bluuebunny/crossref_metadata_2025 huggingface dataset:
Absolute Reliability and Concurrent Validity of the Modified Goniometric Platform for Measuring Trunk Rotation in the Sitting Position
Authors: Gao Jianhong , Thung Jin Seng , Wei Shanshan , Pavlů Dagmar , Chee Chen Soon , Ramasamy Yuvaraj , Mohd Ali Azril Syazwan Bin , Mat Yatim Rosnah Binti
Published: September 2022

The modified goniometric platform (MGP) is a novel instrument used to measure trunk rotation while sitting. A lack of reliable and valid evidence has been reported to measure trunk rotation using MGP. Therefore, this study was aimed to investigate the intra- and inter-rater reliabilities and validity of the MGP for measuring trunk rotation while sitting. Methods: Seventeen participants performed right trunk rotation followed by left trunk rotation (three repetitions for each trial) and two random measurements at 40-minute intervals. Inter-rater and intra-rater reliabilities were calculated using intraclass correlation coefficients (ICCs). Validity was assessed using the Pearson correlation coefficient (r). Results: The test and re-test inter-rater reliabilities for right trunk rotation were 0.990 and 0.986, respectively, and those for left trunk rotation were 0.989 and 0.978, respectively. The intra-rater reliabilities for right trunk rotation were 0.949 and 0.954, respectively, and those for left trunk rotation were 0.944 and 0.946, respectively. The right and left trunk rotation validities were 0.986 and 0.981, respectively. Conclusion: MGP is reliable and valid for measuring right and left trunk rotations while sitting.
A Systematic Control Design Method with Active Damping Control in Voltage Source Converters
Authors: Gholami-Khesht Hosein , Davari Pooya , Wu Chao , Blaabjerg Frede
Published: September 2022

This paper proposes a systematic control design method for active damping control of grid-connected voltage source converters (VSCs). The proposed control method considers the conventional cascaded control loops and improves them by including additional states feedback-based active damping. In such a way, all control gains are lumped into one control gain matrix based on the proposed formulation. The lumping of all control gains into one matrix leads to a linear optimization problem, so different techniques can be used to calculate control gains. This work calculates them by using a simple but effective optimal control theorem as a noteworthy feature. The proposed control method can overcome the challenges of designing multiple control loops, evaluating wide time scale dynamics, and tuning required control parameters. Moreover, direct relationships between the proposed tuning parameters and system well-known stability and performance indicators such as maximum damping factor, minimum damping ratio, and the control efforts are identified, providing good physical insight. Finally, the proposed control structure and optimal gain calculations ensure power converter robustness against uncertainties in the grid’s short-circuit ratio (SCR) and different operating-point conditions. When the grid’s SCR changes from 10 (strong grid condition) to 1 (ultra-weak grid condition), the system under the proposed control method maintains good stability margins and simultaneously provides a fast dynamic response by facilitating the implementation of a high-bandwidth phase-locked loop (PLL). The performance of the proposed control strategy was investigated analytically and practically by conducting eigenvalue analysis, simulations, and experiments.
Evaluation of Body Posture during Class II Functional Treatment with Fränkel II: A Longitudinal Study
Authors: Caroccia Francesco , Lopes Chiara , Pipitone Rossana , D’Addazio Gianmaria , Moscagiuri Francesco , D’Attilio Michele
Published: September 2022

The aim of the current study was to evaluate the changes in body posture in pubertal subjects characterized by Skeletal Class II with mandibular retrusion pre- and post-Fränkel II (FR-2). The treatment of Skeletal Class II with functional therapy has been already correlated with changes in cervical posture, but no previous studies investigated the possible relation with the posture of the whole body. This is an observational longitudinal study conducted on 17 Caucasian subjects (6 males, 11 female) with average age 10.7 ± 3.5. Posturostabilometric evaluation was performed before the beginning of the orthodontic treatment (t0), after 12 ± 2 months (t1) and after 24 ± 3 months at the end of the treatment with FR-2 (t2). The following stabilometric parameters were extracted: weight distribution (WD), bar torsion angle (BTA), and barycenter (Xmm). Both WD (p = 0.0154) and BTA (p = 0.0003) showed a significant improvement during the treatment with Friedman test and ANOVA test, respectively, showing how the overall balance and weight distribution of the body can benefit from a functional therapy with jaw advancement. The posturostabilometric platform can be considered a functional indicator of therapy effectiveness because it shows the improving trend of the parameters. Future research is needed, based on the promising results obtained in the current study.
Parametric Assessment of Surface Topography and Its Influence on Joint Tightness of Non-Separable Joints for Thin Wall Applications
Authors: Wróbel Nikodem , Rejek Michał , Królczyk Jolanta , Franka Mateusz , Gupta Munish Kumar , Śliwiński Marcin , Królczyk Grzegorz
Published: September 2022

This article describes the research carried out on six thin-walled groups of samples produced from the aluminum alloy 6060 T4 by a turning and milling operation. Additionally, the analysis of the surface topography was carried out, focusing on three-dimensional parameters, such as Sq, Ssk, Sku, Sp, Sv, Sz, Sa, Spd, and Spc. Moreover, the article contains the tests of the tightness of various types of surfaces with different clamping forces of the tested elements. Furthermore, an attempt was made to find significant representatives of the surface topography to obtain the smallest leakage between the mating surfaces. The maximum clamping force obtained in the tests between the pairs was 9060 N. Finally, it is worth mentioning that the presented surface tests can serve as the required parameters for joined elements in the production of non-detachable joints by, for example, clinching.
Unveiling the Influence of Carbon Nanotube Diameter and Surface Modification on the Anchorage of L-Asparaginase
Authors: Cristóvão Raquel O. , Barros Rita A. M. , Pinho João G. , Teixeira Lília S. , Neves Márcia C. , Freire Mara G. , Faria Joaquim L. , Santos-Ebinuma Valéria C. , Tavares Ana P. M. , Silva Cláudia G.
Published: September 2022

L-asparaginase (ASNase, EC 3.5.1.1) is an amidohydrolase enzyme known for its anti-cancer properties, with an ever-increasing commercial value. Immobilization has been studied to improve the enzyme’s efficiency, enabling its recovery and reuse, enhancing its stability and half-life time. In this work, the effect of pH, contact time and enzyme concentration during the ASNase physical adsorption onto pristine and functionalized multi-walled carbon nanotubes (MWCNTs and f-MWCNTs, respectively) with different size diameters was investigated by maximizing ASNase relative recovered activity (RRA) and immobilization yield (IY). Immobilized ASNase reusability and kinetic parameters were also evaluated. The ASNase immobilization onto f-MWCNTs offered higher loading capacities, enhanced reusability, and improved enzyme affinity to the substrate, attaining RRA and IY of 100 and 99%, respectively, at the best immobilization conditions (0.4 mg/mL of ASNase, pH 8, 30 min of contact time). In addition, MWCNTs diameter proved to play a critical role in determining the enzyme binding affinity, as evidenced by the best results attained with f-MWCNTs with diameters of 10–20 nm and 20–40 nm. This study provided essential information on the impact of MWCNTs diameter and their surface functionalization on ASNase efficiency, which may be helpful for the development of innovative biomedical devices or food pre-treatment solutions.
Characterization of Microbial Communities and Naturally Occurring Radionuclides in Soilless Growth Media Amended with Different Concentrations of Biochar
Authors: Osei George K. , Abazinge Michael , Ngatia Lucy , Chauhan Ashvini , Bolques Alejandro , Jagoe Charles , Pathak Ashish
Published: September 2022

Biochar, derived from the pyrolysis of plant materials has the potential to enhance plant growth in soilless media. Howevetar, little is known about the impact of biochar amendments to soilless growth media, microbial community composition, and fate of chemical constituents in the media. In this study, different concentrations of biochar were added to soilless media and microbial composition, and chemical constituents were analyzed using metagenomics and gamma spectroscopy techniques, respectively. Across treatments, carboxyl-C, phenolic-C, and aromatic-C were the main carbon sources that influenced microbial community composition. Flavobacterium (39.7%), was the predominantly bacteria genus, followed by Acidibacter (12.2%), Terrimonas (10.1%), Cytophaga (7.5%), Ferruginibacter (6.0%), Lacunisphaera (5.9%), Cellvibrio (5.8%), Opitutus (4.8%), Mucilaginibacter (4.0%) and Bryobacter (4.0%). Negative relationships were found between Cytophaga and 226Ra (r = −0.84, p = 0.0047), 40K (r = −0.82, p = 0.0069) and 137Cs (r = −0.93, p = 0.0002). Similarly, Mucilaginibacter was negatively correlated with 226Ra (r = −0.83, p = 0.0054) and 137Cs (r = −0.87, p = 0.0021). Overall, the data suggest that high % biochar amended samples have high radioactivity concentration levels. Some microorganisms have less presence in high radioactivity concentration levels.
Multi-Criteria Comparison of Energy and Environmental Assessment Approaches for the Example of Cooling Towers
Authors: Wenzel Paula M. , Radgen Peter
Published: September 2022

Cooling towers remove economically or technically unusable heat using considerable amounts of electricity and, in many cases, water. Several approaches, which vary in methodology, scope, and level of detail, are used for environmental evaluations of these cooling systems. Although the chosen approach has a significant impact on decisions made at the plant level, no methodology has yet been standardized for selecting the approach that best serves the objectives of the evaluation. Thus, this paper provides comparison criteria for the systematic selection of suitable evaluation methods for cooling towers and classifies how the methods score in this respect. These criteria, such as ‘life cycle thinking’, ‘inventoried physical quantities’, ‘temporal resolution’, ‘formalization’, and ‘data availability’, are grouped by overall evaluation objectives such as ‘thoroughness’, ‘scientific soundness’, and ‘usability’. Subsequently, these criteria were used to compare material flow analysis, energy analysis, environmental network analysis, life cycle inventory, life cycle assessment, environmental footprint methods, emergy analysis, exergy analysis, and the physical optimum method. In conclusion, material flow analysis is best suited for the analysis of cooling towers when impact assessment is not required; otherwise, life cycle assessment meets most of the defined criteria. Moreover, only exergy-based methods allow for the inclusion of volatile ambient conditions.
Multi-Model Ensemble Prediction of Summer Precipitation in China Based on Machine Learning Algorithms
Authors: Yang Jie , Xiang Ying , Sun Jiali , Xu Xiazhen
Published: September 2022

The development of machine learning (ML) provides new means and methods for accurate climate analysis and prediction. This study focuses on summer precipitation prediction using ML algorithms. Based on BCC CSM1.1, ECMWF SEAS5, NCEP CFSv2, and JMA CPS2 model data, we conducted a multi-model ensemble (MME) prediction experiment using three tree-based ML algorithms: the decision tree (DT), random forest (RF), and adaptive boosting (AB) algorithms. On this basis, we explored the applicability of ML algorithms for ensemble prediction of seasonal precipitation in China, as well as the impact of different hyperparameters on prediction accuracy. Then, MME predictions based on optimal hyperparameters were constructed for different regions of China. The results showed that all three ML algorithms had an optimal maximum depth less than 2, which means that, based on the current amount of data, the three algorithms could only predict positive or negative precipitation anomalies, and extreme precipitation was hard to predict. The importance of each model in the ML-based MME was quantitatively evaluated. The results showed that NCEP CFSv2 and JMA CPS2 had a higher importance in MME for the eastern part of China. Finally, summer precipitation in China was predicted and tested from 2019 to 2021. According to the results, the method provided a more accurate prediction of the main rainband of summer precipitation in China. ML-based MME had a mean ACC of 0.3, an improvement of 0.09 over the weighted average MME of 0.21 for 2019–2021, exhibiting a significant improvement over the other methods. This shows that ML methods have great potential for improving short-term climate prediction.
Intra-Seasonal Features of Winter Extreme Cold Events in Northeast–North China and Synergistic Effects of Circulation Systems in Mid-High Latitude
Authors: Gao Qingjiu , Wang Li , Li Yan , Wang Yafei
Published: September 2022

Based on the daily minimum air temperature (Tmin) data from the China Meteorological Data Network and the NCEP/DOE reanalysis data, the intra-seasonal circulation characteristics and evolution of extreme cold events (ECEs) in Northeast–North China (NE-N) during the winter of 1979–2018 are explored, and the synergistic effects of key circulation systems in the mid-high latitude on ECEs are discussed. The results show that: (1) the winter daily Tmin in the NE-N region presents a significant low-frequency period of 10–30 d; during the cooling phases, a pair of cyclone–anticyclone in the lower troposphere moves southeastward, accompanying the intensifying Siberian High, and leads to the abnormal northerly; the developing wave trains in the middle troposphere result in enhancing and maintaining cold air; furthermore, the situation of the upper tropospheric jet weakening in the north and strengthening in the south is favorable for cold air to move southward and accumulate in the NE-N region. (2) There are two wave trains in the Eurasian at 200 hPa level. The north one moves southeastward through the Ural Mountains to the coast of East Asia, with the upstream wave activity flux dispersing to NE-N region, causing the northeast cold vortex to develop. The south one with relatively weak intensity disperses the wave flux northward, and enhances the cold vortex. (3) The key circulation systems of ECEs are the Siberian High, the Ural Mountain Blocking High, the Northeast Cold Vortex, and the East Asian Subtropical Jet. The Ural Mountains Blocking High leads four phases earlier than low temperature, and the rest of the systems are basically in phase with low temperature. The synergistic effect of circulation systems will lead to extended-range cold in the NE-N region.
A Tutorial and Review on Flight Control Co-Simulation Using Matlab/Simulink and Flight Simulators
Authors: Horri Nadjim , Pietraszko Mikolaj
Published: September 2022

Flight testing in a realistic three-dimensional virtual environment is increasingly being considered a safe and cost-effective way of evaluating aircraft models and their control systems. The paper starts by reviewing and comparing the most popular personal computer-based flight simulators that have been successfully interfaced to date with the MathWorks software. This co-simulation approach allows combining the strengths of Matlab toolboxes for functions including navigation, control, and sensor modeling with the advanced simulation and scene rendering capabilities of dedicated flight simulation software. This approach can then be used to validate aircraft models, control algorithms, flight handling chatacteristics, or perform model identification from flight data. There is, however, a lack of sufficiently detailed step-by-step flight co-simulation tutorials, and there have also been few attempts to evaluate more than one flight co-simulation approach at a time. We, therefore, demonstrate our own step-by-step co-simulation implementations using Simulink with three different flight simulators: Xplane, FlightGear, and Alphalink’s virtual flight test environment (VFTE). All three co-simulations employ a real-time user datagram protocol (UDP) for data communication, and each approach has advantages depending on the aircraft type. In the case of a Cessna-172 general aviation aircraft, a Simulink co-simulation with Xplane demonstrates successful virtual flight tests with accurate simultaneous tracking of altitude and speed reference changes while maintaining roll stability under arbitrary wind conditions that present challenges in the single propeller Cessna. For a medium endurance Rascal-110 unmanned aerial vehicle (UAV), Simulink is interfaced with FlightGear and with QGroundControl using the MAVlink protocol, which allows to accurately follow the lateral UAV path on a map, and this setup is used to evaluate the validity of Matlab-based six degrees of freedom UAV models. For a smaller ZOHD Nano Talon miniature aerial vehicle (MAV), Simulink is interfaced with the VFTE, which was specifically designed for this MAV, and with QGroundControl for the testing of advanced H-infinity observer-based autopilots using a software-in-the-loop (SIL) simulation to achieve robust low altitude flight under windy conditions. This is then finally extended to hardware-in-the-loop (HIL) implementation on the Nano Talon MAV using a controller area network (CAN) databus and a Pixhawk-4 mini autopilot with simulated sensor models.
Prediction of the Total Output Value of China’s Construction Industry Based on FGM (1,1) Model
Authors: Zhang Xiao , Wang Jingyi , Wu Liusan , Cheng Ming , Zhang Dongqing
Published: September 2022

The total output value of the construction industry (TOVCI) reflects its own development level to a certain extent. An accurate prediction of the construction industry’s total output value is beneficial to the government’s dynamic regulation. The grey prediction model is widely used for its simple calculation process and high prediction accuracy. Based on the TOVCI of China from 2017 to 2020, this paper constructs an FGM (1,1) model, calculates r by a simulated annealing algorithm, and forecasts the TOVCI of China in next few years. At present, the Particle Swarm Optimization algorithm (PSO) is employed in the calculation of r in the literature. However, the advantage of the simulated annealing algorithm is its powerful global search performance. The prediction results indicate that the TOVCI of China will continue to grow, but the growth rate will slow down. Therefore, the construction industry of China should not simply pursue the high-speed growth of the total output value, but pay more attention to high-quality development, such as technological innovation, energy conservation and environmental protection. Finally, the limitations and future research directions are elucidated.
Zinc as a Promising Anodic Material for All-Solid-State Lithium-Ion Batteries
Authors: Singh Kishore , Yao Yuchen , Ichikawa Takayuki , Jain Ankur , Singh Rini
Published: September 2022

Electrochemical energy storage is considered a remarkable way to bridge the gap between demand and supply due to intermittent renewable energy production. All-solid-state batteries are an excellent alternative and are known to be the safest class of batteries. In the present scenario to accomplish the energy demands, high-capacity and stable anodes are warranted and can play a vital role in technology upgradation. Among the variety of anodes, alloying-type anodes are superior due to their high gravimetric capacity and stability. In the present work, zinc metal was implemented as electrode material in an all-solid-state lithium-ion battery. This anode material was tested with two different solid-state electrolytes, i.e., lithium borohydride (LiBH4) and halide-stabilized LiBH4 (i.e., LiBH4.LiI). In a coin cell, Li foil was placed as a counter electrode. The establishment of a reaction mechanism during the charging and discharging was obtained through X-ray diffraction (XRD) and cyclic voltammetry (CV). Systematic studies using the temperature dependence performance were also conducted. The volumetric density with both electrolytes was found at more than 3000 mAh/cm3. The coulombic efficiency for the electrode material was also observed at ~94%. These impressive numbers present zinc electrodes as a promising material for future electrode material for all-solid-state Li-ion batteries.
Modified Sol–Gel Synthesis of Mesoporous Borate Bioactive Glasses for Potential Use in Wound Healing
Authors: Kermani Farzad , Sadidi Hossein , Ahmadabadi Ali , Hoseini Seyed Javad , Tavousi Seyed Hasan , Rezapanah Alireza , Nazarnezhad Simin , Hosseini Seyede Atefe , Mollazadeh Sahar , Kargozar Saeid
Published: September 2022

In this study, we successfully utilized nitrate precursors for the synthesis of silver (Ag)-doped borate-based mesoporous bioactive glass (MBGs) based on the 1393B3 glass formulation in the presence of a polymeric substrate (polyvinyl alcohol (PVA)) as a stabilizer of boric acid. The X-ray diffraction (XRD) analysis confirmed the glassy state of all the MBGs. The incorporation of 7.5 mol% Ag into the glass composition led to a decrease in the glass transition temperature (Tg). Improvements in the particle size, zeta potential, surface roughness, and surface area values were observed in the Ag-doped MBGs. The MBGs (1 mg/mL) had no adverse effect on the viability of fibroblasts. In addition, Ag-doped MBGs exhibited potent antibacterial activity against gram-positive and gram-negative species. In summary, a modified sol–gel method was confirmed for producing the Ag-doped 1393B3 glasses, and the primary in vitro outcomes hold promise for conducting in vivo studies for managing burns.
Classification Model for Diabetic Foot, Necrotizing Fasciitis, and Osteomyelitis
Authors: Kim Jiye , Yoo Gilsung , Lee Taesic , Kim Jeong Ho , Seo Dong Min , Kim Juwon
Published: September 2022

Diabetic foot ulcers (DFUs) and their life-threatening complications, such as necrotizing fasciitis (NF) and osteomyelitis (OM), increase the healthcare cost, morbidity and mortality in patients with diabetes mellitus. While the early recognition of these complications could improve the clinical outcome of diabetic patients, it is not straightforward to achieve in the usual clinical settings. In this study, we proposed a classification model for diabetic foot, NF and OM. To select features for the classification model, multidisciplinary teams were organized and data were collected based on a literature search and automatic platform. A dataset of 1581 patients (728 diabetic foot, 76 NF, and 777 OM) was divided into training and validation datasets at a ratio of 7:3 to be analyzed. The final prediction models based on training dataset exhibited areas under the receiver operating curve (AUC) of the 0.80 and 0.73 for NF model and OM model, respectively, in validation sets. In conclusion, our classification models for NF and OM showed remarkable discriminatory power and easy applicability in patients with DFU.
Survival and Interplay of γ-Aminobutyric Acid-Producing Psychobiotic Candidates with the Gut Microbiota in a Continuous Model of the Human Colon
Authors: Mousavi Rojaalsadat , Mottawea Walid , Audet Marie-Claude , Hammami Riadh
Published: September 2022

Over decades, probiotic research has focused on their benefits to gut health. Recently, the gut microbiota has been proven to share bidirectional connections with the brain through the gut–brain axis. Therefore, the manipulation of this axis via probiotics has garnered interest. We have recently isolated and characterized in vitro probiotic candidates producing γ-aminobutyric acid (GABA), a major neuromodulator of the enteric nervous system. This study investigates the growth and competitiveness of selected GABA-producing probiotic candidates (Bifidobacterium animalis, Streptococcus thermophilus, and Lactobacillus delbrueckii subsp. bulgaricus) in the presence of human gut microbiota ex vivo in a model mimicking physiological and microbiological conditions of the human proximal colon. Supplementation with GABA-producing probiotic candidates did not affect the overall gut microbiota diversity over 48 h of treatment. However, these candidates modulated the microbiota composition, especially by increasing the Bacteroidetes population, a key gut microbe associated with anti-inflammatory activities. The level of microbiota-generated SCFAs within 12 h of treatment was also increased, compared to the control group. Results from this study demonstrate the probiotic potential of the tested GABA-producing bacteria and their impact on gut microbiota structure and metabolism, suggesting their suitability for gut health-promoting applications.
Transcriptional Dynamics Induced by Diapause Hormone in the Silkworm, Bombyx mori
Authors: Chen Lijuan , Zhang Zhongjie , Chen Kai , Yu Ye , Hu Bo , Song Hongsheng , Liu Xiaojing
Published: September 2022

Diapause is a form of dormancy that organisms use to adapt to extreme environments by exhibiting developmental arrest. In the silkworm, Bombyx mori, diapause is thought to be elicited by diapause hormone (DH) signaling, which consists of interactions between DH and the DH receptor (DHR). However, the steps downstream of the DH signaling pathway are largely unknown. In the present study, we directly injected synthesized DH into the female pupae of a multivoltine, non-diapausing strain at 36 h after pupation. We found that the mRNA level of DHR declined at 4 h and recovered at 12 h after the injection of DH. Thus, we sequenced the transcriptome of the ovaries at 4 h and 12 h after the injection of DH. We identified 60 and 221 differentially expressed genes at 4 h and 12 h after the injection, respectively. All DEGs were identified, relating to 20E-related genes, JH-related genes, cellular detoxification, ribosomal proteins, lipid metabolism, and epigenetic modifications. Eleven genes were selected from the above categories to verify the transcriptome data. The qRT-PCR and RNA-Seq expression patterns of the genes were consistent, which indicated the authenticity and reliability of the transcriptome data. This study dramatically expands upon our knowledge of gene expression variation at the early phase of DH release.
Whole-Genome Sequencing and Drug-Susceptibility Analysis of Serial Mycobacterium abscessus Isolates from Thai Patients
Authors: Kaewprasert Orawee , Nonghanphithak Ditthawat , Chetchotisakd Ploenchan , Namwat Wises , Ong Rick Twee-Hee , Faksri Kiatichai
Published: September 2022

Mycobacterium abscessus is an important pathogen that can cause serious human diseases and is difficult to treat due to antibiotic resistance. In this study, we analyzed, using whole-genome sequence (WGS) data, M. abscessus strains serially isolated from patients at various time intervals. We undertook genetic diversity analysis between subspecies, mutation-rate estimation and identification of drug-resistant mutations with minimum inhibitory concentration (MIC) analysis. Clonal isolates of M. abscessus:—subsp. abscessus (MAB) and subsp. massiliense (MMAS)—causing persistent infection through time, differed by 0–7 and 0–14 SNPs, respectively, despite being isolated 1 to 659 days apart. Two cases caused by MMAS differed by ≥102 SNPs at 350 days apart and were regarded as examples of reinfection. Isolates collected ≤7 days apart exhibited a high mutation rate (133.83 ± 0.00 SNPs/genome (5 Mb)/year for MMAS and 127.75 SNPs/genome (5 Mb)/year for MAB). Mutation rates declined in a time-dependent manner in both subspecies. Based on isolates collected > 180 days apart, MMAS had a significantly higher average mutation rate than MAB (2.89 ± 1.02 versus 0.82 ± 0.83 SNPs/genome (5 Mb)/year, (p = 0.01), respectively). All well-known drug-resistance mutations were found to be strongly associated with high MIC levels for clarithromycin and ciprofloxacin. No known mutations were identified for strains resistant to linezolid and amikacin. MAB strains in the study were susceptible to amikacin, while most MMAS strains were susceptible to clarithromycin, amikacin and linezolid. No hetero-resistance was found in the strains analyzed. Our study reports the genetic diversity and mutation rate of M. abscessus between the two major subspecies and confirms the drug resistance-associated mutations. Information about drug-resistance and associated mutations can be applied in diagnosis and patient management.
PD-L1-Mediated Immunosuppression in Hepatocellular Carcinoma: Relationship with Macrophages Infiltration and Inflammatory Response Activity
Authors: Guo Shuang , Wang Xinyue , Zhou Hanxiao , Gao Yue , Wang Peng , Zhi Hui , Sun Yue , Zhang Yakun , Gan Jing , Xiao Yun , Ning Shangwei
Published: September 2022

Immune dysfunction and pro-oncogenic inflammation play critical roles in malignant progression and non-response to immunotherapy for hepatocellular carcinoma (HCC). In particular, PD-1/PD-L1 blockade therapy could induce durable tumor remissions and improve the prognosis of patients to a certain extent. However, PD-L1, as a promising biomarker, has limited knowledge about its relevance to tumor microenvironment (TME) characterization and endogenous inflammatory immune responses. In this study, we systematically investigated and characterized the important intercommunication of PD-L1 with immunosuppressive TME and inflammatory response activity in HCC and predicted promising therapeutic drugs to improve the current therapeutic strategy for specific patients. We identified aberrant expression patterns of PD-L1 in HCC and completely different clinical and molecular characteristics among the PD-L1 subgroups. PD-L1 positively associated with immunosuppressive macrophages and macrophage-derived cytokines, which may contribute to the polarization of macrophages. Moreover, inflammatory response activity exhibited significant differences between high and low PD-L1 expression groups and had robust positive correlativity of the infiltration level of tumor-associated macrophages. Notably, given the immunosuppressive and inflammatory microenvironment in HCC, we screened four candidate drugs, including dasatinib, vemurafenib, topotecan and AZD6482, and corroborated in two pharmacogenomics databases, which might have potential therapeutic implications in specific HCC patients. Our results enhanced the understanding of linkage in PD-L1 expression patterns with macrophages and inflammation, which may provide new insight into the pathogenic mechanisms and potential therapeutic strategy for HCC.
Identification of a Multi-Messenger RNA Signature as Type 2 Diabetes Mellitus Candidate Genes Involved in Crosstalk between Inflammation and Insulin Resistance
Authors: Ali Hebatalla Said , Boshra Mariam Sameh , Agwa Sara H. A. , Hakeem Mohamed S. Abdel , Meteini Mahmoud Shawky El , Matboli Marwa
Published: September 2022

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease associated with inflammation widening the scope of immune-metabolism, linking the inflammation to insulin resistance and beta cell dysfunction. New potential and prognostic biomarkers are urgently required to identify individuals at high risk of β-cell dysfunction and pre-DM. The DNA-sensing stimulator of interferon genes (STING) is an important component of innate immune signaling that governs inflammation-mediated T2DM. NOD-like receptor (NLR) reduces STING-dependent innate immune activation in response to cyclic di-GMP and DNA viruses by impeding STING-TBK1 interaction. We proposed exploring novel blood-based mRNA signatures that are selective for components related to inflammatory, immune, and metabolic stress which may reveal the landscape of T2DM progression for diagnosing or treating patients in the pre-DM state. In this study, we used microarray data set to identify a group of differentially expressed mRNAs related to the cGAS/STING, NODlike receptor pathways (NLR) and T2DM. Then, we comparatively analyzed six mRNAs expression levels in healthy individuals, prediabetes (pre-DM) and T2DM patients by real-time PCR. The expressions of ZBP1, DDX58, NFKB1 and CHUK were significantly higher in the pre-DM group compared to either healthy control or T2DM patients. The expression of ZBP1 and NFKB1 mRNA could discriminate between good versus poor glycemic control groups. HSPA1B mRNA showed a significant difference in its expression regarding the insulin resistance. Linear regression analysis revealed that LDLc, HSPA1B and NFKB1 were significant variables for the prediction of pre-DM from the healthy control. Our study shed light on a new finding that addresses the role of ZBP1 and HSPA1B in the early prediction and progression of T2DM.
Sex-Related Differences in Voluntary Alcohol Intake and mRNA Coding for Synucleins in the Brain of Adult Rats Prenatally Exposed to Alcohol
Authors: Kokhan Viktor S. , Chaprov Kirill , Ninkina Natalia N. , Anokhin Petr K. , Pakhlova Ekaterina P. , Sarycheva Natalia Y. , Shamakina Inna Y.
Published: September 2022

Maternal alcohol consumption is one of the strong predictive factors of alcohol use and consequent abuse; however, investigations of sex differences in response to prenatal alcohol exposure (PAE) are limited. Here we compared the effects of PAE throughout gestation on alcohol preference, state anxiety and mRNA expression of presynaptic proteins α-, β- and γ-synucleins in the brain of adult (PND60) male and female Wistar rats. Total RNA was isolated from the hippocampus, midbrain and hypothalamus and mRNA levels were assessed with quantitative RT-PCR. Compared with naïve males, naïve female rats consumed more alcohol in “free choice” paradigm (10% ethanol vs. water). At the same time, PAE produced significant increase in alcohol consumption and preference in males but not in females compared to male and female naïve groups, correspondingly. We found significantly lower α-synuclein mRNA levels in the hippocampus and midbrain of females compared to males and significant decrease in α-synuclein mRNA in these brain areas in PAE males, but not in females compared to the same sex controls. These findings indicate that the impact of PAE on transcriptional regulation of synucleins may be sex-dependent, and in males’ disruption in α-synuclein mRNA expression may contribute to increased vulnerability to alcohol-associated behavior.
Liver X Receptor Regulation of Glial Cell Functions in the CNS
Authors: Song Xiaoyu , Wu Wanfu , Warner Margaret , Gustafsson Jan-Åke
Published: September 2022

In this review, we discuss the role of liver X receptors (LXRs) in glial cells (microglia, oligodendrocytes and astrocytes) in the central nervous system (CNS). LXRs are oxysterol-activated nuclear receptors that, in adults, regulate genes involved in cholesterol homeostasis, the modulation of inflammatory responses and glutamate homeostasis. The study of LXR knockout mice has revealed that LXRβ plays a key role in maintaining the health of dopaminergic neurons in the substantia nigra, large motor neurons in the spinal cord and retinal ganglion cells in the eye. In the peripheral nervous system (PNS), LXRβ is responsible for the health of the spiral ganglion neurons (SGNs) in the cochlea. In addition, LXRs are essential for the homeostasis of the cerebrospinal fluid (CSF), and in LXRαβ−/− mice, the lateral ventricles are empty and lined with lipid-laden cells. As LXRαβ−/− mice age, lipid vacuoles accumulate in astrocytes surrounding blood vessels. By seven months of age, motor coordination becomes impaired, and there is a loss of motor neurons in the spinal cord of LXRβ−/− mice. During development, migration of neurons in the cortex and cerebellum is retarded in LXRβ−/− mice. Since LXRs are not expressed in dopaminergic or motor neurons in adult mice, the neuroprotective effects of LXRs appear to come from LXRs in glial cells where they are expressed. However, despite the numerous neurological deficits in LXR−/− rodents, multiple sclerosis has the clear distinction of being the only human neurodegenerative disease in which defective LXR signaling has been identified. In this review, we summarize the regulation and functions of LXRs in glial cells and analyze how targeting LXRs in glial cells might, in the future, be used to treat neurodegenerative diseases and, perhaps, disorders caused by aberrant neuronal migration during development.
The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis
Authors: Lin Shiuan-Chen , Ma Chun , Chang Kao-Jung , Cheong Han-Ping , Lee Ming-Cheng , Lan Yuan-Tzu , Wang Chien-Ying , Chiou Shih-Hwa , Huo Teh-Ia , Hsu Tsui-Kang , Tsai Ping-Hsing , Yang Yi-Ping
Published: September 2022

The with-no-lysine (WNK) kinase family, comprising four serine-threonine protein kinases (WNK1-4), were first linked to hypertension due to their mutations in association with pseudohypoaldosteronism type II (PHAII). WNK kinases regulate crucial blood pressure regulators, SPAK/OSR1, to mediate the post-translational modifications (PTMs) of their downstream ion channel substrates, such as sodium chloride co-transporter (NCC), epithelial sodium chloride (ENaC), renal outer medullary potassium channel (ROMK), and Na/K/2Cl co-transporters (NKCCs). In this review, we summarize the molecular pathways dysregulating the WNKs and their downstream target renal ion transporters. We summarize each of the genetic variants of WNK kinases and the small molecule inhibitors that have been discovered to regulate blood pressure via WNK-triggered PTM cascades.
Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma
Authors: Tompa Marton , Kraboth Zoltan , Galik Bence , Kajtar Bela , Gyenesei Attila , Kalman Bernadette
Published: September 2022

Background: Immune evasion in glioblastoma (GBM) shields cancer cells from cytotoxic immune response. Methods: We investigated CpG methylation in promoters, genes, and pathways in 22 pairs of formalin-fixed paraffin-embedded sequential (FFPE) GBM using restricted resolution bisulfite sequencing (RRBS) and bioinformatic analyses. Results: Gene ontology revealed hypermethylation in elements of the innate and adaptive immune system when recurrent GBM samples (GBMrec) were compared to control (CG) and primary GBM samples (GBMprim). Higher methylation levels of the IL-7 signaling pathway and response to IL-7 were found in GBMrec suggesting a progressive blockade of the IL-7 driven T cell response in sequential GBM. Analyses of the Cancer Genome Atlas array-based data confirmed hypermethylation of the IL-7 pathway in recurrent compared with primary GBM. We also quantified DNA CpG methylation in promoter and gene regions of the IL-7 ligand and IL-7 α-receptor subunit in individual samples of a large RRBS-based sequential cohort of GBM in a Viennese database and found significantly higher methylation levels in the IL-7 receptor α-subunit in GBMrec compared with GBMprim. Conclusions: This study revealed the progressive suppression of the IL-7 receptor-mediated pathway as a means of immune evasion by GBM and thereby highlighted it as a new treatment target.
Glycemic Variability in Type 1 Diabetes Mellitus Pregnancies—Novel Parameters in Predicting Large-for-Gestational-Age Neonates: A Prospective Cohort Study
Authors: Leksic Gloria , Baretić Maja , Gudelj Lara , Radic Marija , Milicic Iva , Ivanišević Marina , Jurisic-Erzen Dubravka
Published: September 2022

Pregnancies with type 1 diabetes mellitus (T1DM) have a high incidence of large-for-gestational-age neonates (LGA) despite optimal glycemic control. In recent years, glycemic variability (GV) has emerged as a possible risk factor for LGA, but the results of the conducted studies are unclear. This study analyzed the association between GV and LGA development in pregnancies with T1DM. This was a prospective cohort study of patients with T1DM who used continuous glucose monitoring (CGM) during pregnancy. Patients were followed from the first trimester to birth. GV parameters were calculated for every trimester using the EasyGV calculator. The main outcomes were LGA or no-LGA. Logistic regression analysis was used to assess the association between GV parameters and LGA. In total, 66 patients were included. The incidence of LGA was 36%. The analysis extracted several GV parameters that were significantly associated with the risk of LGA. The J-index was the only significant parameter in every trimester of pregnancy (odds ratios with confidence intervals were 1.33 (1.02, 1.73), 3.18 (1.12, 9.07), and 1.37 (1.03, 1.82), respectively. Increased GV is a risk factor for development of LGA. The J-index is a possible novel GV parameter that may be assessed in all three trimesters of pregnancy together with glycated hemoglobin and time-in-range.
Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma
Authors: Vatrella Alessandro , Maglio Angelantonio , Pelaia Corrado , Ciampo Luigi , Pelaia Giulia , Vitale Carolina
Published: September 2022

Severe asthma is characterized by different endotypes driven by complex pathologic mechanisms. In most patients with both allergic and non-allergic asthma, predominant eosinophilic airway inflammation is present. Given the central role of eosinophilic inflammation in the pathophysiology of most cases of severe asthma and considering that severe eosinophilic asthmatic patients respond partially or poorly to corticosteroids, in recent years, research has focused on the development of targeted anti-eosinophil biological therapies; this review will focus on the unique and particular biology of the eosinophil, as well as on the current knowledge about the pathobiology of eosinophilic inflammation in asthmatic airways. Finally, current and prospective anti-eosinophil therapeutic strategies will be discussed, examining the reason why eosinophilic inflammation represents an appealing target for the pharmacological treatment of patients with severe asthma.
Network Pharmacology and Molecular Docking Reveal the Mechanism of Tanshinone IIA against Pulmonary Hypertension
Authors: Zhang Kaijian , Sun Haozhong , Hu Kang , Shi Zhan , Zhang Buchun
Published: September 2022

Background: Pulmonary hypertension (PH) is a complex disease caused by a wide range of underlying conditions, Tanshinone IIA (Tan IIA) has been widely used in PH patients. The study aimed to explore the possible molecular mechanism of Tan IIA against PH by network pharmacology and molecular docking. Methods: Tan IIA and PH-related targets were retrieved from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) network were used to investigate the protein targets and mechanism. The binding activity of core targets and Tan IIA were verified by molecular docking. Results: A total of 26 overlapping target proteins between Tan IIA and PH were screened. PPI network identified HSP90AA1, PTPN11, ATM, CA2, TERT, PRKDC, and APEX1 as key pharmacological targets. The results of GO function enrichment analysis included regulation of smooth muscle cell proliferation and migration, regulation of mitotic cell cycle, and regulation of G1/S transition of mitotic cell cycle. KEGG pathway analysis showed that nitrogen metabolism, NF-kappa B signaling pathway, cell cycle, necroptosis, apoptosis, and JAK-STAT signaling pathway were associated with Tan IIA in PH. The molecular docking results showed that Tan IIA can closely bind three core targets (HSP90AA1, PTPN11, and CA2). Conclusions: The present work initially clarified the effective therapeutic targets, biological processes, and signaling pathways of Tan IIA treatment of PH, which lay a foundation for further research on the pharmacological effects of Tan IIA.
Rational Construction of a Mitochondria-Targeted Reversible Fluorescent Probe with Intramolecular FRET for Ratiometric Monitoring Sulfur Dioxide and Formaldehyde
Authors: Lyu Jinxiao , Wang Chunfei , Zhang Xuanjun
Published: September 2022

Sulfur dioxide (SO2) and formaldehyde (FA) are important species that maintain redox homeostasis in life and are closely related to many physiological and pathological processes. Therefore, it is of great significance to realize the reversible monitoring of them at the intracellular level. Here, we synthesized a reversible ratiometric fluorescent probe through a reasonable design, which can sensitively monitor SO2 derivatives and FA, and the detection limit can reach 0.16 μM. The probe can specifically target mitochondria and successfully monitor the fluctuations of SO2 and FA in living cells. It also works well in the detection of SO2 and FA in zebrafish. This high-performance probe is expected to find broad in vitro and in vivo applications.
Type I Photosensitizers Based on Aggregation-Induced Emission: A Rising Star in Photodynamic Therapy
Authors: Li Danxia , Liu Peiying , Tan Yonghong , Zhang Zhijun , Kang Miaomiao , Wang Dong , Tang Ben Zhong
Published: September 2022

Photodynamic therapy (PDT), emerging as a minimally invasive therapeutic modality with precise controllability and high spatiotemporal accuracy, has earned significant advancements in the field of cancer and other non-cancerous diseases treatment. Thereinto, type I PDT represents an irreplaceable and meritorious part in contributing to these delightful achievements since its distinctive hypoxia tolerance can perfectly compensate for the high oxygen-dependent type II PDT, particularly in hypoxic tissues. Regarding the diverse type I photosensitizers (PSs) that light up type I PDT, aggregation-induced emission (AIE)-active type I PSs are currently arousing great research interest owing to their distinguished AIE and aggregation-induced generation of reactive oxygen species (AIE-ROS) features. In this review, we offer a comprehensive overview of the cutting-edge advances of novel AIE-active type I PSs by delineating the photophysical and photochemical mechanisms of the type I pathway, summarizing the current molecular design strategies for promoting the type I process, and showcasing current bioapplications, in succession. Notably, the strategies to construct highly efficient type I AIE PSs were elucidated in detail from the two aspects of introducing high electron affinity groups, and enhancing intramolecular charge transfer (ICT) intensity. Lastly, we present a brief conclusion, and a discussion on the current limitations and proposed opportunities.
Gold Nanoparticle-Based Enzyme-Assisted Cyclic Amplification for the Highly-Sensitive Detection of miRNA-21
Authors: Qing Yang , Yang Yuxing , Ouyang Ping , Fang Chenxin , Fang Haobin , Liao Yazhen , Li Haiyu , Wang Zhencui , Du Jie
Published: September 2022

Because microRNAs (miRNAs) are biological indicators for the diagnosis, treatment, and monitoring of tumors, cancers, and other diseases, it is significant to develop a rapid, sensitive, and reliable miRNA detection platform. In this study, based on miRNA-21 detection, DNA-a with a 3′ end overhang and Texas Red fluorophore-labeled 5′ end was designed, which reacts with miRNA-21 and hybridizes with exonuclease III (Exo III), where the part connected to miRNA-21 is hydrolyzed, leaving a-DNA. At the same time, miRNA-21 is released to participate in the following reaction, to achieve cyclic amplification. a-DNA reacts with DNA-b conjugated to gold nanoparticles to achieve fluorescence quenching, with the quenching value denoted as F; additionally, after adding DNA-d and linked streptavidin immunomagnetic beads (SIBs), fluorescence recovery was achieved using DNA-c, with the recovered fluorescence recorded as F0. By comparing the difference in the fluorescence (F0 − F) between the two experiments, the amount of DNA-a hydrolyzed to produce a-DNA was established to determine the target miRNA-21 content. Under optimized conditions, by comparing the changes in the fluorescence signal, the developed strategy shows good sensitivity and repeatability, with a detection limit of 18 pM, good discriminative ability and selectivity, and promise for the early diagnosis of breast and intestinal cancers.