bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot–Marie–Tooth 2B Disease
Authors: Mulligan Ryan J. , Winckler Bettina
Published: September 2023

Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of the cellular signaling pathways that emanate from activated growth factor receptors after endocytosis. Endosomal trafficking, sorting, and motility are coordinated by the activity of small GTPases, including Rab proteins, whose function as molecular switches direct activity at endosomal membranes through effector proteins. Rab7 is particularly important in the coordination of the degradative functions of the pathway. Rab7 effectors control endosomal maturation and the properties of late endosomal and lysosomal compartments, such as coordination of recycling, motility, and fusion with downstream compartments. The spatiotemporal regulation of endosomal receptor trafficking is particularly challenging in neurons because of their enormous size, their distinct intracellular domains with unique requirements (dendrites vs. axons), and their long lifespans as postmitotic, differentiated cells. In Charcot–Marie–Tooth 2B disease (CMT2B), familial missense mutations in Rab7 cause alterations in GTPase cycling and trafficking, leading to an ulcero-mutilating peripheral neuropathy. The prevailing hypothesis to account for CMT2B pathologies is that CMT2B-associated Rab7 alleles alter endocytic trafficking of the neurotrophin NGF and its receptor TrkA and, thereby, disrupt normal trophic signaling in the peripheral nervous system, but other Rab7-dependent pathways are also impacted. Here, using TrkA as a prototypical endocytic cargo, we review physiologic Rab7 effector interactions and control in neurons. Since neurons are among the largest cells in the body, we place particular emphasis on the temporal and spatial regulation of endosomal sorting and trafficking in neuronal processes. We further discuss the current findings in CMT2B mutant Rab7 models, the impact of mutations on effector interactions or balance, and how this dysregulation may confer disease.
Comprehensive Organ-Specific Profiling of Douglas Fir (Pseudotsuga menziesii) Proteome
Authors: Teyssier Caroline , Rogier Odile , Claverol Stéphane , Gautier Florian , Lelu-Walter Marie-Anne , Duruflé Harold
Published: September 2023

The Douglas fir (Pseudotsuga menziesii) is a conifer native to North America that has become increasingly popular in plantations in France due to its many advantages as timber: rapid growth, quality wood, and good adaptation to climate change. Tree genetic improvement programs require knowledge of a species’ genetic structure and history and the development of genetic markers. The very slow progress in this field, for Douglas fir as well as the entire genus Pinus, can be explained using the very large size of their genomes, as well as by the presence of numerous highly repeated sequences. Proteomics, therefore, provides a powerful way to access genomic information of otherwise challenging species. Here, we present the first Douglas fir proteomes acquired using nLC-MS/MS from 12 different plant organs or tissues. We identified 3975 different proteins and quantified 3462 of them, then examined the distribution of specific proteins across plant organs/tissues and their implications in various molecular processes. As the first large proteomic study of a resinous tree species with organ-specific profiling, this short note provides an important foundation for future genomic annotations of conifers and other trees.
Presenilin-1-Derived Circular RNAs: Neglected Epigenetic Regulators with Various Functions in Alzheimer’s Disease
Authors: Sanadgol Nima , Amini Javad , Beyer Cordian , Zendedel Adib
Published: September 2023

The presenilin-1 (PSEN1) gene is crucial in developing Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the most common cause of dementia. Circular RNAs (circRNAs) are non-coding RNA generated through back-splicing, resulting in a covalently closed circular molecule. This study aimed to investigate PSEN1-gene-derived circular RNAs (circPSEN1s) and their potential functions in AD. Our in silico analysis indicated that circPSEN1s (hsa_circ_0008521 and chr14:73614502-73614802) act as sponge molecules for eight specific microRNAs. Surprisingly, two of these miRNAs (has-mir-4668-5p and has-mir-5584-5p) exclusively interact with circPSEN1s rather than mRNA-PSEN1. Furthermore, the analysis of pathways revealed that these two miRNAs predominantly target mRNAs associated with the PI3K-Akt signaling pathway. With sponging these microRNAs, circPSEN1s were found to protect mRNAs commonly targeted by these miRNAs, including QSER1, BACE2, RNF157, PTMA, and GJD3. Furthermore, the miRNAs sequestered by circPSEN1s have a notable preference for targeting the TGF-β and Hippo signaling pathways. We also demonstrated that circPSEN1s potentially interact with FOXA1, ESR1, HNF1B, BRD4, GATA4, EP300, CBX3, PRDM9, and PPARG proteins. These proteins have a prominent preference for targeting the TGF-β and Notch signaling pathways, where EP300 and FOXA1 have the highest number of protein interactions. Molecular docking analysis also confirms the interaction of these hub proteins and Aβ42 with circPSEN1s. Interestingly, circPSEN1s-targeted molecules (miRNAs and proteins) impacted TGF-β, which served as a shared signaling pathway. Finally, the analysis of microarray data unveiled distinct expression patterns of genes influenced by circPSEN1s (WTIP, TGIF, SMAD4, PPP1CB, and BMPR1A) in the brains of AD patients. In summary, our findings suggested that the interaction of circPSEN1s with microRNAs and proteins could affect the fate of specific mRNAs, interrupt the function of unique proteins, and influence cell signaling pathways, generally TGF-β. Further research is necessary to validate these findings and gain a deeper understanding of the precise mechanisms and significance of circPSEN1s in the context of AD.
Impact of Polyphenols on Inflammatory and Oxidative Stress Factors in Diabetes Mellitus: Nutritional Antioxidants and Their Application in Improving Antidiabetic Therapy
Authors: Krawczyk Michal , Burzynska-Pedziwiatr Izabela , Wozniak Lucyna A. , Bukowiecka-Matusiak Malgorzata
Published: September 2023

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and oxidative stress. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications. Nutritional antioxidants derived from dietary sources have gained significant attention due to their potential to improve antidiabetic therapy. This review will delve into the world of polyphenols, investigating their origins in plants, metabolism in the human body, and relevance to the antioxidant mechanism in the context of improving antidiabetic therapy by attenuating oxidative stress, improving insulin sensitivity, and preserving β-cell function. The potential mechanisms of, clinical evidence for, and future perspectives on nutritional antioxidants as adjuvant therapy in diabetes management are discussed.
Exploring Pan-Genomes: An Overview of Resources and Tools for Unraveling Structure, Function, and Evolution of Crop Genes and Genomes
Authors: Naithani Sushma , Deng Cecilia H. , Sahu Sunil Kumar , Jaiswal Pankaj
Published: September 2023

The availability of multiple sequenced genomes from a single species made it possible to explore intra- and inter-specific genomic comparisons at higher resolution and build clade-specific pan-genomes of several crops. The pan-genomes of crops constructed from various cultivars, accessions, landraces, and wild ancestral species represent a compendium of genes and structural variations and allow researchers to search for the novel genes and alleles that were inadvertently lost in domesticated crops during the historical process of crop domestication or in the process of extensive plant breeding. Fortunately, many valuable genes and alleles associated with desirable traits like disease resistance, abiotic stress tolerance, plant architecture, and nutrition qualities exist in landraces, ancestral species, and crop wild relatives. The novel genes from the wild ancestors and landraces can be introduced back to high-yielding varieties of modern crops by implementing classical plant breeding, genomic selection, and transgenic/gene editing approaches. Thus, pan-genomic represents a great leap in plant research and offers new avenues for targeted breeding to mitigate the impact of global climate change. Here, we summarize the tools used for pan-genome assembly and annotations, web-portals hosting plant pan-genomes, etc. Furthermore, we highlight a few discoveries made in crops using the pan-genomic approach and future potential of this emerging field of study.
SOX11 and Epithelial-Mesenchymal Transition in Metastatic Serous Ovarian Cancer
Authors: Psilopatis Iason , Schaefer Jule Ida , Arsenakis Dimitrios , Bolovis Dimitrios , Levidou Georgia
Published: September 2023

Background: Ovarian cancer is the leading cause of death from gynecological malignancies, with serous carcinoma being the most common histopathologic subtype. Epithelial–mesenchymal transition (EMT) correlates with increased metastatic potential, whereas the transcription factor SRY-box transcription factor 11 (SOX11) is overexpressed in diverse malignancies. Methods: In the present study, we aimed to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and vimentin expression as well as with patients’ clinicopathological data. Results: Most of the examined cases showed concurrent expression of E-cadherin and vimentin, whereas SOX11 was expressed in a minority of the cases (26.7%). Interestingly, the positive cases more frequently had a metastatic disease at the time of diagnosis compared with the negative cases (p = 0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-cadherin and SOX11 expression (p = 0.0077) and a positive correlation between vimentin and SOX11 expression (p = 0.0130). Conclusions: The present work, for the first time, provides preliminary evidence of a possible implication of SOX11 overexpression in the promotion of EMT in metastatic serous ovarian cancer, thereby endorsing tumor metastasis.
DAT1 5′-Un-Translated-Region Methylation Patterns as Bio-Markers of ADHD Psycho-Pathology: Contribution to Disease Prognosis and to Monitoring of a Successful Therapy
Authors: Carpentieri Valentina , Cugno Silvia , Lockic Katarina , Pascale Esterina , Adriani Walter
Published: September 2023

Epigenetic modifications, such as changes in DNA methylation, have been linked to several diseases in recent years. The purpose of our study was to search for biomarkers that (using non-invasive techniques) could assist the clinician in the prognosis of infant/adolescent psychopathology. We previously showed that changes in methylation of the 5’-UTR in the DAT1/SLC6A3 gene can be used as a biomarker for the prognosis of initial severe ADHD: treatment-resistant severe ADHD children were characterized by methylated CpG 1 in particular, while methylated CpGs 2 and 6 were then found in children who improved after the therapy. Further, we confirmed these outcomes and provided the hypothesis that symptomatology might be influenced by the children’s genotype and family environment. In particular, levels of CpG 3 methylation in the heterozygous ADHD children were associated with high paternal own risk or stress. Eventually, we found that the same biomarkers are more broadly useful in the field of internalizing or externalizing symptoms (when a certain vulnerability is already present in the child). In particular, it was seen how inheriting specific 9-repeat or 10-repeat VNTR alleles from the mother or from the father could modify the pattern of methylation at the 5′-UTR of the DAT1 gene. A specific pattern of methylations (with CpG 2 following either CpGs 1 + 3 or CpG 6 at the DAT1 5′-UTR) has been associated, therefore, with the likelihood of an internalizing or externalizing developmental trajectory entailing ADHD-like psycho-pathological characteristics. Since each individual responds differently to a specific treatment, we suggest that these methylation patterns may be used as biomarkers to monitor the outcome and/or predict the success of a given therapy (personalized medicine).
Hyperinflammatory Immune Response in COVID-19: Host Genetic Factors in Pyrin Inflammasome and Immunity to Virus in a Spanish Population from Majorca Island
Authors: Martínez-Pomar Natalia , Cunill Vanesa , Segura-Guerrero Marina , Pol-Pol Elisabet , Escobar Oblitas Danilo , Pons Jaime , Ayestarán Ignacio , Pruneda Patricia C. , Losada Inés , Toledo-Pons Nuria , García Gasalla Mercedes , Ferrer Balaguer Joana Maria
Published: September 2023

The hyperinflammatory response caused by SARS-CoV-2 infection contributes to its severity, and many critically ill patients show features of cytokine storm (CS) syndrome. We investigated, by next-generation sequencing, 24 causative genes of primary immunodeficiencies whose defect predisposes to CS. We studied two cohorts with extreme phenotypes of SARS-CoV-2 infection: critical/severe hyperinflammatory patients (H-P) and asymptomatic patients (AM-risk-P) with a high risk (older age) to severe COVID-19. To explore inborn errors of the immunity, we investigated the presence of pathogenic or rare variants, and to identify COVID-19 severity-associated markers, we compared the allele frequencies of common genetic polymorphisms between our two cohorts. We found: 1 H-P carries the likely pathogenic variant c.887-2 A>C in the IRF7 gene and 5 H-P carries variants in the MEFV gene, whose role in the pathogenicity of the familial Mediterranean fever (FMF) disease is controversial. The common polymorphism analysis showed three potential risk biomarkers for developing the hyperinflammatory response: the homozygous haplotype rs1231123A/A-rs1231122A/A in MEFV gene, the IFNAR2 p.Phe8Ser variant, and the CARMIL2 p.Val181Met variant. The combined analysis showed an increased risk of developing severe COVID-19 in patients that had at least one of our genetic risk markers (odds ratio (OR) = 6.2 (95% CI) (2.430–16.20)).
Biocompatible Alginate Hydrogel Film Containing Acetic Acid Manifests Broad-Spectrum Antiviral and Anticancer Activities
Authors: Cano-Vicent Alba , Tuñón-Molina Alberto , Bakshi Hamid , Alfagih Iman M. , Tambuwala Murtaza M. , Serrano-Aroca Ángel
Published: September 2023

Acetic acid, a colourless liquid organic acid with a characteristic acrid smell, is obtained naturally and has applications in both the food and pharmaceutical industries. It has been reported to have beneficial uses for lifestyle-related diseases, and its efficient disinfectant properties are well known. In this study, an alginate crosslinked with Ca2+ hydrogel film was treated with acetic acid to explore its biological properties for biomedicine. The results showed that the novel calcium alginate/acetic acid film was biocompatible in vitro using human keratinocyte cells and in vivo with Caenorhabditis elegans. It also had antiviral properties against enveloped and non-enveloped viruses and anticancer properties against melanoma and colon cancer cells. This novel film thus showed promise for the biomedical and pharmaceutical industries, with applications for fabricating broad-spectrum antiviral and anticancer materials.
Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models
Authors: Lu Gang , Su Xianwei , Wang Lihong , Leung Chi-Kwan , Zhou Jingye , Xiong Zhiqiang , Wang Wuming , Liu Hongbin , Chan Wai-Yee
Published: September 2023

Background: Stroke represents the second leading cause of death and the primary cause of long-term disability in humans. The transplantation of mesenchymal stem cells (MSC) reportedly improves functional outcomes in animal models of cerebral ischemia. Here, we evaluate the neuroprotective potential of extracellular vesicles secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-EV) using preclinical cell-based and animal-based models of ischemic strokes. Methods: hiPS-MSC-EV were isolated using an ultrafiltration method. HT22 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury for 2 h, followed by treatment with hiPS-MSC-EV (100 μg/mL). Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) followed by an intravenous injection of hiPS-MSC-EV (100 μg) at three distinct time points. Results: Our experimental approach revealed hiPS-MSC-EV promoted HT22 cell proliferation, reduced apoptosis, and altered cellular morphology following OGD/R. In addition, hiPS-MSC-EV reduced the volume of infarcts, improved spontaneous movement abilities, and enhanced angiogenesis by expressing the VEGF and CXCR4 proteins in the infarcted hemisphere of the MCAO-treated mouse model. Conclusion: Our findings provide evidence of the potential neuroprotective effects of hiPS-MSC-derived extracellular vesicles (hiPS-MSC-EVs) in both in vitro and in vivo mouse models of ischemic stroke. These results suggest that hiPS-MSC-EVs may play a role in neurorestoration and offer insights into potential cell-free strategies for addressing cerebral ischemia.
VprBP/DCAF1 Triggers Melanomagenic Gene Silencing through Histone H2A Phosphorylation
Authors: Shin Yonghwan , Kim Sungmin , Liang Gangning , Ulmer Tobias S. , An Woojin
Published: September 2023

Vpr binding protein (VprBP), also known as DDB1- and CUL4-associated factor1 (DCAF1), is a recently identified atypical kinase and plays an important role in downregulating the transcription of tumor suppressor genes as well as increasing the risk for colon and prostate cancers. Melanoma is the most aggressive form of skin cancer arising from pigment-producing melanocytes and is often associated with the dysregulation of epigenetic factors targeting histones. Here, we demonstrate that VprBP is highly expressed and phosphorylates threonine 120 (T120) on histone H2A to drive the transcriptional inactivation of growth-regulatory genes in melanoma cells. As is the case for its epigenetic function in other types of cancers, VprBP acts to induce a gene silencing program dependent on H2AT120 phosphorylation (H2AT120p). The significance of VprBP-mediated H2AT120p is further underscored by the fact that VprBP knockdown- or VprBP inhibitor-induced lockage of H2AT120p mitigates melanoma tumor growth in xenograft models. Collectively, our results establish VprBP-mediated H2AT120p as a key epigenetic signal for melanomagenesis and suggest the therapeutic potential of targeting VprBP kinase activity for effective melanoma treatment.
Exploring the Impact of Smartphone Addiction on Risk Decision-Making Behavior among College Students Based on fNIRS Technology
Authors: Liu Xiaolong , Tian Ruoyi , Liu Huafang , Bai Xue , Lei Yi
Published: September 2023

Smartphone Addiction is a social issue caused by excessive smartphone use, affecting decision-making processes. Current research on the risky decision-making abilities of smartphone addicts is limited. This study used the functional Near-Infrared Spectroscopy (fNIRS) brain imaging technique and a Sequential Risk-Taking Task experimental paradigm to investigate the decision-making behavior and brain activity of smartphone addicts under varying risk levels. Using a mixed experimental design, the research assessed decision-making ability and brain activation levels as dependent variables across two groups (addiction and control), two risk amounts (high and low), and two outcomes (gain and loss). The study included 42 participants, with 25 in the addiction group and 17 in the control group. Results indicated that risk level significantly impacted the decision-making ability of smartphone addicts, with high-risk levels leading to weaker decision-making ability and increased risk-taking. However, at low-risk levels, decision-making abilities between addicts and healthy individuals showed no significant difference. Furthermore, brain imaging results using fNIRS revealed stronger brain activation in the dorsolateral Prefrontal Cortex (dlPFC) region for smartphone addicts under loss outcome conditions, with no significant differences between the two groups in terms of brain activation at varying risk volumes. These findings are critical in promoting healthy smartphone use, guiding clinical treatment, and advancing brain mechanism research.
Abnormal and Changing Information Interaction in Adults with Attention-Deficit/Hyperactivity Disorder Based on Network Motifs
Authors: Wu Xubin , Guo Yuxiang , Xue Jiayue , Dong Yanqing , Sun Yumeng , Wang Bin , Xiang Jie , Liu Yi
Published: September 2023

Network motif analysis approaches provide insights into the complexity of the brain’s functional network. In recent years, attention-deficit/hyperactivity disorder (ADHD) has been reported to result in abnormal information interactions in macro- and micro-scale functional networks. However, most existing studies remain limited due to potentially ignoring meso-scale topology information. To address this gap, we aimed to investigate functional motif patterns in ADHD to unravel the underlying information flow and analyze motif-based node roles to characterize the different information interaction methods for identifying the abnormal and changing lesion sites of ADHD. The results showed that the interaction functions of the right hippocampus and the right amygdala were significantly increased, which could lead patients to develop mood disorders. The information interaction of the bilateral thalamus changed, influencing and modifying behavioral results. Notably, the capability of receiving information in the left inferior temporal and the right lingual gyrus decreased, which may cause difficulties for patients in processing visual information in a timely manner, resulting in inattention. This study revealed abnormal and changing information interactions based on network motifs, providing important evidence for understanding information interactions at the meso-scale level in ADHD patients.
Optimal Design of Galvanic Vestibular Stimulation for Patients with Vestibulopathy and Cerebellar Disorders
Authors: Nguyen Thanh Tin , Lee Seung-Beop , Kang Jin-Ju , Oh Sun-Young
Published: September 2023

Objectives: Galvanic vestibular stimulation (GVS) has shown positive outcomes in various neurological and psychiatric disorders, such as enhancing postural balance and cognitive functions. In order to expedite the practical application of GVS in clinical settings, our objective was to determine the best GVS parameters for patients with vestibulopathy and cerebellar disorders using optimal design calculation. Methods: A total of 31 patients (26 males, mean age 57.03 ± 14.75 years, age range 22–82 years) with either unilateral or bilateral vestibulopathy (n = 18) or cerebellar ataxia (n = 13) were enrolled in the study. The GVS intervention included three parameters, waveform (sinusoidal, direct current [DC], and noisy), amplitude (0.4, 0.8, and 1.2 mA), and duration of stimulation (5 and 30 min), resulting in a total of 18 GVS intervention modes as input variables. To evaluate the effectiveness of GVS, clinical vertigo and gait assessments were conducted using the Dizziness Visual Analogue Scale (D-VAS), Activities-specific Balance Confidence Scale (ABC), and Scale for Assessment and Rating of Ataxia (SARA) as output variables. Optimal design and local sensitivity analysis were employed to determine the most optimal GVS modes. Results: Patients with unilateral vestibulopathy experienced the most favorable results with either noisy or sinusoidal GVS at 0.4 mA amplitude for 30 min, followed by DC GVS at 0.8 mA amplitude for 5 min. Noisy GVS at 0.8 or 0.4 mA amplitude for 30 min demonstrated the most beneficial effects in patients with bilateral vestibulopathy. For patients with cerebellar ataxia, the optimal choices were noisy GVS with 0.8 or 0.4 mA amplitude for 5 or 30 min. Conclusions: This study is the first to utilize design optimization methods to identify the GVS stimulation parameters that are tailored to individual-specific characteristics of dizziness and imbalance. A sensitivity analysis was carried out along with the optimal design to offset the constraints of a limited sample size, resulting in the identification of the most efficient GVS modes for patients suffering from vestibular and cerebellar disorders.
Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review
Authors: Kozlowski Tomasz , Bargiel Weronika , Grabarczyk Maksymilian , Skibinska Maria
Published: September 2023

Five major psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, autistic spectrum disorder, and attention-deficit/hyperactivity disorder, show a shared genetic background and probably share common pathobiological mechanisms. S100B is a calcium-binding protein widely studied in psychiatric disorders as a potential biomarker. Our systematic review aimed to compare studies on peripheral S100B levels in five major psychiatric disorders with shared genetic backgrounds to reveal whether S100B alterations are disease-specific. EMBASE, Web of Science, and PubMed databases were searched for relevant studies published until the end of July 2023. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA) guidelines. Overall, 1215 publications were identified, of which 111 full-text articles were included in the systematic review. Study designs are very heterogeneous, performed mostly on small groups of participants at different stages of the disease (first-episode or chronic, drug-free or medicated, in the exacerbation of symptoms or in remission), and various clinical variables are analyzed. Published results are inconsistent; most reported elevated S100B levels across disorders included in the review. Alterations in S100B peripheral levels do not seem to be disease-specific.
A Systematic Review and Meta-Analysis of Cognitive Effects of rTMS in Caucasian Patients with Mild Cognitive Impairment
Authors: Licht Christiane , Herbrandt Swetlana , van Meegen Carmen , Lehfeld Hartmut , Hillemacher Thomas , Richter Kneginja
Published: September 2023

In recent years, repetitive transcranial magnetic stimulation (rTMS) has received much attention as a non-invasive, effective treatment modality for mild cognitive impairment (MCI). Although several meta-analyses have reported that rTMS can improve cognitive abilities, improvements in individual memory domains (speech, language, concentration, and memory) are poorly understood. In addition, stimulation parameters may be flawed in studies of global populations because of ethnic differences between Caucasians and Asians. This meta-analysis aimed to systematically characterize the efficacy of different combinations of rTMS parameters on different cognitive domains in Caucasian patients with MCI. We conducted a systematic literature search in Medline PubMed, Pubpsych, and Embase on the use of rTMS in MCI patients through November 2022. Randomized, double-blind, and sham-controlled trials (RCTs) from the Caucasian patient population were included. The studies reported outcome measures for different domains of cognition, such as language, concentration, or memory. Possible effects of covariates were examined using meta-regressions. The search yielded five publications. The analyses found that rTMS improved cognitive functions, memory, concentration, and language in patients with MCI and treatment with rTMS compared with the sham stimulation group. The statistical analysis results of the studies showed that rTMS could improve various cognitive functions, such as memory and concentration, in Caucasian MCI patients. A particular effect was found at a frequency of 10 Hz and stimulation of the LDLPFC. However, further studies are needed to validate these findings and explore more effective stimulation protocols and targets.
Inflammatory Mechanisms in a Neurovascular Disease: Cerebral Cavernous Malformation
Authors: Li Ying , Srinath Abhinav , Alcazar-Felix Roberto , Hage Stephanie , Bindal Akash , Lightle Rhonda , Shenkar Robert , Shi Changbin , Girard Romuald , Awad Issam
Published: September 2023

Cerebral cavernous malformation (CCM) is a common cerebrovascular malformation causing intracranial hemorrhage, seizures, and focal neurologic deficits. A unique CCM lesional inflammatory microenvironment has been shown to influence the clinical course of the disease. This review addresses the inflammatory cell infiltrate in the CCM lesion and the role of a defined antigen-driven immune response in pathogenicity. We summarize immune mechanisms associated with the loss of the CCM gene and disease progression, including the potential role of immunothrombosis. We also review evidence of circulating inflammatory biomarkers associated with CCM disease and its clinical activity. We articulate future directions for this research, including the role of individual cell type contributions to the immune response in CCM, single cell transcriptomics of inflammatory cells, biomarker development, and therapeutic implications. The concepts are applicable for developing diagnostic and treatment strategies for CCM and for studying other neurovascular diseases.
Interpretation Center for the Revaluation of Flora and Fauna in Cusco, Perú
Authors: Esenarro Doris , Vasquez Patricia , Morales Walter , Raymundo Vanessa
Published: September 2023

The purpose of this research is to propose an architectural design for an Interpretation Center aimed at the revaluation of the flora and fauna of Cusco, Peru, in 2023. Due to the lack of awareness spaces, deforestation, water pollution, and the planting of introduced species in the area, there is a loss of endemic flora and fauna. The methodologies used in this study included climatic analysis of the location, characterization of the flora and fauna, and the application of bioclimatic design strategies supported by the use of software (AutoCAD, Revit, and 3D Sun-path). Additionally, urban design strategies were employed based on the Inca worldview and the Sustainable Development Goals. The feasibility of implementing this urban and architectural proposal was compared with other projects such as the Sydney Water Restoration Project and the Ataria Nature Interpretation Center. As a result, an ecological network was designed for the preservation of endemic species. The project also includes green spaces, which account for 51% of the total area. These green spaces will facilitate carbon dioxide absorption and contribute to the revaluation of the Huantanay River and the creation of microclimates in the area.
Study of Mechanical Properties of Saline Soils under Different Stress Paths
Authors: Cheng Shukai , Wang Qing , Wang Jiaqi , Han Yan
Published: September 2023

The stress path is a critical factor affecting the mechanical properties of saline soils. In order to study the mechanical properties of saline soils under different stress paths, in situ saline soils in the Qian’an area of western Jilin province were selected for this study, and triaxial shear tests under six different stress paths were conducted, including the consolidated undrained triaxial test under the conventional stress path under the isobaric consolidation condition; the consolidated drained triaxial test under the conventional, equal p, reduced p, and increased p stress paths under the isobaric consolidation condition; and the consolidated drained triaxial test under the conventional stress path under the K0 consolidation condition. The effects of the consolidation conditions, drainage conditions, and stress paths on the mechanical properties of in situ saline soils were investigated. The results reveal that the stress–strain relationship curves of soil samples decrease continuously in the order of increased p, conventional, equal p, and decreased p, and they all show the characteristics of strain hardening. The stress path curves have the same slope under the same stress path. For different confining pressures, only the relative positions of the curves are different. Under the conventional stress path, the slope is 1; under the increased p stress path, the slope is 1/3; under the equal p stress path, the slope is 3; and under the decreased p stress path, the slope of the curve is −1. For the same confining pressure, the magnitude relationships of shear strength under the different stress paths are as follows: increased p > conventional > equal p > decreased p. For the cohesion c and internal friction angle φ, the consolidation condition has a greater effect on the cohesion c and a smaller effect on the internal friction angle φ; the drainage condition has a smaller effect on the cohesion c and a larger effect on the internal friction angle φ; and the stress paths have a greater effect on both cohesion c and internal friction angle φ.
Seismic Response and Security Assessment of Cross-Fault Hydraulic-Tunnel Lining Structures
Authors: Yuan Qingteng , Xiao Ming , Kong Ci , Wang Kaicheng
Published: September 2023

The foundation of a seismic safety assessment of cross-fault hydraulic tunnels is an acceptable and accurate seismic response. A dynamic contact force algorithm that may take into consideration the interaction between the fault–surrounding rock–lining structure was devised in light of the contact characteristics of various media in cross-fault hydraulic tunnels under seismic activity. A quantitative instability criterion using a relative displacement ratio as the criterion was devised based on the cusp catastrophe model. By using the cross-fault hydraulic tunnel of the Lawa Hydropower Station as an example, it was possible to evaluate and assess the impacts of four working circumstances on the seismic response of the tunnel lining structure. The findings demonstrated that the lining haunch exhibited stronger stress and displacement responses when subjected to seismic activity. The consideration of fault–surrounding rock–lining interaction exacerbated the displacement and stress seismic responses of the lining structure. The haunch, bottom arch, and top arch of the lining’s characteristic parts—which ranged in size from large to small—responded more seismically as peak ground acceleration rose. Applying the aforementioned instability criterion, the haunch, bottom arch, and top arch of the liner structure could withstand maximum peak ground accelerations of 0.10 g, 0.20 g, and 0.35 g, respectively. The aforementioned technique offers a fresh perspective on how to evaluate the seismic response and seismic safety of the tunnel’s lining structure, and the study’s findings can serve as a guide for seismic design.
Study on Dynamic Load of Air-Conditioning System in Subway Station Based on Hourly Passenger Flow
Authors: Wang Liang , Li Yangli , Deng Shudan , Zhao Juan
Published: September 2023

The research focuses on the air-conditioning system in a public area of a subway station. To address this, an optimization model based on the grid time segmentation method was constructed, specifically a GM (1,1) model. We explored the influence of the hourly passenger flow fluctuation on the load of the subway air-conditioning system, obtained the dynamic change law of the air conditioning system load in the subway station, and then dynamically adjusted the air conditioning system according to the dynamic change law to reduce the operation energy consumption of the system. Through the analysis of the simulation results, the model predicted that compared with the actual passenger flow data, the average maximum relative error was 14.97%. On this basis, the change law of the dynamic load of the subway air-conditioning system which caused by the change in passenger flow from time to time could be calculated and analyzed. Compared with the calculated load of the air conditioning system, the working day load was decreased by 1469.77 kW, or 22.00%. The findings indicate that in response to the dynamic load of fluctuations, timely adjustment of the air supply parameter of the air-conditioning system offers a significant reference point for optimizing energy efficiency in subway stations.
Multi-Zone Infection Risk Assessment Model of Airborne Virus Transmission on a Cruise Ship Using CONTAM
Authors: Xia Zhuang , Guan Hang , Qi Zixuan , Xu Peng
Published: September 2023

Since the onset of the pandemic, the cruise industry has faced substantial challenges, experiencing an 81% year-on-year decline in 2020. Notably, China’s cruise industry has remained shuttered for nearly two years. The conventional epidemiological investigations relying on human memory have proven inadequate in regard to swiftly and reliably identifying high-risk populations, thus leading to excessive pandemic prevention or other inappropriate measures. Furthermore, current research endeavors have not adequately addressed the critical issues of isolation location selection and the estimation of isolation scale within multi-zone indoor environments. Therefore, how to control the epidemic with minimal impact on the public has become an urgent problem. To solve the problems mentioned above, a multi-zone infection risk assessment model of airborne virus transmission was proposed to rapidly qualify the risk of infection, identify the high-risk population, and provide guidance. The model can be divided into two parts, including a multi-zone airflow model and a risk assessment model based on the Wells–Riley model. A large in-service ro-ro passenger ship already in service was used for the application of the proposed method. The results show that the number of isolated rooms shall be at least 5% of the occupancy and the isolation location can be chosen through the multi-zone infection risk assessment model. This paper provides insights into risk assessment to mitigate the spread of epidemics on a large cruise ship, and the method can be easily applied to all kinds of multi-zone indoor environments.
Typo-Morphological Approaches for Maintaining the Sustainability of Local Traditional Culture: A Case Study of the Damazhan and Xiaomazhan Historical Area in Guangzhou
Authors: Jiao Lu , Wu Yifei , Fang Kailun , Liu Xiaotian
Published: September 2023

This paper studies the spatial forms and cultural sustainability of the Damazhan and Xiaomazhan historical area, the only area that reflects the development of the assembled-clan hall culture in Guangzhou. In the face of modernization and reconstruction, traditional culture plays an increasingly crucial role in modern cities, determining the expression of architectural uniqueness and continuous development that adapts to social needs. Therefore, preserving cultural characteristics is more relevant than ever. This study combines historical literature research with typo-morphological analysis to establish analytical strategies that link cultural sustainability with spatial evolution from the perspective of sustainable development. The analytical framework consists of three parts: First of all, through historical literature research, a thorough analysis is conducted on the cultural and social influencing factors from the Dynasties of Song, Yuan, Ming, Qing and the Republic of China to the reform and opening up period. Secondly, feature elements of the location are extracted, and a typo-morphological approach is used to analyze the sustained changes in spatial forms. Finally, the relationship between changes in block form and building types and the inheritance and development of traditional culture are demonstrated. The analytical results indicate that the continuity of cultural characteristics is embodied in the continuity of the block and architectural spatial characteristics, while cultural transformation and man-made social factors affect the changes in spatial forms. This paper combines the perspective of cultural sustainability analysis with the traditional typo-morphological approaches of urban spatial analysis, supplementing the existing typo-morphological methodology. In addition, guiding the development of urban morphology from the perspective of cultural sustainability is of prominent practical significance.
Engineering Characteristics of SBS/Nano-Silica-Modified Hot Mix Asphalt Mixtures and Modeling Techniques for Rutting
Authors: Khan Inamullah , Khattak Abdul Wahab , Bahrami Alireza , Khattak Shahab , Ejaz Ali
Published: September 2023

Flexible pavements are mostly affected by meteorological factors in addition to traffic loads, which results in premature pavement failures like rutting and moisture-induced damage. This study focuses on the impacts of adding various contents of nano-silica (NS), i.e., 2%, 4%, 6%, and 8% (percentage weight of asphalt), along with a constant value of 4.5% styrene-butadiene-styrene (SBS). To assess the effectiveness of modified and unmodified mixtures, the indirect tensile strength (ITS) test, resilient modulus (MR) test, and wheel tracking test were conducted. The MR test was performed at dual temperature values, i.e., 25 °C and 40 °C, and demonstrated different metrological conditions in this region. The tensile strength ratio was used to estimate the mitigation of water losses in hot mix asphalt (HMA) mixtures (specimens) utilizing ITS test results of the conditioned and unconditioned specimens. Moreover, a model was developed for the rutting potential of the modified specimens using multi expression programming (MEP), a sophisticated technique that employs experimental data and suggests an equation for different input variables. The results indicated that the addition of NS to SBS-modified bitumen enhanced different mechanical properties of the specimens, including the stiffness and moisture and rutting resistances. The temperature had adverse effects on the stiffness of the specimens, while the modifiers had a direct relationship with the stiffness. The two-way factorial method justified the effect of the temperature and modifiers on MR with 95% precision, while the MEP model for rutting showed an R2 value of >0.95, which revealed a good relationship between the experimental and predicted data. Furthermore, NS and SBS had a good impact on the mechanical properties of the HMA specimens.
Design Optimisation for Cable Dome Structures Based on Progressive Collapse Resistance
Authors: Chen Lian-Meng , Yan Sun-Kai , Jiang Zhi-Chao , Huang Kai-Yu , Li Ze-Bin , Li Wei , Zhou Yi-Yi , Dong Shi-Lin
Published: September 2023

This study proposed a framework of optimal design for flexible cable dome structures based on progressive collapse resistance. First, a quantitative evaluation method for nonlinear robustness based on robustness control theory to reflect the structural progressive collapse resistance was proposed. Second, an actual engineering structure was used as a case study to evaluate the effects of design parameters on structural robustness. Finally, a genetic algorithm was used as an optimisation algorithm to further optimise the element cross-section and the structural shape and obtain a combined optimisation rate. The results indicated that increasing the element cross-sectional area, decreasing the structural span, and increasing the rise-to-span ratio effectively improved the structural robustness. The structural robustness was also effectively improved through the optimal design of element cross-sections by increasing element cross-sections sensitive to structural robustness and decreasing those insensitive to structural robustness. In this study, the combined optimisation rate was 38.27%, which was not only greater than the individual optimisation rates of 11.2% for element cross-sectional area optimisation and 22.5% for structural shape optimisation but also the sum of these two rates.
Experimental Study of Indoor Air Distribution and Thermal Environment in a Ceiling Cooling Room with Mixing Ventilation, Underfloor Air Distribution and Stratum Ventilation
Authors: Wu Xiaozhou , Gao Hao , Zhao Mingming , Gao Jie , Tian Zhen , Li Xiangli
Published: September 2023

A ceiling cooling system integrated with a mechanical ventilation system has been widely used in modern buildings with large sensible cooling loads due to the high thermal comfort level and large energy efficiency. However, there is a lack of systematic research on the influence factors such as ceiling surface temperature and cooling load on the indoor air distribution and thermal environment, and the impact of ventilation system type in the ceiling cooling room is still unclear. Therefore, this paper presented an experimental study of indoor air distribution and thermal environment in a ceiling cooling (CC) room with mixing ventilation (MV), underfloor air distribution (UFAD) and stratum ventilation (SV); the ceiling surface temperature was 17 °C–26 °C and the internal or external cooling load was 41.5 W/m2–69.5 W/m2. The results showed that the vertical air temperature difference and contaminant removal effectiveness were 0.2 °C–0.4 °C and 0.53–0.85 with CC + MV, 0 °C–1.2 °C and 0.68–1.25 with CC + UFAD and 0.3 °C–0.9 °C and 0.50–0.83 with CC + SV, and the corresponding heat removal effectiveness and air diffusion performance index were 0.96–1.11 and 96–100%, 0.9–1.5 and 57–100% and 1.11–1.34 and 71–100%, respectively. Moreover, the difference between mean radiant temperature and air temperature and the predicted mean vote of thermal sensation were from 0 °C to 0.9 °C and between 0 and 0.26 with CC + MV, from −0.1 °C to 2.2 °C and between −0.1 and 0.42 with CC + UFAD and from −0.1 °C to 0.9 °C and between −0.2 and 0.13 with CC + SV. Hence, the ventilation system type clearly affected the indoor air distribution and thermal environment in the ceiling cooling room, and the experimental results would be beneficial for the design and control of a ceiling cooling system combined with a mechanical ventilation system in practice.
Simplified Multi-Life Cycle Assessment at the Urban Block Scale: GIS-Based Comparative Methodology for Evaluating Energy Efficiency Solutions
Authors: Costantino Carlo , Benedetti Anna Chiara , Gulli Riccardo
Published: September 2023

The Italian residential building stock consists of 12.2 million buildings, with 7.2 constructed post-World War II during the economic boom. These structures were designed without specific regulations for seismic safety, fire resistance, and energy efficiency, and today lies the current state of strong obsolescence. Therefore, energy refurbishment may not always be the best cost/benefit solution due to these intrinsic issues. Consequently, the transition to construction systems based on circular economy principles brings new opportunities and becomes key to proposing replacement interventions for this heritage. This paper presents a comparative GIS-based bottom-up approach to evaluate the lifecycle impact of residential building blocks, encompassing energy, environmental, and economic aspects. Two tools are introduced: one for measuring energy consumption and the other for quantifying the quantities of materials stored in buildings. This methodology permits comparing the new circular buildings and different refurbishment scenarios to identify the most suitable solution from an environmental impact and financial point of view. The application of a case study, a residential urban block in Bologna, built in 1945–1965, highlights how the demolition and reconstruction scenario based on circular economy principles presents the lowest environmental impacts and is economically competitive compared to standard deep renovation techniques.