Scientists can use the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system, which is a powerful and flexible tool for changing the genome, to change only certain parts of the genome. This has helped researchers figure out how target genes work in biology and disease. CRISPR/Cas9 is made up of a sequence-specific CRISPR RNA (crRNA) set and a generic Cas9 nuclease. The crRNA set tells Cas9 where to cut DNA and cause double-strand breaks. In the next step of cellular DNA repair, insertions, deletions, and swaps are made at specific spots. For CRISPR/Cas9-mediated DNA cleavage to be specific, the target sequences must match the crRNA, and a protospacer nearby motif must be placed after the target sequences. In this article, we talk about how CRISPR/Cas9 works at the molecular level, what it can be used for, what it can't do, and what its future clinical treatment promise might be.

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Although initially described as a tumor-cytotoxic agent, over time, it has also been recognized as an essential pro-inflammatory cytokine implicated in the pathogenesis of different autoimmune diseases, such as multiple sclerosis (MS). Several studies have shown an increase in TNF expression both in acute and chronic active MS brain lesions, as well as its involvement in maintaining a chronic inflammatory intrathecal process known as “compartmentalized inflammation”, which contributes to disease progression and disability accumulation in MS, even more than acute inflammatory activity. Indeed, high TNF levels were observed in the serum and cerebrospinal fluid of subjects with MS and correlated to disease severity, promoting axonal damage and, consequently, neurodegeneration. In this review we discuss the current knowledge of TNF and its receptors involvement in MS progression, focusing on disability progression independent of relapse activity (PIRA), meant as the disability accumulation evident in relapsing MS patients not related to acute inflammatory events.

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for Multiple Sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for Multiple Sclerosis patients.

Contaminated soils are a challenge for implementing biotechnology in bioremediation, recovery of Critical and Strategic Raw Materials (CRMs and SRMs), and food security. European Union (EU) Governments have established strict limits on As, Pb, Cd, and Hg in foods (Document 32023R0915), and requested the recovery of 34 CRMs within a circular economy (CE) (5th CRMs list). This study proposed a biotechnological tool for the decontamination of soil with heavy metal(loids) by arbuscular mycorrhizal (AM)-assisted phytoextraction and subsequent recovery of CRMs, or by phytostabilization to prevent their entry into the food chain. It consisted of placing Baccharis salicifolia plants, inoculated or non-inoculated with AM fungi, into Bioreactors (BRs) containing mining soil with Cd, Ni, and Cu, according to the argentinian Patent (AR090183B1). The bioextractive potential (BP) was also estimated at the highest Technological Readiness Level (TRL) using a Vegetable Depuration Module (VDM, TRL 6). Inoculated plants showed significantly higher aerial bioaccumulation coefficients (Cd: 68.62; P: 2.99; Ni: 2.51; Cu: 0.18) in BRs, and the BP values reached 1.16 g, 9.75 g, 2.40 g, and 213.1 g for Ni, Cd, Cu, and P, respectively. Finally, those CRMs and SRMs could be recovered from biomass through hydrometallurgy within a CE framework.

(1) Background: Youths with multiple risks and severe disadvantages experience poorer health and educational outcomes than less disadvantaged peers. To address problems with coping and self-regulation in this group, mental skills training (MST) approaches more commonly used in sport are an emerging intervention approach. (2) Methods and Results: This narrative review synthesizes literature to explain the need for MST, how it works, and evidence to support it works by focusing on two well evaluated programmes: LifeMatters and My Strengths Training for Life™. (3) Conclusions: To support positive youth development, MST is a strengths-based, flexible and adaptable approach to help fill the shortage of available evidence-based programs for those youths facing multiple disadvantages. The findings of this review may facilitate policy makers, commissioners, program planners, and researchers in the uptake of MST or similar psychoeducational approaches in future.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF-target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application, utilizing the R programming language, which predicts TF-target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF-target gene networks. Despite its current limitation to human data, it provides a platform for exploring gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species.

Estimating parameters for multiple datasets can be time consuming, especially when the number of datasets is large. One solution is to sample from multiple datasets simultaneously using Bayesian methods such as adaptive multiple importance sampling (AMIS). Here we use the AMIS approach to fit a von Misses distribution to multiple datasets for wind trajectories derived from a Lagrangian Particle Dispersion Model driven from a 3D meteorological data. The primary objective is to characterise the uncertainties in wind trajectories in a form that can be used as inputs for predictive models of wind-dispersed insect pests and pathogens of agricultural crops for use in evaluating risk and in planning mitigation actions. Our results show that AMIS can significantly improve the efficiency of parameter inference for multiple datasets.

(1) Background: The rapid development of information technology has changed the traditional concept of space, gradually shifting the "container space" to the "relational space" . The constraints of geographical spatial elements are diminishing, and the theory of virtual agglomeration is gaining attention. (2) Methods: In this study, we constructed an evaluation system for virtual agglomeration, comprising four primary indicators: virtual infrastructure level, virtual output level, virtual input level, and virtual service level. The TOPSIS method was used to calculate the virtual agglomeration level for each province, and the DEA-Malmquist method was employed to measure provincial total factor productivity (TFP) in China. Using panel data from 30 provincial regions in China from 2013 to 2021, we examined the mechanism and impact path of virtual agglomeration on TFP. (3) Result: There is an inverted U-shaped relationship between virtual agglomeration and TFP in China. The overall development level of virtual agglomeration is relatively low, within the range where the marginal effect of virtual agglomeration on TFP is positive but diminishing, indicating significant potential for further development. The impact of virtual agglomeration on TFP is stronger in the Yangtze River Economic Belt compared to non-Yangtze River areas, and the highest stable point of TFP is higher in central provinces than in eastern and western provinces. (4) Conclusions: This study provides a theoretical basis and practical reference for improving the level of virtual agglomeration.

The spread of fake news poses a serious threat to public trust and informed decision-making. The emergence of AI-generated fake news exacerbates this issue, as it can be produced more rapidly and convincingly than human-generated content. Addressing this issue, our paper introduces a robust approach to detect AI-generated fake news that is applicable across major disinformation domains: Politics and Elections, Health and Medicine, Science and Technology, and Entertainment and Celebrities. Our models differentiate between AI-generated and human-generated news articles while assessing their truthfulness. Utilizing large language models such as ChatGPT, we curated datasets spanning both AI and human generated fake and genuine news. Following extensive data preprocessing and the application of diverse feature extraction techniques, our models were trained using multiple machine learning algorithms. Our results show the feasibility of accurately identifying AI-generated fake news, thereby adding a significant layer of defense in combating misinformation across various sectors. In addition, we have explored the potential utility of transferable machine learning models trained on data from one domain (e.g., politics), when tested on another domain (e.g., health).

Rock materials failures are accompanied by the co-existence of various failure mechanisms, in-cluding rock fracturing, shearing, and compaction yield. These mechanisms manifest macro-scopically as multiple failure modes and nonlinear strength characteristics related to stress levels. Considering the limitations of current rock mechanics strength theories, which are primarily derived from single failure mechanisms, this study evaluates the applicability of alternative strength theories. Based on the extensional-strain criterion and the PMC (Paul-Mohr-Coulomb) model, a piecewise linear strength model was proposed that is suitable for analyzing multiple failure mechanisms in rocks and revealing the intrinsic mechanisms of multi-mechanism rock material failure. A multiple failure mechanism strength model in the form of inequalities was proposed, using the generalized shear stress, mean stress, and stress Lode angle as parameters. Strength tests conducted on sandstone and granite rock material samples under different stress conditions revealed distinct piecewise linear strength characteristics for both rock types, vali-dating the rationality and applicability of the multiple failure mechanism model. The findings construct a multi-mechanism failure model for rocks, providing enhanced predictive capabilities and aiding in the prevention of rock structural failures.

Research into lightweight structural concrete using volcanic tuff is of great importance to the construction industry. These materials have excellent thermal insulation properties, which helps improve the energy efficiency of buildings. A three-factor experimental design was used to build the statistical model. The test methods used were methods for determining the crushability of volcanic tuff, determining the average density, compressive strength and thermal conductivity of lightweight structural concrete. The influence of basalt fiber on the properties of lightweight structural concrete has been determined. The optimal compositions of lightweight structural concrete using tuff have been selected. The compressive strength of lightweight structural concrete reached 32.0 MPa. The average density range is 1754.6-2114.0 kg/m³. Good thermal conductivity values ​​were obtained in the range of 0.653-0.818 W/m·K. The article obtained the optimal compositions of lightweight structural concrete using volcanic tuff as a filler.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

MIMO (multiple-input multiple-output) radar provides much more flexibility than the traditional radar for its ability to realize far more observation channels than the actual number of T/R (transmit and receive) elements. Designing the array of MIMO imaging radar, the commonly used virtual array theory generally assumes that all elements are placed on the same line. However, due to the physical size of the antennas and coupling effect between T/R elements, a certain height difference between T/R arrays is essential, resulting in the defocusing of edge points of the scene. On the other hand, the virtual array theory implies far-field approximation, leading to inevitable high grating lobes in the imaging result of near-field edge points of the scene observed by common MIMO array. To tackle these problems, this paper derives the relationship between target’s PSF (point spread function) and pattern of T/R arrays, by which the design criterion of near-field imaging MIMO array is presented. Firstly, the proper height between T/R arrays is designed to focus the near-field edge points well. Secondly, the far-field array is modified to suppress the grating lobes in the near-field area. Finally, the validity of the proposed methods is verified by simulations and an experiment.

This paper focuses on studying the mapping properties of singular integral operators on product spaces. The boundedness of such operators is established on Triebel-Lizorkin spaces whenever their kernel functions belong to Grafakos and Stefanov class. Our results generalize and improve some previously known results.

This paper introduces a novel framework for zero-shot learning (ZSL), i.e., to recognize new categories that are unseen during training, by distilling knowledge from foundation models. Specifically, we first employ ChatGPT and DALL-E to synthesize reference images of unseen categories from text prompts. Then, the test image is aligned with text and reference images using CLIP and DINO. Finally, the predicted logits are aggregated according to their confidence to produce the final prediction.Experiments are conducted on multiple datasets, including CIFAR-10, CIFAR-100, and TinyImageNet. The results demonstrate that our model can significantly improve classification accuracy compared to previous approaches, achieving AUROC scores above 96\% across all test datasets. Our code is available at https://github.com/1134112149/MICW-ZIC.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

An increased demand for natural products nowadays most specifically probiotics (PRO) is evident since it comes in conjunction with beneficial health effects for the consumers. In this regard, it is well known that encapsulation could affect positively the PRO's viability throughout food manufacturing and long-term storage. This paper aims to analyze and review various multilayer strategies for encapsulation of PRO. Double-layer encapsulation of PRO by electro-hydrodynamic atomization or electrospray technology has been reported along with layer-by-layer assembly and water-in-oil-in-water (W1/O/W2) double emulsions to produce multilayer PRO-loaded carriers. Finally, their applications in food products are presented. The resistance (cover material) and viability of (PRO) to mechanical damage, during gastrointestinal transit and shelf life of these trapping systems are also described. The PRO encapsulation in double and multiple-layer coatings combined with other technologies can be examined to increase the opportunities for new functional products with amended functionalities opening a novel horizon in food technology.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Segment Anything Model 2 (SAM 2) is a state-of-the-art development by Meta AI Research, designed to address the limitations of its predecessor, SAM, particularly in the realm of video segmentation. SAM 2 employs a transformer-based architecture enhanced with streaming memory, enabling real-time processing for both images and videos. This advancement is important given the exponential growth of multimedia content and the subsequent demand for efficient video analysis. Utilizing the SA-V dataset, SAM 2 excels in handling the intricate spatio-temporal dynamics inherent in video data, ensuring accurate and efficient segmentation. Key features of SAM 2 include its ability to provide real-time segmentation with minimal user interaction, maintaining robust performance even in dynamic and cluttered visual environments. This study provides a comprehensive overview of SAM 2, detailing its architecture, functionality, and diverse applications. It further explores the model's potential in improving practical implementations across various domains, emphasizing its significance in advancing real-time video analysis.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

Network Function Virtualization (NFV) allows for the dynamic provisioning of Virtualized Network Functions, adapting services to the complex and real-time network environment for enhanced network performance. Despite the benefits of NFV, virtual network functions (VNFs) migration and the energy consumption pose significant challenges due to the dynamic nature of the physical network, especially in the edge-cloud continuum network. Currently, people tackle this challenge by predicting the network traffic and then proactively migrating the VNFs using the predicted values. There are two challenges here. First, when SFCs belong to different network service providers, the historical network traffic data is held by the service providers, and they are reluctant to share the historical data due to privacy concerns. Without the historical network traffic data of each SFC, the resource provider that owns the underlying network cannot effectively predict the network traffic; in addition, without the feedback of the migration results of the underlying physical network, the network traffic prediction will be difficult to match the needs of the physical network. In this manuscript, we solve the problem of network traffic prediction in the NFV-based edge-cloud continuum network for multiple network service providers. We aim to improve migration performance and reduce energy consumption while ensuring resource and latency requirements. To protect the privacy of each network service provider, we apply an FL algorithm. After that, to improve the migration performance, we tailor the loss function. In the loss function, factors such as the number of migrations, the number of migration failures, and the energy consumption of the NFV-based edge-cloud continuum network are added. Additionally, to obtain the results of the SFC migration, we develop a mathematical model for the problem of multiple network service providers in the NFV-based network. The effectiveness of our algorithm is evaluated through extensive simulations, and the results show a significant reduction in the number of migrated nodes and energy consumption while improving the SFC acceptance ratio compared to state-of-the-art schemes which only use the difference between predicted and actual flows to define the loss function.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

The number of physical devices connected to the Internet such as vehicles, household appliances and other "things" has been steadily increasing in recent years, thus forming the basis for the Internet of Things (IoT). IoT ecosystem extends beyond country borders and application domains, combining thousands of versatile devices that differ in terms of their structures, capabilities, and available resources. It is therefore not surprising that the landscape of wireless communication technologies and the degree of IoT devices available today is excessively broad and diverse. Interference between networks leads to frame collisions and consequent packet loss. Frame collisions occur when two or more packets overlap in time and frequency and use the same Long Range (LoRa) parameters, i.e. the same Spreading Factor (SF), Bandwidth (BW) and Carrier Frequency (CF). When most devices use the same configuration, collision probability is higher. The probability of frame collisions is also affected by traffic characteristics, particularly the periodicity of the transmission and the payload size. Larger payload sizes and more frequent transmissions accumulate with higher Time on Air (ToA) and channel occupancy [1]. Transmission powers and the location of the gateways also influences this situation. The aim of this experimental work is to verify the effects of collisions and interference in Long Range Wide Area Network (LoRaWAN), regarding the periodicity of transmissions and the payload sizes in a context of an inter-SF interference scenario. And to validate measuring tools like Received Signal Strength Indicator (RSSI), ToA and Packet Delivery Ratio (PDR) in the reliability of a network. We validate our conclusions by analyzing ToA according with RSSI and different data sizes, the RSSI for different SFs and different data sizes and finally the packet loss through the PDR for a better understanding of the reliability of packet transmission in our link. In the end we conclude that in an environment with inter-SF interference, the choice of SFs and packet lengths impacts ToA. When dealing with multiple devices near gateways, different SFs and varying packet lengths can lead to increased latency and longer ToA. Consequently, the risk of packet loss becomes more significant, especially if the signal-to-interference ratio (SIR) is low. This limitation will therefore affect scalability, particularly in Non-Line-Of-Sight (NLOS) scenarios.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Energy from biogas is one of the most promising renewable energy sources. Significant, for technical, economic, and environmental reasons, is the construction of agricultural microgas plants next to households specialising in cattle rearing. The availability of free substrate makes it possible not only to produce one's electricity and heat but also to produce a more environmentally and human-friendly manure. The operation of biogas plants is, unfortunately, associated with technical problems. This paper presents the results of a study of the quality of electricity generated in an agricultural biogas plant built at a farm specialising in dairy cows, where the owner reported a problem with the voltage in the power supply network. Therefore, selected power quality parameters occurring at the connection point of the biogas plant were analysed in detail. As the authors' research showed, in the case in question, the agricultural biogas plant was connected via a cable with too small a conductor cross-section, which resulted in significant voltage exceedances, making it impossible to switch on the second of the biogas plant's generators. Replacement of the feed-in cable has enabled both generators to run, but significant fluctuations in the feed-in voltage values were still noticeable. Analysis of the subsequent measurements revealed the need for changes in the design of the digester itself. The proposal for change is to replace the two current digester mixers (each rated at 9 kW) with more mixers of lower power. The new mixers would operate in an alternating system, where only one would always be activated.

Forests have multifunctional roles. They not only increase forest carbon sinks through afforestation and management, but also indirectly realize multiple benefits of "economy + ecology + society". Therefore, we construct a multiple output-benefit system of forest carbon sinks based on the development of forest carbon sinks in provinces of China. This system is also able to distinguish the importance of forest carbon sinks from other outputs. For the efficiency evaluation of multi-level output systems, this paper constructs a cross-evaluation model based on evidential reasoning method, the original efficiency information by conducting efficiency evaluation before information fusion. Further, the spillover effects and influencing factors of forest carbon sink efficiency are analyzed through a spatial regression model to explore the spatial characteristics of forest carbon sink efficiency in China. The results show that: (1) there is a large gap between the cross-efficiency levels of forest carbon sinks in various regions of China, with significant spatial correlation. For the perspective of direct output benefits, the cross-efficiency of the eastern region is higher, while the cross-efficiency of the northwestern region is lower; for the perspective of indirect output benefits, the cross-efficiency of the southeastern region is higher. (2) China's forest carbon sink has a significant positive spillover effect, and the indirect output cross-efficiency has a significant negative impact on the forest carbon sink in its own region. Further analyzing the impact of indirect output cross-efficiency, it is found that the cross-efficiency of the ecological dimension and the cross-efficiency of the social dimension have a significant negative impact on the forest carbon sink in its own region, and the economic dimension has a significant positive impact on the forest carbon sink in its own region. In conclusion, corresponding policy recommendations are proposed for the development of forest carbon sinks to promote the realization of the dual-carbon goal.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients, and healthy subjects with (GBA-C) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn & Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-C and HC were also considered. Clinical assessment included the MDS-UPDRS and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-C (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p<0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p<0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-DHP. Allopregnanolone was the only neurosteroid significantly lower (p<0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

This article proposes an interferometer which should in principle split further an initially split beam to yield new sets of beams, effectively multiplying the number of beams that can be subjected to detectable interference. It can be considered a modification to the Michelson interferometer that introduces additional arrays of beam splitters, mirrors and detectors. It is expected of the interferometer to provide us with a set or sets of data holding details of phase changes in multiple interference patterns detectable by multiple detectors, enabling comparative analysis of data for multiple interference patterns recorded from a single measurement or activity. The number of multiplied beams possible is not limited, as it only depends on the specific amount of beam splitters required for certain experiments and practicals. The interference of multiple beams may improve sensitivity and detection for instrumentation purposes. The use of multiplied beam interferometry may also extend to quantum computation, particularly in linear optical quantum computation scheme as it enable production of multiple coherent beams which may exhibit properties of entanglement, making it suitable for developing optical multi-qubit systems.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

In this paper, we investigated the formation isolation regulation issue regarding multiple autonomous underwater vehicles (AUVs) characterized by a "leader-follower" framework. Considering the cooperative-competitive relationship among the follower AUVs and the impact of unknown external disturbances, an extended state observer was designed based on backstepping to mitigate these disturbances, and an event-triggered control scheme was designed to realize the two-part consensus control within the multi-AUV system. Through rigorous theoretical analysis, it is shown that the system achieves asymptotic steadiness and is free from zeno behavior under the proposed event-triggered control scheme. Finally, numerical simulations confirm the efficiency of the regulation strategy in achieving formation separation within the multi-AUV, where the trajectory tracking errors of individual AUVs gather in a compact vicinity close to the source and the structure converges was achieved, with the absence of zeno behavior also demonstrated.

Most research on sustainable small-scale, local producer lifestyles emphasises healthy food production, lacking integration of mental and spiritual well-being into a holistic concept of a healthy lifestyle. This study explores the motives behind the production activity of producers engaged in sustainable food production in several Western Hungarian sub-regions, aiming to identify their attitudes and motivations. The small-scale entrepreneurial mindset encompasses needs beyond physical and ethical aspects, such as involvement, socio-cultural attachment to the past, tradition, nature, place, and local culture. An online questionnaire was conducted with 73 local producers in the second quarter of 2024. The results of the factor and cluster analyses were used to classify the producers into two clusters: the "Value-Creator" and the "Proud" clusters. The main features of these two clusters were illustrated in persona profiles. The "Value-Creator" cluster, mainly women, feel a strong connection to the local community and view sustainable production as a lifestyle choice. The "Proud" cluster, consisting of young men, focus on the quality and uniqueness of their products. This research contributes to a deeper understanding of sustainable production by exploring producers' intrinsic motivations and lifestyle choices. The findings could also inform other entrepreneurial projects, such as urban initiatives.

Alignment of picornavirus proteinase/polymerase sequences reveals this family evolved into five ‘supergroups’. Interestingly, the nature of the 2A region of the picornavirus polyprotein is highly correlated with this phylogeny. Viruses within supergroup 4, the Paavivirinae, have complex 2A regions with many viruses encoding multiple 2A^NPGP sequences. In vitro transcription/translation analyses of a synthetic polyprotein comprising green fluorescent protein (GFP) linked to b-glucuronidase (GUS) via individual 2A^NPGPs showed two main phenotypes: highly active 2A^NPGP sequences - similar to Foot-and-Mouth Disease Virus 2A^NPGP and, surprisingly, a novel phenotype of some 2A^NPGP sequences which apparently terminate translation at the C-terminus of 2A^NPGP - without detectable re-initiation of downstream sequences (GUS). Probing databases with the short sequences between 2A^NPGPs did not reveal any potential ‘accessory’ functions. The novel, highly active, 2A-like sequences we identified substantially expands the toolbox for biomedical / biotechnological co-expression applications.

Plain lakes play a crucial role in the hydrological cycle of a watershed, but their interactions with adjacent rivers and downstream water bodies can create complex river-lake relationships, often leading to frequent flooding disasters. Taking Poyang Lake as an example, this paper delves into its interaction with the Yangtze River, revealing the spatiotemporal patterns of flood propagation within the lake and its impact on surrounding flood control measures. The aim is to provide insights for flood management in similar environments worldwide. This study employs a comprehensive approach combining hydrological statistical analysis and two-dimensional hydrodynamic modeling, based on extensive hydrological, topographic, and socio-economic data. The results indicate that the annual maximum outflow from Poyang Lake is primarily controlled by floods within the watershed, while the highest annual lake water level is predominantly influenced by floods from the Yangtze River. The peak discharge typically reaches the lake outlet within 48 hours, with the peak water level taking slightly longer at 54 hours. However, water storage in the lake can shorten the time for the peak discharge to arrive. When converging with floods from the Yangtze River, the peak water level may be delayed by up to 10 days due to the top-supporting interaction. Furthermore, floods from the "Five Rivers" propagate differently within the lake, affecting various lake regions to differing degrees. Notably, floods from the Fu River cause the most significant rise in lake water level under the same flow rate. The top-supporting effect from the Yangtze River also significantly impacts the water surface slope of Poyang Lake. When the Yangtze River flood discharge far exceeds that of the "Five Rivers" (i.e., when the top-supporting intensity f value exceeds 4), the lake surface becomes as flat as a reservoir. During major floods in the watershed, the water level difference in the lake can increase dramatically, potentially creating a "dynamic storage capacity" of up to 840 million cubic meters.

Suicide is a public health problem influenced by a variety of biological, psychological, social, and environmental factors. Recognizing the warning signs at each stage is crucial for prevention and helping those at risk. In this context, body awareness, especially interoceptive body awareness, emerges as a potentially relevant and underexplored factor. In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation in Colombian university students. In addition, the bootstrap technique was used to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings are consistent with previous literature on the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship in depth.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

In this paper, we investigate a class of hierarchical variational inequalities (HVIPs, i.e., strongly monotone variational inequality problems defined on the solution set of multiple-set split common fixed point problems) with quasi-pseudocontractive mappings in real Hilbert spaces, which special cases can be found in many important engineering practical applications such as image recognizing, signal processing and machine learning. In order to solve HVIPs of potential application value, inspired by the primal-dual algorithm, we propose a novel accelerated cyclic iterative algorithm that combines the inertial method with a correction term and a self-adaptive step-size technique. Our approach eliminates the need for prior knowledge of the bounded linear operator norm. Under appropriate assumptions, we establish strong convergence of the algorithm. Finally, we apply our novel iterative approximation to solve multiple-set split feasibility problems and verify the effectiveness of the proposed iterative algorithm through numerical results.

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

Rice yield underperformance coupled with production instability in Odisha state of India is primarily due to low irrigation potential, the spatiotemporal disparity in rainfall pattern and relentless confrontation with biotic and abiotic stresses. System of Rice Intensification (SRI) was introduced in the state with the promises of higher production horizon. However, the present scenario of patchy adoption pattern has necessitated comprehensive study on dynamics and determinants of adoption of SRI. We found that, 57 percent farmers continued SRI, 28 percent discontinued and rest were practicing conventional rice farming. The focused group discussion among the farmers helped us to triangulate the determinants of SRI adoption.The increased SRI area allocation was observed at the expense of reduced number of adopting farmers. Economic scarcity of skilled labour, difficulties in transplantation and mechanical weeding, low irrigation potential and poor on-farm water management were major constraints in SRI practice. Farmers’ compliance in following different resilient SRI components that also varied spatiotemporally has resulted in realized incremental yield. SRI was proved to be resilient to severe drought during 2015-16 and yielded 27 percentage higher than conventional one with considerable decline in hazardous chemicals usage. Farmers’ decision on SRI adoption/discontinuation was analysed using probit regression analysis. The results indicated that, active social involvements of NGOs, on-farm training and demonstrations, and realized incremental rice income influenced SRI adoption. On the other hand, SRI area expansion hindered mainly because of infeasible land topography, area saturation and lack of farmers’ interest. The sustainability index was developed to analyse SRI’s performance to other conventional methods at farm level. Comparatively, SRI adopters benefitted in terms of incremental net return by enhancing ecological balance and sustained productivity of soil, use of eco-friendly and own farm inputs. Nonetheless, higher women labour displacement observed under SRI can be curtailed by providing training to young farm women.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

In this study, we provided an empirical testability of the FF3FM against the co-moment-augmented FF3FM using the Newey–West GMM methods to account for potential endogeneity. The results showed that value risk is not significantly priced, and systematic skewness and systematic kurtosis play more important roles in explaining asset return than market and size factors. We discovered that there is much to gain in moving from the incumbent FF3FM to the co-moment-augmented FF3FM. By extending this study to Nigeria and using out-of-sample data that span across the recent COVID-19 period, the study has contributed to existing knowledge significantly. The study concludes that the co-moment-augmented FF3FM is superior to the incumbent FF3FM in pricing assets, and the anomalies associated with the return-size risk factor relationship are reduced by accounting for systematic skewness and systematic kurtosis in the FF3FM. Therefore, we recommend that investors should take a long position in size-hedged portfolios and hold systematic skewness and kurtosis as constant, and vice visa.

In view of the fact that the field monitoring information can more intuitively and accurately reflect the stability state of slopes, this paper takes the warning threshold of slope deformation rate monitoring as the slope stability evaluation standard, and puts forward a method for solving the safety coefficient of rocky slopes. The discrete element method 3DEC, which is suitable for rocky slopes, is selected as the numerical calculation tool, and the convergence criterion of its strength reduction method is modified to the slope deformation rate threshold, and the method is realized by the bifurcation method through its built-in FISH programming language. The results of the classical case show that, by selecting the slope deformation rate threshold in the appropriate interval, the results of this paper's method are very close to those of the finite unit stress method and the limit equilibrium method, which verifies the reliability of this paper's method. Further, the method of this paper is applied to an open-pit mine slope project, based on the slope deformation on-site monitoring data, through the time series prediction method to determine the slope deformation rate warning threshold, using the threshold as an evaluation criterion to solve the slope's coefficient of safety, the calculation results show that: the slope's coefficient of safety in natural working conditions is 1.086, basically stable, suffered from continuous rainfall, the slope body is gradually saturated, the slope's coefficient of safety is reduced to 0.987, the slope's safety is reduced to 0.987. After continuous rainfall and gradual saturation of the slope, the coefficient of safety decreased to 0.987, destabilizing and destroying, which is consistent with the site conditions.

Background/Objectives: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety is limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods: Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsy-chiatric AE and one of the MM-approved mAbs as the suspect drug (i.e., daratumumab, elo-tuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results: Unknown signals of disproportionate reporting (SDR) included cerebral infarction for daratumumab (n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC025-IC075 = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guil-lain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthos-tatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elontuzumab (4; 28.31, 10.58-75.73; 5 , 3.24-6.08). Conclusions: Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsy-chiatric AEs, including GBS, further investigations are necessary.

Recently, microfluidics deformability cytometry has emerged as a powerful tool for high throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints through exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids such as methyl-cellulose dissolved in phosphate-buffered saline is significantly influential to the resulting cellular deformation. We conducted CFD simulations that are conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e. HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses.

This article aims to assess Pakistan's National Spatial Data Infrastructure implementation efforts through well-established approaches including the SDI readiness model, organizational aspects, and state of play. The findings underscored challenges related to human resources, SDI education/culture, long-term vision, GI awareness, sustainable funding, metadata availability, online geospatial services, and geospatial standards hindering the NSDI development in Pakistan. However, certain factors, such as the legal framework for NSDI establishment, web connectivity, geospatial software availability, core spatial dataset availability, and institutional leadership, exhibit favorable standings. Thus, to enhance the development of NSDI for Pakistan, recommendations include bolstering financial and human resources, improving online geospatial presence, and fostering a long-term vision for NSDI.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

The number of physical devices connected to the Internet such as vehicles, household appliances and other "things" has been steadily increasing in recent years, thus forming the basis for the Internet of Things (IoT). IoT ecosystem extends beyond country borders and application domains, combining thousands of versatile devices that differ in terms of their structures, capabilities, and available resources. It is therefore not surprising that the landscape of wireless communication technologies and the degree of IoT devices available today is excessively broad and diverse. Interference between networks leads to frame collisions and consequent packet loss. Frame collisions occur when two or more packets overlap in time and frequency and use the same LoRa parameters, i.e. the same spreading factor (SF), bandwidth (BW) and carrier frequency (CF). When most devices use the same configuration, collision probability is higher. The probability of frame collisions is also affected by traffic characteristics, particularly the periodicity of the transmission and the payload size. Larger payload sizes and more frequent transmissions accumulate with higher time on air (ToA) and channel occupancy [1]. Transmission powers and the location of the gateways also influences this situation. The aim of this experimental work is to verify the effects of collisions and interference in LoRaWAN, regarding the periodicity of transmissions and the payload sizes. The hardware used is an Arduino board programmed in C/C++, a LoRa Bee module operating at a frequency of 868 MHz and a LoRaWAN LG02 gateway. Different scenarios were tested in an outdoor environment, with Line of Sight and Non-Line of Sight, and different variables such as: SFs equal to 7, 9 and 12; distances of 20, 40 and 60 meters and different data sizes of 14, 32 and 51 bytes, over the same channel. The packets with different SF’s and different data sizes were transmitted in a (pseudo) random way, one after the other, overlapping different SFs in the same channel and testing this way (theoretical) orthogonality among them. By fixing the bandwidth in 125 kHz, and testing different SFs we intend to increase the probability of cause packet loss by applying to our connection a combination of emitted power/short distance that leaves an interference power received, strong enough [2] for the effect. We validate our conclusions by analyzing ToA according with RSSI and different data sizes, the RSSI for different SFs and different data sizes and finally the packet loss through the PDR-Packet Delivery Ratio for a better understanding of the reliability of packet transmission in our link.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

The sleeping and grazing behaviors of horses play a crucial role in their health and welfare. In the horse industry, with the prevalent trend of individual single-stall farming in stable, accurately identifying various behaviors of horses within stables is imperative. This study has established a spatio-temporal dataset for horse postures and behaviors, proposed an algorithm utilizing a SE-SlowFast network with an enhanced loss function. This algorithm achieves automatic recognition of multiple postures and behaviors of horse simultaneously. The model developed in this study demonstrates high accuracy in identifying three postures within the stable: Standing, Crouching, and Lying, achieving respective accuracies of 92.73%, 91.87%, and 92.58%. Additionally, it accurately recognizes two behaviors: Sleeping and Grazing, achieving best accuracies of 93.56% and 98.77%. The overall best accuracy of the model is 93.9%. Experiments on video recognition confirm that the suggested model recognizes horse video data accurately. This study marks the first time computer vision technology has been used in the horse farming industry, achieving non-intrusive recognition of multiple horse postures and behaviors. This study provides valuable data support for livestock managers to evaluate the health conditions of horses, enhances the welfare of horses in stables, and contributes to the advancement of modern horse husbandry practices.

Background: Population studies have shown that prehypertension is associated with adverse cardiometabolic risk profile even among apparently healthy populations. Although associations between serum triglyceride (TG) concentrations and the risk of atherosclerotic cardiovascular disease have been reported, there are lack of data on the association of hypertriglyceridemia with cardiovascular risk (CVR) in a low risk prehypertensive population. Aim: Our aim was to analyze the cardiorenometabolic characteristics of prehypertensives (PHT) compared to normotensives (NT) and untreated hypertensives (HT) and its associations with CVR. Materials and methods: In our cross-sectional study we included 323 apparently healthy untreated subjects 18-45 years who underwent basic anthropometric and standardized blood pressure measurement, fasting blood sampling, spot urine collection and transthoracic echocardiogram. Results: Higher BMI, waist circumference, HOMA-IR, LDL-cholesterol, TG, uric acid and LVMI contribute to higher CVR in PHT compared to true NT (p

In the context of smart agriculture, accurately estimating plant leaf chemical parameters is crucial for optimizing crop management and improving agricultural yield. Hyperspectral imaging, with its ability to capture detailed spectral information across various wavelengths, has emerged as a powerful tool in this regard. However, the complex and high-dimensional nature of hyperspectral data poses significant challenges in extracting meaningful features for precise estimation. To address this challenge, this study proposes an end-to-end estimation network for multiple chemical parameters of Astragalus leaves based on attention mechanism (AM) and multivariate hyperspectral features (AM-MHENet). We leveraging HybridSN and multilayer perception (MLP) to extract prominent features from the hyperspectral data of Astragalus membranaceus var. mongholicus (AMM) leaves and stems, as well as the surface and deep soil surrounding AMM roots. This methodology allows us to capture the most significant characteristics present in these hyperspectral data with high precision. The AM is subsequently used to assign weights and integrate the hyperspectral features extracted from different parts of the AMM. The MLP is then employed to simultaneously estimate the chlorophyll content (CC) and nitrogen content (NC) of AMM leaves. Compared with estimation networks that utilize only hyperspectral data from AMM leaves as input, our proposed end-to-end AM-MHENet demonstrates superior estimation performance. Specifically, AM-MHENet achieves an R2 of 0.983 with an RMSE of 0.73 for the estimation of CC in AMM leaves. For NC estimation, AM-MHENet achieves an R2 value of 0.977 with an RMSE of 0.27. These results underscore AM-MHENet’s effectiveness in significantly enhancing the accuracy of both CC and NC estimation in AMM leaves. Moreover, these findings indirectly suggest a strong correlation between the development of AMM leaves and stems, as well as the surface and deep soil surrounding the roots of AMM, and directly highlight the ability of AM to effectively focus on the relevant spectral features within the hyperspectral data. This findings from this study could offer valuable insights into the simultaneous estimation of multiple chemical parameters in plants, thereby making a contribution to the existing body of research in this field.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

When dealing with limited sample sizes or missing values in time series data, achieving high accuracy in forecasting becomes challenging. This challenge is particularly common in wind energy forecasting, where many wind farms lack complete data. In this paper, we employ the widely-used ARIMA (Autoregressive Integrated Moving Average) model for time series forecasting. To address the difficulties posed by limited sample sizes and missing values, we adopt a unique approach by utilizing multiple ARIMA models for different datasets. A key distinction from other multiple models methods for time series forecasting lies in each model within our approach using its own dataset, making the fusion process more intricate. To overcome this, we incorporate neural networks and two techniques for model fusion: direct fusion with a learning mechanism and compensation for missing data through training. For each ARIMA model, we introduce a noise estimation method to circumvent the white noise assumptions inherent in ARIMA models. Finally, we apply these methods to wind energy prediction, and our experimental results showcase a significant enhancement in forecasting accuracy.

Deuterium is a heavy nonradioactive isotope of hydrogen, having a neutron as well as a proton, making it twice as heavy. It is a natural element, present at 156 parts per million in seawater. The ATPase pumps in the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage the pumps, producing a stutter that can cause reactive oxygen release and inefficiencies in ATP synthesis. Cellular metabolism incorporates several novel mechanisms to assure low deuterium content in the mitochondria and other organelles. Nicotinamide adenine dinucleotide (NAD) is a major carrier of deuterium depleted (deupleted) protons to supply the mitochondria. Many enzymes, especially flavoproteins, are able to use proton tunneling to fractionate out deuterium. In this paper, we argue that the amino acid proline is able to trap and sequester deuterium, and that peptidyl prolyl isomerases (PPIases) play a central role in facilitating deuterium trapping in proline-rich proteins, most notably collagen. The endothelial glycocalyx also sequesters deuterium in gelled water lining the blood vessels, creating a battery and promoting low deuterium in the circulation. Excess deuterium promotes cancer growth, and cancer cells release large quantities of lactate via aerobic glycolysis to help reverse deuterium overload, systemically.

Marine sand, in addition to oil and gas resources, is the second largest marine mineral resource. The rational development and utilization of marine sand resources are conducive to the growth of the marine economy. Marine sand can be categorized into surface marine sand and buried marine sand. Buried marine sand deposits are buried beneath the sea floor, making it challenging to locate them due to their thin distribution. Consequently, there exist numerous technical difficulties associated with marine sand exploration. In this study, various geophysical methods such as sub-bottom profile survey and single-channel seismic survey were employed in the northern offshore waters of the South China Sea along with offshore engineering geological drilling. As a result, two distinct marine sand bodies were delineated within the study area. Additionally, five reflective interfaces (R0, R1, R2, R3 and R4) were identified from top to bottom. These interfaces can be divided into five seismic sequences: A2, B2, C2, D2 and E2 respectively. Three sets of strata were recognized: the Quaternary Holocene Marine sedimentary layer (Q4m), the Upper Pleistocene alluvial layer, and the diluvial sedimentary layer (Q3al+pl) as well as the Upper Pleistocene Marine sedimentary layer (Q3m). Sequence A2 and B2 corresponded to Quaternary Holocene Formation (Q4m) within the study area while sequence C2 corresponded to B2 as well as upper Pleistocene alluvial and alluvial deposits (Q3al+pl), which represent one of the main occurring layers of sand in this region. Lastly, E2 represents a layer composed mainly of silty clay and round gravel known as upper Pleistocene marine sediment layer (Q3m). In total, two ore bodies containing marine sand have been discovered during this study. The estimated total resource amounts approximately 46 million m³ with an average thickness around 11 meters.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

The early 2-factor (E2F) family of transcription factors, including E2F1-8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment.To predict the possibility of GBM patient survival and progression, we classified and comparedthe expression of E2Fs according to BVZ-responsive subtypes and employed a machine learning method-TreeBagger, one random forest algorithm. Multiple bioinformatics analyses have shown that the significant increased E2F8 post BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, indicating one of the mechanisms of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. Our findings suggest that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers and therapeutic targets and recommending precise BVZ treatment for GBM patients.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in laboratory small animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homologue of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells or replication in primary neuronal cells. In western blots of EHV-1-infected cell lysates, an EHV-1 Us9-specific polyclonal antibody detected multiple bands ranging from 35 to 42-kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76 and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that the ORF76 (US9) plays an essential role in the anterograde spread EHV-1.

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium’s biological activities will enhance its therapeutic application across various medical fields, offering promising avenues for the treatment of infectious diseases, cancer, and inflammatory conditions.

Newton's kinetic energy equation delineates the laws of motion for objects travelling at speeds much less than the speed of light, an equation extensively validated at these lower velocities. Any new, more complete formulation of kinetic energy must approximate Newton's kinetic energy equation under these conditions. Einstein's special relativity, utilizing the Lorentz factor, introduces a new perspective on spacetime, adhering to the requirement that the Newtonian kinetic energy equation serves as an approximation at low velocities. In this paper, we identify all factor expressions satisfying the condition that their approximate solutions at low velocities align with Newton's kinetic energy equation. We introduce the Yuyunrui factor, incorporating two real number hyperparameters, $\alpha$ and $\beta$, encompassing all potentially correct factors, with the Lorentz factor as a specific instance where $(\alpha=0$, $\beta=1)$. We classify all potentially correct $(\alpha, \beta)$ combinations into six categories based on their distinct scaling effects and present the corresponding scaling effects. The combinations of $(\alpha, \beta)$ values applicable in the real world are necessarily included within these candidates, with the precise values requiring rigorous experimental validation. This work aims to refine our understanding of special relativity beyond the Lorentz factor.

A single mode waveguide grating coupler based on multiple Si-SiO₂ pairs onto Si substrate has been designed. Numerical analysis has been carried out to calculate optimum thickness of the layers of Si-SiO₂ that ensures the constructive interference between reflected waves and actual guided wave for high coupling efficiency. Based on the results, an optimal design is developed and modeled by using a 2-D finite difference time domain (2-D FDTD) simulator that dictates a coupling efficiency of as much as 78% (-1.07 dB) at the wavelength of 1550 nm, and a 1-dB bandwidth of 77 nm. The numerical method will be useful to calculate the optimum thicknesses of the layers for any reflector based grating coupler of different materials.

Aim: To analysis the relationship between healthy adults right ventricular diameter (RVD) and geographical factors. Location: China’s 22 provinces, municipalities and autonomous regions. Methods: Using correlation analysis the relationship between RVD and nine geographic factors, build predictive models by factor analysis. Results: There is significant correlation between RVD and geographical factors, and the annual average temperature is most relevant geographical factors, a predictive model was built by factor analysis: Ŷ = 19.46 + 0.0007072X1 + 0.001034X2 -0.05412X3 -0.001405X4 -0.0006351X5 + 0.02903X6 + 0.01243X7 -0.01033X8 + 0.03816X9 ± 0.63. Then using Kriging interpolation interpolate the geographical distribution of Chinese healthy adult right ventricular diameter reference value in ArcGIS software. Main Conclusion: If geographic factors can be derived in anywhere of China, RVD can be calculated by the model, you can also get RVD from geographical distribution.

Recently, methods to detect DoS and spoofing attacks that occur on in-vehicle networks using CAN Protocol are being studied through deep learning models such as CNN, RNN, and LSTM. These studies have produced significant results in the field of In-Vehicle Network attack detection using deep learning models. In addition, significant results are being achieved through research on applying time series-based deep learning models such as LSTM to detect DoS attacks and replay attacks occurring in in-drone networks by expanding them to drones using the UAVCAN protocol. In this paper, we conducted an experiment to detect in-drone network attacks through non-time series analysis using machine learning models and deep learning models, and through appropriate learning for each attack type, it can also be analyzed through non-time series analysis. The results showed that it was possible to detect attacks.

Accurately estimating shrub biomass in arid and semi-arid regions is critical for understanding ecosystem productivity and carbon stocks at both local and global scales. However, capturing the shrub biomass accurately by satellite observations is challenging due to the short and sparse features of shrubs. In this study, we presented a framework to estimate shrub biomass at a 10m spatial resolution by integrating ground in-situ data, unmanned aerial vehicle (UAV), Sentinel-2, and Sentinel-1 observations. The pilot study was conducted in the Helan mountains of Ningxia province, China. First, the spatial distribution map of shrubland and other land cover types was generated in 2023. Then, a prediction model of shrub biomass was developed in a Random Forest Regression (RFR) approach driven by different predicted variable datasets based on in-situ measurements, UAV, and satellite images. Finally, the developed model was used to produce the biomass map of shrubland in 2023. The uncertainty was characterized by creating a standard deviation (SD) map using the Leave-One-Out Cross-Validation (LOOCV) method in the shrub biomass estimates. The resultant shrubland distribution map in 2023 has an F1 score of 0.92. The shrub biomass model driven by spectral bands and vegetation indices (R2= 0.62) demonstrated superior performance than that only driven by spectral bands (R2=0.33) or vegetation indices (R2=0.55). The uncertainty of the estimated biomass was lower than 4%, with the lowest values (<2%) happening in the high shrub coverage (>30%) and biomass production (>30kg/m2) regions. Furthermore, the findings show that the magnitude of shrub biomass was affected by the aridity and precipitation significantly in the study region. This study provides a workflow to accurately monitor the biomass of shrublands in a complicated environment based on remote sensing images from multi-platform observations.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the buildup of misfolded alpha-synuclein proteins. While its exact cause remains unknown, several factors may influence its development. This review examines how factors like chronic constipation, head injuries, cholesterol and uric acid levels, pesticide exposure, smoking, NSAIDs, and caffeine intake may affect PD risk. Chronic constipation appears to be linked to a higher risk of PD, potentially serving as an early warning sign. Head injuries, especially mild-to-moderate ones, may also play a role in increasing PD risk. Surprisingly, higher levels of cholesterol seem to protect against PD, while lower levels of uric acid might increase the risk in the presence of some differences according to gender type. Exposure to certain pesticides is associated with a higher PD risk. NSAIDs, on the other hand, may or may not have a protective effect, with conflicting evidence. Interestingly, caffeine and tobacco smoking appear to lower the PD risk. Further studies are needed to fully understand the complex interplay between these factors and PD. It's also important to remember that these are just general trends, and individual risk factors will vary depending on a person's unique genetic makeup, medical history, and overall health.

Cotton fiber is the leading natural textile material, and fiber elongation plays an essential role in the formation of cotton yield and quality. Although a wealth of components in the molecular network controlling cotton fiber elongation have been reported, a lot of players still need to be functionally dissected to understand the regulatory mechanism of fiber elongation comprehensively. In the present study, an R2R3-MYB transcription factor gene, GhMYB201, was characterized and functionally verified via CRISPR/Cas9 mediated gene editing. GhMYB201 was homologous to Arabidopsis AtMYB60, and both coding genes (GhMYB201At and Dt) were preferentially expressed in elongating cotton fibers. Knocking-out of GhMYB201 significantly reduced the rate and duration of fiber elongation, resulting in shorter and coarser mature fibers. It was found that GhMYB201 could bind and activate the transcription of cell wall loosening genes (GhRDLs), and also β-ketoacyl-CoA synthase (GhKCSs) genes to enhance very-long-chain fatty acid (VLCFA) levels in elongating fibers. Taken together, our data demonstrated that the transcription factor GhMYB201s play essential roles in promoting fiber elongation via activating genes related to cell wall loosening and VLCFA biosynthesis.

A comprehensive multi-jet physics program is anticipated for experiments at future colliders. Key physics processes necessitate detectors that can distinguish signals from W and Z bosons and the recently discovered Higgs boson. Typical examples include channels with W^{+}W^{-} or Z^{o}Z^{o} pairs and processes involving New Physics, in those cases where neutral particles must be disentangled from charged ones due to the presence of W or Z bosons in their final states. Such a physics program demands calorimetric energy resolution at or beyond the limits of traditional calorimetric techniques. Multiple-readout calorimetry, which aims to reduce fluctuations in energy measurements of hadronic showers, is a promising approach. The first part of this article reviews dual and triple readout calorimetry within a mathematical framework describing the underlying compensating mechanism. The second part proposes a potential implementation using an integrally active and total absorption detector. This model serves as the basis for several Monte Carlo studies, illustrating how the response of a multiple-readout calorimeter depends on construction parameters. Among the layouts considered, one configuration operating in triple-readout mode shows the potential to achieve an energy resolution approaching 20\%/\sqrt{E}.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

This review article discusses the involvement of the Brain-Derived Neurotrophic Factor (BDNF) in the control of pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of nociception and pain. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF's involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice.

The object of study in the article is the auxiliary variable-frequency electric drive onboard of an AC electric locomotive, and more precisely, the structure and parameters of the control system of the active corrector of power factor (ACPF), which is part of the electric drive, as a unit that ensures electromagnetic compatibility of the electric drive with other equipment on board the electric locomotive and catenary and its energy efficiency. The topic of the article's research is the substantiation of the structure of the ACPF control system, the choice of types (transfer functions) of controllers and the calculation of their parameters. The research method chosen was the calculation of the transfer functions of the controllers of the cascaded loops control system, followed by computer simulation using the OrCAD software. The results of simulating a cascaded two loops control system of an ACPF with different types of controllers are presented and analytically compared. It is concluded that it is advisable to use a cascaded two loops control system, containing a voltage control loop and a current control loop. The best results show the simulation when using an aperiodic current controller (A-controller) and a proportional-integral voltage controller (PI-controller). The data obtained serve as the basis for further improvement of the operation of the ACPF by enhancing and optimizing the settings, structure and algorithms of the control system, which, with the selected hardware of power converter unit, will allow the ACPF to perform its functions with a high degree of reliability in an entire range of disturbing and control influences.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Extracting entities from large volumes of chicken epidemic texts is crucial for knowledge sharing, integration, and application. However, Named Entity Recognition (NER) encounters significant challenges in this domain, particularly due to the prevalence of nested entities and domain-specific named entities, coupled with a scarcity of labeled data. To address these challenges, we compiled a corpus from 50 books on chicken diseases, covering 28 different disease types. Utilizing this corpus, we developed a nested NER model, MFGFF-BiLSTM-EGP. This model integrates the Multiple Fine-Grained Feature Fusion (MFGFF) module with a BiLSTM neural network and employs an Efficient Global Pointer (EGP) for predicts the entity location encoding. In MFGFF module we designed three encoders, character encoder, word encoder and sentence encoder, this design effectively captures fine-grained features and improves the recognition accuracy of nested entities. Experimental results show that the model performs robustly, with F1 scores of 91.98%, 73.32%, and 82.54% on the CDNER, CMeEE V2, and CLUENER datasets, respectively, outperforming other commonly used NER models. Specifically, on the CDNER dataset, the model achieved an F1 score of 79.68% for nested entity recognition. This research not only advances the development of knowledge graph and intelligent question-answering system for chicken diseases but also provides a viable solution for extracting disease information that can be applied to other livestock species.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

In the context of evolving perceptions of sexuality, particularly within the realm of health and disability, this study investigates the impact of multiple sclerosis (MS) on female sexual function and quality of life. A quantitative study involving 130 female MS patients aged 35 to 50 was conducted, employing measures such as The Female Sexual Function Index (FSFI), The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and The Fatigue Severity Scale (FSS). Results indicate a significant association between greater sexual dysfunction and poorer quality of sex life, alongside the correlation of increased fatigue with diminished sexual satisfaction. Factors such as education level, time of diagnosis, and treatment regimen also influenced outcomes. Findings underscore the importance of supportive interventions, including counseling, to enhance the quality of sex life for women with disabilities, particularly those with MS.

Introduction. Anesthesia is widely used in various fields of dentistry to reduce patient discomfort when the treatment would be painful. The dentist may need to infiltrate the anesthetic into multiple locations and this is usually done with the same needle which passes through the soft tissues several times to distribute the anesthetic solution over a larger area. The present study aims to evaluate, through a morphological analysis under a scanning electron microscope (SEM), how the beveled tip of a 30G needle, used to inject anesthetic several times into different areas of the vestibular mucosa, changes. Materials and methods. 30G needles with two different brands were tested, in vivo used for a variable number of sequential injections from 1 to 6 on 192 patients. The specimens were analyzed under SEM observation to evaluate any deformations induced by contact with the vestibular soft tissues. Results. The amount of deformation, measured along the axis parallel to the needle, was proportional to the number of injections. The protrusion of deformations, measured on an axis perpendicular to the needle, were maximum on the needles used 3 times. For the needles used 4,5 and 6 injections, no further increase in deformations was noted. Conclusion. From the data it seems that the tested needles are not produced to withstand multiple injections consequently after the first injection on soft tissues, they undergo a deformation which could increase the risk of injury to the mucosa itself or to nerves and vessels with which they come into contact. It would be advisable to use the single needle for a reduced number of injections.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

A large number of novel treatments for myeloma have been developed and approved, however alkylating drugs continue to be part of standard regimens, additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors knowledge of the field to review the history, current use and novel concepts around traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of standard-of-care in myeloma, and new alkylators are coming to the market.

The features of a class of cubic curves with a shape factor are analyzed by means of the theory of envelope and topological mapping. The effects of the shape factor on the cubic curves are made clear. Necessary and sufficient conditions are derived for the curve to have one or two inflection points, a loop or a cusp, or to be locally or globally convex. Those conditions are completely characterized by the relative position of the edge vectors of the control polygon and the shape factor. The results are summarized in a shape diagram, which is useful when the cubic parametric curves are used for geometric modeling. Furthermore we discussed the influences of the shape factor on the shape diagram and the ability for adjusting the shape of the curve.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

Background: Disparity in adult mortality (AM) with reference to social dynamics and health care has not been sufficiently examined. This study aimed to identify the gap in the understanding of AM in relation to religion, political stability, economic level, and universal health coverage (UHC). Methods: A cross-national study was performed with different sources of data, using the administrative record linkage theory. We created a new data set using data from the 2013 World Bank data catalogue by region, The Economist (Political instability index 2013), Stuckler David et al. (Universal health coverage, 2010), and religious categories of all UN country members. Descriptive statistics, a t-test, an ANOVA followed by a post hoc test, and a linear regression were used where applicable. Result: The average AM rate for males and females was 0.20 ± 0.10 and 0.14 ± 0.10, respectively. AM was significantly higher in economically weak countries, countries with political instability, countries with traditional religion, without achievement of UHC, and Sub-Saharan Africa (p<0.01). There was high disparity of AM between countries with and without UHC (F = male: 61.89, female: 51.85, p<0.001) and between groups with low and high income (F = male: 36.33, female: 42.39, p<0.001). UHC and political stability would significantly reduce AMR by > 0.41 in both sexes and high economic status would reduce male AMR by 0.44, and female AMR by 0.70, in relation to countries without UHC, with political instability, and low economic status. Conclusions: Disparities in AM can be reduced after the achievement of UHC and economically productive activities for those adults affected by conflict and political unrest.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p&lt;0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

MAACS is a software architecture which layers multiple standard cipher algorithms together to increase the overall strength of the encrypted data stream, without modifying the standard algorithms, which have been heavily vetted from a cryptanalysis perspective and are already widely deployed. This layering technique makes the combination of algorithms significantly more resistant to traditional cryptanalysis attacks, while also addressing increased concerns over future quantum computing attacks against these algorithms. For example, concerns over published attacks against 256-bit AES and potential future attacks emanating from Grover’s algorithm and other unknowns in the quantum computing era are explored. Several approaches for evolving AES are considered. MAACS uses a concept termed "aperiodic modulation", whereby of a set of cryptographic algorithms are modified by an- other, independent software algorithm in an unpredictable, pseudo-random manner. In the MAACS reference architecture, a 256-bit ChaCha20 cryptographically secure pseudorandom number generator (CSPRNG) drives an aperiodic modulator that orchestrates encryption/decryption processes multiplexed across eight parallel 128-bit AES instances, yielding a cryptosystem with a composite strength of 1,376 bits or more in larger configurations.

A novel determination method using flow-through cartridge purification and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of 30 mycotoxins (aflatoxin B1, B2, G1, G2, sterigmatocysin, T-2 toxin, diacetoxyscirpenol, roquefortine C, methylergonovine, ergocornine, lysergol, enniatin A, enniatin A1, enniatin B, enniatin B1, beauvericin, deoxynivalenol, 3-acetylDeoxynivalenol, 15-acetylDeoxynivalenol, patulin, verruculogen, neosolaniol, gliotoxin, HT-2 toxin, wortmannin, zearalenone, α-zearalenol, β-zearalenol, α-zearalanol, and β-zearalanol) in feedstuffs. Mycotoxins were extracted from sample by 0.1% formic acid aqueous solution/acetonitrile (16/84 v/v), then purified by a Cleanert® MC clean-up column. As a result, the pigments and other matrices were efficient removed from the sample extract solution. The purified eluate was collected, then evaporated and redissolved by 0.1% formic acid aqueous solution/acetonitrile (70:30 v/v) for UPLC-MS/MS detection. A BEH Shield RP18 chromatographic column was employed for separation of 30 mycotoxins in a total of 14 min. Multiple-reaction monitoring (MRM) mode was applied for qualitative and quantitative analysis, and matrix calibration curves obtained with the external-standard method was used for quantitation of target analytes. Under optimized conditions, the linearity range was from 2 to 1000 ng/g, and the limit of quantification of the developed method was from 2 to 50 ng/g. The recoveries of 30 mycotoxins spiked in urine samples were from 72.0% to 118.5%, and the relative standard deviation was below 20%. The method was also well approved by certified reference sample, and applied on the real feedstuff samples testing successfully.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Proposed in 1889 by Svante Arrhenius, the Arrhenius equation is an important result in physical chemistry which aims to find the relationship between temperature and reaction rates. It is also an essential equation for analytic chemistry which helps to determine the energy barrier for a given reaction. In this article, we will go through a detailed derivation of the exponential factor in the Arrhenius Equation based on the Boltzmann distribution of particle energy probability. Then, we will attempt to model the pre-exponential factor in accordance with the principles of collision theory for bi-molecular reaction with gaseous reactants. Understanding the basic principles of chemical reaction provides valuable tools to analyze complex reaction mechanisms in the perspective of optimizing existing industrial processes.

Hypoxia is one of the most common pathological conditions which results from ischemic injury, trauma, inflammatory conditions, tumors, The adaptation of the body to hypoxia is a phenomenon that is of great importance both in normal conditions and in Most of the cellular response’ reactions to hypoxia is associated with a family of transcription factors called hypoxia-inducible factors (HIF). They induce the expression of a wide range of genes that help cells adapt to a hypoxic HIF functions are currently being extensively studied. In 2019, William G. Kaelin and Gregg Semenza from the USA and Sir Peter J. Ratcliffe from the UK received the Nobel Prize in Physiology or Medicine for the discovery of the basic mechanisms of adaptation to hypoxia and investigation of the role of HIF factor in the regulation of the hormone erythropoietin Based on its pivotal physiological importance, the HIF factor attracts more and more attention as a new potential target for treating a large number of diseases associated with Most of the experimental work dealing with the HIF factor is focused on its role in liver and However, increasing amount of experimental results clearly demonstrates that the HIF factor-based response represents an universal adaptation mechanism for all kinds of tissues, including the nervous system where HIF is critical for regulating neurogenesis, nerve cell differentiation, and neuronal This review provides actual overview about the complex role of HIF-1 in the adaptation of nerve cells to hypoxia with the focus on its potential role by various neuronal

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of hepatocyte growth factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Microbial composition across substrates in mangroves, particularly in the Middle East, remains unclear. This study characterized bacterial communities in sediment, water, Terebralia palustris snail guts, and plastic associated with Avicennia marina mangrove forests in two coastal lagoons in the Sea of Oman using 16S rDNA gene MiSeq sequencing. The genus Vibrio dominated all substrates except water, which featured unique genera Sunxiuqinia and Pseudomonas. There were significant differences in bacterial communities on different substrata, in particular plastic. Snail guts harbored the highest number of unique Operational Taxonomic Units (OTUs) in both lagoons. Plastic in the polluted Sawadi lagoon with low salinity harbored distinct genera like Vibrio, Aestuariibacter, Zunongwangia, and Jeotgalibacillus absent in Qurum lagoon with higher salinity and low pollution. Sawadi lagoon exhibited higher species diversity in sediment and plastic substrates, Qurum lagoon demonstrated lower overall species diversity. The PCA indicates that environmental factors like salinity, pH, and nutrient levels significantly influence bacterial community composition across substrates. Variations in organic matter and potential anthropogenic influences, particularly from plastics, further shape bacterial communities. This study highlights the complex microbial communities in mangrove ecosystems, emphasizing the importance of considering multiple substrates in mangrove microbial ecology studies.