bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Objective Parametric Optimization Design for Mirrors Combined with Non-Dominated Sorting Genetic Algorithm
Authors: Sun Lu , Zhang Bao , Wang Ping , Gan Zhihong , Han Pengpeng , Wang Yijian
Published: March 2023

The process of intelligent multi-objective parametric optimization design for mirrors is discussed in detail in this paper, with the error of the mirror surface shape and the total mass being examined as the optimization objectives. The establishment of complex objective functions for solving the optimization problem of the mirror surface shape error was realized, and manual modification of the model was avoided. Moreover, combining this with a non-dominated sorting genetic algorithm (NSGA) helped the Pareto front move towards an ideal optimal set of solutions. To verify the effectiveness of the proposed method, an aluminum alloy mirror with an aperture of 140 mm was taken as an example. The Pareto optimal solution set of the mass and surface shape error under 1 g gravity was obtained for finding the required solution and satisfying the optimization goal. In addition, this method is applicable to other complex structural design problems.
Evaluation of Western North Pacific Typhoon Track Forecasts in Global and Regional Models during the 2021 Typhoon Season
Authors: Chen Guomin , Li Tim , Yang Mengqi , Zhang Xiping
Published: March 2023

The track forecasts of tropical cyclones (TC) in the western North Pacific (WNP) basin during 2021 typhoon season with five global models and four regional models are evaluated here. The results show that the average direct position errors (DPEs) of the global and regional models are approximately 80, 150, 200, 300, and 400 km at 24 h, 48 h, 72 h, 96 h, and 120 h lead-times, respectively. The European Centre for Medium-Range Weather Forecasts Integrated Forecasting System (ECMWF-IFS) achieved the best track forecast performance at each lead among the five global models. Among the four regional models, The China Meteorological Administration Tropical Regional Atmosphere Model for the South China Sea (CMA-TRAMS) attained the smallest DPEs within a 72 h lead, while The Hurricane Weather Research and Forecasting (HWRF) achieved the best track forecast performance at 96 h and 120 h leads. Most of the models produced an obvious westward systematic bias on track forecast from a 24 h to a 120 h lead. Further correlation and cluster analyses indicate that initial TC intensity and size and environmental steering flow can be regarded as good predictors for TC DPEs. TCs with a stronger initial intensity, a bigger initial size, and a larger environmental steering flow in general attain a smaller DPE, and the improvements may go up to 36% at short lead-time.
Brochosomes and Other Bioaerosols in the Surface Layer of the Atmosphere of Moscow Metropolis
Authors: Gubanova Dina P. , Vinogradova Anna A. , Sadovskaya Nataliya V.
Published: March 2023

The paper presents the results of the morphological study of aerosol particles in the urban air of Moscow (Russia) in 2019–2022 by scanning electron microscopy (SEM). Our monitoring revealed mineral and anthropogenic particles, and also primary bioaerosols (PBA), such as pollen, spores, plant fibers, etc., typical for the urban environment. Moreover, in July 2021, brochosomes, lipid secretions of semi-hard-winged insects Cicadellidae (or leafhopper), were found in several aerosol samples. They are quasi-spherical hollow porous semi-regular polyhedra (truncated icosahedra) of 0.2–0.7 microns in size, consisting mainly of carbon and oxygen. Despite the prevalence and diversity of leafhoppers, identification of their secretions in atmospheric aerosols in situ is rather rare: single articles from South Korea, Spain, the Himalayas, and the United States. In this sense, the results obtained are interesting and novel. PBA particles cover a wide size range and have a complex and diverse shape, which determines the distance and efficiency of their atmospheric transport. Pollen and fungal spores have a high allergenic potential and can have harmful effects on human health. Any new information about PBA can be useful for studying the development and dynamics of ecosystems.
Methodology for Mobile Toxics Deterministic Human Health Risk Assessment and Case Study
Authors: Munshed Mohammad , Van Griensven Thé Jesse , Fraser Roydon
Published: March 2023

Air toxic emissions from on-road mobile sources are significant contributors to the degradation of air quality in urban and dense population centers. Research led by the United States Environmental Protection Agency (EPA) identified more than 1162 hazardous air pollutants (HAPs) in the exhaust and evaporative emissions from on-road mobile sources. However, less than 70 hazardous air pollutants are monitored by regulatory agencies. HAPs emitted from Mobile Sources are known as Mobile Source Air Toxics (MSATs). The EPA estimates that approximately half of the cancer risk and 74% of noncancer health impacts from air toxics is attributed to mobile sources. The quantification of the risk associated with MSATs exposure remains limited to date, and only a few MSATs have ambient air quality standards to protect human health and welfare. This work presents a novel and validated methodology to quantify the myriad health risks associated with exposure to on-road mobile emissions. This methodology is introduced in the form of a pipelined analysis process, which may be employed in existing and new transportation projects. The proposed new methodology integrates results from three different types of models: on-road vehicle emissions inventory models such as MOVES and IVE, air dispersion models such as AERMOD and SCIPUFF, and risk estimate models for human and ecological receptors such as the 2005 Final U.S. EPA Human Health Risk Assessment Protocol for Hazardous Waste Combustion Facilities. The result of this research work is a new methodology that provides regulators and risk analysts with a more detailed awareness of the health impacts of MSATs. A case study of Saint Paul, Minnesota, validated the air dispersion modeled results against monitored data, and the agreement was acceptable (i.e., the estimates were within a factor of two of the observations). Three high-population locations in the Saint Paul area were evaluated for human health risk, with the observation that at two of these locations, the Saint Paul—Ramsey Health Center and Anderson Office Building, the calculated cancer risk is in excess of the target risk level of 1.0E-05 for benzo(a)pyrene. The methodology presented in this paper allows regulators, risk analysts, and air quality engineers to better estimate multi-pathway cancer and noncancer risk associated with acute and chronic exposure to MSATs. Moreover, this work provides a science-based aid to policy decision makers when considering factors that most significantly affect population health and ecology.
A Modified Gamma Model: Properties, Estimation, and Applications
Authors: Alshehri Mashael A. , Kayid Mohamed
Published: March 2023

Statistical methods are essential for describing, predicting, and modeling natural phenomena in numerous application areas. These methods are helpful for modeling and predicting data in medicine, reliability engineering, actuarial science, and other fields. This paper presents a novel, simple, and fully flexible modified gamma model. The new model provides various forms of densities, including symmetric, asymmetric, unimodal, and reversed-J shapes, as well as a bathtub-shaped failure rate, which is suitable for modeling the lifespan of patients with an increased risk of death. Some basic and dynamic properties of the model are examined. Four methods for estimating its parameters are discussed, and a simulation study is used to examine the consistency and efficiency of these estimators. Finally, the usefulness of the proposed model is demonstrated in the analysis of some data sets.
The Kinetic Theory of Mutation Rates
Authors: Pareschi Lorenzo , Toscani Giuseppe
Published: March 2023

The Luria–Delbrück mutation model is a cornerstone of evolution theory and has been mathematically formulated in a number of ways. In this paper, we illustrate how this model of mutation rates can be derived by means of classical statistical mechanics tools—in particular, by modeling the phenomenon resorting to methodologies borrowed from classical kinetic theory of rarefied gases. The aim is to construct a linear kinetic model that can reproduce the Luria–Delbrück distribution starting from the elementary interactions that qualitatively and quantitatively describe the variations in mutated cells. The kinetic description is easily adaptable to different situations and makes it possible to clearly identify the differences between the elementary variations, leading to the Luria–Delbrück, Lea–Coulson, and Kendall formulations, respectively. The kinetic approach additionally emphasizes basic principles which not only help to unify existing results but also allow for useful extensions.
Metaheuristic-Based Hyperparameter Tuning for Recurrent Deep Learning: Application to the Prediction of Solar Energy Generation
Authors: Stoean Catalin , Zivkovic Miodrag , Bozovic Aleksandra , Bacanin Nebojsa , Strulak-Wójcikiewicz Roma , Antonijevic Milos , Stoean Ruxandra
Published: March 2023

As solar energy generation has become more and more important for the economies of numerous countries in the last couple of decades, it is highly important to build accurate models for forecasting the amount of green energy that will be produced. Numerous recurrent deep learning approaches, mainly based on long short-term memory (LSTM), are proposed for dealing with such problems, but the most accurate models may differ from one test case to another with respect to architecture and hyperparameters. In the current study, the use of an LSTM and a bidirectional LSTM (BiLSTM) is proposed for dealing with a data collection that, besides the time series values denoting the solar energy generation, also comprises corresponding information about the weather. The proposed research additionally endows the models with hyperparameter tuning by means of an enhanced version of a recently proposed metaheuristic, the reptile search algorithm (RSA). The output of the proposed tuned recurrent neural network models is compared to the ones of several other state-of-the-art metaheuristic optimization approaches that are applied for the same task, using the same experimental setup, and the obtained results indicate the proposed approach as the better alternative. Moreover, the best recurrent model achieved the best results with R2 of 0.604, and a normalized MSE value of 0.014, which yields an improvement of around 13% over traditional machine learning models.
A Systematic Approach to Standard Dissipative Continua
Authors: Stark Sebastian
Published: March 2023

Many isothermal dissipative continuum problems can be formulated in a variational setting using the concept of “standard dissipative continua”. A major advantage of this approach is that complex problems can be cast into a compact, thermodynamically consistent formulation based on a single space–time continuous functional together with a corresponding variational principle. Formulating the problem in terms of a functional provides an immediate avenue for performing spatial and temporal discretization, which are the prerequisites for a numerical solution. Within the present contribution, a novel systematic approach to standard dissipative formulations is proposed, with the main goal being the development and implementation of generic procedures and algorithms for the formulation as well as the computational solution of a subset of isothermal dissipative continuum problems. In order to demonstrate the capabilities of the approach, its application to example problems is discussed.
Strong and Δ-Convergence Fixed-Point Theorems Using Noor Iterations
Authors: Tassaddiq Asifa , Kanwal Shazia , Lakhani Farha , Srivastava Rekha
Published: March 2023

A wide range of new research articles in artificial intelligence, logic programming, and other applied sciences are based on fixed-point theorems. The aim of this article is to present an approximation method for finding the fixed point of generalized Suzuki nonexpansive mappings on hyperbolic spaces. Strong and Δ-convergence theorems are proved using the Noor iterative process for generalized Suzuki nonexpansive mappings (GSNM) on uniform convex hyperbolic spaces. Due to the richness of uniform convex hyperbolic spaces, the results of this paper can be used as an extension and generalization of many famous results in Banach spaces together with CAT(0) spaces.
Incentive Contracts for a Queueing System with a Strategic Server: A Principal-Agent Perspective
Authors: Tu Jun , Hu Xiaoying , Huang Min
Published: March 2023

Queueing systems with strategic servers are common in the service industry. The self-interested service rate decision of the strategic server will be detrimental to the queueing system. To improve the service rates, designing incentive contracts for the server from the queueing system owner’s perspective is critical. This study investigates the incentive contracts of queueing systems under exogenous and endogenous price scenarios. The unit-price and cost-sharing contracts are introduced to coordinate the queueing system. The effects of pricing mechanisms and contract types on the queueing system are investigated theoretically and experimentally. The results reveal that regardless of whether the price scenario is exogenous or endogenous, the cost-sharing contract is more effective than the unit-price contract in incentivizing the server to make a service effort. The cost-sharing contract with endogenous price can reduce the service price. The cost-sharing contract can boost profits for both the owner and server, albeit with conditions.
Investigating the Thermal Runaway Behaviour of Fresh and Aged Large Prismatic Lithium-Ion Cells in Overtemperature Experiments
Authors: Menz Fabian , Bauer Marius , Böse Olaf , Pausch Moritz , Danzer Michael A.
Published: March 2023

When using lithium-ion batteries (LiBs) with nickel-rich cathodes, safety issues such as thermal runaway (TR) propagation must be considered. To design safe LiBs, effective countermeasures against TR propagation must be developed. For this purpose, knowledge about the TR behaviour, especially the TR onset temperature, of fresh and aged lithium-ion cells is required. Therefore, the aim of this work is to investigate the TR behaviour of several fresh and aged lithium-ion cells with different cathode chemistries in overtemperature tests using an oven test setup to determine changes in the TR behaviour due to cyclisation. For the investigation of the TR behaviour of large format lithium-ion cells, the oven test setup turns out to be an effective alternative to the accelerating rate calorimetry test. Analysing the results shows that the initial TR temperature after cyclisation for one cell chemistry is significantly decreased due to the failure of one cell component. In addition, from a series of tests and the measured TR onset temperatures it can be deduced that an underlying probability distribution should be taken into account when designing safe LiBs.
Biomechanical Modulation of Dental Pulp Stem Cell (DPSC) Properties for Soft Tissue Engineering
Authors: Gross Tara , Dieterle Martin Philipp , Vach Kirstin , Altenburger Markus Joerg , Hellwig Elmar , Proksch Susanne
Published: March 2023

Dental pulp regeneration strategies frequently result in hard tissue formation and pulp obliteration. The aim of this study was to investigate whether dental pulp stem cells (DPSCs) can be directed toward soft tissue differentiation by extracellular elasticity. STRO-1-positive human dental pulp cells were magnetically enriched and cultured on substrates with elasticities of 1.5, 15, and 28 kPa. The morphology of DPSCs was assessed visually. Proteins relevant in mechanobiology ACTB, ITGB1, FAK, p-FAK, TALIN, VINCULIN, PAXILLIN, ERK 1/2, and p-ERK 1/2 were detected by immunofluorescence imaging. Transcription of the pulp marker genes BMP2, BMP4, MMP2, MMP3, MMP13, FN1, and IGF2 as well as the cytokines ANGPT1, VEGF, CCL2, TGFB1, IL2, ANG, and CSF1 was determined using qPCR. A low stiffness, i.e., 1.5 kPa, resulted in a soft tissue-like phenotype and gene expression, whereas DPSCs on 28 kPa substrates exhibited a differentiation signature resembling hard tissues with a low cytokine expression. Conversely, the highest cytokine expression was observed in cells cultured on intermediate elasticity, i.e., 15 kPa, substrates possibly allowing the cells to act as “trophic mediators”. Our observations highlight the impact of biophysical cues for DPSC fate and enable the design of scaffold materials for clinical pulp regeneration that prevent hard tissue formation.
SenGlove—A Modular Wearable Device to Measure Kinematic Parameters of The Human Hand
Authors: David Jonas Paul , Helbig Thomas , Witte Hartmut
Published: March 2023

For technical or medical applications, the knowledge of the exact kinematics of the human hand is key to utilizing its capability of handling and manipulating objects and communicating with other humans or machines. The optimal relationship between the number of measurement parameters, measurement accuracy, as well as complexity, usability and cost of the measuring systems is hard to find. Biomechanic assumptions, the concepts of a biomechatronic system and the mechatronic design process, as well as commercially available components, are used to develop a sensorized glove. The proposed wearable introduced in this paper can measure 14 of 15 angular values of a simplified hand model. Additionally, five contact pressure values at the fingertips and inertial data of the whole hand with six degrees of freedom are gathered. Due to the modular design and a hand size examination based on anthropometric parameters, the concept of the wearable is applicable to a large variety of hand sizes and adaptable to different use cases. Validations show a combined root-mean-square error of 0.99° to 2.38° for the measurement of all joint angles on one finger, surpassing the human perception threshold and the current state-of-the-art in science and technology for comparable systems.
Advances in Zebrafish for Diabetes Mellitus with Wound Model
Authors: Lin Bangchang , Ma Jiahui , Fang Yimeng , Lei Pengyu , Wang Lei , Qu Linkai , Wu Wei , Jin Libo , Sun Da
Published: March 2023

Diabetic foot ulcers cause great suffering and are costly for the healthcare system. Normal wound healing involves hemostasis, inflammation, proliferation, and remodeling. However, the negative factors associated with diabetes, such as bacterial biofilms, persistent inflammation, impaired angiogenesis, inhibited cell proliferation, and pathological scarring, greatly interfere with the smooth progress of the entire healing process. It is this impaired wound healing that leads to diabetic foot ulcers and even amputations. Therefore, drug screening is challenging due to the complexity of damaged healing mechanisms. The establishment of a scientific and reasonable animal experimental model contributes significantly to the in-depth research of diabetic wound pathology, prevention, diagnosis, and treatment. In addition to the low cost and transparency of the embryo (for imaging transgene applications), zebrafish have a discrete wound healing process for the separate study of each stage, resulting in their potential as the ideal model animal for diabetic wound healing in the future. In this review, we examine the reasons behind the delayed healing of diabetic wounds, systematically review various studies using zebrafish as a diabetic wound model by different induction methods, as well as summarize the challenges and improvement strategies which provide references for establishing a more reasonable diabetic wound zebrafish model.
Management of Invasive Infections in Diabetes Mellitus: A Comprehensive Review
Authors: Khanam Anjum , Hithamani Gavirangappa , Naveen Jayapala , Pradeep Seetur R. , Barman Susmita , Srinivasan Krishnapura
Published: March 2023

Patients with diabetes often have more invasive infections, which may lead to an increase in morbidity. The hyperglycaemic environment promotes immune dysfunction (such as the deterioration of neutrophil activity, antioxidant system suppression, and compromised innate immunity), micro- and microangiopathies, and neuropathy. A greater number of medical interventions leads to a higher frequency of infections in diabetic patients. Diabetic individuals are susceptible to certain conditions, such as rhino-cerebral mucormycosis or aspergillosis infection. Infections may either be the primary symptom of diabetes mellitus or act as triggers in the intrinsic effects of the disease, such as diabetic ketoacidosis and hypoglycaemia, in addition to increasing morbidity. A thorough diagnosis of the severity and origin of the infection is necessary for effective treatment, which often entails surgery and extensive antibiotic use. Examining the significant issue of infection in individuals with diabetes is crucial. Comprehensive research should examine why infections are more common amongst diabetics and what the preventive treatment strategies could be.
Complete Mitochondrial Genomes of Four Pelodiscus sinensis Strains and Comparison with Other Trionychidae Species
Authors: Chen Jing , Jiao Jinbiao , Yuan Xuemei , Huang Xiaohong , Huang Lei , Lin Lingyun , Yin Wenlin , Yao Jiayun , Zhang Haiqi
Published: March 2023

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an important aquaculture reptile with rich nutritional and medicinal values. In recent decades, the wild resources of P. sinensis have been depleting due to natural and artificial factors. Herein, we report the complete mitochondrial genome of four P. sinensis strains, including the Japanese (RB) strain, Qingxi Huabie (HB) strain, Jiangxi (JB) strain, and Qingxi Wubie (WB) strain. The nucleotide composition within the complete mitogenomes was biased towards A + T with a variable frequency ranging from 59.28% (cox3) to 70.31% (atp8). The mitogenomes of all four strains contained 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, 1 control region, and a replication origin region of the L-strand replication (OL), which was consistent with most vertebrates. Additionally, the atp8, nad4l, nad6, and nad3 genes possessed high genetic variation and can be used as potential markers for the identification of these P. sinensis strains. Additionally, all PCGs genes were evolving primarily under purifying selection. Through comparative analysis, it was revealed that most of the tRNAs were structurally different in the TψC stem, DHU stem, and acceptor stem. The length of the tandem repeats in the control region was variable in the four P. sinensis strains, ranging from 2 bp to 50 bp. Phylogenetic analysis indicated that all P. sinensis strains clustered into one branch and were closely related to other Trionychinae species. Overall, this study provides mitochondrial genome information for different P. sinensis strains to support further species identification and germplasm resource conservation.
Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes
Authors: Margioula-Siarkou Georgia , Margioula-Siarkou Chrysoula , Petousis Stamatios , Vavoulidis Eleftherios , Margaritis Kosmas , Almperis Aristarchos , Haitoglou Costas , Mavromatidis George , Dinas Konstantinos
Published: March 2023

Breast cancer is a common type of cancer diagnosed during pregnancy, with increasing incidence over the last years, as more women choose to delay childbearing. Compared to breast cancer in general population, pregnancy-associated breast cancer (PABC) is significantly different in its terms of epidemiology, diagnostic and therapeutic management, while it exhibits particularly aggressive behavior, deriving from its unique molecular and biological profile. Although not fully elucidated, the pathophysiological basis of PABC can be traced back to a combination of hormonal and immune changes during pregnancy, breast involution and altered gene expression. There is considerable controversy in the existing literature about the influence of PABC on pregnancy outcomes, regarding both short- and long-term effects on maternal and fetal/neonatal health. The majority of PABC patients have advanced-stage disease at initial diagnosis and face a significantly poorer prognosis, with decreased survival rates. The most commonly reported adverse obstetrical–fetal events are preterm delivery and prematurity-associated neonatal morbidity, while other neonatal treatment-associated complications might also occur, even when safe therapeutic options are applied during pregnancy. The objective of the present comprehensive review was to summarize current knowledge and up-to-date evidence about the pathophysiological, molecular and biological basis of PABC, as well as its association with adverse maternal, obstetrical, fetal and neonatal outcomes.
Friend or Foe: Regulation, Downstream Effectors of RRAD in Cancer
Authors: Sun Zhangyue , Li Yongkang , Tan Xiaolu , Liu Wanyi , He Xinglin , Pan Deyuan , Li Enmin , Xu Liyan , Long Lin
Published: March 2023

Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is primarily a cytosolic protein that actives in the plasma membrane. RRAD is highly expressed in type 2 diabetes patients and as a biomarker of congestive heart failure. Mounting evidence showed that RRAD is important for the progression and metastasis of tumor cells, which play opposite roles as an oncogene or tumor suppressor gene depending on cancer and cell type. These findings are of great significance, especially given that relevant molecular mechanisms are being discovered. Being regulated in various pathways, RRAD plays wide spectrum cellular activity including tumor cell division, motility, apoptosis, and energy metabolism by modulating tumor-related gene expression and interacting with multiple downstream effectors. Additionally, RRAD in senescence may contribute to its role in cancer. Despite the twofold characters of RRAD, targeted therapies are becoming a potential therapeutic strategy to combat cancers. This review will discuss the dual identity of RRAD in specific cancer type, provides an overview of the regulation and downstream effectors of RRAD to offer valuable insights for readers, explore the intracellular role of RRAD in cancer, and give a reference for future mechanistic studies.
Caenorhabditis elegans as a Model System to Study Human Neurodegenerative Disorders
Authors: Roussos Antonis , Kitopoulou Katerina , Borbolis Fivos , Palikaras Konstantinos
Published: March 2023

In recent years, advances in science and technology have improved our quality of life, enabling us to tackle diseases and increase human life expectancy. However, longevity is accompanied by an accretion in the frequency of age-related neurodegenerative diseases, creating a growing burden, with pervasive social impact for human societies. The cost of managing such chronic disorders and the lack of effective treatments highlight the need to decipher their molecular and genetic underpinnings, in order to discover new therapeutic targets. In this effort, the nematode Caenorhabditis elegans serves as a powerful tool to recapitulate several disease-related phenotypes and provides a highly malleable genetic model that allows the implementation of multidisciplinary approaches, in addition to large-scale genetic and pharmacological screens. Its anatomical transparency allows the use of co-expressed fluorescent proteins to track the progress of neurodegeneration. Moreover, the functional conservation of neuronal processes, along with the high homology between nematode and human genomes, render C. elegans extremely suitable for the study of human neurodegenerative disorders. This review describes nematode models used to study neurodegeneration and underscores their contribution in the effort to dissect the molecular basis of human diseases and identify novel gene targets with therapeutic potential.
Expression Mapping and Functional Analysis of Orphan G-Protein-Coupled Receptor GPR158 in the Adult Mouse Brain Using a GPR158 Transgenic Mouse
Authors: Chang Jinlong , Song Ze , Wei Shoupeng , Zhou Yunxia , Ju Jun , Yao Peijia , Jiang Youheng , Jin Hui , Chi Xinjin , Li Ningning
Published: March 2023

Aberrant expression of G-protein-coupled receptor 158 (GPR158) has been reported to be inextricably linked to a variety of diseases affecting the central nervous system, including Alzheimer’s disease (AD), depression, intraocular pressure, and glioma, but the underlying mechanism remains elusive due to a lack of biological and pharmacological tools to elaborate its preferential cellular distribution and molecular interaction network. To assess the cellular localization, expression, and function of GPR158, we generated an epitope-tagged GPR158 mouse model (GPR158Tag) that exhibited normal motor, cognitive, and social behavior, no deficiencies in social memory, and no anxiety-like behavior compared to C57BL/6J control mice at P60. Using immunofluorescence, we found that GPR158+ cells were distributed in several brain regions including the cerebral cortex, hippocampus, cerebellum, and caudate putamen. Next, using the cerebral cortex of the adult GPR158Tag mice as a representative region, we found that GPR158 was only expressed in neurons, and not in microglia, oligodendrocytes, or astrocytes. Remarkably, the majority of GPR158 was enriched in Camk2a+ neurons whilst limited expression was found in PV+ interneurons. Concomitant 3D co-localization analysis revealed that GPR158 was mainly distributed in the postsynaptic membrane, but with a small portion in the presynaptic membrane. Lastly, via mass spectrometry analysis, we identified proteins that may interact with GPR158, and the relevant enrichment pathways were consistent with the immunofluorescence findings. RNA-seq analysis of the cerebral cortex of the GPR158−/− mice showed that GPR158 and its putative interacting proteins are involved in the chloride channel complex and synaptic vesicle membrane composition. Using these GPR158Tag mice, we were able to accurately label GPR158 and uncover its fundamental function in synaptic vesicle function and memory. Thus, this model will be a useful tool for subsequent biological, pharmacological, and electrophysiological studies related to GPR158.
A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing
Authors: Sahu Indrajit , Bajorek Monika , Tan Xiaolin , Srividya Madabhushi , Krutauz Daria , Reis Noa , Osmulski Pawel A. , Gaczynska Maria E. , Glickman Michael H.
Published: March 2023

The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the seven outer α subunits. In the resting state, the N-termini of neighboring α subunits form a gate blocking access to the channel. The attachment of the activators or regulatory particles rearranges the blocking α subunit N-termini facilitating the entry of substrates. By truncating or mutating each of the participating α N-termini, we report that whereas only a few N-termini are important for maintaining the closed gate, all seven N-termini participate in the open gate. Specifically, the open state is stabilized by a hydrogen bond between an invariant tyrosine (Y) in each subunit with a conserved aspartate (D) in its counterclockwise neighbor. The lone exception is the α1–α2 pair leaving a gap in the ring circumference. The third residue (X) of this YD(X) motif aligns with the open channel. Phenylalanine at this position in the α2 subunit comes in direct contact with the translocating substrate. Consequently, deletion of the α2 N-terminal tail attenuates proteolysis despite the appearance of an open gate state. In summary, the interlacing N-terminal YD(X) motifs regulate both the gating and translocation of the substrate.
Identification and Analysis of Necroptosis-Related Genes in COPD by Bioinformatics and Experimental Verification
Authors: Wang Yingxi , Su Xin , Yin Yan , Wang Qiuyue
Published: March 2023

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex progressive inflammatory disease. Necroptosis is a newly identified type of programmed cell death. However, the role of necroptosis in COPD is unclear. This study aimed to identify necroptosis-related genes in COPD and explore the roles of necroptosis and immune infiltration through bioinformatics. The analysis identified 49 differentially expressed necroptosis-related genes that were primarily engaged in inflammatory immune response pathways. The infiltration of CD8+ T cells and M2 macrophages in COPD lung tissue was relatively reduced, whereas that of M0 macrophages was increased. We identified 10 necroptosis-related hub genes significantly associated with infiltrated immune cells. Furthermore, 7 hub genes, CASP8, IL1B, RIPK1, MLKL, XIAP, TNFRSF1A, and CFLAR, were validated using an external dataset and experimental mice. CFLAR was considered to have the best COPD-diagnosing capability. TF and miRNA interactions with common hub genes were identified. Several related potentially therapeutic molecules for COPD were also identified. The present findings suggest that necroptosis occurs in COPD pathogenesis and is correlated with immune cell infiltration, which indicates that necroptosis may participate in the development of COPD by interacting with the immune response.
Metabolites and Bioactivity of the Marine Xestospongia Sponges (Porifera, Demospongiae, Haplosclerida) of Southeast Asian Waters
Authors: Khodzori Fikri Akmal , Mazlan Nurzafirah Binti , Chong Wei Sheng , Ong Kuan Hung , Palaniveloo Kishneth , Shah Muhammad Dawood
Published: March 2023

Sponges are aquatic, spineless organisms that belong to the phylum Porifera. They come in three primary classes: Hexactinellidae, Demospongiae, and Calcarea. The Demospongiae class is the most dominant, making up over 90% of sponge species. One of the most widely studied genera within the Demospongiae class is Xestospongia, which is found across Southeast Asian waters. This genus is of particular interest due to the production of numerous primary and secondary metabolites with a wide range of biological potentials. In the current review, the antioxidant, anticancer, anti-inflammatory, antibacterial, antiviral, antiparasitic, and cytotoxic properties of metabolites from several varieties of Southeast Asian Xestospongia spp. were discussed. A total of 40 metabolites of various natures, including alkaloids, fatty acids, steroids, and quinones, were highlighted in X. bergquistia, X. testudinaria, X. muta, X. exigua, X. ashmorica and X. vansoesti. The review aimed to display the bioactivity of Xestospongia metabolites and their potential for use in the pharmaceutical sector. Further research is needed to fully understand their bioactivities.
Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
Authors: Garduno Alexis , Martinez Gustavo Sganzerla , Ostadgavahi Ali Toloue , Kelvin David , Cusack Rachael , Martin-Loeches Ignacio
Published: March 2023

Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient’s clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide.
Novel Variant of the SLC4A1 Gene Associated with Hereditary Spherocytosis
Authors: Bogusławska Dżamila M. , Kraszewski Sebastian , Skulski Michał , Potoczek Stanisław , Kuliczkowski Kazimierz , Sikorski Aleksander F.
Published: March 2023

Hereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern European ancestry. HS is mainly associated with pathogenic variants of genes encoding defects in five membrane proteins, including anion exchanger 1 encoded by the SLC4A1 gene. In this study, in a family affected with HS, we identified a hitherto unreported AE1 defect, variant p.G720W. The result of it is most likely the HS phenotype. Molecular dynamics simulation study of the AE1 transmembrane domain may indicate reasonable changes in AE1 domain structure, i.e., significant displacement of the tryptophan residue towards the membrane surface connected with possible changes in AE1 function. The WES analysis verified by classical sequencing in conjunction with biochemical analysis and molecular simulation studies shed light on the molecular mechanism underlying this case of hereditary spherocytosis, for which the newly discovered AE1 variant p.G720W seems crucial.
Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
Authors: Marino Ylenia , Arangia Alessia , Cordaro Marika , Siracusa Rosalba , D’Amico Ramona , Impellizzeri Daniela , Cupi Rosalia , Peritore Alessio Filippo , Gugliandolo Enrico , Fusco Roberta , Cuzzocrea Salvatore , Di Paola Rosanna
Published: March 2023

Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the role of IL-6 in fibromyalgia and the related pain-like symptoms. Methods: This work aimed to evaluate Sprague–Dawley rats, which were injected for three consecutive days with 1 mg/kg of reserpine; IL-6-R Ab was intraperitoneally injected at 1.5 mg/kg seven days after the first reserpine injection. Behavioral analyses were conducted at the beginning of the experiment and at seven and twenty-one days from the first reserpine injection. At this timepoint, the animals were sacrificed, and tissues were collected for molecular and histological analysis. Results: Our data showed the analgesic effect of IL-6-R-Ab administration on mechanical allodynia and thermal hyperalgesia. Additionally, the reserpine + IL-6-R-Ab group showed a reduced expression of the pain-related mediators cFOS and NFG and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (Cxcl5, Cxcl10 and Cx3cl1). From the molecular point of view, the IL-6-R-Ab administration reduced the gp130 phosphorylation and the activation of the Jak/STAT3 pathway. Additionally, the IL-6-R Ab reduced the activation of neuroinflammatory cells. Conclusions: Our study showed that IL-6 plays a crucial role in fibromyalgia by triggering the Jak/STAT3 pathway, leading to an increase in chemokine levels and activating glial cells.
Charge Redistribution of Co9S8/MoS2 Heterojunction Microsphere Enhances Electrocatalytic Hydrogen Evolution
Authors: Zhang Lili , Zhang Jitang , Xu Aijiao , Lin Zhiping , Wang Zongpeng , Zhong Wenwu , Shen Shijie , Wu Guangfeng
Published: March 2023

The electrocatalytic hydrogen evolution activity of transition metal sulfide heterojunctions are significantly increased when compared with that of a single component, but the mechanism behind the performance enhancement and the preparation of catalysts with specific morphologies still need to be explored. Here, we prepared a Co9S8/MoS2 heterojunction with microsphere morphology consisting of thin nanosheets using a facile two-step method. There is electron transfer between the Co9S8 and MoS2 of the heterojunction, thus realizing the redistribution of charge. After the formation of the heterojunction, the density of states near the Fermi surface increases, the d-band center of the transition metal moves downward, and the adsorption of both water molecules and hydrogen by the catalyst are optimized. As a result, the overpotential of Co9S8/MoS2 is superior to that of most relevant electrocatalysts reported in the literature. This work provides insight into the synergistic mechanisms of heterojunctions and their morphological regulation.
Guided Bone Regeneration with Occlusive Titanium Barrier: A Case Report and Clinical Considerations
Authors: Milillo Lucio , Petruzzi Massimo
Published: March 2023

The need to obtain adequate bone volumes for prosthetic rehabilitation supported by implants, using different techniques and materials, represents an urgent need in modern dentistry. We report a case regarding the management of implant-prosthetic rehabilitation of the first and second upper right molars, in which no less than 4 mm of crestal bone remained to insert two implants. Regeneration of the residual bone was previously performed using a customized titanium barrier and a filler of a blood clot with tricalcium beta phosphate. The bone gain (3 mm) was evaluated by comparing CBCT images, while the implant stability (mean 70) was assessed with the ISQ measurement. A regenerated bone sample was taken for histological analysis. Guided bone regeneration obtained with a titanium barrier and blood clot allowed for the insertion of stable implants in a mature bone without heterologous material.
Co-Culture of Glomerular Endothelial Cells and Podocytes in a Custom-Designed Glomerulus-on-a-Chip Model Improves the Filtration Barrier Integrity and Affects the Glomerular Cell Phenotype
Authors: ‘t Hart Daan C. , Yildiz Dilemin , Palacio-Castañeda Valentina , Li Lanhui , Gumuscu Burcu , Brock Roland , Verdurmen Wouter P. R. , van der Vlag Johan , Nijenhuis Tom
Published: March 2023

Crosstalk between glomerular endothelial cells and glomerular epithelial cells (podocytes) is increasingly becoming apparent as a crucial mechanism to maintain the integrity of the glomerular filtration barrier. However, in vitro studies directly investigating the effect of this crosstalk on the glomerular filtration barrier are scarce because of the lack of suitable experimental models. Therefore, we developed a custom-made glomerulus-on-a-chip model recapitulating the glomerular filtration barrier, in which we investigated the effects of co-culture of glomerular endothelial cells and podocytes on filtration barrier function and the phenotype of these respective cell types. The custom-made glomerulus-on-a-chip model was designed using soft lithography. The chip consisted of two parallel microfluidic channels separated by a semi-permeable polycarbonate membrane. The glycocalyx was visualized by wheat germ agglutinin staining and the barrier integrity of the glomerulus-on-a-chip model was determined by measuring the transport rate of fluorescently labelled dextran from the top to the bottom channel. The effect of crosstalk on the transcriptome of glomerular endothelial cells and podocytes was investigated via RNA-sequencing. Glomerular endothelial cells and podocytes were successfully cultured on opposite sides of the membrane in our glomerulus-on-a-chip model using a polydopamine and collagen A double coating. Barrier integrity of the chip model was significantly improved when glomerular endothelial cells were co-cultured with podocytes compared to monocultures of either glomerular endothelial cells or podocytes. Co-culture enlarged the surface area of podocyte foot processes and increased the thickness of the glycocalyx. RNA-sequencing analysis revealed the regulation of cellular pathways involved in cellular differentiation and cellular adhesion as a result of the interaction between glomerular endothelial cells and podocytes. We present a novel custom-made glomerulus-on-a-chip co-culture model and demonstrated for the first time using a glomerulus-on-a-chip model that co-culture affects the morphology and transcriptional phenotype of glomerular endothelial cells and podocytes. Moreover, we showed that co-culture improves barrier function as a relevant functional readout for clinical translation. This model can be used in future studies to investigate specific glomerular paracrine pathways and unravel the role of glomerular crosstalk in glomerular (patho) physiology.
Reduced Graphene Oxide-Polydopamine-Gold Nanoparticles: A Ternary Nanocomposite-Based Electrochemical Genosensor for Rapid and Early Mycobacterium tuberculosis Detection
Authors: Chaturvedi Mansi , Patel Monika , Bisht Neha , Shruti  , Das Mukherjee Maumita , Tiwari Archana , Mondal D. P. , Srivastava Avanish Kumar , Dwivedi Neeraj , Dhand Chetna
Published: March 2023

Tuberculosis (TB) has been a devastating human illness for thousands of years. According to the WHO, around 10.4 million new cases of tuberculosis are identified every year, with 1.8 million deaths. To reduce these statistics and the mortality rate, an early and accurate TB diagnosis is essential. This study offers a highly sensitive and selective electrochemical biosensor for Mycobacterium tuberculosis (MTB) detection based on a ternary nanocomposite of reduced graphene oxide, polydopamine, and gold nanoparticles (rGO-PDA-AuNP). Avidin-biotin coupling was used to bind the MTB probe DNA onto the rGO-PDA-AuNP modified glassy carbon electrode (ssDNA/avidin/rGO-PDA-AuNP). UV-Visible, Raman, XRD, and TEM were used to evaluate the structural and morphological characteristics of rGO-PDA-AuNP. Furthermore, DNA immobilization is validated using FESEM and FT-IR techniques. The modified electrodes were electrochemically analyzed using cyclic voltammetry (CV) and linear sweep voltammetry (LSV), and the results indicate that the produced electrode can detect target DNA up to 0.1 × 10−7 mM with 2.12 × 10−3 mA µM−1 sensitivity and a response time of 5 s. The constructed genosensor displayed high sensitivity and stability, and it also provides a unique strategy for diagnosing MTB at an early stage. Furthermore, our rGO-PDA-AuNP/GCE-based electrochemical platform has broad potential for creating biosensor systems for detecting various infectious pathogens and therapeutically significant biomarkers.