed 93 peer-reviewed journal articles. However, only 41 articles were used in the final review after the inclusion and exclusion process. A thematic review of these 41 articles identified five clusters representing the ontological framework findings, namely (1) designer competency, (2) planning and design decision making, (3) technologies related to building safety, (4) design features and workplace condition, and (5) laws and building legislation. The finding is expected to improve the understanding and implementation of the PtD concept to further develop an architectural safety design framework.