bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis for the Applicability of Global Precipitation Measurement Mission (GPM) IMERG Precipitation Data in Typhoons
Authors: Fan Nengzhu , Lin Xiaohong , Guo Hong
Published: July 2023

This study selected examples of 17 typhoons that landed in Fujian after passing through Taiwan. The study evaluated the precipitation in different time scales and the spatial distribution of daily precipitation of varying magnitudes in the southeastern coastal area by comparing satellite precipitation estimation products with meteorological observation station data. The evaluation used a correlation coefficient, mean relative error, relative bias, and graded assessment indexes (probability of detection, false alarm rate, and critical success index). Correlation coefficient analysis revealed that maximum daily precipitation performed best, followed by process total precipitation. The relative bias indicates that the precipitation estimated by the satellite is lower than the rainfall recorded by the automatic weather station. Mean relative error analysis showed that hourly precipitation had the highest error, followed by maximum daily precipitation. The GPM IMERG precipitation products’ retrieval of daily precipitation of varying magnitudes was assessed using three indicators. The assessment revealed that the satellite had a low under-reporting rate for light rain events but a high under-reporting rate for torrential rain events, especially extremely heavy rainstorm events, in terms of probability of detection. For the false alarm rate, the satellite had a small probability of false predictions for light rain events, while extremely heavy rainstorm events had the highest probability. For the critical success index, the satellite’s estimation of light rain events was basically consistent with reality; however, its ability to estimate precipitations above rainstorm levels was low. The results of the spatial assessment of heavy precipitation show that the satellite’s ability to detect heavy precipitation’s structure, intensity, and location is fair and has some reference value, especially for regions where conventional information is scarce.
The Spatio-Temporal Cloud Frequency Distribution in the Galapagos Archipelago as Seen from MODIS Cloud Mask Data
Authors: Zander Samira , Turini Nazli , Ballari Daniela , Bayas López Steve Darwin , Celleri Rolando , Delgado Maldonado Byron , Orellana-Alvear Johanna , Schmidt Benjamin , Scherer Dieter , Bendix Jörg
Published: July 2023

Clouds play an important role in the climate system; nonetheless, the relationship between climate change in general and regional cloud occurrence is not yet well understood. This particularly holds for remote areas such as the iconic Galapagos archipelago in Ecuador. As a first step towards a better understanding, we analyzed the spatio-temporal patterns of cloud cover over Galapagos. We found that cloud frequency and distribution exhibit large inter- and intra-annual variability due to the changing influence of climatic drivers (trade winds, sea surface temperature, El Niño/La Niña events) and spatial variations due to terrain characteristics and location within the archipelago. The highest cloud frequencies occur in mid-elevations on the slopes exposed to the southerly trade winds (south-east slopes). Towards the highlands ( >900 m a.s.l), cloud frequency decreases, with a sharp leap towards high-level crater areas mainly on Isabela Island that frequently immerse into the trade inversion layer. With respect to the diurnal cycle, we found a lower cloud frequency over the islands in the evening than in the morning. Seasonally, cloud frequency is higher during the hot season (January–May) than in the cool season (June–December). However, spatial differences in cloudiness were more pronounced during the cool season months. We further analyzed two periods beyond average atmospheric forcing. During El Niño 2015, the cloud frequency was higher than usual, and differences between altitudes and aspects were less pronounced. La Niña 2007 led to negative anomalies in cloud frequency over the islands, with intensified differences between altitude and aspect.
A Study on the Influence of Air Pollution on Temperature Forecast Skill Based on Operational Weather Forecast in BTH Region
Authors: Zhang Ziyin , Lei Yangna , Cheng Siyu
Published: July 2023

Surface air temperature is a comprehensive function of aerosols in the atmosphere and various weather factors. However, there is no real-time aerosol concentration feedback in most operational numerical weather prediction (NWP) models. This raises a scientific question of how abnormal changes in air pollutants in a short period of time will affect the temperature prediction skill of NWP models. Thus, the study was carried out to investigate the possible influence of air pollution on the temperature forecast skill based on the operational NWP model over the Beijing–Tianjin–Hebei (BTH) region during January–February 2020. The results show that the average concentrations of PM2.5, SO2, NO2 and CO over the BTH region in February were smaller than those in January by 38.5%, 35.1%, 48.0% and 33.1%, respectively. Simultaneously, the forecast skills for surface temperature in February from both regional (RMAPS, Rapid-refresh Multi-scale Analysis and Prediction System) and global (ECMWF, European Centre for Medium-Range Weather Forecasts) operational NWP models improved markedly compared with that in January. In both models, the underestimation of maximum temperature and the overestimation of minimum temperature in most cities over the BTH region in February were significantly reduced. With the 24 h (24 h) forecast lead time, the RMSE (root mean square error) of BTH daily mean, maximum and minimum temperature prediction in February based on RMAPS were 17.3%, 9.8% and 21.6% lower than that in January, respectively. These are generally consistent with the other statistical indices such as deviation and regression coefficient. As the forecast lead time extended to 48 h and 72 h forecast, the phenomena still existed and were also evident in the ECMWF model. The improvement of temperature forecast skill of NWP models may be attributed to the unexpected dramatical reduction of air pollutants. Less aerosols during the daytime allow more solar radiation reaching the surface and cause a warming in the near-surface temperature, while less aerosols during the nighttime favor the outgoing long-wave radiation and then lead to a cooling near the ground.
Influence of Urban Spatial Structure on the Spatial Distribution of Gaseous Pollutants
Authors: Ren Qixin , Shan Baoyan , Zhang Qiao , Shui Changkuan
Published: July 2023

The spatial distribution pattern of urban spatial structure affects air flow and local meteorological conditions, which in turn influence the diffusion of air pollutants. This study built the urban spatial structure index system based on DEM, urban road networks, and big data. The ordinary kriging interpolation method was used to analyze the spatial distribution of gaseous pollutant concentrations in Jinan City. Correlation analysis, stepwise regression analysis, and bivariate global spatial autocorrelation analysis were used to study the influence of the urban spatial structure index on the spatial distribution of gaseous pollutant concentration. The main conclusions were as follows: (1) Evident spatial and temporal differences were observed in the concentration distribution of gaseous pollutants in Jinan. The spatial distribution of NO2 and CO concentrations showed a gradual decrease from north to south. Spatial heterogeneity was observed in the distribution of SO2 and O3 concentrations. (2) The urban spatial structure indicators had varying effects on the spatial distribution of different gaseous pollutant concentrations. The important factors that influenced the spatial distribution of urban gaseous pollutant concentrations included terrain elevation, building density, building volume, and floor area ratio. The greater the terrain undulation, the denser the building distribution, the greater the difference in building volume, and the greater the plot ratio, the greater the impact on the diffusion and spatial distribution of urban gaseous pollutants. (3) The spatial distribution of urban gaseous pollutant concentrations was significantly affected by the urban spatial structure indicators in the surrounding areas. Furthermore, the spatial distributions of NO2, SO2, CO, and O3 concentrations had a significant negative spatial correlation with the average DEM and standard deviation of the surrounding adjacent areas and a significant positive spatial correlation with the average and standard deviation of building height, standard deviation of building area, and building density in the surrounding adjacent areas (in June).
Long Observation Window Reveals the Relationship between the Local Earth Magnetic Field and Acute Myocardial Infarction
Authors: Qammar Naseha Wafa , Petronaitis Darius , Jokimaitis Arvydas , Ragulskis Minvydas , Smalinskas Vilmantas , Žiubrytė Greta , Jaruševičius Gediminas , Vainoras Alfonsas , McCraty Rollin
Published: July 2023

A substantial body of research has demonstrated the relationships between cardiac arrhythmias and geomagnetic activity. In this work, the idea is centered on finding the relationship between the local magnetic field (LMF) and acute myocardial infarction (AMI). It is hypothesized and demonstrated via a series of statistical analyses that the relationship between the LMF and AMI is maintained over long-term observation windows. The data are collected from the two hospitals and one public institute of health in Lithuania from 2014 till 2019. The data are categorized into (1) daily average of the Schumann resonance for the local magnetic field measured by the Lithuanian magnetometer, which is used as the input variable; and (2) the total number of patients hospitalized in Lithuania per day with the diagnosis of AMI (the output variable). The data are classified both weekly as well as by gender. Following the data categorization and classification, the data were subjected to rigorous statistical analysis to determine the relationship between the input and output variables. This paper shows that only the beta and gamma (S-beta, S-gamma) frequency ranges of the Schumann resonances contribute to maintaining the long-term relationship between the LMF and AMI.
Applications of Fuzzy Differential Subordination for a New Subclass of Analytic Functions
Authors: Khan Shahid , Ro Jong-Suk , Tchier Fairouz , Khan Nazar
Published: July 2023

This work is concerned with the branch of complex analysis known as geometric function theory, which has been modified for use in the study of fuzzy sets. We develop a novel operator Lα,λm:An→An in the open unit disc Δ using the Noor integral operator and the generalized Sălăgean differential operator. First, we develop fuzzy differential subordination for the operator Lα,λm and then, taking into account this operator, we define a particular fuzzy class of analytic functions in the open unit disc Δ, represented by Rϝλ(m,α,δ). Using the idea of fuzzy differential subordination, several new results are discovered that are relevant to this class. The fundamental theorems and corollaries are presented, and then examples are provided to illustrate their practical use.
Integrating Fuzzy Rough Sets with LMAW and MABAC for Green Supplier Selection in Agribusiness
Authors: Puška Adis , Štilić Anđelka , Nedeljković Miroslav , Božanić Darko , Biswas Sanjib
Published: July 2023

The evolving customer demands have significantly influenced the operational landscape of agricultural companies, including the transformation of their supply chains. As a response, many organizations are increasingly adopting green supply chain practices. This paper focuses on the initial step of selecting a green supplier, using the case study of the Semberka Company. The objective is to align the company with customer requirements and market trends. Expert decision making, grounded in linguistic values, was employed to facilitate the transformation of these values into fuzzy numbers and subsequently derive rough number boundaries. Ten economic-environmental criteria were identified, and six suppliers were evaluated against these criteria. The fuzzy rough LMAW (Logarithm Methodology of Additive Weights) method was employed to determine the criteria weights, with emphasis placed on the quality criterion. The fuzzy rough MABAC (Multi-Attributive Border Approximation Area Comparison) method was then utilized to rank the suppliers and identify the top performer. The validity of the results was established through validation techniques and sensitivity analysis. This research contributes a novel approach to green supplier selection, employing the powerful tool of fuzzy rough sets. The flexible nature of this approach suggests its potential application in future investigations. The limitation of this study is more complicated calculations for the decision maker. However, this approach is adapted to human thinking and minimizes ambiguity and uncertainty in decision making, and in future research, it is necessary to combine this approach with other methods of multi-criteria analysis.
Asynchronous Switching Control of Discrete Time Delay Linear Switched Systems Based on MDADT
Authors: Yu Jimin , Qi Xiaoyu , Shao Yabin
Published: July 2023

Ideally, switching between subsystems and controllers occurs synchronously. In other words, whenever a subsystem requires switching, its corresponding sub-controller will be promptly activated. However, in reality, due to network delays, system detection, etc., the activation of candidate controllers frequently lags, which causes issues with asynchronous switching between controllers and subsystems. This asynchronous switching problem may affect system performance and even make the system unstable because the state between the subsystem and the controller may be inconsistent, resulting in the controller not being able to control the subsystem correctly. To keep the system stable while using asynchronous switching, this work suggests an asynchronous control technique for a class of discrete linear switching systems with time delay based on the mode-dependent average dwell time (MDADT). First, we construct a state feedback controller and establish a closed-loop system. In the asynchronous and synchronous intervals of subsystems and controllers, different Lyapunov functions are selected, and sufficient conditions for exponential stability and the H∞ performance of the closed-loop system under asynchronous switching are obtained. In addition, using the MDADT switching strategy, the relevant parameters of each subsystem are designed and the corresponding state–feedback controller gain matrix can be obtained. Finally, a switching system with three subsystems is shown. The approach is confirmed by simulating it using the average dwell time (ADT) switching strategy and the MDADT switching strategy separately.
Effects of the Wiener Process and Beta Derivative on the Exact Solutions of the Kadomtsev–Petviashvili Equation
Authors: Al-Askar Farah M. , Cesarano Clemente , Mohammed Wael W.
Published: July 2023

We take into account the (2 + 1)-dimensional stochastic Kadomtsev–Petviashvili equation with beta-derivative (SKPE-BD) in this paper. To develop new hyperbolic, trigonometric, elliptic, and rational solutions, the Riccati equation and Jacobi elliptic function methods are employed. Because the KP equation is required for explaining the development of quasi-one-dimensional shallow-water waves, the solutions obtained can be used to interpret various attractive physical phenomena. To display how the multiplicative white noise and beta-derivative impact the exact solutions of the SKPE-BD, we plot a few graphs in MATLAB and display different 3D and 2D figures. We deduce how multiplicative noise stabilizes the solutions of SKPE-BD at zero.
A Lower Bound for the Volatility Swap in the Lognormal SABR Model
Authors: Alòs Elisa , Rolloos Frido , Shiraya Kenichiro
Published: July 2023

In the short time to maturity limit, it is proved that for the conditionally lognormal SABR model the zero vanna implied volatility is a lower bound for the volatility swap strike. The result is valid for all values of the correlation parameter and is a sharper lower bound than the at-the-money implied volatility for correlation less than or equal to zero.
Outcome of Application of Cryopreserved Amniotic Membrane Grafts in the Treatment of Chronic Nonhealing Wounds of Different Origins in Polymorbid Patients: A Prospective Multicenter Study
Authors: Svobodova Alzbeta , Horvath Vojtech , Balogh Lukas , Zemlickova Martina , Fiala Radovan , Burkert Jan , Brabec Marek , Stadler Petr , Lindner Jaroslav , Bednar Jan , Jirsova Katerina
Published: July 2023

To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm2 were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated. If the wound healed less than 20% of the baseline size after 6 weeks, the patient was transferred to the AM group (35 patients, 43 wounds). Weekly visits included an assessment of the patient’s condition, photo documentation, wound debridement, and dressing. Quality of life and the pain degree were subjectively reported by patients. After SOC, 7 wounds were healed completely, 1 defect partially, and 28 defects remained unhealed. AM application led to the complete closure of 24 wounds, partial healing occurred in 10, and 9 remained unhealed. The degree of pain and the quality of life improved significantly in all patients after AM application. This study demonstrates the effectiveness of cryopreserved AM grafts in the healing of NHW of polymorbid patients and associated pain reduction.
Real-Time Tracking of Laryngeal Motion via the Surface Depth-Sensing Technique for Radiotherapy in Laryngeal Cancer Patients
Authors: Lee Wan-Ju , Leu Yi-Shing , Chen Jing-Sheng , Dai Kun-Yao , Hou Tien-Chi , Chang Chung-Ting , Li Chi-Jung , Hua Kai-Lung , Chen Yu-Jen
Published: July 2023

Radiotherapy (RT) is an important modality for laryngeal cancer treatment to preserve laryngeal function. During beam delivery, laryngeal motion remains uncontrollable and may compromise tumor-targeting efficacy. We aimed to examine real-time laryngeal motion by developing a surface depth-sensing technique with preliminary testing during RT-based treatment of patients with laryngeal cancer. A surface depth-sensing (SDS) camera was set up and integrated into RT simulation procedures. By recording the natural swallowing of patients, SDS calculation was performed using the Pose Estimation Model and deep neural network technique. Seven male patients with laryngeal cancer were enrolled in this prospective study. The calculated motion distances of the laryngeal prominence (mean ± standard deviation) were 1.6 ± 0.8 mm, 21.4 ± 5.1 mm, 6.4 ± 3.3 mm, and 22.7 ± 4.9 mm in the left–right, cranio–caudal, and anterior–posterior directions and for the spatial displacement, respectively. The calculated differences in the 3D margins for generating the planning tumor volume by senior physicians with and without SDS data were −0.7 ± 1.0 mm (−18%), 11.3 ± 6.8 mm (235%), and 1.8 ± 2.6 mm (45%) in the left–right, cranio–caudal, and anterior–posterior directions, respectively. The SDS technique developed for detecting laryngeal motion during swallowing may be a practical guide for individualized RT design in the treatment of laryngeal cancer.
Effects of Terpenes on the Osteoarthritis Cytokine Profile by Modulation of IL-6: Double Face versus Dark Knight?
Authors: Farì Giacomo , Megna Marisa , Scacco Salvatore , Ranieri Maurizio , Raele Maria Vittoria , Noya Enrica Chiaia , Macchiarola Dario , Bianchi Francesco Paolo , Carati Davide , Gnoni Antonio , Inchingolo Alessio Danilo , Qorri Erda , Scarano Antonio , Scacco Antonio , Arrigoni Roberto , Rapone Biagio
Published: July 2023

Background: Hemp seed oil and terpenes are emerging as a dietary supplement and complementary therapy for patients suffering from knee osteoarthritis (KOA). However, the mechanisms and effects induced by these molecules on inflammatory cytokines are not yet fully understood. The aim of this study was to evaluate the changes in the cytokine IL-1β, IL-1α, IL-2, IL-6, and TNF-α levels from two oral hemp seed oil-based dietary supplements, of which only one included the addition of terpenes, in a population of KOA patients. Methods: Sera from venous blood samples were collected from thirty-eight patients who were divided into two subgroups. The control group underwent a 45-day treatment with a dietary supplement containing only hemp seed oil, while the treatment group assumed a hemp seed oil and terpene-based dietary supplement for the same number of days. A Bio-Plex Human Cytokine assay was performed by a customized human cytokine five-plex panel for IL-1β, IL-1α, IL-2, IL-6, and TNF-α. Patients were evaluated before the beginning of the treatment (T0) and soon after it (T1). Results: No measurable levels of IL-2 and TNF-α were found in any of the subjects. Low levels of IL-1β were found, which were significantly decreased in the treatment group. No change in IL-1α levels was observed, while treated patients had a significant increase in IL-6 levels. Conclusions: Hemp seed oil and terpene treatment modified the IL-1β and IL-6 levels, counteracting KOA inflammation in this way. In this study, IL-6 revealed its new and alternative action, since it is traditionally known as a pro-inflammatory factor, but it recently has been found to have anti-inflammatory activity in the muscle-derived form, which is the one it assumes as a myokine when activated by terpenes.
Composition and Long-Term Variation Characteristics of Coral Reef Fish Species in Yongle Atoll, Xisha Islands, China
Authors: Zhao Jinfa , Li Chunhou , Wang Teng , Shi Juan , Song Xiaoyu , Liu Yong
Published: July 2023

Yongle Atoll was the largest atoll in the Xisha Islands of the South China Sea, and it was a coral reef ecosystem with important ecological and economic values. In order to better protect and manage the coral reef fish resources in Yongle Atoll, we analyzed field survey data from artisanal fishery, catches, and underwater video from 2020 to 2022 and combined historical research to explore the changes in fish species composition and community structure in Yongle Atoll over the past 50 years. The results showed that a total of 336 species of fish were found on Yongle Atoll, belonging to 17 orders and 60 families. Among them, Perciformes had the most fish species with 259 species accounting for 77.08% of the total number of species. The number of fish species in the coral reef of Yongle Atoll was exponentially correlated with its corresponding maximum length and significantly decreases with its increase. The fish community structure of Yongle Atoll changed, and the proportion of large carnivorous fish decreased significantly, while the proportion of small-sized and medium-sized fish increased. At the same time, Yongle Atoll has 18 species of fish listed on the IUCN Red List, 15 of which are large fish. The average taxonomic distinctness (Delta+, Δ+) and the variation taxonomic distinctness (Lambda+, Λ+) in 2020–2022 were lower than the historical data, and the number of fish orders, families, and genera in Yongle Atoll has decreased significantly, which indicates that the current coral reef fish species in Yongle Atoll have closer relatives and higher fish species uniformity. In addition, the similarity of fish species in Yongle Atoll was relatively low at various time periods, further proving that the fish community structure has undergone significant variation. In general, due to multiple impacts, such as overfishing, fishing methods, environmental changes, and habitat degradation, the fish species composition of Yongle Atoll may have basically evolved from carnivorous to herbivorous, from large fish to small fish, and from complexity to simplicity, leaving Yongle Atoll in an unstable state. Therefore, we need to strengthen the continuous monitoring of the coral reef ecosystem in Yongle Atoll to achieve the protection and restoration of its ecological environment and fishery resources, as well as sustainable utilization and management.
3D Culture and Interferon-γ Priming Modulates Characteristics of Mesenchymal Stromal/Stem Cells by Modifying the Expression of Both Intracellular and Exosomal microRNAs
Authors: Bulati Matteo , Gallo Alessia , Zito Giovanni , Busà Rosalia , Iannolo Gioacchin , Cuscino Nicola , Castelbuono Salvatore , Carcione Claudia , Centi Claudio , Martucci Gennaro , Bertani Alessandro , Baiamonte Maria Pia , Chinnici Cinzia Maria , Conaldi Pier Giulio , Miceli Vitale
Published: July 2023

Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the molecular mechanisms underlying miRNA-mediated MSC effects are not fully understood. We used 3D culture and IFN-γ to prime/enhance the MSC therapeutic effects in terms of functional miRNAs. After priming, our analysis revealed stable variations in intracellular miRNA among the MSC biological replicates. Conversely, a significant variability of miRNA was observed among EXOs released from biological replicates of the priming treatment. For each priming, we observed distinct miRNA expression profiles between the MSCs and their EXOs. Moreover, in both types of priming, gene ontology (GO) analysis of deregulated miRNAs highlighted their involvement in tissue repair/regeneration pathways. In particular, the 3D culture enhanced angiogenic properties in both MSCs and EXOs, while IFN-γ treatment enriched miRNAs associated with immunomodulatory pathways. These findings suggest that 3D culture and IFN-γ treatment are promising strategies for enhancing the therapeutic potential of MSCs by modulating miRNA expression. Additionally, the identified miRNAs may contribute to understanding the molecular mechanisms underlying the miRNA-mediated therapeutic effects of MSCs.
Structural Adaptation of the Excitation–Contraction Coupling Apparatus in Calsequestrin1-Null Mice during Postnatal Development
Authors: Murzilli Stefania , Serano Matteo , Pietrangelo Laura , Protasi Feliciano , Paolini Cecilia
Published: July 2023

The precise arrangement and peculiar interaction of transverse tubule (T-tubule) and sarcoplasmic reticulum (SR) membranes efficiently guarantee adequate contractile properties of skeletal muscle fibers. Fast muscle fibers from mice lacking calsequestrin 1 (CASQ1) are characterized by the profound ultrastructural remodeling of T-tubule/SR junctions. This study investigates the role of CASQ1, an essential component of calcium release units (CRUs), in the postnatal development of muscle fibers. By using CASQ1-knockout mice, we examined the maturation of CRUs and the involvement of different junctional proteins in the juxtaposition of the membrane system. Our morphological investigation of both wild-type (WT) and CASQ1-null extensor digitorum longus (EDL) fibers, from 1 week to 4 months of age, yielded noteworthy findings. Firstly, we observed that the absence of CASQ1 hindered the full maturation of CRUs, despite the correct localization of key junctional components (ryanodine receptor, dihydropyridine receptor, and triadin) to the junctional SR in adult animals. Furthermore, analysis of protein expression profiles related to T-tubule biogenesis and organization (junctophilin 1, amphiphysin 2, caveolin 3, and mitsugumin 29) demonstrated delayed progression in their expression during postnatal development in the absence of CASQ1, suggesting the impaired maturation of CRUs. The absence of CASQ1 directly impacts the proper assembly of CRUs during development and influences the expression and coordination of other proteins involved in T-tubule biogenesis and organization.
Kidney Damage in Long COVID: Studies in Experimental Mice
Authors: Ramamoorthy Rajalakshmi , Hussain Hussain , Ravelo Natalia , Sriramajayam Kannappan , Di Gregorio Dibe M. , Paulrasu Kodisundaram , Chen Pingping , Young Karen , Masciarella Andrew D. , Jayakumar Arumugam R. , Paidas Michael J.
Published: July 2023

Signs and symptoms involving multiple organ systems which persist for weeks or months to years after the initial SARS-CoV-2 infection (also known as PASC or long COVID) are common complications of individuals with COVID-19. We recently reported pathophysiological changes in various organs post-acute infection of mice with mouse hepatitis virus-1 (MHV-1, a coronavirus) (7 days) and after long-term post-infection (12 months). One of the organs severely affected in this animal model is the kidney, which correlated well with human studies showing kidney injury post-SARS-CoV-2 infection. Our long-term post-infection pathological observation in kidneys includes the development of edema and inflammation of the renal parenchyma, severe acute tubular necrosis, and infiltration of macrophages and lymphocytes, in addition to changes observed in both acute and long-term post-infection, which include tubular epithelial cell degenerative changes, peritubular vessel congestion, proximal and distal tubular necrosis, hemorrhage in the interstitial tissue, and vacuolation of renal tubules. These findings strongly suggest the possible development of renal fibrosis, in particular in the long-term post-infection. Accordingly, we investigated whether the signaling system that is known to initiate the above-mentioned changes in kidneys in other conditions is also activated in long-term post-MHV-1 infection. We found increased TGF-β1, FGF23, NGAL, IL-18, HIF1-α, TLR2, YKL-40, and B2M mRNA levels in long-term post-MHV-1 infection, but not EGFR, TNFR1, BCL3, and WFDC2. However, only neutrophil gelatinase-associated lipocalin (NGAL) increased in acute infection (7 days). Immunoblot studies showed an elevation in protein levels of HIF1-α, TLR-2, and EGFR in long-term post-MHV-1 infection, while KIM-1 and MMP-7 protein levels are increased in acute infection. Treatment with a synthetic peptide, SPIKENET (SPK), which inhibits spike protein binding, reduced NGAL mRNA in acute infection, and decreased TGF-β1, BCL3 mRNA, EGFR, HIF1-α, and TLR-2 protein levels long-term post-MHV-1 infection. These findings suggest that fibrotic events may initiate early in SARS-CoV-2 infection, leading to pronounced kidney fibrosis in long COVID. Targeting these factors therapeutically may prevent acute or long-COVID-associated kidney complications.
Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers
Authors: Han Ning , Yuan Man , Yan Libo , Tang Hong
Published: July 2023

Liver X receptor α (LXRα), a member of the nuclear receptor superfamily, is identified as a protein activated by ligands that interacts with the promoters of specific genes. It regulates cholesterol, bile acid, and lipid metabolism in normal physiological processes, and it participates in the development of some related diseases. However, many studies have demonstrated that LXRα is also involved in regulating numerous human malignancies. Aberrant LXRα expression is emerging as a fundamental and pivotal factor in cancer cell proliferation, invasion, apoptosis, and metastasis. Herein, we outline the expression levels of LXRα between tumor tissues and normal tissues via the Oncomine and Tumor Immune Estimation Resource (TIMER) 2.0 databases; summarize emerging insights into the roles of LXRα in the development, progression, and treatment of different human cancers and their diversified mechanisms; and highlight that LXRα can be a biomarker and therapeutic target in diverse cancers.
Counting the Toll of Inflammation on Schizophrenia—A Potential Role for Toll-like Receptors
Authors: Patlola Saahithh Redddi , Donohoe Gary , McKernan Declan P.
Published: July 2023

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that are ubiquitously expressed in the human body. They protect the brain and central nervous system from self and foreign antigens/pathogens. The immune response elicited by these receptors culminates in the release of cytokines, chemokines, and interferons causing an inflammatory response, which can be both beneficial and harmful to neurodevelopment. In addition, the detrimental effects of TLR activation have been implicated in multiple neurodegenerative diseases such as Alzheimer’s, multiple sclerosis, etc. Many studies also support the theory that cytokine imbalance may be involved in schizophrenia, and a vast amount of literature showcases the deleterious effects of this imbalance on cognitive performance in the human population. In this review, we examine the current literature on TLRs, their potential role in the pathogenesis of schizophrenia, factors affecting TLR activity that contribute towards the risk of schizophrenia, and lastly, the role of TLRs and their impact on cognitive performance in schizophrenia.
Synthesis and Characterization of Polyhydroxyalkanoate/Graphene Oxide/Nanoclay Bionanocomposites: Experimental Results and Theoretical Predictions via Machine Learning Models
Authors: Champa-Bujaico Elizabeth , Díez-Pascual Ana M. , García-Díaz Pilar
Published: July 2023

Predicting the mechanical properties of multiscale nanocomposites requires simulations that are costly from a practical viewpoint and time consuming. The use of algorithms for property prediction can reduce the extensive experimental work, saving time and costs. To assess this, ternary poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)-based bionanocomposites reinforced with graphene oxide (GO) and montmorillonite nanoclay were prepared herein via an environmentally friendly electrochemical process followed by solution casting. The aim was to evaluate the effectiveness of different Machine Learning (ML) models, namely Artificial Neural Network (ANN), Decision Tree (DT), and Support Vector Machine (SVM), in predicting their mechanical properties. The algorithms’ input data were the Young’s modulus, tensile strength, and elongation at break for various concentrations of the nanofillers (GO and nanoclay). The correlation coefficient (R2), mean absolute error (MAE), and mean square error (MSE) were used as statistical indicators to assess the performance of the models. The results demonstrated that ANN and SVM are useful for estimating the Young’s modulus and elongation at break, with MSE values in the range of 0.64–1.0% and 0.14–0.28%, respectively. On the other hand, DT was more suitable for predicting the tensile strength, with the indicated error in the range of 0.02–9.11%. This study paves the way for the application of ML models as confident tools for predicting the mechanical properties of polymeric nanocomposites reinforced with different types of nanofiller, with a view to using them in practical applications such as biomedicine.
The Role of Poly(ADP-ribose) Polymerase 1 in Nuclear and Mitochondrial Base Excision Repair
Authors: Herrmann Geoffrey K. , Yin Y. Whitney
Published: July 2023

Poly(ADP-ribose) (PAR) Polymerase 1 (PARP-1), also known as ADP-ribosyl transferase with diphtheria toxin homology 1 (ARTD-1), is a critical player in DNA damage repair, during which it catalyzes the ADP ribosylation of self and target enzymes. While the nuclear localization of PARP-1 has been well established, recent studies also suggest its mitochondrial localization. In this review, we summarize the differences between mitochondrial and nuclear Base Excision Repair (BER) pathways, the involvement of PARP-1 in mitochondrial and nuclear BER, and its functional interplay with other BER enzymes.
Exogenous Jasmonic Acid Alleviates Blast Resistance Reduction Caused by LOX3 Knockout in Rice
Authors: Su Shunyu , Tang Ping , Zuo Rubin , Chen Hongfeng , Zhao Tianqi , Yang Shumin , Yang Jing
Published: July 2023

Lipoxygenase 3 (LOX3) is a lipid peroxidase found in rice embryos that is known to affect seed quality. Interestingly, deletion of the LOX3 gene has been shown to improve rice seed quality but decrease resistance to rice blast disease and drought. To investigate these opposing effects, we generated a LOX3 knockout construct (ΔLox3) in rice (Oryza sativa L.) plants. Blast resistance and transcription levels of rice genes in ΔLox3 rice plants and the effects of exogenous jasmonic acid (JA) on resistance and transcriptional levels of rice genes in Magnaporthe oryzae-infected ΔLox3 rice plants were further elucidated. The results showed that the ΔLox3 plants exhibited normal phenotypes, with high levels of methyl-linolenate and reactive oxygen species (ROS), and the genes involved in three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contributed to rice seed quality. M. oryzae-infected ΔLox3 plants exhibited serious blast symptoms with a reduced defense response but increased ROS-mediated cell death, and the genes involved in seven KEGG pathways contributed to rice seed quality. Exogenous JA treatment alleviated blast symptoms in infected ΔLox3 plants by hindering hyphal expansion, inhibiting ROS-mediated cell death, and increasing the defense response, and genes involved in 12 KEGG pathways contributed to rice seed quality. These findings demonstrate that LOX3 plays an important role in rice growth and defense, and its knockout improves rice quality at the expense of disease resistance. Exogenous JA provides a means to compensate for the reduction in defense responses of LOX3 knockout rice lines, suggesting potential applications in agricultural production.
Role of Mitochondria–ER Contact Sites in Mitophagy
Authors: Rühmkorf Alina , Harbauer Angelika Bettina
Published: July 2023

Mitochondria are often referred to as the “powerhouse” of the cell. However, this organelle has many more functions than simply satisfying the cells’ metabolic needs. Mitochondria are involved in calcium homeostasis and lipid metabolism, and they also regulate apoptotic processes. Many of these functions require contact with the ER, which is mediated by several tether proteins located on the respective organellar surfaces, enabling the formation of mitochondria–ER contact sites (MERCS). Upon damage, mitochondria produce reactive oxygen species (ROS) that can harm the surrounding cell. To circumvent toxicity and to maintain a functional pool of healthy organelles, damaged and excess mitochondria can be targeted for degradation via mitophagy, a form of selective autophagy. Defects in mitochondria–ER tethers and the accumulation of damaged mitochondria are found in several neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, which argues that the interplay between the two organelles is vital for neuronal health. This review provides an overview of the different mechanisms of mitochondrial quality control that are implicated with the different mitochondria–ER tether proteins, and also provides a novel perspective on how MERCS are involved in mediating mitophagy upon mitochondrial damage.
Neuroprotective Potential of Raloxifene via G-Protein-Coupled Estrogen Receptors in Aβ-Oligomer-Induced Neuronal Injury
Authors: Nohara Tetsuhito , Tsuji Mayumi , Oguchi Tatsunori , Momma Yutaro , Ohashi Hideaki , Nagata Miki , Ito Naohito , Yamamoto Ken , Murakami Hidetomo , Kiuchi Yuji
Published: July 2023

Amyloid-β (Aβ) is one of the causes of Alzheimer’s disease (AD), damaging nerve membranes and inducing neurotoxicity. AD is more prevalent in female patients than in male patients, and women are more susceptible to developing AD due to the decline in estrogen levels around menopause. Raloxifene, a selective estrogen receptor modulator, exhibits protective effects by activating the transmembrane G-protein-coupled estrogen receptor (GPER). Additionally, raloxifene prevents mild cognitive impairment and restores cognition. However, the influence of raloxifene via GPER on highly toxic Aβ-oligomers (Aβo)-induced neurotoxicity remains uncertain. In this study, we investigated the GPER-mediated neuroprotective effects of raloxifene against the neurotoxicity caused by Aβo-induced cytotoxicity. The impact of raloxifene on Aβo-induced cell damage was evaluated using measures such as cell viability, production of reactive oxygen species (ROS) and mitochondrial ROS, peroxidation of cell-membrane phospholipids, and changes in intracellular calcium ion concentration ([Ca2+]i) levels. Raloxifene hindered Aβo-induced oxidative stress and reduced excessive [Ca2+]i, resulting in improved cell viability. Furthermore, these effects of raloxifene were inhibited with pretreatment with a GPER antagonist. Our findings suggest that raloxifene safeguards against Aβo-induced neurotoxicity by modifying oxidative parameters and maintaining [Ca2+]i homeostasis. Raloxifene may prove effective in preventing and inhibiting the progression of AD.
Bronchial Fibroblasts from Asthmatic Patients Display Impaired Responsiveness to Direct Current Electric Fields (dcEFs)
Authors: Pavlenko Anastasiia , Lasota Sławomir , Wnuk Dawid , Paw Milena , Czyż Jarosław , Michalik Marta , Madeja Zbigniew
Published: July 2023

Accumulating evidence suggests that an important role is played by electric signals in modifying cell behaviour during developmental, regenerative and pathological processes. However, their role in asthma has not yet been addressed. Bronchial fibroblasts have recently been identified having important roles in asthma development. Therefore, we adapted an experimental approach based on the lineages of human bronchial fibroblasts (HBF) derived from non-asthmatic (NA) donors and asthmatic (AS) patients to elucidate whether their reactivity to direct current electric fields (dcEF) could participate in the asthmatic process. The efficient responsiveness of NA HBF to an electric field in the range of 2–4 V/cm was illustrated based on the perpendicular orientation of long axes of the cells to the field lines and their directional movement towards the anode. These responses were related to the activity of TGF-β signalling, as the electrotaxis and re-orientation of NA HBF polarity was impaired by the inhibitors of canonical and non-canonical TGF-β-dependent pathways. A similar tendency towards perpendicular cell-dcEF orientation was observed for AS HBF. However, their motility remained insensitive to the electric field applied at 2–4 V/cm. Collectively, these observations demonstrate the sensitivity of NA HBF to dcEF, as well as the inter-relations between this parameter and the canonical and non-canonical TGF-β pathways, and the differences between the electrotactic responses of NA and AS HBF point to the possible role of their dcEFs in desensitisation in the asthmatic process. This process may impair the physiologic behaviour of AS HBF functions, including cell motility, ECM deposition, and contractility, thus promoting bronchial wall remodelling, which is a characteristic of bronchial asthma.
New Technologies in Digestive Endoscopy for Ulcerative Colitis Patients
Authors: Biamonte Paolo , D’Amico Ferdinando , Fasulo Ernesto , Barà Rukaia , Bernardi Francesca , Allocca Mariangela , Zilli Alessandra , Danese Silvio , Furfaro Federica
Published: July 2023

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the colon and rectum. Endoscopy plays a crucial role in the diagnosis and management of UC. Recent advancements in endoscopic technology, including chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and the use of artificial intelligence, have revolutionized the assessment and treatment of UC patients. These innovative techniques enable early detection of dysplasia and cancer, more precise characterization of disease extent and severity and more targeted biopsies, leading to improved diagnosis and disease monitoring. Furthermore, these advancements have significant implications for therapeutic decision making, empowering clinicians to carefully consider a range of treatment options, including pharmacological therapies, endoscopic interventions and surgical approaches. In this review, we provide an overview of the latest endoscopic technologies and their applications for diagnosing and monitoring UC. We also discuss their impact on treatment decision making, highlighting the potential benefits and limitations of each technique.
Integrating Chinese Herbs and Western Medicine for New Wound Dressings through Handheld Electrospinning
Authors: Zhou Jianfeng , Wang Liangzhe , Gong Wenjian , Wang Bo , Yu Deng-Guang , Zhu Yuanjie
Published: July 2023

In this nanotechnology era, nanostructures play a crucial role in the investigation of novel functional nanomaterials. Complex nanostructures and their corresponding fabrication techniques provide powerful tools for the development of high-performance functional materials. In this study, advanced micro-nanomanufacturing technologies and composite micro-nanostructures were applied to the development of a new type of pharmaceutical formulation, aiming to achieve rapid hemostasis, pain relief, and antimicrobial properties. Briefly, an approach combining a electrohydrodynamic atomization (EHDA) technique and reversed-phase solvent was employed to fabricate a novel beaded nanofiber structure (BNS), consisting of micrometer-sized particles distributed on a nanoscale fiber matrix. Firstly, Zein-loaded Yunnan Baiyao (YB) particles were prepared using the solution electrospraying process. Subsequently, these particles were suspended in a co-solvent solution containing ciprofloxacin (CIP) and hydrophilic polymer polyvinylpyrrolidone (PVP) and electrospun into hybrid structural microfibers using a handheld electrospinning device, forming the EHDA product E3. The fiber-beaded composite morphology of E3 was confirmed through scanning electron microscopy (SEM) images. Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis revealed the amorphous state of CIP in the BNS membrane due to the good compatibility between CIP and PVP. The rapid dissolution experiment revealed that E3 exhibits fast disintegration properties and promotes the dissolution of CIP. Moreover, in vitro drug release study demonstrated the complete release of CIP within 1 min. Antibacterial assays showed a significant reduction in the number of adhered bacteria on the BNS, indicating excellent antibacterial performance. Compared with the traditional YB powders consisting of Chinese herbs, the BNS showed a series of advantages for potential wound dressing. These advantages include an improved antibacterial effect, a sustained release of active ingredients from YB, and a convenient wound covering application, which were resulted from the integration of Chinese herbs and Western medicine. This study provides valuable insights for the development of novel multiscale functional micro-/nano-composite materials and pioneers the developments of new types of medicines from the combination of herbal medicines and Western medicines.