The present paper investigates flaw strength distributions established using various flexural tests on batches of SiC bar test specimens, namely four-point bending as well as three-point bending tests with different span lengths. Flaw strength is provided by the elemental stress operating on the critical flaw at the fracture of a test specimen. Fracture-inducing flaws and their locations are identified using fractography. A single population of pores was found to dominate the fracture. The construction of diagrams of p-quantile vs. elemental strengths was aimed at assessing the Gaussian nature of flaw strengths. Then, empirical cumulative distributions of strengths were constructed using the normal distribution function. The Weibull distributions of strengths are then compared to the normal reference distributions. The parameters of the Weibull cumulative probability distributions are estimated using maximum likelihood and moment methods. The cumulative distributions of flexural strengths for the different bending tests are predicted from the flaw strength density function using the elemental strength model, and from the cumulative distribution of flexural strength using the Weibull function. Flaw strength distributions that include the weaker flaws that are potentially present in larger test pieces are extrapolated using the p-quantile diagrams. Implications are discussed regarding the pertinence of an intrinsically representative flaw strength distribution, considering failure predictions. Finally, the influence of the characteristics of fracture-inducing flaw populations expressed in terms of flaw strength interval, size, dispersion, heterogeneity, and reproducibility with volume change is examined. Full article

Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders. Full article

The mechatronic industry is currently subject to huge changes challenging it to offer products matching individual customer requirements at competitive prices. The design of such products calls for sophisticated and complex components integration following different technologies. Since we are on the cusp of the Fourth Industrial Revolution, in which the world of mechatronic production, network connectivity, the Internet of Things, and cyber-physical systems are correlated, the complexity of these systems increases exponentially, and we are talking about advanced mechatronic systems. To assist these changes, various methods, sweeping all project phases, are used by business houses. Predictive dependability assessment in the earlier design stage is considered a powerful metric used to evaluate the performances of different kinds of mechatronic products before the production phase. Altogether, dependability analysis ties the design directly to the desired functionality, operability, and integrity of the system. This paper explores an approach to assessing the dependability attributes, reliability, availability, and maintainability (RAM), of repairable mechatronic systems based on timed colored Petri nets and a Monte Carlo simulation, integrating simultaneously diverse components technologies: mechanical, electronic, and software. The proposed approach is tested taking the case of a regenerative braking system. The methodology appears to be efficient for evaluating predictive RAM indicators (MTTFF, MTTR, MTBF…) for the whole system and for each individual component separately. Full article

With a growing need to reduce greenhouse gas emissions, innovative carbon dioxide sorbents are being sought. One of the sorbents being tested is nanoparticle ferric hydrosol (FFH). In parallel with sorbent testing, it is also necessary to test the used sorbent after carbon dioxide capture (FFHCO2) and to develop an optimal method for its processing and management. The research described in this article evaluated the potential use of FFHCO2 in dewatering, coagulation and bioleaching processes. The research results indicate that the basic strategy for dealing with waste FFHCO2 sorbent should be to minimize the amount of waste by volume reduction—dewatering. Recycling of FFHCO2 as an iron waste coagulant or its processing products by bioleaching had no technological justification. It is only proposed to recover the material—iron compounds—if it is environmentally and economically justified. Full article

The objective of this study was to investigate the modification of glass surfaces by the synergistic combination of cold plasma and chemical surface modification techniques. Glass surface hydrophobicity was obtained as a result of various plasma and deposition operational conditions. The mechanisms governing the hydrophobization process were also studied. Glass plates were activated with plasma using different gases (oxygen and argon) at different treatment times, ranging from 30 to 1800 s. Then, the plasma-treated surfaces were exposed to hexamethyldisilazane vapors at different temperatures, i.e., 25, 60, and 100 °C. Complete characterization, including contact angle measurements, surface free energy calculations, 3D profilometry, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy, was accomplished. It was found that the extent of the hydrophobicity effect depends on both the plasma pre-treatment and the specific conditions of the hexamethyldisilazane deposition process. Plasma activation led to the formation of active sites on the glass surface, which promoted the adsorption and reaction of hexamethyldisilazane species, thereby inducing surface chemical modification. Longer plasma pre-treatment resulted in stronger modification on the glass surface, resulting in changes in the surface roughness. The largest water contact angle of ≈100° was obtained for the surface activated by argon plasma for 1800 s and exposed to hexamethyldisilazane vapors at 25 °C. The changes in the surface properties were caused by the introduction of the hydrophobic trimethylsilyl groups onto the glass surface as well as roughness development. Full article

Background: This article analyzes differences in microbiological parameters and periodontal health conditions among three patient groups: those undergoing conventional orthodontic treatment with fixed appliances, patients undergoing orthodontic treatment with clear aligners, and a control group receiving no treatment. Materials and Methods: In this study, 60 patients were enrolled. The microbiological analysis employed a qualitative and semi-quantitative methodology of bacterial morphotype analysis. Results: The analyses revealed a significant difference in favor of clear oral and periodontal health aligners. This could be attributed to better bacterial biofilm removal and reduced mechanical stress on the periodontal ligament, factors facilitated by the ease of clear aligner removal. Significant differences (p-value < 0.05) were observed for the Full-Mouth Plaque Score, Full-Mouth Bleeding Score, Plaque Index, and periodontal health assessment measurements. Conclusions: Although overall hygiene appears to be improved in patients in the aligners group compared to those treated with conventional orthodontic appliances, there are no statistically significant results regarding plaque composition. Microbiological aspects will be further addressed using more specific techniques in the follow-up of this research. Full article

The PD-1/PD-L1 complex is an immune checkpoint responsible for regulating the natural immune response, but also allows tumors to escape immune surveillance. Inhibition of the PD-1/PD-L1 axis positively contributes to the efficacy of cancer treatment. The only available therapeutics targeting PD-1/PD-L1 are monoclonal antibody-based drugs, which have several limitations. Therefore, small molecule compounds are emerging as an attractive alternative that can potentially overcome the drawbacks of mAb-based therapy. In this article, we present a novel class of small molecule compounds based on the terphenyl scaffold that bind to PD-L1. The general architecture of the presented structures is characterized by axial symmetry and consists of three elements: an m-terphenyl core, an additional aromatic ring, and a solubilizing agent. Using molecular docking, we designed a series of final compounds, which were subsequently synthesized and tested in HTRF assay and NMR binding assay to evaluate their activity. In addition, we performed an in-depth analysis of the mutual arrangement of the phenyl rings of the terphenyl core within the binding pocket of PD-L1 and found several correlations between the plane angle values and the affinity of the compounds towards the protein. Full article

The study examines the unique production process of Aceto Balsamico Tradizionale di Modena PDO (ABTM), emphasizing its complex phases and the impact of raw materials and artisanal skill on its flavor characteristics. Analytical tests focused on the volatile composition of vinegars from different wood barrels at different aging stages, using solid-phase micro-extraction (SPME) coupled with gas chromatography, either with mass spectrometry (GC/MS) or flame ionization detector (FID). Multivariate analysis, including principal component analysis (PCA), was employed to investigate the presence of peculiarities among the volatile profiles of samples of different barrel origin. The research focuses on characterizing the volatile composition of vinegars sourced from individual wood barrels, such as Cherry, Chestnut, Mulberry, Juniper, and Oak. Although it was not possible to identify molecules directly connected to the woody essence, some similarities emerged between vinegar samples from mulberry and cherry barrels and between those of juniper and oak. The former group is characterized by analytes with high molecular weights, such as furfural and esters, while the latter group shows more intense peaks for ethyl benzoate. Moreover, ethyl benzoate appears to predominantly influence samples from chestnut barrels. Due to the highly complex production process of ABTM, where each battery is influenced by several factors, this study’s findings are specific to the current experimental conditions. Full article

Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult to access the complex microenvironments of the inner ear and investigate specific pathological indicators through conventional techniques. Omics technologies have the potential to play a vital role in revolutionising the diagnosis of ear disorders by providing a comprehensive understanding of biological systems at various molecular levels. These approaches reveal valuable information about biomolecular signatures within the cochlear tissue or fluids such as the perilymphatic and endolymphatic fluid. Proteomics identifies changes in protein abundance, while metabolomics explores metabolic products and pathways, aiding the characterisation and early diagnosis of diseases. Although there are different methods for identifying and quantifying biomolecules, mass spectrometry, as part of proteomics and metabolomics analysis, could be utilised as an effective instrument for understanding different inner ear disorders. This study aims to review the literature on the application of proteomic and metabolomic approaches by specifically focusing on Meniere’s disease, ototoxicity, noise-induced hearing loss, and vestibular schwannoma. Determining potential protein and metabolite biomarkers may be helpful for the diagnosis and treatment of inner ear problems. Full article

Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments. Full article

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC_50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L⁻¹) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L⁻¹), sarafloxacin and clinafloxacin (12.23 µg L⁻¹), and ofloxacin (17.12 µg L⁻¹). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use. Full article

The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they are sent to the brain to be interpreted as images. The retina is unique in that it is continuously exposed to light and has the highest metabolic rate and demand for energy amongst all the tissues in the body. Consequently, the retina is very susceptible to oxidative stress. VDAC, a pore in the outer membrane of mitochondria, shuttles metabolites between mitochondria and the cytosol and normally protects cells from oxidative damage, but when a cell’s integrity is greatly compromised it initiates cell death. There are three isoforms of VDAC, and existing evidence indicates that all three are expressed in the retina. However, their precise localization and function in each cell type is unknown. It appears that most retinal cells express substantial amounts of VDAC2 and VDAC3, presumably to protect them from oxidative stress. Photoreceptors express VDAC2, HK2, and PKM2—key proteins in the Warburg pathway that also protect these cells. Consistent with its role in initiating cell death, VDAC is overexpressed in the retinal degenerative diseases retinitis pigmentosa, age related macular degeneration (AMD), and glaucoma. Treatment with antioxidants or inhibiting VDAC oligomerization reduced its expression and improved cell survival. Thus, VDAC may be a promising therapeutic candidate for the treatment of these diseases. Full article

Nitrite is one of the most common nitrogenous compounds, which is not only an important indicator of aquaculture water but also widely used as a food additive. Its potential toxicity poses a huge threat to aquatic products and human health. Therefore, it is important to develop a convenient and rapid sensor for the high-efficient onsite detection of nitrite. In this work, a novel electrochemical sensor was developed for the qualitative and quantitative analysis of nitrite. The developed nitrite electrochemical detection system is easily applied in onsite detection. The electrochemical working electrode was constructed based on the combination of Ag-CeO₂ and conductive carbon paste (CPE) with excellent electrocatalysis activity and rapid electron transfer ability. By the application of the developed system and under the optimal conditions, the linear range was from 40.0 μM to 500.0 μM, and the detection limit was reduced to 4.3 μM. The recovery was between 92.1% and 108.1%, and the relative standard deviations (RSDs) were 0.49%~9.31%. The sensor exhibited superior reproducibility, high stability sensitivity, and anti-interference ability, confirming its effectiveness for nitrite analysis. Finally, the developed electrochemical sensor was successfully applied to detect nitrite in beverages and aquaculture water samples, indicating that this approach has great potential in onsite food testing and environmental monitoring. Full article

The light-weighting of a robotic arm is an important aspect of robot research. In the operation of existing welding robots, excessive vibrations in the welding actuators have been observed, which lead to reduced welding precision and work efficiency. The direct connection between the forearm and the welding actuator is a key component that affects vibrations. Based on this, a study on light-weighting the forearm is proposed. Using the theory of topology optimization with variable density structure, the structural dimensions, shapes, and geometric parameters of the forearm are optimized. The material removal methods of “hole cutting” and “local hollowing” are employed to reconstruct the forearm structure model. Static, modal, and transient simulations were performed on the forearm model pre-optimization and post-optimization. The optimization results show that the mass of the forearm is reduced by 19.8%. The static simulation comparative analysis shows that, under the same constraints and load conditions, the maximum total deformation of the optimized forearm is reduced by 3.6%, the maximum stress is reduced by 3.2%, and the maximum equivalent elastic strain is reduced by 5.7%. The optimized forearm structure is more reasonable and exhibits better mechanical performance. Modal simulation comparative analysis shows that the first and second natural frequencies of the optimized forearm are increased by 9.8% and 7.0%, respectively. Transient simulation comparative analysis demonstrates that, under the maximum operating condition, the vibration frequency and amplitude of the optimized welding robot forearm are reduced by 19.4% and 26.9%, respectively. The maximum amplitudes of the maximum equivalent stress curve and maximum equivalent elastic strain curve are reduced by 51.0% and 46.0%, respectively. This study provides a guarantee for reducing vibrations in welding actuators, improving welding precision, and enhancing the work efficiency of the welding robot. Full article

In multilayer complex networks, the uncertainty in node states leads to intricate behaviors. It is, therefore, of great importance to be able to estimate the states of target nodes in these systems, both for theoretical advancements and practical applications. This paper introduces a state observer-based approach for the state estimation of such networks, focusing specifically on a class of complex dynamic networks with nodes that correspond one-to-one. Initially, a chaotic system is employed to model the dynamics of each node and highlight the essential state components for analysis and derivation. A network state observer is then constructed using a unique diagonal matrix, which underpins the driver and response-layer networks. By integrating control theory and stability function analysis, the effectiveness of the observer in achieving synchronization between complex dynamic networks and target systems is confirmed. Additionally, the efficacy and precision of the proposed method are validated through simulation. Full article

Background/Objectives: The aim of this study was to establish a histologic baseline for cryoanalgesia of 2 min duration and evaluate the effects of different freeze durations. Methods: A porcine model was used in which the application of bilateral cryoanalgesia from intercostal spaces T3–T7 was completed via partial median sternotomy. The animals were kept alive for 7 days and the ribcages were sent to a specialized center for histopathologic analysis of the freezing injury. Results: Forty freezing lesions were completed and analyzed histologically. Thirty-eight (95%) of the cryo-lesions presented 100% nerve fiber degeneration at or distal to the ablation site, with preservation of the perineural connective tissue, as intended. The two unaffected nerves were found to be physically located outside of the freezing area. Conclusions: The complete axonal degeneration with preservation of the perineural tissue opens the possibility to shorter freezing times than the recommended 2 min. Visualization of the nerve and positioning of the probe is important in ensuring the proper effect on the nerve. This histologic analysis confirms the process triggered by cryoanalgesia that, until now, had only been assumed. Full article

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case–control study, we used Taiwan’s nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan’s National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan. Full article

The occurrence, distribution, and ecological risk assessment of 36 antibiotics from five groups, including macrolides (MLs), fluoroquinolones (FQs), tetracyclines (TCs), amphenicols (APs), and sulfonamides (SAs), were investigated for the first time in the Anning River, Sichuan Province, China. The results show that antibiotics were widely present in the sediments of the Anning River, with a total of 22 antibiotics detected. FQs were among the most abundant antibiotics, followed by TCs, MLs, APs, and SAs. The total concentrations of antibiotics in surface sediments varied from 0.05 to 53.35 ng/g, with an average of 8.09 ng/g. Among these groups, MLs, FQs, and TCs emerged as the predominant classes of antibiotics. The midstream sediments showed the highest residual levels of antibiotics, with lower levels observed in the downstream and upstream sediments. Anthropogenic activities, such as human clinical practices and animal breeding, might be sources of antibiotics released into the river. An ecological risk assessment revealed that trimethoprim from the SA group exhibited high risks, and MLs showed medium risks in the Anning River, whereas most antibiotics presented minimal to low risks. This study provides valuable information on antibiotic pollution in the upstream region of the Yangtze River, and future management measures are needed for the Anning River. Full article

The purpose of this cross-sectional study was to investigate the relationship between Body Mass Index (BMI), cholesterol, and cancer in United States (US) adults. Data were collected from the 2020 Medical Expenditure Panel Survey (MEPS). Eligible participants were US adults (≥18 years) with data on BMI, cholesterol, and cancer status, who were alive at the end of the data collection period. An adjusted logistic regression model assessed associations between eight possible combinations of BMI and cholesterol status (independent variable) with cancer diagnosis (dependent variable). Among 27,805 individuals in the 2020 MEPS data, 20,818 met the eligibility criteria (weighted N = 252,340,615). Of these 2668 (weighted N = 29,770,359) had cancer and 18,150 (weighted N = 222,570,256) did not have cancer. In the adjusted logistic regression model, underweight and normal weight individuals with high cholesterol were associated with higher odds of cancer (odds ratio, OR = 2.002, and 95% confidence interval, CI = 1.032–3.885, and OR = 1.326 and 95% CI = 1.047–1.681, respectively), while obese individuals with normal cholesterol were associated with lower odds of cancer (OR = 0.681; 95% CI = 0.543–0.853) compared to normal weight individuals with normal cholesterol. This study offers insights into specific groups of individuals who may be prioritized for cancer prevention. Further research is required to investigate these findings in additional subpopulations. Full article

While insertion of a central venous catheter (CVC) for intravascular access, diagnosis, and intensive care medical treatment is frequently needed in critically ill patients, retention of the guidewire used for CVC placement with Seldinger’s technique is a very rare complication. In patients treated with extracorporeal membrane oxygenation (ECMO), significant negative pressures in the thoracal and abdominal venous system are generated by the venous ECMO drainage cannula. Therefore, during CVC placement in patients treated with ECMO, special vigilance is required because the significant negative pressures generated by the venous ECMO drainage cannula facilitate venous suction of an unsecured guidewire. Full article

Hybrid rice results from crossing a male-sterile line (the A line) with a pollen doner (the restorer or R line). In 3-line hybrid breeding systems, a fertile B line is also required to maintain A line populations. Heterosis is defined as a condition of traits whereby the hybrid exceeds the average of the parental lines. Heterobeltiosis is where the hybrid exceeds both parents. Hybrid rice may display heterosis/heterobeltiosis for growth, yield and resistance to herbivores, among other traits. In a greenhouse experiment, we assessed the frequency of heterosis for resistance to the brown planthopper (Nilaparvata lugans (BPH)), whitebacked planthopper (Sogatella furcifera (WBPH)) and yellow stemborer (Scirpophaga incertulas (YSB)) in eight hybrids under varying soil nitrogen conditions. We also assessed plant biomass losses due to herbivore feeding as an approximation of tolerance (the plant’s capacity to compensate for damage). Nitrogen reduced resistance to all three herbivores but was also associated with tolerance to WBPH and YSB based on improved plant survival, growth and/or yields. Plant biomass losses per unit weight of WBPH also declined under high nitrogen conditions for a number of hybrids, and there were several cases of overcompensation in rice for attacks by this herbivore. There was one case of nitrogen-related tolerance to BPH (increased grain yield) for a hybrid line with relatively high resistance, likely due to quantitative traits. Heterosis and heterobeltiosis were not essential to produce relatively high herbivore resistance or tolerance across hybrids. Full article

In this paper, we study the nonlinear optical bistability (OB) in a symmetrical multilayer structure. This multilayer structure is constructed by embedding a nonlinear three-dimensional Dirac semimetal (3D DSM) into a Fabry–Perot cavity composed of one-dimensional photonic crystals. The OB phenomenon stems from the third order nonlinear conductivity of 3D DSM. The local field of resonance mode could enhance the nonlinearity and reduce the thresholds of OB. This structure achieves the tunability of OB due to the fact that the transmittance could be modulated by the Fermi energy. It is found that the OB threshold and threshold width could be remarkably reduced by increasing the Fermi energy of the 3D DSM. Besides, we also found that the OB curve depends heavily on the angle of incidence of the incident light, the structural parameters of the Fabry–Perot cavity, and the position of the 3D DSM inside the cavity. After parameter optimization, we obtained OB with a threshold of ${10}^6 \mathrm{V}/\mathrm{m}$. We believe this simple multilayer structure could provide a reference idea for realizing low-threshold and tunable all-optical switching devices. Full article