In recent trends, a rising demand for renewable energy has driven wind turbines to larger proportions, where lighter blade designs are often adopted to reduce the costs associated with logistics and production. This causes modern utility-scale wind turbine blades to be inherently more flexible, and their amplified aeroelastic sensitivity results in complex multi-physics reactions to variant atmospheric conditions, including dynamic patterns of aerodynamic loading at the rotor and vortex structure evolutions within the wake. In this paper, we analyze the influence of inflow variance for wind turbines with large, flexible rotors through simulations of the National Rotor Testbed (NRT) turbine, located at Sandia National Labs’ Scaled Wind Farm Technology (SWiFT) facility in Lubbock, Texas. The Common Ordinary Differential Equation Framework (CODEF) modeling suite is used to simulate wind turbine aeroelastic oscillatory behavior and wind farm vortex wake interactions for a range of flexible NRT blade variations, operating in differing conditions of variant atmospheric flow. CODEF solutions of turbine operation in Steady-In-The-Average (SITA) wind conditions are compared to SITA wind conditions featuring a controlled gust-like pulse overimposed, to isolate the effects of typical wind fluctuations. Finally, simulations of realistic time-varying wind conditions from SWiFT meteorological tower measurements are compared to the solutions of SITA wind conditions. These increasingly complex atmospheric inflow variations are tested to show the differing effects evoked by various patterns of spatiotemporal atmospheric flow fluctuations. An analysis is presented for solutions of wind turbine aeroelastic response and vortex wake evolution, to elucidate the consequences of variant inflow, which pertain to wind turbine dynamics at an individual and farm-collective scale. The comparisons of simulated farm flow for SITA and measured fluctuating wind conditions show that certain regions of the wake contain up to a 12% difference in normalized axial velocity, due to the introduction of wind fluctuations. The findings of this study prove valuable for practical applications in wind farm control and optimization strategies, with particular significance for modern utility-scale wind power plants operating in variant atmospheric conditions. Full article

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA. Full article

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFβ-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM. Full article

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies. Full article

Graphene-based materials are actively being investigated as sensing elements for the detection of different analytes. Both graphene grown by chemical vapor deposition (CVD) and graphene oxide (GO) produced by the modified Hummers’ method are actively used in the development of biosensors. The production costs of CVD graphene- and GO-based sensors are similar; however, the question remains regarding the most efficient graphene-based material for the construction of point-of-care diagnostic devices. To this end, in this work, we compare CVD graphene aptasensors with the aptasensors based on reduced GO (rGO) for their capabilities in the detection of NT-proBNP, which serves as the gold standard biomarker for heart failure. Both types of aptasensors were developed using commercial gold interdigitated electrodes (IDEs) with either CVD graphene or GO formed on top as a channel of liquid-gated field-effect transistor (FET), yielding GFET and rGO-FET sensors, respectively. The functional properties of the two types of aptasensors were compared. Both demonstrate good dynamic range from 10 fg/mL to 100 pg/mL. The limit of detection for NT-proBNP in artificial saliva was 100 fg/mL and 1 pg/mL for rGO-FET- and GFET-based aptasensors, respectively. While CVD GFET demonstrates less variations in parameters, higher sensitivity was demonstrated by the rGO-FET due to its higher roughness and larger bandgap. The demonstrated low cost and scalability of technology for both types of graphene-based aptasensors may be applicable for the development of different graphene-based biosensors for rapid, stable, on-site, and highly sensitive detection of diverse biochemical markers. Full article

Soil microorganisms play crucial roles in the stability of the global carbon pool, particularly in permafrost peatlands that are highly sensitive to climate change. Microtopography is a unique characteristic of peatland ecosystems, but how microtopography affects the microbial community structures and their functions in the soil is only partially known. We characterized the bacterial and fungal community compositions by amplicon sequencing and their abundances via quantitative PCR at different soil depths in three microtopographical positions (hummocks, flats, and hollows) in permafrost peatland of the Greater Xing’an Mountains in China. The results showed that the soil of hummocks displayed a higher microbial diversity compared to hollows. Microtopography exerted a strong influence on bacterial community structure, while both microtopography and soil depth greatly impacted the fungal community structure with variable effects on fungal functional guilds. Soil water content, dissolved organic carbon, total phosphorus, and total nitrogen levels of the soil mostly affected the bacterial and fungal communities. Microtopography generated variations in the soil water content, which was the main driver of the spatial distribution of microbial abundances. This information stressed that the hummock–flat–hollow microtopography of permafrost peatlands creates heterogeneity in soil physicochemical properties and hydrological conditions, thereby influencing soil microbial communities at a microhabitat scale. Our results imply that changes to the water table induced by climate warming inducing permafrost degradation will impact the composition of soil microbes in peatlands and their related biogeochemical functions, eventually providing feedback loops into the global climate system. Full article

The orderly withdrawal from rural homesteads is an important path for the smooth promotion of rural revitalization and new urbanization. This study aims to explore the influence and mechanism of social networks on the willingness of farm households to withdraw from homesteads. The study is based on a sample of 1971 farmer households in Jiangsu Province and analyzes the data using the logit model and mediation effect model. The results show that the social network has a significant positive effect on farmers’ willingness to withdraw from homesteads. As the social network expands, the probability for forming the willingness to withdraw from the homestead is higher for farmers with weaker social networks. In addition, the effect of social networks is different according to the level of regional economic development. The mechanism analysis suggests that social networks can indirectly increase the willingness to withdraw from homesteads by improving farmers’ risk resilience. Based on these findings, this study puts forward targeted policy recommendations: focusing on the cultivation and enhancement of farmers’ social networks, strengthening farmers’ risk resilience, and designing differentiated homestead exit policies. Full article

Extracellular vesicles (EVs) are membrane-bound particles released by cells to perform multitudes of biological functions. Owing to their significant implications in diseases, the pathophysiological role of EVs continues to be extensively studied, leading research to neglect the need to explore their role in normal physiology. Despite this, many identified physiological functions of EVs, including, but not limited to, tissue repair, early development and aging, are attributed to their modulatory role in various signaling pathways via intercellular communication. EVs are widely perceived as a potential therapeutic strategy for better prognosis, primarily through utilization as a mode of delivery vehicle. Moreover, disease-associated EVs serve as candidates for the targeted inhibition by pharmacological or genetic means. However, these attempts are often accompanied by major challenges, such as off-target effects, which may result in adverse phenotypes. This renders the clinical efficacy of EVs elusive, indicating that further understanding of the specific role of EVs in physiology may enhance their utility. This review highlights the essential role of EVs in maintaining cellular homeostasis under different physiological settings, and also discusses the various aspects that may potentially hinder the robust utility of EV-based therapeutics. Full article

In this paper, a fully differential amplifier is proposed in a 1.8 V-0.18 μm CMOS (Complementary Metal-Oxide-Semiconductor) technology, which can accommodate both voltage (V-mode) and current (C-mode) inputs. Post-layout simulation results show a fixed gain amplifier exhibiting a 26 dB (V-mode)/89 dBΩ (C-mode) gain and a programmable gain amplifier featuring a 6–26 dB gain, overall yielding a 26.8–46.4 dB dB (V-mode)/89.6–109.2 dBΩ (C-mode) programmable gain range, with a 100 MHz bandwidth and a power and area consumption of 360.5 µW and 0.0177 mm², respectively. This amplifier has been designed considering the constraints and specifications (including low voltage, low power, reduced noise and high common mode rejection ratio) for its use in an analogue Lock-in-based Frequency Response Analyser-Impedance Spectroscopy (FRA-IS) device. The proposed design introduces a novel fully differential open-loop structure based on a transconductance–transimpedance (TC-TI) topology for high performance applications with a broad programmable bandwidth. To compare this work, different figures of merit (FoMs) are introduced as well as a comparison table with other simulated and experimental results, reporting an overall better performance in terms of gain, frequency and power-area consumption. Full article

Loess is widely distributed in Northwestern China and serves as the preferred engineering construction material for anti-fouling barriers. Heavy metal contamination in soil presents significant challenges to the engineering safety of vulnerable loess structures. Hence, there is an urgent need to investigate the impact of heavy metal ions on their percolation performance. In order to investigate the effectiveness of microbially induced carbonate precipitation (MICP) using Sporosarcina pasturii (CGMCC1.3687) bacteria in reducing internal seepage erosion, a saturated permeability test was conducted on reshaped loess under constant water head saturation conditions. The response of loess to deionized water (DW) and ZnCl₂ solution seepages was analyzed by monitoring changes in cation concentration over time, measuring Zeta potential, and using scanning electron microscopy (SEM). The results indicate that the hydrolysis of Zn²⁺ creates an acidic environment, leading to the dissolution of carbonate minerals in the loess, which enhances its permeability. The adsorption of Zn²⁺ ions and the resulting diffusion double-layer (DDL) effect reduce the thickness of the diffusion layer and increase the number of free water channels. Additionally, the permeability of loess exposed to ZnCl₂ solution seepage significantly increased by 554.5% compared to loess exposed to deionized water (DW) seepage. Following the seepage of ZnCl₂ solutions, changes in micropore area ratio were observed, decreasing by 48.80%, while mesopore areas increased by 23.9%. MICP treatment helps reduce erosion and volume shrinkage in contaminated loess. Carbonate precipitation enhances the erosion resistance of contaminated loess by absorbing or coating fine particles and creating bridging connections with coarse particles. These research results offer new perspectives on enhancing the seepage properties of saturated loess in the presence of heavy metal erosion and the geochemical mechanisms involved. Full article

Background/Objectives: Hip fractures exert a substantial burden on hospital systems. Within Scotland 20% of the population resides rurally, warranting investigation of how this impacts prompt access to surgical care. This study aims to determine whether indirect hospital admission via hospital transfer affects the likelihood of surgical management within 36 h for hip fracture patients. Methods: A retrospective cohort study was performed. This used Scottish Hip Fracture Audit data including patients aged ≥50 split into two propensity matched groups based on their transfer status. Descriptive analysis compared patient characteristics. Regression assessed achieving surgery within 36 h of admission in the unmatched and matched cohorts. Secondary outcomes included time to surgery, mortality, mobilization, returning to residence and length of stay. A sensitivity analysis was undertaken to assess for residual confounding effects. Results: The unmatched analysis included 20,132 patients. Transfer patients were younger (p = 0.007) and less-comorbid (p < 0.001). In the matched population, 711 (63.6%) transfer patients had surgery with 36 h of presentation to hospital, compared to 852 (75.3%) non-transfer patients. Transfer patients had 43% reduced odds of timely surgery (OR (95% CI) 0.57 (0.48 to 0.69); p < 0.001). No disparities emerged in mortality, mobilisation or returning to residence., Transfer patients experienced a significant increase in length of stay in hospital (median (IQR) 16 (8 to 33) vs. 13 (8 to 30); p = 0.024). Conclusions: Hospital transfer is associated with significantly reduced odds of timely surgery, a longer time to surgery and longer length of stay. Development of structured network pathways that minimize delay to transfer are required to potentially optimize outcomes and reduce associated cost. Full article

Caspase-5 is a protease that induces inflammation in response to lipopolysaccharide (LPS), a component of the cell envelope of Gram-negative bacteria. The expression level of the CASP5 gene is very low in the basal state, but strongly increases in the presence of LPS. Intracellular LPS binds to the caspase activation and recruitment domain (CARD) of caspase-5, leading to the formation of a non-canonical inflammasome. Subsequently, the catalytic domain of caspase-5 cleaves gasdermin D and thereby facilitates the formation of cell membrane pores through which pro-inflammatory cytokines of the interleukin-1 family are released. Caspase-4 is also able to form a non-canonical inflammasome upon binding to LPS, but its expression is less dependent on LPS than the expression of caspase-5. Caspase-4 and caspase-5 have evolved via the duplication of a single ancestral gene in a subclade of primates, including humans. Notably, the main biomedical model species, the mouse, has only one ortholog, namely caspase-11. Here, we review the structural features and the mechanisms of regulation that are important for the pro-inflammatory roles of caspase-5. We summarize the interspecies differences and the evolution of pro-inflammatory caspases in mammals and discuss the potential roles of caspase-5 in the defense against Gram-negative bacteria and in sepsis. Full article

Kohlrabi is an important swollen-stem cabbage variety belonging to the Brassicaceae family. However, few complete chloroplast genome sequences of this genus have been reported. Here, a complete chloroplast genome with a quadripartite cycle of 153,364 bp was obtained. A total of 132 genes were identified, including 87 protein-coding genes, 37 transfer RNA genes and eight ribosomal RNA genes. The base composition analysis showed that the overall GC content was 36.36% of the complete chloroplast genome sequence. Relative synonymous codon usage frequency (RSCU) analysis showed that most codons with values greater than 1 ended with A or U, while most codons with values less than 1 ended with C or G. Thirty-five scattered repeats were identified and most of them were distributed in the large single-copy (LSC) region. A total of 290 simple sequence repeats (SSRs) were found and 188 of them were distributed in the LSC region. Phylogenetic relationship analysis showed that five Brassica oleracea subspecies were clustered into one group and the kohlrabi chloroplast genome was closely related to that of B. oleracea var. botrytis. Our results provide a basis for understanding chloroplast-dependent metabolic studies and provide new insight for understanding the polyploidization of Brassicaceae species. Full article

Recent reports indicate that the development of electricity generation using wind turbines will continue to grow. Despite the long service life of wind turbine blades, their technological life comes to an end at a certain point. Currently, there is no industrial method for recycling them, and the proposed solutions need to consider a complete and comprehensive approach to this material. In many countries, these blades are stored in special landfills and await proposals for rational recycling. It has been proposed that this recyclable yet still troublesome raw material be used in building sheathing boards. Sheathing boards used in the construction industry have a relatively long lifecycle. Three types of polymer chips and two resins, i.e., PF and MUF, were used in the study. The boards’ quality was assessed per the standards specified for particle boards. The resulting boards were characterized by strengths above 20 N/mm² and an elastic modulus close to 4000 N/mm². Slightly better results were obtained with the MUF resin. Full article

White crowberries (Corema album) are a fruit from an endemic shrub found in Southern European Atlantic costal dunes. Although this shrub and its fruits never became a formal commercial crop for a number of reasons, it has a long-lasting relevance and tradition, much associated with summer, beach and holidays. The main goal of this study was to conduct a thematic analysis of the words and small expressions people associate with white crowberries. For that, a questionnaire was used, and the participants were asked to indicate in an open-ended question which top-of-mind words/small expressions they associate with white crowberries. A total of 501 people participated in this study, of which only 394 knew about white crowberries, and from those, only 229 answered the open-ended question of interest to this purpose. The results showed that the words/small expressions given by the participants were distributed between five categories (1—Memories of places, people and times, 2—Emotions and experiences, 3—Sensorial perception, 4—Properties and uses, and 5—Natural resources’ valuation). Additionally, 18 subcategories were also identified. The most representative of the categories was sensorial perception and the most relevant of the subcategories was habitats (a subcategory from category 1). The most frequent words mentioned by the participants were beach, berry and summer. In addition, the effect of sociodemographic groups was investigated and some variations were observed in the categories of the words mentioned by the participants according to sex, living environment or region. This work allowed for the identification of a high variability in the words or expressions that account for a rich patrimony of tacit knowledge, memories, emotions and perceptions of the population towards white crowberries, thus confirming their social as well as nutritional relevance. Full article

Tetragonal ZrO₂, synthesized by the sol–gel method and dip-coating technique, was found to be photocatalytically active for the degradation of methylene blue. The ZrO₂ thin films were characterized by X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and UV-vis spectroscopy. The photocatalytic degradation of methylene blue was carried out with this material. We identified the tetragonal phase in ZrO₂ thin film at different annealing temperatures from 400 °C to 550 °C. The XRD study indicated that the films were monocrystalline in nature with preferred grain orientation along (011) plane and exhibited a tetragonal crystal structure. The crystallite size of the films increased with increasing annealing temperature. FTIR explained the bonding nature and confirmed the formation of the composite. UV-Vis showed the optical absorbance was high in the visible region and the optical band gap value increased with annealing temperature. The photocatalytic experimental results revealed that ZrO₂ thin films degraded MB by 20%, 24%, 29%, and 36%, with annealing temperatures of 400 °C at 550 °C for 10 h, respectively. Our results provide useful insights into the development of photocatalytic materials and degradation of methylene blue. Full article

Glioblastoma (GBM) is a devastating brain cancer for which new effective therapies are urgently needed. GBM, after an initial response to current treatment regimens, develops therapeutic resistance, leading to rapid patient demise. Cancer cells exhibit an inherent elevation of endoplasmic reticulum (ER) stress due to uncontrolled growth and an unfavorable microenvironment, including hypoxia and nutrient deprivation. Cancer cells utilize the unfolded protein response (UPR) to maintain ER homeostasis, and failure of this response promotes cell death. In this study, as integrins are upregulated in cancer, we have evaluated the therapeutic potential of individually targeting all αβ1 integrin subunits using RNA interference. We found that GBM cells are uniquely susceptible to silencing of integrin α3. Knockdown of α3-induced proapoptotic markers such as PARP cleavage and caspase 3 and 8 activation. Remarkably, we discovered a non-canonical function for α3 in mediating the maturation of integrin β1. In its absence, generation of full length β1 was reduced, immature β1 accumulated, and the cells underwent elevated ER stress with upregulation of death receptor 5 (DR5) expression. Targeting α3 sensitized TRAIL-resistant GBM cancer cells to TRAIL-mediated apoptosis and led to growth inhibition. Our findings offer key new insights into integrin α3’s role in GBM survival via the regulation of ER homeostasis and its value as a therapeutic target. Full article

Polyether amines are versatile compounds characterized by a flexible structure, consisting of polyoxypropylene and polyoxyethylene as the backbone, with amine groups at each end. They have widespread applications in various industrial processes and daily life. Despite their versatility, the utilization of polyether amines as base catalysts is rare. In this study, one kind of three-arm polyether amine 1 was employed as an environmentally friendly, cost-effective catalyst for the aerobic oxidation of thiophenols, leading to the synthesis of disulfides. The oxidative coupling of thiols serves as a fundamental pathway for the production of disulfides, which are vital in both chemical and biological processes. In contrast to known methods for thiol oxidation, this polyether amine-based catalytic process eliminates the need for expensive stoichiometric oxidants and minimizes the formation of over-oxidized by-products. Using a mere 0.5 mol % of the polyether amine 1 as the catalyst, a remarkable > 96% yield was achieved for all 16 tested substrates, encompassing a diverse range of functional groups, under the catalytic aerobic oxidation conditions. Furthermore, it is noteworthy that over 90% of the polyether amine catalyst can be efficiently recovered for reuse without loss of activity, making this a sustainable and cost-effective catalytic approach. Full article

Over the past few decades, Canadian courts have exerted strong influence over the meaning and operation of parliamentary privileges. Starting with a television producer’s Charter rights claim to access a provincial legislature’s public gallery and followed by an employment law claim made by the chauffeur to the Speaker of the House of Commons, the Supreme Court of Canada has articulated an approach under which judges closely scrutinise privileges invoked by legislatures when defending themselves against litigated claims. By applying the doctrine of necessity, Canadian courts make authoritative rulings on what counts as a valid legislative function and the processes and activities needed to fulfil those functions. Canadian courts also require the scope of parliamentary privileges to be pleaded in narrow terms that correspond to the details of a plaintiff’s claim, which has resulted in a hollowed-out conception of privilege over time. In scrutinising the necessity and scope of privilege, Canadian courts have chipped away at the separation of powers. Further, the Canadian approach unjustifiably prioritises the judicial vindication of private rights over the institutional needs of the legislature. Courts in other jurisdictions should reject the Canadian approach and avoid scrutinising the propriety of the exercise of privilege through a necessity test. Instead, courts should engage in a more limited jurisdictional test to confirm the availability of a relevant category of parliamentary privilege in law or historical practice. Judicialising parliamentary privileges weakens the autonomy and vitality of legislative institutions, with the Canadian approach serving as a cautionary tale. Ultimately, the legislature is accountable to the electorate for the exercise of its privileges. To promote fairness and reduce the risk of court interference, parliaments should strengthen the accountability and transparency associated with the exercise of their privileges, including by developing guidelines for their appropriate use. Full article

This study aimed to assess the influence of varying dietary levels of astaxanthin (AST) on the growth, antioxidant capacity and lipid metabolism of juvenile swimming crabs. Six diets were formulated to contain different AST levels, and the analyzed concentration of AST in experimental diets were 0, 24.2, 45.8, 72.4, 94.2 and 195.0 mg kg⁻¹, respectively. Juvenile swimming crabs (initial weight 8.20 ± 0.01 g) were fed these experimental diets for 56 days. The findings indicated that the color of the live crab shells and the cooked crab shells gradually became red with the increase of dietary AST levels. Dietary 24.2 mg kg⁻¹ astaxanthin significantly improved the growth performance of swimming crab. the lowest activities of glutathione (GSH), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and peroxidase (POD) were found in crabs fed without AST supplementation diet. Crabs fed diet without AST supplementation showed lower lipid content and the activity of fatty acid synthetase (FAS) in hepatopancreas than those fed diets with AST supplementation, however, lipid content in muscle and the activity of carnitine palmitoyl transferase (CPT) in hepatopancreas were not significantly affected by dietary AST levels. And it can be found in oil red O staining that dietary 24.2 and 45.8 mg kg⁻¹ astaxanthin significantly promoted the lipid accumulation of hepatopancreas. Crabs fed diet with 195.0 mg kg⁻¹ AST exhibited lower expression of ampk, foxo, pi3k, akt and nadph in hepatopancreas than those fed the other diets, however, the expression of genes related to antioxidant such as cMn-sod, gsh-px, cat, trx and gst in hepatopancreas significantly down-regulated with the increase of dietary AST levels. In conclusion, dietary 24.2 and 45.8 mg kg⁻¹ astaxanthin significantly promoted the lipid accumulation of hepatopancreas and im-proved the antioxidant and immune capacity of hemolymph. Full article

The feature matching of the near-bottom visual SLAM is influenced by underwater raised sediments, resulting in tracking loss. In this paper, the novel visual SLAM system is proposed in the underwater raised sediments environment. The underwater images are firstly classified based on the color recognition method by adding the weights of pixel location to reduce the interference of similar colors on the seabed. The improved adaptive median filter method is proposed to filter the classified images by using the mean value of the filter window border as the discriminant condition to retain the original features of the image. The filtered images are finally processed by the tracking module to obtain the trajectory of underwater vehicles and the seafloor maps. The datasets of seamount areas captured in the western Pacific Ocean are processed by the improved visual SLAM system. The keyframes, mapping points, and feature point matching pairs extracted from the improved visual SLAM system are improved by 5.2%, 11.2%, and 4.5% compared with that of the ORB-SLAM3 system, respectively. The improved visual SLAM system has the advantage of robustness to dynamic disturbances, which is of practical application in underwater vehicles operated in near-bottom areas such as seamounts and nodules. Full article

Multiple myeloma is a malignancy characterized by the accumulation of malignant plasma cells in bone marrow and the production of monoclonal immunoglobulin. A hallmark of cancer is the evasion of immune surveillance. Histone deacetylase inhibitors have been shown to promote the expression of silenced molecules and hold potential to increase the anti-MM efficacy of immunotherapy. The aim of the present work was to assess the potential effect of tinostamustine (EDO-S101), a first-in-class alkylating deacetylase inhibitor, in combination with daratumumab, an anti-CD38 monoclonal antibody (mAb), through different preclinical studies. Tinostamustine increases CD38 expression in myeloma cell lines, an effect that occurs in parallel with an increment in CD38 histone H3 acetylation levels. Also, the expression of MICA and MICB, ligands for the NK cell activating receptor NKG2D, augments after tinostamustine treatment in myeloma cell lines and primary myeloma cells. Pretreatment of myeloma cell lines with tinostamustine increased the sensitivity of these cells to daratumumab through its different cytotoxic mechanisms, and the combination of these two drugs showed a higher anti-myeloma effect than individual treatments in ex vivo cultures of myeloma patients’ samples. In vivo data confirmed that tinostamustine pretreatment followed by daratumumab administration significantly delayed tumor growth and improved the survival of mice compared to individual treatments. In summary, our results suggest that tinostamustine could be a potential candidate to improve the efficacy of anti-CD38 mAbs. Full article