Liver fibrosis, characterized by excessive extracellular matrix (ECM) deposition, can progress to cirrhosis and increases the risk of liver cancer. Hepatic stellate cells (HSCs) play a pivotal role in fibrosis progression, transitioning from a quiescent to activated state upon liver injury, wherein they proliferate, migrate, and produce ECM. Calcium signaling, involving the inositol 1,4,5-trisphosphate receptor (IP3R), regulates HSC activation. This study investigated the efficacy of a novel IP3R inhibitor, desmethylxestospongin B (dmXeB), in preventing HSC activation. Freshly isolated rat HSCs were activated in vitro in the presence of varying dmXeB concentrations. The dmXeB effectively inhibited HSC proliferation, migration, and expression of fibrosis markers without toxicity to the primary rat hepatocytes or human liver organoids. Furthermore, dmXeB preserved the quiescent phenotype of HSCs marked by retained vitamin A storage. Mechanistically, dmXeB suppressed mitochondrial respiration in activated HSCs while enhancing glycolytic activity. Notably, methyl pyruvate, dimethyl α-ketoglutarate, and nucleoside supplementation all individually restored HSC proliferation despite dmXeB treatment. Overall, dmXeB demonstrates promising anti-fibrotic effects by inhibiting HSC activation via IP3R antagonism without adverse effects on other liver cells. These findings highlight dmXeB as a potential therapeutic agent for liver fibrosis treatment, offering a targeted approach to mitigate liver fibrosis progression and its associated complications. Full article

Entomocomposting is fast and environmentally friendly, boosts soil quality and crop production, and improves resilience to climate change. The black soldier fly larvae (BSFL) catalyze the composting process, but their efficiency is highly influenced by environmental factors and the quality of the substrate. This study employs response surface methodology to discern physical–chemical factors that influence the nutrient quality of BSF frass fertilizer. Internet of Things (IoT) sensors were deployed to monitor in real-time both independent variables (air temperature, moisture content, humidity, and substrate temperature) and dependent variables (nitrogen, phosphorous, and potassium); the data were relayed to the cloud. A non-linear regression model was used to study the relationship between the dependent and independent variables. Results showed that air humidity and air temperature did not have a significant effect on nitrogen and phosphorus accumulation in frass fertilizer, respectively, but phosphorus was significantly influenced by air humidity. On the other hand, neither air temperature nor moisture content has a significant effect on potassium concentration in frass fertilizer. We found that an air temperature of 30 °C and 41.5 °C, substrate temperature of 32.5 °C and 35 °C, moisture content between 70 and 80%, and relative humidity beyond 38% can be conducive for the production of high-quality BSF frass fertilizer. Model validation results showed better robustness of prediction with $R^2$ values of 63–77%, and $R_{\mathrm{adj}}^2$ values of 62–76% for nitrogen, phosphorous, and potassium. Our findings highlight the potential for the application of digital tools as a fast and cost-effective decision support system to optimize insect farming for the production of high-quality frass fertilizer for use in sustainable agriculture and crop production. Full article

This comprehensive review explores the potential of using lactobacilli as a probiotic in the management of COVID-19. Our findings suggest that lactobacilli show promise in reducing the risk of death, gastrointestinal and overall symptoms, and respiratory failure, as well as in lowering cytokines and inflammatory markers associated with the disease. The molecular mechanisms by which lactobacilli protect against COVID-19 and other viral infections may be related to the reduction in inflammation, modulation of the immune response, and direct interaction with viruses to produce antiviral substances. However, the selected studies demonstrate the presence of mixed findings for various clinical, biochemical, hematological, and immunological parameters, which may be attributed to methodological differences among studies. We highlight the importance of clearly describing randomization processes to minimize bias and caution against small sample sizes and inappropriate statistical tests that could lead to errors. This review offers valuable insights into the therapeutic potential of lactobacilli in the context of COVID-19 and identifies avenues for further research and applications. These findings hold promise for the development of novel approaches to managing COVID-19 and warrant further investigation into the potential benefits of lactobacilli in combating the disease. Full article

The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders. Full article

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling. Through both direct and indirect connections to fibroblasts, monocyte-derived macrophages and resident cardiac macrophages play complex, bidirectional, regulatory roles in cardiac fibrosis. In this review, we discuss emerging interactions between fibroblasts and macrophages in physiology and pathologic conditions, providing insights for future research aimed at targeting macrophages to combat cardiac fibrosis. Full article

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood–brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering −3.31, −1.68, and −6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states’ properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated. Full article

It has been demonstrated that benzene, toluene, and xylene are carcinogens. Its combined effects with other contaminants have the potential to harm several ecosystem components. Since most human benzene exposure takes place inside, it is important to understand how outdoor benzene emissions from traffic and industry affect interior concentrations. However, this area of study has not received enough attention to date. Herein, we examine the outdoor concentrations of benzene, toluene, and xylene (BTX) in a Steelpoort mining area. BTX pollutants were passively sampled on the first seven days of the month, from January to December 2021 using Radiello samplers. The effects of meteorological parameters such as temperature, relative humidity, wind speed, and solar radiation on BTX concentrations were also statistically tested. For all seasons, BTX concentrations were greater in the winter than in the summer with concentrations of 0.69 µg/m³, 2.97 µg/m³ and 0.80 µg/m³ for benzene, toluene and xylene, respectively. In addition, toluene was the most common BTX compound with the highest concentrations when compared to benzene and xylene. Benzene, toluene and xylene, had yearly average concentrations of 0.61 µg/m³, 1.48 µg/m³ and 0.64 µg/m³, respectively. The benzene and xylene concentrations were below international exposure limits (annual, 5 µg/m³ for benzene; weekly, 260 µg/m³ for toluene), as in comparison to the World Health Organization, as well as within South African exceedance limits. Both positive and negative correlations between BTX and meteorological parameters were demonstrated by statistical models. Temperature, wind speed, and relative humidity depicted a weak negative correlation with benzene of 0.003, 0.019 and 0.006, respectively. Toluene showed a positive correlation with wind speed (1.90) and relative humidity (0.041). Overall, the concentration of benzene is of major concern since it is an agent of cancer and it is there in the atmosphere. Full article

The growing integration of distributed energy resources underscores the critical importance of having precise insights into the dynamics of an electrical power system (EPS). Consequently, an estimator must align with the EPS dynamics to enhance the overall reliability, safety, and system stability. This alignment ensures that operators can make informed decisions during system operations. An initial step in gaining insight into the system’s state involves examining its state vector, which is represented by voltage phasors. These results are derived through the application of a distributed state-estimation process in large-scale systems. This study delved into the effectiveness of Bayesian filters, with a particular emphasis on the extended Kalman filter (EKF) algorithm in the context of distributed state estimation. To analyze the outcomes, the nodal partitioning process was incorporated within the distributed state-estimation framework. The synergy between the EKF algorithm and the partitioning method was evaluated using the IEEE118 test system. Full article

In recent years, CAD/CAM technology has allowed indirect ceramic restorations to become a part of everyday chairside clinical practice. Therefore, the impact of different cavity-preparation designs on the fracture resistance of CAD/CAM fabricated ceramics was assessed in this study. Three designs of cuspal covering (none, palatal, and entire) and two widths of the occlusal isthmus (75% and 100% of the intercuspal distance) were used for the preparation of inlays and onlays to form six groups (n = 10/group). Moreover, thermomechanical cyclic loading was applied to every tooth under a chewing simulator. A universal testing machine was used to measure each group’s fracture resistance. The tested specimens were inspected for any signs of fractures and cracks to categorize failure patterns. Thereby, the values of fracture strength showed that there were statistically nonsignificant differences between the tested groups (p < 0.05). However, a significant difference (p = 0.01) was found between group 1 (inlays) (1950 ± 405) and group 6 (onlays) (3900 ± 770). Type III or type IV fracture modes were seen in the majority of the specimens. In conclusion, inlays and onlays made of zirconia using CAD/CAM technology were deemed reliable for restoring premolars, irrespective of the cavity-preparation design, except for inlays with a 75% intercuspal distance. Full article

While the current literature on Niceness in higher education has examined the discourses and practices of Niceness in academic spaces, making it more identifiable, less is known about how minoritized faculty navigate and disrupt the culture of Niceness. The purpose of this article is to offer a resistance-based framework to combat academia’s Niceness culture through the lens of the authors. Using theory in the flesh as theory and methodology, we use collaborative autoethnography to conceptualize Whisper Care to give language and articulate an orientation and philosophy rooted in Kindness. Our findings present a process to confront Niceness while guiding, supporting, and protecting each other in higher education institutions. We conclude with implications for future research and practice for faculty and higher education leaders. Full article

Fishery bycatch poses a significant threat to sea turtles. This study provides an updated assessment of Loggerhead turtle (Caretta caretta) bycatch in the Gulf of Gabès, focusing on the impact of the Garrasia gillnets. Through 61 onboard observations conducted alongside fishermen in Zarzis deploying a bottom-set gillnet, called “Garrasia”, and targeting elasmobranch species, comprehensive data were collected, including the number of sea turtles captured, soak time, length of gillnets, location, and biometric data of sea turtles. Analysis revealed a catch per unit effort (CPUE) for sea turtles of 0.63 (95% CI [0.355–0.893]) turtles per kilometer per 24 h with a notably high mortality rate of 92.06% (95% CI [87.3–96.8]). In the Gulf of Gabès, 23 vessels are reported to use Garrasia, resulting in an estimated annual total capture of 3756.53 turtles with a 95% CI [1907.81–5902.30]. These findings underscore the significant impact of Garrasia on sea turtle populations in the Gulf of Gabès. The study calls for immediate collaborative efforts among researchers, local stakeholders, authorities and fishermen to elaborate balanced conservation strategies that consider both ecological sustainability and socio-economic factors, aiming to achieve a sustainable marine ecosystem. Full article

Background and Objectives: Epidemiological studies have demonstrated the potential oncogenic effects of cumulative radiation exposure, particularly during childhood. One group experiencing repeated exposure to radiation at an early age for multiple years is patients treated for idiopathic scoliosis (IS). This study aimed to determine the relationship between childhood radiological exposure and adult cancer prevalence in children treated for IS. Materials and Methods: Data from 337 predominantly female patients treated at our hospital between January 1981 and January 1995 were gathered and compared to the Dutch national cancer rates. The standardized prevalence ratios for cancer in IS patients were compared with the cancer prevalence rates from the general Dutch population. Results: The overall cancer prevalence in women was 5.0%, with no significant difference compared to the general population (p = 0.425). The results of this study do not suggest that female patients treated for idiopathic scoliosis during childhood have an increased risk of cancer later in life. Conclusion: Despite being the largest recent study in its field, the modest participant number limits its ability to draw conclusions. However, the detailed data collected over a long observation period, alongside data from a period with comparable radiation rates, contributes to refining clinical practice and laying the groundwork for future systematic reviews. Full article

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level). Full article

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p=0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC. Full article

In hypoxic regions of malignant solid tumors, cancer cells acquire resistance to conventional therapies, such as chemotherapy and radiotherapy, causing poor prognosis in patients with cancer. It is widely recognized that some of the key genes behind this are hypoxia-inducible transcription factors, e.g., hypoxia-inducible factor 1 (HIF-1). Since HIF-1 activity is suppressed by two representative 2-oxoglutarate-dependent dioxygenases (2-OGDDs), PHDs (prolyl-4-hydroxylases), and FIH-1 (factor inhibiting hypoxia-inducible factor 1), the inactivation of 2-OGDD has been associated with cancer therapy resistance by the activation of HIF-1. Recent studies have also revealed the importance of hypoxia-responsive mechanisms independent of HIF-1 and its isoforms (collectively, HIFs). In this article, we collate the accumulated knowledge of HIF-1-dependent and independent mechanisms responsible for resistance of hypoxic cancer cells to anticancer drugs and briefly discuss the interplay between hypoxia responses, like EMT and UPR, and chemoresistance. In addition, we introduce a novel HIF-independent mechanism, which is epigenetically mediated by an acetylated histone reader protein, ATAD2, which we recently clarified. Full article

In this study, the variability of major glucosinolates in the leaf lamina of 134 Chinese cabbage accessions was investigated using Acquity ultra-performance liquid chromatography (UPLC-ESI-MS/MS). A total of twenty glucosinolates were profiled, of which glucobrassicanapin and gluconapin were identified as the predominant glucosinolates within the germplasm. These two glucosinolates had mean concentration levels above 1000.00 μmol/kg DW. Based on the principal component analysis, accessions IT186728, IT120044, IT221789, IT100417, IT278620, IT221754, and IT344740 were separated from the rest in the score plot. These accessions exhibited a higher content of total glucosinolates. Based on the VIP values, 13 compounds were identified as the most influential and responsible for variation in the germplasm. Sinigrin (r = 0.73), gluconapin (r = 0.78), glucobrassicanapin (r = 0.70), epiprogoitrin (r = 0.73), progoitrin (r = 0.74), and gluconasturtiin (r = 0.67) all exhibited a strong positive correlation with total glucosinolate at p < 0.001. This indicates that each of these compounds had a significant influence on the overall glucosinolate content of the various accessions. This study contributes valuable insights into the metabolic diversity of glucosinolates in Chinese cabbage, providing potential for breeding varieties tailored to consumer preferences and nutritional demands. Full article

The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior–posterior to left–right embryonic plane polarity through the polarization of cilia in the Kupffer’s vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP. Full article

Sub-Nyquist synthetic aperture radar (SAR) based on pseudo-random time–space modulation has been proposed to increase the swath width while preserving the azimuthal resolution. Due to the sub-Nyquist sampling, the scene can be recovered by an optimization-based algorithm. However, these methods suffer from some issues, e.g., manually tuning difficulty and the pre-definition of optimization parameters, and a low signal–noise ratio (SNR) resistance. To address these issues, a reweighted optimization algorithm, named pseudo-ℒ₀-norm optimization algorithm, is proposed for the sub-Nyquist SAR system in this paper. A modified regularization model is first built by applying the scene prior information to nearly acquire the number of nonzero elements based on Bayesian estimation, and then this model is solved by the Cauchy–Newton method. Additionally, an error correction method combined with our proposed pseudo-ℒ₀-norm optimization algorithm is also present to eliminate defocusing in the motion-induced model. Finally, experiments with simulated signals and strip-map TerraSAR-X images are carried out to demonstrate the effectiveness and superiority of our proposed algorithm. Full article

The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds’ ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A₂, showcasing the viability of small-molecule compounds in managing toxin-induced injuries. Full article

Composite polymer materials have high strength and lightness, which makes them attractive for use in a variety of structures and products. The present article contains an overview of modern works devoted to the production of composite materials based on poly(methyl methacrylate) (PMMA) with improved characteristics. The possibility of obtaining such materials can be a key area for creating more efficient and durable products in various industries. Various methods were considered to improve the characteristics of PMMA by doping the polymer matrix with carbon nanotubes (CNTs), graphite, nanohydroxyapatite particles, micro-zirconia nanoparticles, titanium dioxide, etc. The possibilities of using the obtained composite materials in various industries such as aviation, automotive, construction, medical and others are discussed. This article also presents the results of our own research on the mechanisms of interaction of PMMA with single-layer CNTs, leading to the creation of a composite polymer system “PMMA+CNT”, achieved using the modern quantum chemical method DFT. This article presents a review of the recent research on the effect of CNTs on the mechanical and electrically conductive properties of nanocomposite materials. The outcomes of this study can be important for the development of science and technology in various fields, from fundamental chemistry to applied scientific research. Full article

This study experimentally investigates the influence of metal chips and glass fibers on the mode I fracture toughness, energy absorption, and tensile strength of polymer concretes (PCs) manufactured by waste aggregates. A substantial portion of the materials employed in manufacturing and enhancing the tested polymer concrete are sourced from waste material. To achieve this, semi-circular bend (SCB) samples were fabricated, both with and without a central crack, to analyze the strength and fracture behavior of the composite specimens. The specimens incorporated varying weight percentages comprising 50 wt% coarse mineral aggregate, 25 wt% fine mineral aggregate, and 25 wt% epoxy resin. Metal chips and glass fibers were introduced at 2, 4, and 8 wt% of the PC material to enhance its mechanical response. Subsequently, the specimens underwent 3-point bending tests to obtain tensile strength, mode I fracture toughness, and energy absorption up to failure. The findings revealed that adding 4% brass chips along with 4% glass fibers significantly enhanced energy absorption (by a factor of 3.8). However, using 4% glass fibers alone improved it even more (by a factor of 10.5). According to the results, glass fibers have a greater impact than brass chips. Introducing 8% glass fibers enhanced the fracture energy by 92%. However, in unfilled samples, aggregate fracture and separation hindered crack propagation, and filled samples presented added barriers, resulting in multiple-site cracking. Full article