bluuebunny/crossref_metadata_2025 huggingface dataset:
Security Analysis and Enhancement of INTERBUS Protocol in ICS Based on Colored Petri Net
Authors: Feng Tao , Liu Chengfan , Gong Xiang , Lu Ye
Published: October 2023

The integration of buses in industrial control systems, fueled by advancements such as the Internet of Things (IoT), has led to their widespread adoption, significantly enhancing operational efficiency. However, with the increasing interconnection of systems, ensuring the security of bus communications and protocols has become an urgent priority. This paper focuses on addressing the specific security concerns associated with the widely adopted INTERBUS protocol—a fieldbus protocol. Our approach leverages the theory of colored Petri nets (CPN) for modeling, enabling a comprehensive analysis of the protocol’s security. Rigorous formal verification and analysis of the security protocol are conducted by employing the Dolev–Yao adversary model. Our investigation reveals the presence of three critical vulnerabilities: replay attacks, tampering, and impersonation. To fortify the security of the protocol, we propose the introduction of a key distribution center and the utilization of hash values. Through meticulous analysis and verification, our proposed enhancements effectively reinforce the security performance of the INTERBUS protocol.
Incorporation of Antimony Ions in Heptaisobutyl Polyhedral Oligomeric Silsesquioxanes
Authors: Marchesi Stefano , Bisio Chiara , Carniato Fabio , Boccaleri Enrico
Published: October 2023

The direct incorporation of Sb(V) ions into a polycondensed silsesquioxane network based on heptaisobutyl POSS units (Sb(V)-POSSs) through a corner-capping reaction is reported for the first time in this work. As a reference sample, a completely condensed monomeric Sb(III)-POSS was prepared using a similar synthetic protocol. The chemical properties of both Sb-containing POSSs were investigated with different analytical and spectroscopic techniques. The analyses confirm the success of the corner-capping reaction for both samples and indicate that an Sb(V)-POSS sample is characterized by a heterogenous multimeric arrangement with an irregular organization of POSS cages linked to Sb(V) centers, and has a more complex structure with respect to the well-defined monomeric Sb(III)-POSS.
Investigating Monophyly of Typhlocybini Based on Complete Mitochondrial Genomes with Characterization and Comparative Analysis of 19 Species (Hemiptera: Cicadellidae: Typhlocybinae)
Authors: Zhou Xian , Lei Yuejie , Dietrich Christopher H. , Huang Min
Published: October 2023

Tribes of the leafhopper subfamily Typhlocybinae have traditionally been defined based on differences in forewing and hindwing venation. Except for Typhlocybini (sensu lato), the classification of tribes is relatively stable. The monophyly of Typhlocybini needs to be examined, and the relationships among genera within Typhlocybini have not been resolved. Few mitogenome sequences representative of major lineages of Typhlocybini have been available to facilitate a comprehensive phylogenetic analysis of the tribe. In this study, the complete mitogenomes of 19 species of Typhlocybini were sequenced. The gene arrangements of the 19 new mitogenomes are consistent with ancestral insect mitogenomes. Phylogenetic analyses by both maximum-likelihood and Bayesian methods of 67 species of Typhlocybinae suggest that Zyginellini is paraphyletic with respect to Typhlocybini. The phylogenetic relationships within Typhlocybini are discussed, and the major results show that the Farynala and Linnavuoriana complexes previously recognized based on morphological characters correspond to monophyletic lineages.
Habitat Temperatures of the Red Firebug, Pyrrhocoris apterus: The Value of Small-Scale Climate Data Measurement
Authors: Käfer Helmut , Kovac Helmut , Stabentheiner Anton
Published: October 2023

Ambient temperature is a main parameter that determines the thriving and propagation of ectothermic insects. It affects egg and larval development as well as adults’ survival and successful overwintering. Pyrrhocoris apterus is a herbivorous bug species almost ubiquitous in Eurasia. Its distribution extends from the Atlantic Coast to Siberia, Northwest China and Mongolia. After introduction, it established successfully in the USA, Central America, India and Australia, which indicates a high invasive potential of this species. We determined the climatic conditions in Central Europe in a habitat where P. apterus has been continuously observed for decades. We conducted temperature measurements in the habitat and in the microhabitats where individuals could be found during the year and set them against freely available climate data commonly used to characterize habitat climate. Our temperature measurements were also compared to thermal limits (critical thermal minima and maxima). Although ambient temperatures outside the thermal boundaries of P. apterus can and do occur in the habitat, the bugs thrive and propagate. Microhabitat measurement in winter showed that individuals sought areas with favorable temperatures for hibernation. In particular, these areas are not (always) represented in large-scale climate tables, leading to possible misinterpretation of future patterns of spread of invasive species spread.
Model Problems on Oscillations of Mechanical and Biological Membranes
Authors: Kostikov Yury , Romanenkov Aleksandr
Published: October 2023

Various models of membrane oscillations emerging in the theory of elasticity of mechanical systems, biomechanics of the internal ear of vertebrata, and in the theory of electrical circuits are discussed in the article. The considered oscillations have different natures, but their mathematical models are described using similar initial boundary value problems for the second-order hyperbolic equation with the nontrivial boundary condition. The differential equations in these problems are the same. Thus, for example, the model of voltage distribution in the telegraph line emerges for the one-dimensional equation of oscillations. The model of oscillations of a circular homogeneous solid membrane, a membrane with a hole, and the model of gas oscillations in a sphere and spherical region emerge for the two-dimensional and three-dimensional operators, but take into account the radial symmetry of oscillations. The model problem on membrane oscillation can be considered as the problem on ear drum membrane oscillations. The unified approach to reducing the corresponding problems to the initial boundary value problem with zero boundary conditions is suggested. The technique of formulating the solution in the form of a Fourier series using eigenfunctions of the corresponding Sturm–Liouville problem is described.
Role of ECLS in Managing Post-Myocardial Infarction Ventricular Septal Rupture
Authors: Sandoval Boburg Rodrigo , Kondov Stoyan , Karamitev Mladen , Schlensak Christian , Berger Rafal , Haeberle Helene , Jost Walter , Fagu Albi , Beyersdorf Friedhelm , Kreibich Maximilian , Czerny Martin , Siepe Matthias
Published: October 2023

Objectives: The aim of this study was to analyze outcomes in patients undergoing surgery for ventricular septal rupture (VSR) after myocardial infarction (MI) and the preoperative use of extracorporeal life support (ECLS) as a bridge to surgery. Methods: We included patients undergoing surgery for VSR from January 2009 until June 2021 from two centers in Germany. Patients were separated into two groups, those with and without ECLS, before surgery. Pre- and intraoperative data, outcome, and survival during follow-up were evaluated. Results: A total of 47 consecutive patients were included. Twenty-five patients were in the ECLS group, and 22 were in the group without ECLS. All the ECLS-group patients were in cardiogenic shock preoperatively. Most patients in the ECLS group were transferred from another hospital [n = 21 (84%) vs. no-ECLS (n = 12 (57.1%), p = 0.05]. We observed a higher number of postoperative bleeding complications favoring the group without ECLS [n = 6 (28.6%) vs. n = 16 (64%), p < 0.05]. There was no significant difference in the persistence of residual ventricular septal defect (VSD) between groups [ECLS n = 4 (16.7%) and no-ECLS n = 3 (13.6%)], p = 1.0. Total in-hospital mortality was 38.3%. There was no significant difference in in-hospital mortality [n = 6 (27.3%) vs. n = 12 (48%), p = 0.11] and survival at last follow-up between the groups (p = 0.50). Conclusion: We detected no statistical difference in the in-hospital and long-term mortality in patients who received ECLS as supportive therapy after MI-induced VSR compared to those without ECLS. ECLS could be an effective procedure applied as a bridge to surgery in patients with VSR and cardiogenic shock.
Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management
Authors: Douglas Abby P. , Stewart Adam G. , Halliday Catriona L. , Chen Sharon C.-A.
Published: October 2023

Nosocomial clusters of fungal infections, whilst uncommon, cannot be predicted and are associated with significant morbidity and mortality. Here, we review reports of nosocomial outbreaks of invasive fungal disease to glean insight into their epidemiology, risks for infection, methods employed in outbreak detection including genomic testing to confirm the outbreak, and approaches to clinical and infection control management. Both yeasts and filamentous fungi cause outbreaks, with each having general and specific risks. The early detection and confirmation of the outbreak are essential for diagnosis, treatment of affected patients, and termination of the outbreak. Environmental sampling, including the air in mould outbreaks, for the pathogen may be indicated. The genetic analysis of epidemiologically linked isolates is strongly recommended through a sufficiently discriminatory approach such as whole genome sequencing or a method that is acceptably discriminatory for that pathogen. An analysis of both linked isolates and epidemiologically unrelated strains is required to enable genetic similarity comparisons. The management of the outbreak encompasses input from a multi-disciplinary team with epidemiological investigation and infection control measures, including screening for additional cases, patient cohorting, and strict hygiene and cleaning procedures. Automated methods for fungal infection surveillance would greatly aid earlier outbreak detection and should be a focus of research.
FvbHLH1 Regulates the Accumulation of Phenolic Compounds in the Yellow Cap of Flammulina velutipes
Authors: Zeng Jiangyi , Shi Dingding , Chen Ying , Bao Xuemei , Zong Yuan
Published: October 2023

Flammulina velutipes is a renowned edible and medicinal fungus. Commercially cultivated F. velutipes occurs in two distinct phenotypes: white and yellow. However, the underlying mechanism contributing to the yellow phenotype and high nutritional value remain uncertain. We reconfirmed that the browning process in F. velutipes is attributable to melanin accumulation, although the initial yellow cap seemed unrelated to melanin. A transcriptomic and metabolomic joint analysis revealed that 477 chemical compounds categorized into 11 classes, among which 191 exhibited significantly different levels of accumulation between different phenotypes. Specifically, 12 compounds were unique to the yellow F. velutipes, including ferulic acid, and 3-Aminosalicylic acid. Free fatty acids and xanthine were identified as the primary compounds correlating with the yellow and oily cap. A total of 44,087 genes were identified, which were more homologous to Pleurotus ostreatus PC15. Structural genes such as PAL (phenylalanine ammonialyase), C4H (cinnamate 4-hydroxylase), C3H (Coumarin-3-hydroxylase), AoMT (caffeoyl coenzyme A-O-methyltransferase), and 4CL (4-coumarate: CoA ligase) were up-regulated, thereby activating the lignin biosynthesis and metabolism pathway. Additionally, FvbHLH1 can lead to the consumption of a huge amount of phenylalanine while generating flavonoids and organic acid compounds. Meanwhile, ferulic acid biosynthesis was activated. Therefore, this study clarifies the chemical and molecular bases for the yellow phenotype and nutritional value of F. velutipes.
The PATIENT Approach: A New Bundle for the Management of Chronic Pain
Authors: Buonanno Pasquale , Marra Annachiara , Iacovazzo Carmine , Vargas Maria , Nappi Serena , Squillacioti Francesco , de Siena Andrea Uriel , Servillo Giuseppe
Published: October 2023

Background: Chronic pain is one of the most challenging diseases for physicians as its etiology and manifestations can be extremely varied. Many guidelines have been published and many therapeutic options are nowadays available for the different types of pain. Given the enormous amount of information that healthcare providers must handle, it is not always simple to keep in mind all the phases and strategies to manage pain. We here present the acronym PATIENT (P: patient’s perception; A: assessment; T: tailored approach; I: iterative evaluation; E: education; N: non-pharmacological approach; T: team), a bundle which can help to summarize all the steps to follow in the management of chronic pain. Methods: We performed a PubMed search with a list of terms specific for every issue of the bundle; only English articles were considered. Results: We analyzed the literature investigating these topics to provide an overview of the available data on each bundle’s issue; their synthesis lead to an algorithm which may allow healthcare providers to undertake every step of a patient’s evaluation and management. Discussion: Pain management is very complex; our PATIENT bundle could be a guide to clinicians to optimize a patient’s evaluation and treatment.
The Effect of Comorbidities and Complications on COVID-19 Mortality: A Detailed Retrospective Study in Western Romania
Authors: Marc Monica Steluta , Rosca Daniela , Bratosin Felix , Fira-Mladinescu Ovidiu , Oancea Cristian , Pescaru Camelia Corina , Velescu Diana , Wellmann Norbert , Motofelea Alexandru Catalin , Ciuca Ioana Mihaiela , Saracin Karina , Manolescu Diana
Published: October 2023

COVID-19 continues to impact global health systems even after being declared over, with some patients exhibiting severe complications linked to pre-existing conditions. This study aimed to investigate the association between comorbidities, complications, and survival outcomes among COVID-19 survivors in Western Romania. Our hypothesis posited that comorbidities and complications significantly influence survival rates. We conducted a retrospective analysis of 1948 COVID-19 survivors admitted from January to December 2021, with 192 selected for detailed analysis based on inclusion and exclusion criteria. The severity of COVID-19 was classified according to WHO guidelines, and conditions like hypertension and obesity were defined using criteria from the European Society of Hypertension (ESH), the European Society of Cardiology (ESC), and WHO, respectively. Among the 192 patients, 33 had mild, 62 had moderate, and 97 had severe COVID-19. The median age across the severity groups was 63.2 years. Patients undergoing tracheostomy had a mortality rate of 83.3% versus 22.2% for non-tracheostomy patients (p < 0.001) and presented with significantly higher lung injury, hospitalization duration, and complications. Remarkably, tracheostomized patients were 17.50 times more likely to succumb to the disease (95% CI 4.39–116.91, p < 0.001). Furthermore, pneumothorax increased the mortality risk significantly (OR 22.11, 95% CI 5.72–146.03, p < 0.001). Intriguingly, certain conditions like grade I hypertension and grade II obesity showed a protective effect against mortality, whereas type 2 diabetes mellitus increased mortality risk (univariate OR 2.89, p = 0.001). The presence of certain comorbidities and complications significantly impacts the survival rates of COVID-19 patients in Western Romania. Notably, tracheostomy, pneumothorax, and T2DM were associated with increased mortality. This study underscores the importance of personalized patient care and provides insights for healthcare policymakers in Western Romania to improve clinical management strategies.
The Association of Endothelin-1 with Early and Long-Term Mortality in COVID-19
Authors: Turgunova Lyudmila , Mekhantseva Irina , Laryushina Yelena , Alina Assel , Bacheva Irina , Zhumadilova Zhibek , Turmukhambetova Anar
Published: October 2023

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.
Clinical Trials and Therapeutic Approaches for Healthcare Challenges in Pakistan
Authors: Ahmed Aamir , Williams Norman R.
Published: October 2023

Pakistan faces tremendous challenges in providing healthcare due to a lack of consistent policymaking, increasing expenditure and exponential growth in population since its inception in 1947. These challenges are not just driven by politics, policy and allocation of resources but also by healthcare, environment and characteristics of the population biology. Clinical trials provide the best way to find population-specific, cost-effective treatments that do not merely mimic those used in wealthier nations. This article analyzes all clinical studies conducted with at least one site in Pakistan listed on ClinicalTrials.gov, combined with a short overview that considers new therapeutic approaches that can be investigated in future clinical trials. Therapies using repurposed medicines are of particular interest as they use affordable drugs that are already widely available.
Production of Acoustic Correlates of Stress by L2 Spanish-Speaking Immigrants to Spain
Authors: Face Timothy L.
Published: October 2023

Little work has examined the L2 acquisition of Spanish stress, and especially the production of its acoustic correlates, and the work that has is largely limited to inexperienced learners. This study examines the production of stress by L1 English/L2 Spanish speakers who are highly experienced with their L2, having lived much of their adult lives as immigrants in Spain. Data were collected from the reading of a short story, an extended reading with a plot was provided so that participants would not be focused on their pronunciation, thus producing speech closer to spontaneous speech while still allowing for control over what they produced. Intensity, duration, pitch and deaccenting were examined and the results from the L2 learners were compared to a control group of native speakers from Spain who performed the same task. While only one L2 learner’s stress production could be classified as completely native-like, as a group, their stress production approximated native speaker norms to a greater degree than has been found for most other aspects of L2 Spanish pronunciation in previous research. Nonetheless, L2 learners seemed to transfer duration patterns from their L1 into their L2 Spanish and also deaccented stressed syllables nearly twice as often as native speakers.
Analysis of Within-Host Mathematical Models of Toxoplasmosis That Consider Time Delays
Authors: Sultana Sharmin , González-Parra Gilberto , Arenas Abraham J.
Published: October 2023

In this paper, we investigate two within-host mathematical models that are based on differential equations. These mathematical models include healthy cells, tachyzoites, and bradyzoites. The first model is based on ordinary differential equations and the second one includes a discrete time delay. We found the models’ steady states and computed the basic reproduction number R0. Two equilibrium points exist in both models: the first is the disease-free equilibrium point and the second one is the endemic equilibrium point. We found that the initial quantity of uninfected cells has an impact on the basic reproduction number R0. This threshold parameter also depends on the contact rate between tachyzoites and uninfected cells, the contact rate between encysted bradyzoite and the uninfected cells, the conversion rate from tachyzoites to bradyzoites, and the death rate of the bradyzoites- and tachyzoites-infected cells. We investigated the local and global stability of the two equilibrium points for the within-host models that are based on differential equations. We perform numerical simulations to validate our analytical findings. We also demonstrated that the disease-free equilibrium point cannot lose stability regardless of the value of the time delay. The numerical simulations corroborated our analytical results.
Effect of Solution Heat Treatment on the Microstructure and Microhardness of 7050 Aluminum Alloy
Authors: Qi Qingwen , Li Min , Duan Yonghua , Bu Hengyong , Li Mengnie
Published: October 2023

Today, 7xxx aluminum alloys are widely used in aerospace and other fields due to their excellent properties such as low density, high specific strength, and good processing performance. The heat treatment process of 7xxx aluminum alloy is crucial in controlling the strengthening phases and grain size, which is a significant way to enhance the alloy’s performance. In this study, solution heat treatment tests of 7050 aluminum alloys were carried out at different temperatures, ranging from 440 °C to 470 °C, with a holding time ranging from 0.5 h to 8 h, using a DIL 805A thermomechanical test machine. The microstructural evolution during the solution heat treatment was characterized using an optical microscope (OM), a scanning electron microscope (SEM), and a transmission electron microscope (TEM). The effects of the solution parameters on the alloy’s microhardness were analyzed using a digital Vickers microhardness tester. According to the ASTM E112-13 standard, The Anelli grain growth models were established to illustrate the grain size evolution during solution heat treatment, and a modified Anelli grain growth model was established. The results indicated that the grain size significantly increases with the increase in the solution heat treatment time and temperature. The Anelli grain growth model can illustrate the phenomenon of grain growth more accurately in the solution heat treatment process of 7050 aluminum alloy. It was found that prolonging the time and elevating the temperature of the solution heat treatment reduced the microhardness of the aluminum alloy because of the dissolution of the precipitates.
Sensitivity Study of Surface Roughness Process Parameters in Belt Grinding Titanium Alloys
Authors: Shang Yueru , Hu Sibo , Qiao Hu
Published: October 2023

In order to obtain the optimum range of process parameters for abrasive belt grinding of titanium alloys to achieve a surface roughness within a given range, titanium alloy TC4 was selected as the research object, and experiments on abrasive belt grinding surface roughness were conducted. Firstly, an empirical formula for the surface roughness of titanium alloys after abrasive belt grinding was constructed based on the balanced weight analysis of the process parameters for titanium alloy surface roughness. Sensitivity analysis was carried out to identify the process parameters with the greatest effect on surface roughness, and the stable and unstable domains of the process parameters were determined. Combined with range analysis in orthogonal experiments, the influence curves of the process parameters on surface roughness were obtained, and the optimal parameter ranges were selected. The research results showed that surface roughness is the most sensitive to changes in abrasive grain size and the least sensitive to changes in abrasive belt linear speed. The optimal ranges of abrasive grain size, abrasive belt linear speed, and grinding pressure were determined to be 120# to 150#, 15 m/s to 20 m/s, and 10 N to 15 N, respectively. This study provides a theoretical method and experimental basis for the control of surface roughness in abrasive belt grinding of titanium alloys.
Structure and Properties of TiNi Shape Memory Alloy after Quasi-Continuous Equal-Channel Angular Pressing in Various Aged States
Authors: Karelin Roman , Komarov Victor , Cherkasov Vladimir , Khmelevskaya Irina , Andreev Vladimir , Yusupov Vladimir , Prokoshkin Sergey
Published: October 2023

The effect of quasi-continuous (QC) equal-channel angular pressing (ECAP) in various pre-aged states on the structure formation and mechanical and functional properties of a hyper-equiatomic titanium nickelide (TiNi) shape memory alloy is studied. QC ECAP with a channel intersection angle of 110° is carried out at a temperature of 450 °C after aging for 1 and 5 h for three passes. To investigate the obtained structure and properties, the following research methods are applied: transmission electron microscopy, XRD analysis, calorimetric study, tension and hardness tests, and a special technique for the determination of functional properties. QC ECAP allows for the considerable refinement of structural elements and results in obtaining a mixed fine-grade structure, with structural elements of average sizes of 92 nm after pre-aging for 1 h and 115 nm after pre-aging for 5 h. Pre-aging for 5 h before QC ECAP, in combination with QC ECAP and post-deformation aging at 430 °C for 1 h, provides the best combination of mechanical and functional properties: a dislocation yield stress of 1410 MPa, ultimate tensile strength of 1562 MPa, and total recoverable strain of 11.6%. These values are comparable with the best results obtained for titanium nickelide and expand opportunities for the application of smart shape memory devices.
Curcumin Mitigates Malathion-Induced Renal Injury: Suppression of Apoptosis and Modulation of NF-κβ/TNF-α and Nrf2, and HO-1 Signaling
Authors: Eldesoqui Mamdouh , Ahmed Magda E. , Abdel-Kareem Mona A. , Badawy Mohamed Moharram , Dawood Amal Fahmy , Mohamed Abdelaty Shawky , Ibrahim Ateya Megahed , El-Mansi Ahmed A. , El-Sherbiny Mohamad , Hendawy Mahmoud
Published: October 2023

Malathion is one of the most used organophosphorus pesticides that is used for many reasons such as agriculture and industry. Human exposure to malathion may occur through various means, such as eating food that has been treated with it. Malathion not only increases oxidative stress but also decreases the antioxidant capacity. Curcumin is a powerful antioxidant with many pharmacological actions. Curcumin can act as a free radical scavenger and inhibit the activation and nuclear translocation of NF-κB. Curcumin could combat the lipid peroxidation and antioxidant depletion that trigger the apoptotic pathways. This study aims to examine the antioxidant, anti-inflammatory, and antiapoptotic effects of curcumin. Twenty-four Sprague Dawley rats were divided into four groups (six rats each): control, curcumin, malathion, and malathion + curcumin groups. At the assigned time, blood samples were used for the assessment of serum creatinine, and the kidneys were excised and washed; parts of them were used for the assessment of total oxidant status (TOS), oxidative stress index (OSI), the oxidative stress marker malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH) activity, other parts were fixed in formalin for further staining. Histopathological evaluation was performed for the fixed specimens after staining with H&E, sirus red, and the immunohistochemical staining for NF-κβ, TNF-α, Caspase-3, Nrf2, and HO-1. Curcumin significantly decreases the serum creatinine after malathion exposure and significantly restores the oxidant/antioxidant balance by increasing TAC and GSH and decreasing TOS, OSI, and MDA. Curcumin exerts its reno-protective effect and restores the histological architecture of the kidney by downregulating the immune expression of NF-κβ, TNF-α, and Caspase-3 and upregulating the expression of Nrf2 and HO-1. This study concluded that curcumin protects against nephrotoxicity caused by malathion by exerting its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.
Fibroblast Growth Factor 21 in Chronic Hepatitis C: A Potential Non-Invasive Biomarker of Liver Status upon Viral Eradication
Authors: Biagi Filippo , Carlomagno Francesco , Carbone Martina , Veralli Roberta , Vespasiani-Gentilucci Umberto , Riva Elisabetta , Manfrini Silvia , Tuccinardi Dario , De Santis Adriano , Gnessi Lucio , Watanabe Mikiko
Published: October 2023

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.
Quantitative Field Emission Imaging for Studying the Doping-Dependent Emission Behavior of Silicon Field Emitter Arrays
Authors: Schels Andreas , Herdl Florian , Hausladen Matthias , Wohlfartsstätter Dominik , Edler Simon , Bachmann Michael , Pahlke Andreas , Schreiner Rupert , Hansch Walter
Published: October 2023

Field emitter arrays (FEAs) are a promising component for novel vacuum micro- and nanoelectronic devices, such as microwave power amplifiers or fast-switching X-ray sources. However, the interrelated mechanisms responsible for FEA degradation and failure are not fully understood. Therefore, we present a measurement method for quantitative observation of individual emission sites during integral operation using a low-cost, commercially available CMOS imaging sensor. The emission and degradation behavior of three differently doped FEAs is investigated in current-regulated operation. The measurements reveal that the limited current of the p-doped emitters leads to an activation of up to 55% of the individual tips in the array, while the activation of the n-type FEA stopped at around 30%. This enhanced activation results in a more continuous and uniform current distribution for the p-type FEA. An analysis of the individual emitter characteristics before and after a constant current measurement provides novel perspectives on degradation behavior. A burn-in process that trims the emitting tips to an integral current-specific ideal field enhancement factor is observed. In this process, blunt tips are sharpened while sharp tips are dulled, resulting in homogenization within the FEA. The methodology is described in detail, making it easily adaptable for other groups to apply in the further development of promising FEAs.
Numerical Simulation and Validation of Laser Polishing of Alumina Ceramic Surface
Authors: Wang Chao , Zhao Zhenyu , Zhou Houming , Zeng Junyong , Zhou Zhanwang
Published: October 2023

Laser polishing is a noncontact and efficient processing method for surface treatment of different materials. It removes surface material and improves its quality by means of a laser beam that acts directly on the surface of the material. The material surface roughness is a major criterion that evaluates the polishing effect when alumina ceramics are polished by a laser. In this study, the effects of three factors, namely, laser power, scanning speed, and pulse frequency, on the surface roughness were investigated through orthogonal tests. The optimum polishing parameters were obtained through a comparison of the experimental results. Compared to the initial surface roughness (Ra = 1.624 μm), the roughness of the polished surface was reduced to Ra = 0.549 μm. A transient two-dimensional model was established by the COMSOL Multiphysics 5.5, and the flow condition of the material inside the molten pool of laser-polished alumina ceramics and the surface morphology of the smoothing process were investigated by utilizing the optimal polishing parameters obtained from the experiments. The simulation results showed that in the process of laser polishing, the fluid inside the molten pool flowed from the peaks to the valleys under the action of capillary force, and the inside of the molten pool tended to be smoothened gradually. In order to verify the correctness of the numerical model, the surface profile at the same position on the material surface was compared, and the results showed that the maximum error between the numerical simulation and the experimental results was 17.8%.
Editorial for the Special Issue on the New Trends in Microwave/Millimeter Antennas/Filters: From Fundamental Research to Applications
Authors: Ibrahim Ahmed A. , Abbas Syed Muzahir
Published: October 2023

The rapid growth of wireless communication systems has led to high demand for the design of microwave/millimeter components with multiband characteristics, high performance, and ease of integration with other devices [...]
Sequencing of SARS-CoV-2 RNA Fragments in Wastewater Detects the Spread of New Variants during Major Events
Authors: Zhakparov Damir , Quirin Yves , Xiao Yi , Battaglia Nicole , Holzer Michael , Bühler Martin , Kistler Walter , Engel Doortje , Zumthor Jon Paulin , Caduff Alexa , Baerenfaller Katja
Published: October 2023

The sequencing of SARS-CoV-2 RNA in wastewater is an unbiased method to detect the spread of emerging variants and to track regional infection dynamics, which is especially useful in case of limited testing and clinical sequencing. To test how major international events influence the spread of new variants we have sequenced SARS-CoV-2 RNA in the wastewater samples of Davos, Landquart, Lostallo, and St. Moritz in the Swiss canton of Grisons in the time around the international sports competitions in Davos and St. Moritz in December 2021, and additionally in May 2022 and January 2023 in Davos and St. Moritz during the World Economic Forum (WEF) in Davos. The prevalence of the variants identified from the wastewater sequencing data showed that the Omicron variant BA.1 had spread in Davos and St. Moritz during the international sporting events hosted there in December 2021. This spread was associated with an increase in case numbers, while it was not observed in Landquart and Lostallo. Another instance of new variant spread occurred during the WEF in January 2023, when the Omicron variant BA.2.75 arrived in Davos but not in St. Moritz. We can therefore conclude that major international events promote the spread of new variants in the respective host region, which has important implications for the protective measures that should be taken.
First Polyphasic Study of Cheffia Reservoir (Algeria) Cyanobacteria Isolates Reveals Toxic Picocyanobacteria Genotype
Authors: Benredjem Lamia , Morais João , Hentschke Guilherme Scotta , Abdi Akila , Berredjem Hajira , Vasconcelos Vitor
Published: October 2023

Monitoring water supply requires, among other quality indicators, the identification of the cyanobacteria community and taking into account their potential impact in terms of water quality. In this work, cyanobacteria strains were isolated from the Cheffia Reservoir and identified based on morphological features, the 16S rRNA gene, phylogenetic analysis, and toxin production by polymerase chain reaction PCR screening of the genes involved in the biosynthesis of cyanotoxins (mcyA, mcyE, sxtA, sxtG, sxtI, cyrJ, and anaC). Thirteen strains representing six different genera: Aphanothece, Microcystis, Geitlerinema, Lyngbya, Microcoleus, and Pseudanabaena were obtained. The results demonstrated the importance of morphological features in determining the genus or the species when incongruence between the morphological and phylogenetic analysis occurs and only the utility of the 16S rRNA gene in determining higher taxonomic levels. The phylogenetic analysis confirmed the polyphyly of cyanobacteria for the Microcystis and Oscillatoriales genera. Unexpectedly, Aphanothece sp. CR 11 had the genetic potential to produce microcystins. Our study gives new insight into species with picoplanktonic (or small) cell size and potentially toxic genotypes in this ecosystem. Thus, conventional water treatment methods in this ecosystem have to be adapted, indicating the requirement for pre-treatment methods that can effectively eliminate picocyanobacteria while preserving cell integrity to prevent toxin release.
Bulk Composition Effects on Vitrification of Mixed Fine Construction–Demolition and Inorganic Solid Waste
Authors: Stabile Paola , Abudurahman Ababekri , Carroll Michael R. , Paris Eleonora
Published: October 2023

Re-use of neglected and frequently landfilled wastes, including earthquake-generated rubble, can reduce the environmental impact of such waste materials, avoiding georesource exploitation, and potentially provide a source for new upcycling applications. Here, the fine fraction (<0.125 mm) of different wastes was selected according to chemical composition (mostly silicate/oxide-rich materials), including construction and demolition waste (CDW), commercial glass, ceramic industry waste and incinerator bottom and fly ashes. Mixtures of these materials were used for vitrification experiments conducted at atmospheric pressure, 1200 °C, 8 h duration, preparing ten mixes containing 30 to 70 wt% of different waste materials added to a CDW starting material. X-ray powder diffraction and SEM/electron microprobe analyses show that the amorphous content (glass) varies from a maximum of 100 wt.% in products made of CDW with 70 wt.% added ceramic materials (e.g., roof tile) to a minimum of ~53 wt.% amorphous material when CDW was mixed with 30 wt.% brick powder. Mixtures of other waste materials (commercial glass, bottom/fly ash, ceramic waste) produced variable amounts of amorphous component, interpreted in terms of thermal minima in the CaO-Al2O3-SiO2 system. Lack crystallinity and characteristic microstructures of experimental products suggest that vitrification is a promising choice for rendering inert chemically complex waste materials like CDW for possible upcycling applications.
Pore Structure Alteration of Shale with Exposure to Different Fluids: The Longmaxi Formation Shale in the Sichuan Basin, China
Authors: Zhang Shuwen , Shen Ziyi , He Yan , Zhu Zhonghua , Ren Qingguo , Zhang Liang
Published: October 2023

The interaction between shale and various fluids is crucial as it modifies pore structures, which govern the effective development of shale gas and the geological storage of carbon dioxide in shale formations. In this study, samples from the Longmaxi Formation shale in Sichuan Basin of China were exposed to different fluids, including 6 MPa CO2, 12 MPa CO2, 6 MPa CO2+brine, and 12 MPa CO2+brine, at 45 °C for 100 days. Various methods, including X-ray diffraction (XRD), X-ray fluorescence (XRF), field-emission scanning electron microscopy (FESEM), and the low-pressure gas adsorption (N2) test, were adopted to evaluate chemical and structural changes during the exposure process. After being treated with supercritical CO2+brine and subcritical CO2+brine, the shale underwent significant changes in its major element composition. The content of Ca, Al, and K in shale saturated with supercritical CO2+brine decreased from 13.00% to 10.34%, from 3.65% to 3.36%, and from 1.56% to 1.37%, respectively. Meanwhile, the content of Si and Na in the same shale increased slightly after saturation. The amount of quartz and dolomite increased, while the levels of clay and calcite slightly decreased. The surface of the shale sample became rougher and small bumps and cracks appeared after saturation with different fluids, as shown by the FESEM analysis results. Furthermore, the changes in both the total pore volume and pore size followed a similar pattern to the alterations in the specific surface areas. The highest level of variation occurred with the shale that was saturated with 12 MPa of CO2, indicating that gas pressure and CO2 phase state have a significant influence on the shale’s pore structure. In addition, the distribution of pore sizes showed a bias towards larger sizes across all diameters; this suggests that the reaction resulted in a decrease in the number of micropores. This also highlights that the impact of varying fluid saturation was primarily focused on micropores and macropores. The results of this study provided experimental evidence to further test the mechanisms and permeability of geological storage of CO2 in organic-rich self-sourced shale.
Design, Synthesis, and Antiproliferative Activity of Selective Histone Deacetylases 6 Inhibitors Containing a Tetrahydropyridopyrimidine Scaffold
Authors: Wang Bin , Liu Youcai , Zhang Lejing , Wang Yajuan , Li Zhaoxi , Chen Xin
Published: October 2023

The development of selective histone deacetylase 6 inhibitors (sHDAC6is) is being recognized as a therapeutic approach for cancers. In this paper, we designed a series of novel tetrahydropyridopyrimidine derivatives as sHDAC6 inhibitors. The most potent compound, 8-(2, 4-bis(3-methoxyphenyl)-5, 8-dihydropyrido [3, 4-d]pyrimidin-7(6H)-yl)-N-hydroxy-8-oxooctanamide (8f), inhibited HDAC6 with IC50 of 6.4 nM, and showed > 48-fold selectivity over other subtypes. In Western blot assay, 8f elevated the levels of acetylated α-tubulin in a dose-dependent manner. In vitro, 8f inhibited RPMI-8226, HL60, and HCT116 tumor cells with IC50 of 2.8, 3.20, and 3.25 μM, respectively. Moreover, 8f showed good antiproliferative activity against a panel of tumor cells.
Repurposing Drugs for Inhibition against ALDH2 via a 2D/3D Ligand-Based Similarity Search and Molecular Simulation
Authors: Jiang Wanyun , Chen Junzhao , Zhang Puyu , Zheng Nannan , Ma Le , Zhang Yongguang , Zhang Haiyang
Published: October 2023

Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH2. Three compounds of Zeaxanthin (q = 0), Troglitazone (q = 0), and Sequinavir (q = +1 e) are singled out as potential inhibitors; Zeaxanthin can only be hit via USRCAT. These drugs displayed a stronger binding strength compared to the reported potent inhibitor CVT-10216. Sarizotan (q = +1 e) and Netarsudil (q = 0/+1 e) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. This likely left a space for substrate binding, and thus they were not ideal inhibitors. The MM–PBSA results indicate that the selected negatively charged compounds from the similarity search and Vina scoring are thermodynamically unfavorable, mainly due to electrostatic repulsion with the receptor (q = −6 e for ALDH2). The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.
Superior Valorisation of Juglans regia L. Leaves of Different Maturity through the Isolation of Bioactive Compounds
Authors: Tociu Mihaela , Manolache Fulvia , Bălănucă Brîndușa , Moroșan Alina , Stan Raluca
Published: October 2023

Extracts rich in bioactive compounds from natural sources have received great interest due to their great impact on human health. The aim of this research is focused on the obtaining and characterization of several extracts from Juglans regia L. leaves in four different maturity phases: young green leaves (YGL), green leaves (GL), mature green leaves (MGL), and yellow leaves (YL), using different solvents: ethanol (e), water (w), or water:ethanol (1:1 (v/v)—m) by employing several methods: magnetic stirring (MS), ultrasound-assisted (UA), as well as maceration (M). The obtained extracts were quantitatively evaluated through spectrophotometric methods: Total Polyphenol Content (TPC-Folin–Ciocalteu assay) and Total Antioxidant Capacity (TEAC assay). Phytochemical screening by means of Fourier-Transform Ion–Cyclotron-Resonance High-Resolution Mass Spectrometry (FT-ICR-MS) indicated the presence of 40 compounds belonging to different phytochemical classes: phenolic acids, flavonoids, flavones, flavanones, flavonones, flavanols, vitamins, tereponoid, steroid, anthocyanidin, and other compounds. Based on TPC and TEAC assays, the water-ethanol mixture was found to be the proper extraction solvent, with the best results being obtained for YL plant material: 146.29 mg GAE/g DM (TPC) and 11.67 mM TE/g DM (TEAC). This type of extract may be used in various domains, such as the cosmetics industry, the biomedical field, and/or the design of functional foods, relying on their phytochemical composition.