Despite recent public health and hygiene advancements, enteric fever, commonly referred to as typhoid fever, remains a common disease in developing nations. The common mode of infection is contaminated water or food. Additionally, person-to-person transmission through poor hygiene and sewage contamination of water supplies has been blamed for most outbreaks. The exact burden of typhoid has yet to be discovered because of the lack of surveillance systems in many developing nations. This makes it difficult to estimate the number of cases. Recent studies have shown that the actual number of cases of typhoid has been estimated to be around 21.6 million annually. The mortality studies suggest that the incidence of typhoid is highest in children under five years old. Typhoid fever and paratyphoid fever have been demonstrated to be life-threatening illnesses. Salmonella serotype Typhi (S. Typhi) is the causative organism of typhoid fever whereas Salmonella serotype Paratyphi is the causative organism for paratyphoid fever. The S. Typhi bacterium is known to be resistant to various drugs. There is a dire need to develop new drugs to treat and overcome the current drug-resistant S. Typhi. The identification of new targets marks the beginning of the process of developing new anti-S. Typhi drugs. The S. Typhic genome sequencing and recent cutting-edge molecular biology tools have led to the discovery of numerous new inhibitors and targets. The goal of this review is to identify the most critical targets in the S. Typhi that are targeted by drugs. It also highlights the various promising vaccines on the market or are still in preclinical studies. A detailed understanding of the targets could help researchers develop safer and more efficient antibacterial agents against S. Typhi.Additionally, the advancement of molecular techniques and the knowledge of the Salmonella pathogenesis pathways have opened better avenues to develop effective antibiotics and vaccines against this pathogen. This review also sought to identify and summarize critical structures of this pathogen that play significant roles in the maturation, development, and pathogenesis of S. Typhi. The endpoint of this work is to provide valuable information on potential therapeutic targets of S. Typhi for drug and vaccine developers.

Side-scan sonar (SSS) detection is a key method in applications such as underwater environmental security and subsea resource development. The use of acoustic images for seabed target detection has gradually become a mainstream underwater detection method. However, many existing detection approaches primarily concentrate on tracking the evolution path of optical image object detection tasks, resulting in complex structures and limited versatility. To tackle this issue, we introduce a pioneering Dual-Domain Multi-Frequency Network (D2MFNet) meticulously crafted to harness the distinct characteristics of SSS image detection. In D2MFNet, aiming at the underwater detection requirements of small scenes, we introduce a novel method for optimize and improve the detection sensitivity of different frequency ranges and propose a Multi-Frequency Combined Attention Mechanism (MFCAM). This mechanism amplifies the relevance of dual-domain features across different channels and space. Moreover, recognizing that SSS images can provide richer insights after frequency domain conversion, we introduce a Dual-Domain Feature Pyramid Network (D2FPN). By incorporating frequency domain information representation, D2FPN significantly augments the depth and breadth of feature information in underwater small datasets. Our methods are seamlessly designed for integration into existing networks, offering plug-and-play functionality with substantial performance enhancements. We have conducted extensive experiments to validate the efficacy of our proposed techniques, and the results showcase their state-of-the-art performance. MFCAM improves the mAP by 16.9% in the KLSG dataset and 15.5% in the SCTD dataset. The mAP of D2FPN was improved by 8.4% in the KLSG dataset and by 9.8% in the SCTD dataset. We will make our code and models publicly available at https://dagshub.com/estrellaww00/D2MFNet.

Sea cucumber detection represents a significate step in underwater environmental perception, which is an indispensable part of the intelligent subsea fishing system. However, various complex factors such as water turbidity declines the clarity of underwater images, presenting a challenge to vision-based underwater target detection. Therefore, accurate, real-time and lightweight detection models are required. First of all, the development of subsea target detection is summarized in this presented work. Besides, since target detection methods based on deep learning such as YOLOv5 and DETR, which are respectively examples of one-stage and anchor-free deep leaning methods, have been increasingly applied in underwater detection scenarios. Based on the analysis of state-of-the-art underwater sea cucumber detection approaches and aiming to provide a reference for practical subsea identification, the sea cucumber detection based on the YOLOv5 and DETR are investigated and compared in detail. For each approach, the detection experiment is carried out on the derived dataset which contains a wide variety of sea cucumber sample images. The compared experiments demonstrate that the overall outperformance of YOLOv5 in terms of low computing consumption and high precision, particularly in detection of small and dense features. Nevertheless, the DETR exhibits rapid development and holds promising prospects in underwater object detection applications, owing to its relatively simple architecture and ingenious attention mechanism.

Remote sensing imagery is of great significance for policy decisions, especially for disaster assessment and disaster relief. To ensure the privacy and inviolability of personal buildings, the information containing these buildings must be anonymized during the remote sensing mapping process. Traditional processing methods for these targets in remote sensing mapping are mainly based on manual retrieval and image editing tools, which are inefficient. Deep learning provides a new direction for target hiding. Although the image inpainting method based on deep learning is faster than the manual method, the cost of training calculation is a disadvantage. And the element-wise product operation used in the model increases the risk of vanished or exploded gradients. We propose a Residual Attention Target Hiding (RATH) model for remote sensing target hiding based on deep learning. RATH uses residual attention modules to replace gated convolutions, reducing parameters and mitigating gradient issues. The residual attention module preserves gated convolution performance but provides an adjustable kernel size. RATH retains gated convolutions for dynamic feature selection and balances model depth and width. Furthermore, this paper modifies the contextual attention layer by adjusting the fusion process to enlarge the fusion patch size. Finally, we extend the edge-guided function to preserve the original target information and confound viewers. Ablation studies on an open dataset prove RATH’s efficiency for image inpainting and target hiding. RATH achieves state-of-the-art results with lower complexity. And it has the highest similarity for edge-guided target hiding. RATH enables robust, efficient target hiding for privacy protection in remote sensing imagery while balancing performance and complexity. Experiments show RATH's superiority over existing methods in hiding arbitrary-shaped targets.

: The radar multi target tracking (MTT) technique requires prior knowledge of a number of parameters about the sensor, the target and backgrounds. The Integrated Track Splitting (ITS) is a fully automatic track-while-scan (TWS) target tracking algorithm capable of extracting and tracking a target in a dense clutter environment using quality false track discrimination (FTD) methodology. The computational complexity in ITS algorithm is limited, compared to other algorithms they use statistical methods to discriminate between false and true tracks, such as multiple hypothesis tracking (MHT), mainly due to the FTD performed. The paper provides an analysis of tracking parameters that allows determining the limit of the possibility of successful target tracking. Extensive experiments have confirmed that the recursive determination of the probability of the existence of a track during tracking can confirm a true track and reject a false track. The clutter density, number of random occurred targets, targets load during the maneuver and the target detection probability were varied. The results of experiments, carried out via Monte Carlo simulations, shown over representative confirmed true tracks (CTT) diagrams, root mean square error position and normalized tracking efficiency parametric diagrams allow the user to select optimal multi-target tracking parameters for different scenarios and clutter densities.

Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that alt-hough preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance and an uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limit-ing factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bac-terial proteins are targeted being the biosynthesis of the cell wall and the energetic metabolism two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and how chemical probes for protein profiling enabled the identification of new targets and bi-omarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

MicroRNAs (MiRNAs) are a class of non-coding single-stranded RNA molecules of approximately 20-24 nucleotides in plants that play an important regulatory role in a variety of biological processes such as plant growth and development and response to various abiotic stresses. For example Drought, Salt, Cold, High temperature, Heavy metals and Nutrition. MiRNAs affect gene expression by manipulating the cleavage, translational expression or DNA methylation of target mRNAs. This review describes the current progress made on the way miRNAs are produced and regulated and the way miRNA/target gene is used in plant responses to abiotic stresses. Studying the molecular mechanism of action of miRNAs downstream target genes can optimize the genetic manipulation of crop growth and development conditions that provide a more theoretical basis for improving crop production.

Pesticides are widely used in agriculture as a pest control strategy. Despite the benefits of pesticides on crop yields, the persistence of chemical residues in soil have an unintended impact on non-targeted microorganisms. In this study, we evaluated the impact of the combined fungicide (difenoconazole, epoxiconazole, and kresoxim-methyl) on fungal and bacterial communities of Phaeozem. In the fungicide-treated soil, the Shannon index of both fungal and bacterial communities was decreased, while Chao1 index did not differ compared to the control soil. Among bacterial taxa, the relative abundance of Athrobacter, Sphingomicrobium, and Sphingomonas increased in fungicide-treated soil due to their ability to utilize fungicides and other toxic compounds. Rhizopus and plant-beneficial Chaetomium were the dominant fungal genera, which increased 2-4 times in the fungicide-treated soil, while the relative abundance of Mortierella and Talaromyces decreased. Fusarium acuminatum was the most abundant phytopathogenic fungus that causes root rot disease of wheat, but applied fungicide treatment decreased their diversity in the soil 2 times, which is consistent on the observed plants.

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a dose reduction of chemo-therapy and its most common sensory symptoms are severe pain, tingling, and numbness in the hands and feet. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory abnormalities may occur for months, or even years after the termination of chemotherapy. This disease has complicated pathophysiology featured by underlying mechanisms not completely known. Although many pharmaco-logical and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized cure to prevent or treat CIPN. According to current guidelines, Duloxe-tine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective thera-pies for CIPN is mandatory. The purpose of this review is to dissect CIPN, the target and immunothera-py-based approaches to this disorder, as well as to offer new insights for novel therapeutic perspectives.

In this paper, a high-performance antenna array system model is presented to analyze moving-object-skin-returns and track them in the presence of stationary objects using frequency modulated continuous wave (FMCW). The main features of the paper are bonding the aspects of antenna array and electromagnetic (EM) wave multi-skin-return modeling and simulation (M&S) with the aspects of algorithm and measurement/tracking system architecture. The M&S aspect models both phase and amplitude of the signal waveform from a transmitter to the signal processing in a receiver. In the algorithm aspect, a novel scheme for FMCW signal processing is introduced by combining time- and frequency-domain methods, including a vector moving target indication filter and a vector direct current canceller in time-domain, and a constant false alarm rate detector and a mono-pulse digital beamforming angle tracker in frequency-domain. In addition, unlike previous designs of using M×N fast Fourier transform (FFT) for an M×N array, only four FFTs are used, which tremendously saves time and space in hardware. With the presented model, the detection of the moving-target-skin-return in stationary objects under a noisy environment is feasible. Therefore, to track long range and high-speed objects, the proposed technique is promising. Using a scenario having 1) a target with 17 dBm2 radar cross section (RCS) at about 40 km range with 5.93 Mach speed and 11.6 dB post processing signal to noise ratio, and 2) a strong stationary clutter with 37 dBm2 RCS located at the proximity of the target, it demonstrates that the root-mean-square errors of range, angle and Doppler measurements are about 26 meters, 0.68 degree and 1100 Hz, respectively.

Ability of quantitative structure – property / activity relationships (QSPRs/QSARs) to serve for epistemological processes in natural sciences is discussed. Some weirdness of QSPR/QSAR state-of-art are listed. There are some contradictions in the research results in this area. Sometimes, these should be classified as paradoxes or weirdness. These points often are ignored. Here these are listed and briefly commented. In addition, hypothesises on the future evolution of the QSPR/QSAR theory and practice are suggested.

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

In recent years, many algorithms based on end-to-end deep networks have been proposed to deal with the target detection problem of videos. However, the deep network models usually consume a lot of computing resources during the procedure of analysis of videos with complex dynamic backgrounds. In this paper, a new method of object detection based on information theory is presented. Firstly, each frame in a video is converted into an effective information map by using the Harris corner detection method. Secondly, the sensitive areas in the frame are extracted by using the context information and the effective information maps of the consecutive video frames. The sensitive areas in the video frame are the candidate areas where the target objects would be appeared at high probabilities. Thirdly, the information entropy features of each sensitive area are extracted to form the feature matrix, based on which, an SVM model is trained for selecting the target areas from the sensitive areas. Finally, the locations of the objects are detected based on the target areas in the video with a complex dynamic background. As a lightweight video detection framework, the method presented in this paper can save a lot of computing resources. Experimental results show that this method can achieve good results in the benchmark of CDnet 2014.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Acute pancreatitis (AP) is a potentially fatal organ disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that generating urate and also responsible to produce reactive oxygen species (ROS). Considerable clinical and mechanical research has been conducted over many decades to explore the function of XO in AP and its promising therapeutic applications. Unquestionably, XO is a key part of starting and progressing AP by ROS production. Not fully known, though, are XO's many other functions besides ROS resource in both local and global processes, such as its role in cellular signaling or metabolism regulation. This review seeks to summarize the function of XO in AP pathophysiology by analyzing the inherent biological and chemical properties of XO, and lastly provide fresh concepts for future research.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

Environmental, social, and governance (ESG) investment has become a common trend in capital markets, and many institutional investors have publicly declared their long-term ESG investment target (ESGIT). This study focuses on investors who conduct strategic asset allocation (SAA) using composite indices but establish their ESGIT outside the SAA process. A mismatch could arise between investors’ planned and actual portfolios because they must pursue their ESGIT by asset selection, which inevitably makes the constituents of their portfolios different from those of composite indices. To scrutinize the potential existence of a misalignment between their SAA and ESGIT, this study analyzes actual stock and bond indices over the past decade using traditional mean-variance optimization. The results reveal significant differences between the expected and realized performances, and the misalignment is more significant when the analysis period is divided into two sub-periods: stable and volatile. Specifically, the results indicate that the efficient frontier constructed using ESG indices significantly differs from that constructed using composite indices, and that the difference between these two efficient frontiers becomes more significant during volatile periods. Furthermore, the results show that investors cannot meet their targets if their ESGIT is established outside the SAA process.

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.

Gaze tracking of high-speed moving targets is a novel application mode for low Earth orbit microsatellites. In this mode, small satellites are equipped with high-resolution narrow-field-of-view video cameras for stable gaze-tracking imaging of high-speed moving targets. This paper proposes a high-precision attitude adaptive integral sliding mode control method with a feedforward compensation disturbance observer to enhance the capability of a microsatellite attitude control system for gaze tracking of high-speed moving targets. Specifically, first, we present the attitude control system model for microsatellites and the calculation method for the desired attitude of target tracking based on image feedback. Then, an adaptive integral sliding mode attitude control algorithm with a feedforward compensation disturbance observer, which meets the requirements of high-precision tracking control, is designed. The developed algorithm utilizes the disturbance observer to observe the friction torque of the flywheel and compensates for it through feedforward control. It also employs the adaptive integral sliding mode control algorithm to reduce the impact of uncertain disturbances, decrease the steady-state error of the system, and enhance the attitude control precision. Simulation experiments demonstrated that the designed disturbance observer can successfully observe the frictional disturbance torque of the flywheel. The attitude Euler angle control precision for high-speed moving target tracking reached 0.009°, and the angular velocity control precision reached 0.005°/s, validating the effectiveness of the proposed approach.

Several traps are recommended for monitoring corn earworm, Helicoverpa zea (Boddie), an important pest of field, vegetable and fruit crops in the U.S. These traps, which are meant to capture H. zea in many cases end up capturing other insects. Helicoverpa zea has recently been found feeding on different seeds and dual-type (seed and fiber) hemp, Cannabis sativa L. (Rosales: Cannabaceae) causing serious damage. Limited work has been done on developing integrated pest management (IPM) for H. zea industrial hemp in Missouri. We evaluated the attractiveness of different traps with the aim of developing a monitoring system for the adult male H. zea in industrial hemp fields in two Missouri locations In addition, we recorded other non-target insects in the traps to determine trap selectivity. Commercially available green, clear, tricolor bucket traps Heliothis Scentry and Scentry Delta 1X traps baited with H. zea sex pheromones were evaluated in 2021 and 2022. Tricolor traps captured significantly more adult male H. zea than the other traps in both years. Non-target insects, mainly Xylocopa virginica (L.) (Hymenoptera: Apidae), Bombus spp (Hymenoptera: Apidae), and Apis mellifera L. (Hymenoptera: Apidae) were also captured. The tricolor trap captured the most bees. The presence of non-target species highlights the risk of using tricolor traps as a monitoring tool. This data provides information for planning the monitoring of corn earworm in industrial hemp farms in Missouri.

This study addresses the escalating threat of data theft ransomware, a form of cyberattack that exfiltrates sensitive information from victim networks and demands ransom for its non-disclosure. Unlike traditional crypto-ransomware, data theft ransomware leverages various infiltration techniques to gain unauthorized access and control over critical data assets. The study introduces a novel Moving Target Defense (MTD) framework, specifically designed for the Windows operating system environment, to counter these sophisticated attacks. MTD increases the unpredictability of the system by dynamically altering its configurations, thereby disrupting the adversary's ability to execute successful attacks. Our research includes the development and empirical evaluation of the MTD framework, demonstrating its effectiveness in reducing ransomware operational capabilities through quantitative analysis, qualitative observations, and statistical significance testing. We also explore the challenges and complexities involved in implementing MTD in real-world scenarios and propose strategies to overcome these barriers. The study concludes with recommendations for future research directions and the potential of MTD in enhancing cybersecurity defense mechanisms.

Advanced cutaneous melanoma is considered the most aggressive type of skin cancer with variable rates of treatment response. Nowadays, there are available some classes of immunotherapy and target therapy for its treatment. Immunotherapy can inhibit tumor growth and its recurrence by triggering host's immune system, while targeted therapy acts inhibiting specific molecules or signaling pathways. However, melanoma response to these treatments are highly heterogenous, and frequently become resistant. Epigenome (DNA/histone modification) contribute to cancer initiation and progression. Epigenetic alterations are divided into four levels of gene expression regulation: DNA methylation, histone modification, chromatin remodeling and non-coding RNAs regulation. The deregulation of lysine methyltransferase enzymes is associated with tumor initiation, invasion, development of metastases, changes in immune microenvironment and drug resistance. The study of lysine histone methyltransferase (KMT) inhibitors is important to cancer epigenetic mechanisms understanding and to biological processes. In addition to immunotherapy and target therapy, the research and development of KMT inhibitors is ongoing. Many studies are exploring the therapeutic implications and possible side effects of these compounds, besides their adjuvant potential to the approved current therapies. Importantly, as with any drug development, safety, efficacy, and specificity are crucial considerations when developing KMT inhibitors for clinical applications.

Background: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different chest wall (CW) delineation according to ESTRO ACROP guideline for patients underwent implant-based reconstruction. Methods: We conducted a retrospective review of breast cancer patients who underwent mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. Results: The study included 26 patients, 15 in prepectoral group and 11 in whole expander group. No significant differences were observed in normal organs exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p=0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. Conclusions: For patients undergoing two-stage expander-implant retropectoral breast reconstruction and PMRT, our data have provided comparable outcomes and normal organs exposure for those omitting the deep lymphatic plexus.

The study sought to investigate the effect of Multi-choice Goal programming in project Portfolio Analysis, using Lagos State Project Portfolio from between 2017-2021 as a study case. Specifically, the objectives examined the effectiveness of multi-choice goal programming in analyzing the project Portfolio of Lagos State Government and investigated the possible lapses in the use of Multi-choice Goal programming in analyzing the project Portfolio of Lagos State Government. Data were gathered from the State financial Statements and analyzed using Lingo-17 Software. Based on the analysis, the study discovered that the goals formulated can be optimally and minimally attained as the positive deviational and negative deviational variables depict zero. This indicates that the cost incurred on the project portfolio was absolutely minimized during the period and at the same time; Lagos State Government derived the most preferred benefits from it. The study therefore concluded that the State minimized the project costs and at the same time maximized benefits while meeting its overall objectives.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalizations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.

Background: The Hengduan Mountains are one of the most species–rich mountainous areas in the world. The origin and evolution of such a remarkable biodiversity are likely to be associated with geological or climatic dynamics, as well as taxon-specific biotic processes (e.g., hybridization, polyploidization, etc.). Here, we investigate the mechanisms fostering the diversification of the endemic Himalopsyche martynovi complex, a poorly known group of aquatic insects. Methods: We used multiple allelic datasets generated from 691 AHE loci to reconstruct species and RaxML phylogenetic trees. We selected the most reliable phylogenetic tree to perform network and gene flow analyses. Results: Phylogenetic reconstructions and network analysis identified three clades, including H. epikur, H. martynovi sensu stricto and H. cf. martynovi. Himalopsyche martynovi sensu stricto and H. cf. martynovi present an intermediate morphology between H. epikur and H. viteceki, the closest known relative to the H. martynovi–complex. The gene flow analysis revealed extensive gene flow among these lineages. Conclusion: Our results suggest that H. viteceki and H. epikur are likely to have contributed to the evolution of H. martynovi sensu stricto and H. cf. martynovi via gene flow, and thus, our study provides insights in the diversification process of a lesser–known ecological group, and hints at the potential role of gene flow in the emergence of biological novelty in the Hengduan Mountains.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Natural products comprise a rich reservoir for innovative drug leads and are a constant source of bioactive compounds. To find pharmacological targets for new or already known natural products using modern computer-aided methods is a current endeavor in drug discovery. Nature’s treasures, however, could be used more effectively. Yet, reliable pipelines for large scale target prediction of natural products are still rare. We have developed an in silico workflow consisting of four independent, stand-alone target prediction tools and evaluated its performance on dihydrochalcones (DHCs) – a well-known class of natural products. Thereby, we revealed four previously unreported protein targets for DHCs, namely 5-lipoxygenase, cyclooxygenase-1, 17β- hydroxysteroid dehydrogenase 3, and aldo-keto reductase 1C3. Moreover, we provide a thorough strategy on how to perform computational target prediction and guidance on using the respective tools.

The standard of care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment in case of symptomatology onset. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive disease presentations are even more common, leading to a change of paradigm of focal treatments. In fact, acknowledgement of behaviour of disease in these setting of patients is carrying aim of radiotherapy towards modalities with radical intent. The aim of this literature review is to analyse available clinical data regarding disease behaviour, imaging, radiotherapy and chemo-radiotherapy integration outcomes for understanding bone metastasis from breast cancer and the potential impact of targeting it.

Covid-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The covid-19 7098 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na⁺ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR.

Since smoke usually occurs before a flame arises, fire smoke detection is especially significant for early warning systems. In this paper, a DSATA(Depthwise Separability And Target Awareness) algorithm based on depthwise separability and target awareness is proposed. Existing deep learning methods with convolutional neural networks pretrained by abundant and vast datasets are always used to realize generic object recognition tasks. In the area of smoke detection, collecting large quantities of smoke data is a challenging task for small sample smoke objects. The basis is that the objects of interest can be arbitrary object classes with arbitrary forms. Thus, deep feature maps acquired by target-aware pretrained networks are used in modelling these objects of arbitrary forms to distinguish them from unpredictable and complex environments. In this paper, this scheme is introduced to deal with smoke detection. The depthwise separable method with a fixed convolution kernel replacing the training iterations can improve the speed of the algorithm to meet the enhanced requirements of real-time fire spreading for detecting speed. The experimental results demonstrate that the proposed algorithm can detect early smoke, is superior to the state-of-the-art methods in accuracy and speed, and can also realize real-time smoke detection.

In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.

The 2030 Agenda for Sustainable Development, the SDGs, are high on the agenda for most countries of the world. In its publication of the SDGs, the UN has provided the goals and target descriptions that, if implemented at a country level, would lead towards a sustainable future. The IAEG (InterAgency Expert Group of the SDGs) was tasked with disseminating indicators and methods to countries that can be used to gather data describing the global progress towards sustainability. However 2030 Agenda leaves it to countries to adopt the targets with each government setting its own national targets guided by the global level of ambition but taking into account national circumstances. At present, guidance on how to go about this is scant, but it is clear that the responsibility is with countries to implement and that it is actions at a country level that will determine the success of the SDGs. SDG reporting by countries takes on two forms 1) global reporting using prescribed indicator methods and data; 2) National Voluntary Reviews where a country reports on its own progress in more detail but is also able to present data that are more appropriate for the country. For the latter, countries need to be able to adapt the global indicators to fit national priorities and context, thus the global description of an indicator could be reduced to describe only what is relevant to the country. Countries may also, for the National Voluntary Review, use indicators that are unique to the country but nevertheless contribute to measurement of progress towards the global SDG target. Importantly, for those indicators that relate to the security of natural resources security (e.g. water) indicators, there are no prescribed numerical targets/standards or benchmarks. Rather countries will need to set their own benchmarks or standards against which performance can be evaluated. This paper presents a procedure that would enable a country to describe national targets with associated benchmarks that are appropriate for the country. The procedure focusses on those SDG targets that are natural resource-security focussed e.g. extent of water-related ecosystems (6.6), desertification (15.3) etc., because the selection of indicator methods and benchmarks is based on the location of natural resources, their use and present state and how they fit into national strategies.

The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca²⁺) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca²⁺-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.

This paper considers target characterization and recognition in radar images with keypoint-based local descriptor. Most of the preceding works rely on the global features or raw intensity values, and hence produce the limited recognition performance. Moreover, the global features are sensitive to the real-world sources of variability, such as aspect view, configu-ration, and incidence angle changes, clutter, articulation, and occlusion. Keypoint-based local descriptor was developed as a powerful strategy to address invariance to contrast change and geometric distortion. This property inspires us to investigate whether the family of local features are relevant for radar target recognition. Most of the preceding works typically devote to finding the correspondences between a collected image and a reference one. The representative applications include image register and change detection. Little work was pursued to target recognition in SAR images. This is because the huge number of local descriptors resulting from radar images make the computational cost and memory consumption unacceptable. To handle the problems, this paper develops two families of methods. The proposed methods are used to achieve target recognition by means of local descriptors. Our first solver refers to building multiple linear regression models, and addresses the problem by the theory of sparse representation. The second scheme rebuilds a new feature by the feature quantization skill, from which the inference can be drawn. Multiple comparative studies are pursued to verify the performance of detectors and descriptors popularly used. The source code was publicly released on https://ganggangdong.github.io/homepage/.

Photophysical properties of a series of bis(arylydene)cycloalkanone dyes with various donor substituentns are studied by quantum chemistry. Their capacity for luminescence and nonradiative relaxation through trans-cis isomerization is related to their structure, in particular, to the donor capacity of the substituents and the degree of conjugation due to the central cycloalkanone moiety. It is shown that cyclohexanone central moiety introduces distortions and disrupts the conjugation, thus leading to a nonmonotonic change in their properties. The increasing donor capacity of the substituents causes increase in the HOMO energy (raise of the oxidation potential) and decrease in the HOMO-LUMO gap, which results in the red shift of the absorption spectra. The ability of the excited dye to relax through fluorescence or through trans-cis isomerization is governed by the height of the barrier between the Franck–Condon and S1-S0 conical intersection regions on the potential energy surface of the lowest π-π* excited state. This barrier also correlates with the donor capacity of the substituents and the degree of conjugation between the central and donor moieties. The calculated fluorescence and trans-cis isomerization rates are in good agreement with the observed fluorescence quantum yields.

This paper discusses the use of networks of Inertial Measurement Units (IMU) for the reconstruction of trajectories from sensor data. Logistics is a natural application domain, to verify the quality of the handling of goods. This is a mass application and the economics of logistics impose that IMUs to be used must be low cost and use basic computational devices. The approach in the paper converts a strategy from the literature, used in the multi-target following problem, to reaching a consensus in a network of IMUs. The paper presents results on how to achieve the consensus in trajectory reconstruction, along with covariance intersection data fusion of the information obtained by all nodes in the network.

Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational method for screening drug candidates targeting a biomolecule that causes diseases. The present study aims to summarize the latest information re-garding potential inhibitors of squalene synthase and farnesyl phosphate synthase with anti-Trypanosomatidae activity. The information was obtained by referencing textbooks and major scientific databases from their inception until April 2023. Based on in vitro experiments, more than seventy compounds were reported to inhibit squalene synthase and farnesyl diphosphate synthase. Among these compounds, more than 30 were found to be active in vitro against Trypanosomatidae, inferring that these compounds can be prospected as scaffolds for the development of new drugs against trypanosomatid-related infections. Over-all, natural and synthetic products can inhibit enzymes that are crucial for the survival and virulence of trypanosomatids. Moreover, in vitro experiments have confirmed the activity of more than half of these inhibitors using cell-based as-says. Nevertheless, additional studies on the cytotoxicity, pharmacokinetics, and lead optimization of potent anti-Trypanosomatid compounds should be investi-gated.

The world's growing population is highly dependent on animal agriculture. Animal products provide nutrient-packed meals that help to sustain individuals of all ages in communities across the globe. As the human demand for animal proteins grows, the agricultural industry must continue to advance its efficiency and quality of production. One of the most commonly farmed livestock is poultry and their significance is felt on a global scale. Current poultry farming practices result in the premature death and rejection of billions of chickens on an annual basis before they are processed for meat. This loss of life is concerning regarding animal welfare, agricultural efficiency, and economic impacts. The best way to prevent these losses is through the individualistic and/or group level assessment of animal on a continuous basis. On large-scale farms, such attention to detail was generally considered to be inaccurate and inefficient, but with the integration of Artificial Intelligence (AI) assisted technology individualized and per-herd assessments of livestock are possible and accurate. Various studies have shown cameras linked with specialized systems of AI can properly analyze flocks for health concerns, thus improving the survival rate and product quality of farmed poultry. Building on the recent advancements, this review explores the aspects of AI in the detection, counting and tracking of the poultry in commercial and research-based applications.

COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccine will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow for society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point of care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of appropriate test for specific use case difficult. In this review, we have used the World Health Organization’s (WHO) recently published Target Product Profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several top-performing POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, that meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection), or indirect diagnosis of past infection (host antibodies) are highlighted here.

The concept of Design Fatigue Factors (DFFs) was introduced for providing desired level of safety in structural fatigue design, often associated with damage calculated from S-N curves. Calculation of fatigue damage from S-N curves can be affected by multiple factors, e.g. types of weld class, corrosion condition, loading conditions, stress concentration on different geometries etc. Each of them can be subject to different level of uncertainties. This study intends to recalibrate the DFFs from a detailed reliability analysis by investigating the probabilistic models derived from the database of S-N curves that has been most frequently used in offshore wind industry. The results of such study indicate that the DFFs can be reduced substantially for the corrosive environmental fatigue models from current standards to the same level of target reliability.

Protein-DNA interactions are critical for the successful functioning of all natural systems. The key role in these interactions is played by processes of protein search for specific sites on DNA. Although it has been studied for many years, only recently microscopic aspects of these processes became more clear. In this work, we present a review on current theoretical understanding of the molecular mechanisms of the protein target search. A comprehensive discrete-state stochastic method to explain the dynamics of the protein search phenomena is introduced and explained. Our theoretical approach utilizes a first-passage analysis and it takes into account the most relevant physical-chemical processes. It is able to describe many fascinating features of the protein search, including unusually high effective association rates, high selectivity and specificity, and the robustness in the presence of crowders and sequence heterogeneity.

This paper presents the results of an experimental investigation about target detecting with passive sonar in Persian Gulf. Detecting propagated sounds in the water is one of the basic challenges of the researchers in sonar field. This challenge will be complex in shallow water (like Persian Gulf) and noise less vessels. Generally, in passive sonar the targets are detected by sonar equation (with constant threshold) which increase the detection error in shallow water. Purpose of this study is proposed a new method for detecting targets in passive sonars using adaptive threshold. In this method, target signal (sound) is processed in time and frequency domain. For classifying, Bayesian classification is used and prior distribution is estimated by Maximum Likelihood algorithm. Finally, target was detected by combining the detection points in both domains using LMS adaptive filter. Results of this paper has showed that proposed method has improved true detection rate about 27% compare other the best detection method.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

This paper presents a Poisson multi-Bernoulli mixture (PMBM) forward-backward smoother for multiple extended target detection and tracking in the random finite sets (RFS) framework. The proposed method consists of forward filtering, achieved by the PMBM filter recursion, followed by backward smoothing, achieved by a parametric updated posterior PMBM density. The performance of the proposed method is evaluated in a simulation study.

Artificial intelligence (AI) shows great potential in medical diagnosis and drug analysis. Through deep learning technology, AI can automatically extract features from large amounts of complex medical data, significantly improving diagnostic accuracy and drug development efficiency. Especially in drug target discovery and antiviral peptide classification, AI technology can accelerate data processing and prediction, helping researchers identify potential therapeutic molecules more quickly and optimize the drug development process. This study proposes and validates a Deep learn-based model, deep-Avpiden, to improve the classification and discovery efficiency of antiviral peptides (AVPs). By using sequential convolutional networks (TCNs), the model outperforms traditional recurrent neural networks (RNNs) and long short-term memory networks (LSTMs) in capturing long-term dependencies and parallel computing capabilities. In terms of dataset, we used AVPs and non-AVPS samples from multiple databases, totaling 5,414 cleaned and de-weighted peptide sequences for model training after data preprocessing and embedding. The Deep-AVPiden model has been shown to outperform existing advanced classifiers in experiments, and its effectiveness has been verified by accuracy, precision, recall rate, and area under the ROC curve (OC-ROC). In addition, to accommodate computing resource constraints, we propose an optimized version of Deep-AvPIDen (DS), which utilizes Deep separation convolution technology to significantly reduce computing resource consumption. Through the online application platform, researchers can efficiently classify antiviral proteins and discover new AVPs. Future research could further optimize the model's computational efficiency, handle larger data sets, and expand its potential for biomedical problems such as drug combination prediction and new drug discovery.

The multi-UAV target search problem is crucial in the field of autonomous Unmanned Aerial Vehicle (UAV) decision-making. The algorithm design of Multi-agent Reinforcement Learning (MARL) methods has become integral to research on multi-UAV target search, due to its adaptability to the rapid online decision-making required by UAVs in complex, uncertain environments. In non-cooperative target search scenarios, targets may have the ability to escape, complicating UAVs' search efforts and hindering the convergence of the MARL algorithm training. This paper investigates the multi-UAV target search problem in scenarios involving static obstacles and dynamic escape targets, modeling the problem within the framework of Decentralized Partially Observable Markov Decision Process. Based on this model, a Spatio-Temporal Efficient Exploration network and a Global Convolutional Local Ascent mechanism are proposed. Subsequently,we introduce a Multi-UAV Escape Target Search Algorithm Based on MAPPO(ETS-MAPPO) for addressing the escape target search difficulty problem. Simulation results demonstrate that the ETS-MAPPO algorithm outperforms five classical MARL algorithms in terms of the number of target searches,the area coverage rate, and other metrics.

In the present research, it has been tried to use the applied research bases in the field of business management with marketing orientation. Since there were wide and diverse spectrums in the field of economic activities in Isfahan province and Isfahan city, the model of economic sectors was used to categorize these activities. In this regard, the specific goals of the research in all five sectors of the model of economic sectors, drawing and prioritizing the components (indices) of the 7P marketing mix model in each of these economic sectors by the related individuals and members of subgroups of guilds and non-governmental organizations in Isfahan province, have been formed, specified and determined. Collecting data for processing and answer the question of this research, after designing a questionnaire in accordance with the AHP model standard, by spending a period of 2 months from September 2022 and ended in November 2022 , from the statistical population has been done.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

Infrared small target detection (ISTD) plays a crucial role in both civilian and military applications. The detection of small targets against dense cluttered backgrounds remains a challenging task, requiring the collaboration of false alarm source elimination and target detection. Existing approaches primarily focus on modeling targets while often neglecting false alarm sources. To address this limitation, we propose a Target and False Alarm Collaborative Detection Network to leverage the information provided by false alarm sources and the background. Firstly, we introduce a False Alarm Source Estimation Block (FEB) that estimates potential interferences present in the background by extracting features on multiple scales and employing stepwise upsampling for feature fusion. Subsequently, we propose a framework that employs multiple FEBs to eliminate false alarm sources across multiple scales. Finally, a Target Segmentation Block (TSB) is introduced to accurately segment the targets to produce the final detection result. Experiments on public datasets demonstrate that, compared to other methods, our model achieves high accuracy in segmenting targets while being able to extract false alarm sources which can be used for further studies.

The retrieval of tree height percentiles with satellite lidar waveforms over the mountainous ar-eas is greatly challenged due to slanted and rugged topographic relief of underlying ground. A novel algorithm is proposed to extract the height percentiles based on the target response waveform (TRW) that is resolved by using a Richardson–Lucy deconvolution algorithm with an adaptive iterative time. The height metrics of the energy percentiles of 25%, 50%, 75% and 95% for the cumulative TRW distribution are determined by their vertical distances relative to the ground elevation in this study. To validate the proposed algorithm, we select the received waveforms of the Global Ecosystem Dynamics Investigation (GEDI) lidar over the Pahvant Mountains of central Utah, USA. The results reveal that the resolved TRWs resemble closely to the actual target response waveforms from the coincident airborne lidar data, with the mean values of the coefficient of correlation, total bias and root mean square error (RMSE) taking val-ue of 0.92, 0.0813 and 0.0016. In addition, the accuracies of the derived height percentiles from the proposed algorithm have been greatly improved compared with the conventional Gaussian de-composition method and the slope-adaptive waveform metrics method. The RMSE values de-crease by the mean values of 1.96 m and 2.72 m, respectively. It demonstrates that the proposed algorithm has good potential in the extraction of forest structure parameter over rugged moun-tainous areas.

Autonomous target recognition (ATR) plays a crucial role in maintaining situational awareness during environmental monitoring. Unmanned aerial vehicles (UAVs) equipped with autonomous target recognition technology can gather and analyze real-time information about targets, including their locations, sizes, and types. However, UAV-captured images in complex real-world environments often display significant variations in perspective and scale due to changes in UAV altitude and distance. Existing methods for autonomous target recognition on UAVs struggle to capture targets from large field-of-view and multi-scale images, resulting in low recognition accuracy and high false-positive rates. This paper introduces two novel Slimmable neural network models, namely SE-YOLOv5s and ST-YOLOv5s, which are based on the YOLOv5s architecture. These models incorporate the Squeeze and Excitation and Swin-Transformer mechanisms to enhance the ability to extract features from large field-of-view and multi-scale images. To evaluate their performance, experiments were conducted on the Visdrone19 aerial dataset. Compared to the state-of-the-art YOLOv5s algorithm, the utilization of SE-YOLOv5s and ST-YOLOv5s for autonomous target recognition on low-altitude drones resulted in improvements in both accuracy and false-positive rates. These proposed methods combine Slimmable neural network design with feature enhancement mechanisms, addressing the challenges posed by complex real-world environments in UAV missions. The advancements in autonomous target recognition on low-altitude drones will significantly contribute to enhancing situational awareness in future environmental monitoring.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

Ship detection in large-scene offshore synthetic aperture radar (SAR) images is crucial in civil and military fields, such as maritime management and wartime reconnaissance. However, the problems of low detection rates, high false alarm rates, and high missed detection rates of offshore ship targets in large-scene SAR images are due to the occlusion of objects or mutual occlusion among targets, especially for small ship targets. To solve this problem, this study proposes a target detection model (TAC_CSAC_Net) that incorporates a multi-attention mechanism for detecting marine vessels in large-scene SAR images. Experiments were conducted on two public datasets, the SAR-Ship-Dataset and high-resolution SAR image dataset (HRSID), with multi-scene and multi-size, and the results showed that the proposed TAC_CSAC_Net model achieves good performance for both small and occluded target detection. Experiments were conducted on a real large-scene dataset, LS-SSDD, to obtain the detection results of subgraphs of the same scene. Quantitative comparisons were made with classical and recently developed deep learning models, and the experiments demonstrated that the proposed model outperformed other models for large-scene SAR image target detection.

Some traditional robots are based on offline programming reciprocal motion, and with the continuous upgrading of vision technology, more and more tasks are replaced by machine vision. For the current problem of insufficient accuracy of robot target localization based on binocular vision, and an improved random sampling consistency algorithm is proposed to complete parallel robot target localization and grasping under the guidance For the current problem of insufficient accuracy of robot target localization based on binocular vision, an improved random sampling consistency algorithm is proposed to complete parallel robot target localization and grasping under the guidance of multi Firstly, the RANSAC algorithm is improved based on the SURF algorithm; then the parallax gradient method is applied to iterate the matched point pairs several times to further optimize the data; then the 3D reconstruction is completed by the program technique; finally the obtained data is finally the obtained data is input into the robot arm and the camera internal and external parameters are obtained by the calibration method so that the robot can accurately locate and The experiments show that the improved algorithm has advantages in recognition accuracy and grasping success rate under multi- The experiments show that the improved algorithm has advantages in recognition accuracy and grasping success rate under multi-vision system.

With technological transformations such as big data, blockchain, artificial intelligence, and cloud computing, digital techniques are penetrating the field of finance. Digital finance is a resource-saving and environmentally friendly innovative financial service. It shows great green attributes and can drive the flow of financial resources towards environmentally friendly enterprises, thereby promoting green and low-carbon development. This paper investigates the effects of digital finance on green and low-carbon cyclic development and the mechanism. First, the level of green and low carbon cyclic development in China is estimated from multiple aspects based on the panel data of 31 provinces by using the spatio-temporal range entropy weight method. Then, the working mechanism of digital finance on green and low carbon cyclic development is revealed by performing empirical tests based on panel regression models, mediating effect models, and threshold models. Finally, the effects of digital finance and conventional variables on green and low-carbon cyclic development are investigated by using a random forest model and a CatBoost model in based on the machine learning. The results show that digital finance has significant positive effects on green and low-carbon cyclic development, and technological innovation plays a key role in the effects of digital finance on green and low-carbon cyclic development; meanwhile, the driving effect of digital finance on green and low carbon cyclic development shows nonlinear features with increasing “marginal effect”; besides, both digital finance and conventional factors have significant impacts on green and low carbon cyclic development. This study provides an empirical basis and path reference for digital finance to achieve “carbon peak, carbon neutralization” in China.

Titanium oxynitride thin films are deposited by DC reactive magnetron sputtering. A pure titanium target is sputtered in a reactive atmosphere composed of argon, oxygen and nitrogen gases. The oxygen mass flow rate as well as that of the nitrogen gas are both pulsed during the deposition time using an independent and rectangular signal for each reactive gas. A constant pulsing period T = 45 s is applied for both reactive gases and a delay time  of 34 s between N2 and O2 injection times is set for all depositions. Oxygen and nitrogen duty cycles are systematically and independently changed from 0 to 100% of their pulsing period. From real time measurements of the Ti target potential and total sputtering pressure, it is shown that the reactive process alternates between oxidized, nitrided and elemental sputtering modes as a function of the oxygen and nitrogen injection times. The full poisoning of the Ti target surface by oxygen and/or nitrogen can be avoided for some given ranges of O2 and N2 duty cycles. Deposition rates of titanium oxynitride films are substantially enhanced and can be adjusted between that of pure Ti and TiN films with a gradual transition of their optical transmittance in the visible range. These results support that titanium oxynitride compounds exhibiting absorbent to transparent behaviors can be precisely sputter-deposited by means of a two reactive gases pulsing process.

This paper investigates the problem of cooperative standoff tracking using multiple fixed-wing unmanned aerial vehicles (UAVs) with control input constraints. In order to achieve accurate target tracking in the presence of unknown background wind and target motion, a coordinated standoff target tracking algorithm is proposed. The objective of the research is to steer multiple UAVs to fly a circular orbit around a moving target with prescribed intervehicle angular spacing. To achieve this goal, two control laws are proposed, including relative range regulation and space phase separation. On one hand, a heading rate control law based on Lyapunov guidance vector field is proposed. The convergence analysis show that the UAVs can asymptotically converge to a desired circular orbit around the target, regardless of their initial position and heading. Through rigorous theoretical proof, it is concluded that the command signal of the proposed heading rate controller will not violate the boundary constraint on heading rate. On the other hand, a temporal phase is introduced to represent the phase separation and avoid discontinuity of the wrapped space phase angle. On this basis, a speed controller is developed to achieve equal phase separation. The proposed airspeed controller met the requirement of airspeed constraint. In addition, to improve the robustness of the aircraft during target tracking, an estimator is developed to estimate the composition velocity of the unknown wind and target motion. The proposed estimator uses the offset vector between the UAV’s actual flight path and the desired orbit which is defined by Lyapunov guidance vector field to estimate the composition velocity. The stability of the estimator is proved. Simulations are conducted under different scenarios to demonstrate the effectiveness of the proposed cooperative standoff target tracking algorithm. The simulation results of indicate that, the temporal-phase-based speed controller can achieve fast convergence speed and small phase separation error. Additionally, the composition velocity estimator exhibits fast response speed and high estimation accuracy.

High salinity in soil affects the normal growth and development of crop. MicroRNA171 (miR171) plays a momentous role in plant resistance to adversity stress. The functions of Sly-miR171d and Sly-miR171e on growth of tomato and fruit nutritional quality under salt stress were studied. The results showed that the seed germination and seedling growth of tomato that silencing of Sly-miR171d/e by short tandem target mimic (STTM) were better than those of wild-type (WT). Silencing of Sly-miR171d/e seeds maintained a high germination rate, while WT tomato seeds barely germinated under 50 mM NaCl stress. Under 100 mM NaCl stress, silencing of Sly-miR171d/e increased the expression of their target gene SlGRAS24 with increasing duration of salt stress, while they enhanced the antioxidant activity, reduced reactive oxygen species (ROS) accumulation, and enhanced the salt tolerance of tomato plant by regulating gibberellin (GA) level. Moreover, the preharvest and postharvest fruit nutritional quality under salt stress was also studied, and the results showed that silencing of Sly-miR171d/e increased soluble solids, lycopene, total carotenoids, Vitamin C, organic acids and phenolic substances in tomato fruit. The present study demonstrated that silencing of Sly-miR171d/e enhanced plant salt tolerance through the GA pathway, and improved fruit nutritional quality under salt stress.

Despite being an abundant marine organism in Indonesia, black sea cucumber is still underutilised due to its slightly bitter taste. Previous studies have hinted at the potential of black sea cucumber as an anti-cancer agent. However, specific identification of bioactive compounds that can interact with cancer proteins is still lacking. In the same place, cancer ranks third as Indonesia's leading cause of death. Therefore, this study aims to identify potential anti-cancer compounds from black sea cucumbers using a comprehensive in silico drug discovery approach. This research uses machine learning, molecular docking, and ADMET analysis to identify bioactive compounds that specifically interact with cancer proteins. A combination of the Cascade Deep Forest algorithm and ECFP-AAIndex1 feature combination proved to be the most effective in predicting these interactions. Through molecular docking validation, four bioactive compounds with strong binding affinity were identified: Afimoxifene, Danazol, Taxifolin, and Terfenadine. ADMET analysis highlighted Taxifolin as the most promising candidate, as it passed most ADMET parameters. Further wet laboratory studies are required to confirm the effects and potential of these compounds as anti-cancer agents. This study builds a foundation for future investigations into alternative cancer treatments using abundant natural resources.

The Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes, such as cellular cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro for determining the changes induced by Ouabain in concentration of 10-5 M, 10-6 M, 10-8 M, 10-9 M on these cellular types, employing specific methods: SEM for morphological evaluation; immunocytochemistry, flowcytometry to assess immunophenotypical markers expression, cell cycle and Annexin V/PI assay for cellular proliferation and viability testing; flowchamber assay to evaluate functional adhesion behavior; RT-PCR for Na+/K+ ATPase subunits molecular expression. Being indicative of the pro-apoptotic and inhibitory effect of Ouabain on tumor invasion and metastasis, the results support the addition of Ouabain to the oncological therapeutic arsenal, trailing the “repurposing drugs” approach.

Infrared dim and small target detection is a key technology of various detection tasks. However, due to the lack of shape, texture, and other information, it is a challenging task to detect dim and small targets. Recently, since many traditional algorithms ingore global information of infrared images, they generate some false alarms in complicated environments. To address this problem, in this paper, a coarse-to-fine deep learning-based method is proposed to detect dim and small targets. Firstly, a coarse-to-fine detection framework integrating deep learning and background prediction is applied for detecting targets. The framework contains of coarse detection module and fine detection module. In coarse detection stage, Region Proposal Network (RPN) is employed to generate masks in target candidate regions. Then, for further optimize the result, inpainting is utilized to predict the background by the global semnantic of images. In this paper, inpainting algorithm with a mask aware dynamic filtering module is incorporated into the fine detection stage to estimate background in candidate target areas. Finally, compared with existing algorithms, the experimental results indicate that the proposed framework have effective detection capability and robustness for complex surroundings.

Automatic target detection of remote sensing images (RSI) plays an important role in military reconnaissance, disaster monitoring, and target rescue. The core task of remote sensing target detection is to judge the target categories and complete precise location. However, the existing target detection algorithms have limited accuracy and weak generalization capability for remote sensing images with complex backgrounds. To achieve accurate detection of different categories targets in remote sensing images, this study presents a novel feature enhancement single shot multibox detector (FESSD) algorithm for remote sensing target detection. The FESSD introduces feature enhancement module and attention mechanism into the convolution neural networks (CNN) model, which can effectively enhance the feature extraction ability and nonlinear relationship between different convolution features. Specifically, the feature enhancement module is used to extract the multi-scale feature information, and enhance the model nonlinear learning ability; the self-learning attention mechanism (SAM) is used to expand the convolution kernel local receptive field, which makes the model extract more valuable features. In addition, the nonlinear relationship between different convolution features is enhanced using the feature pyramid attention mechanism (PAM). The advantage of FESSD over other state-of-the-art target detection methods is validated by experiments on the presented seven-class target detection dataset (SD-RSI) and the public DIOR dataset.

Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with &lt;100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

Nucleoid-associated proteins (NAPs) play an architectural role by bending, bridging, and wrapping the DNA along with a regulatory role of controlling various transcriptional units in the cell. Previews reviews have highlighted the role of HU and its paralog IHF plays in intracellular function as a transcriptional regulator, nucleoid bending protein and sometimes also moonlights in other functions. This review highlights along with the canonical functions of HU and IHF which affects genes responsible for translational machineries, cell wall biosynthesis, aerobic respiration and virulence ; other non-canonical roles which HU plays outside the cellular milieu, notably in acting as an adhesin and playing role in host-cell adhesion, its role in biofilm architecture and its association with cationic low complexity region, resembling histone like H1 proteins. HU and IHF thus has evolved as a hub protein performing a vast type of functions which makes it a important drug target for antibacterial therapy.

Water is an indispensable natural resource that is often prodigiously threatened by anthropomorphic activities. This study evaluated the physicochemical properties of water and selected heavy metals in edible muscles of a piscivorous fish (Protopterus annectens) from Nyabarongo and Nyabugogo rivers of Rwanda. Edibility health risk was evaluated using the target hazard quotient method. Water samples were taken in triplicate from Ruliba station and Kirinda bridge on Nyabarongo river and Giticyinyoni on Nyabugogo river. Fish samples were obtained from the sampling stations on Nyabarongo river. All samples were analyzed following standard methods and analytical results indicated that the average temperature, pH, total dissolved solids and electrolytic conductivity of water from the rivers were within WHO acceptable limits. The statistical mean concentrations of the ionic components of the water samples were 1.61 ± 0.03, 0.53 ± 0.002, 0.24 ± 0.02 and 0.051 ± 0.01 mg/L for Fe, Mn, Cu and Pb respectively at Ruliba station and 0.63 ± 0.02, 0.02 ± 0.002, 0.09 ± 0.01, 0.06 ± 0.002 and 0.75 ± 0.02 mg/L for Fe, Mn, Zn, Cr and Pb respectively at Kirinda bridge. Water from Giticyinyoni had 1.57 ± 0.02, 0.49 ± 0.03, 0.29 ± 0.058, 0.43 ± 0.058, 0.15 ± 0.00 and 0.59 ± 0.058 mg/L of Fe, Mn, Cu, Zn, Cr and Pb respectively. Zinc, Cu, Cr and Cd were below detection limits in samples from Ruliba station and Kirinda bridge (Nyabarongo river). Edible muscles of P. annectens from Nyabarongo river contained 272.8 ± 0.36, 292.2 ± 0.25, 8.8 ± 0.36, 135.2 ± 0.15, 148.0 ± 0.21 and 432. 0 ± 0.50 mgkg^-1 for Fe, Mn, Cu, Zn, Cr and Pb at Ruliba station and 336.0 ± 0.70, 302.6 ± 1.22, 6.4 ± 0.26, 44.7 ± 0.20, 138.2 ± 0.17 and 302.4 ± 1.50 mgkg^-1 for Fe, Mn, Cu, Zn, Cr and Pb respectively at Kirinda bridge. Health risk assessment indicated that consumption of the edible muscles of P. annectens may lead to deleterious health effects as reflected by values of target hazard quotients being greater than one. Therefore, the Rwandese government should lay strategies to reduce pollution of the rivers. Further research should evaluate the heavy metal content of metabolically active organs of P. annectens from Nyabarongo river as well as the microbiological profile of water from the rivers.

Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However some critical issues related to ctDNA assays should be taken in consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC) qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of cfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.

Background and objectives: Induction chemotherapy (ICT) before definitive chemoradiation (CRT) gives high response rates in LA-SCCHN. However, pre-ICT gross tumour volume (GTV) for radiotherapy (RT) planning is still recommended. As ¹⁸F-FDG PET/CT has an advantage of biological tumour information comparing to standard imaging methods, we aimed to evaluate the feasibility of ¹⁸F-FDG PET/CT-based post-ICT GTV delineation for RT planning in LA-SCCHN and to assess the prognostic value of PET parameters: maximum standardized uptake value (SUV_max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Methods: 47 LA-SCCHN patients were treated with 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil) followed by CRT (70 Gy in 35 fractions with weekly cisplatin). Pre- and post-ICT PET/CT examinations were acquired. Planning CT was co-registered with post-ICT PET/CT and RT target volumes were contoured according to post-ICT PET. Post-ICT percentage decrease of SUV_max, MTV and TLG in primary tumour and metastatic regional lymphnodes (LN) was counted. Loco-regional failure patterns, 3-year progression free (PFS) and overall survival (OS) were evaluated. Results: 3-year PFS and OS rates for study population were 67% and 61% respectively. 31.9% of patients progressed loco-regionally. All progresses were localised in high-to-intermediate dose (60–70 Gy) RT volumes and none in low dose (50 Gy) volumes. Decrease of SUV_max ≥74% (p = 0.03), MTV ≥ 68% (p = 0.04), TLG ≥ 76% (p = 0.02) in primary tumour, and LN TLG decrease ≥74% (p = 0.03) were associated with PFS. Decrease of primary tumour SUV_max ≥ 74% (p = 0.04), MTV ≥ 69% (p = 0.04), TLG ≥ 74% (p = 0.02) and LN TLG ≥ 73% (p = 0.02) were prognostic factors for OS. Conclusions: According to our results, 18F-FDG PET/CT-based post-ICT GTV delineation is feasible strategy without negative impact on loco-regional control and survival. Percentage decrease of metabolic PET parameters SUV_max, MTV and TLG has a prognostic value in LA-SCCHN.

In contrast to physical sustainable measures carried out in homes, such as insulation, the installation of a Home Energy Management System (HEMS) has no direct and immediate energy-saving effect. A HEMS gives insight into resident behaviour regarding energy use. When this is linked to the appropriate feedback, the resident is in a position to change his or her behaviour. This should result in reduced gas and/or electricity consumption. The aim of our study is to contribute towards the effective use of home energy management systems (HEMS) by identifying types of homeowners in relation to the use of HEMS. The research methods used were a literature review and the Q-method. A survey using the Q-method was conducted among 39 owners of single-family homes in various Rotterdam neighbourhoods. In order to find shared views among respondents, a principal component analysis (PCA) was performed. Five different types of homeowner could be distinguished: the optimists, the privacy-conscious, the technicians, the sceptics, and the indifferent. Their opinions vary as regards the added value of a HEMS, what characteristics a HEMS should have, how much confidence they have in the energy-saving effect of such systems, and their views on the privacy and safety of HEMS. The target group classification can be used as input for a way in which local stakeholders, e.g. a municipality, can offer HEMS that is in line with the wishes of the homeowner.

NK population is characterized by distinct NK cell subsets which respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e. resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

Synthetic Aperture Radar (SAR) ship target detection has been extensively researched. However, most methods use the same dataset division for both training and validation. In practical applications, it is often necessary to quickly adapt to new loads, new modes, and new data to detect targets effectively. This presents a cross-domain detection problem that requires further study. This paper proposes a method for detecting SAR ships in complex backgrounds using fusion tensor and cross-domain adversarial learning. The method is designed to address the cross-domain detection problem of SAR ships with large differences between the training and test sets. Specifically, it can be used for the cross-domain detection task from the fully-polarised medium-resolution ship dataset (source domain) to the high-resolution single-polarised dataset (target domain). This method proposes a Channel Fusion Module (CFM) based on the YOLOV5s model. The CFM utilises the correlation between polarised channel images during training to enrich the feature information of single-polarised images extracted by the model during inference. The article proposes a module called Cross-Domain Adversarial Learning Module (CALM) to reduce overfitting and achieve adaptation between domains. Additionally, the paper introduces the Anti-Interference Head (AIH) which decouples the detection head to reduce the conflict of classification and localization problems. This improves the anti-interference and generalization ability in complex backgrounds. This paper conducts cross-domain experiments using the constructed medium-resolution SAR full polarization dataset (SFPD) as the source domain and the high-resolution single-polarised ship detection dataset (HRSID) as the target domain. Compared to the best-performing YOLOV8s model among typical mainstream models, this model improves Precision by 4.9%, Recall by 3.3%, AP by 2.4%, and F1 by 3.9%. This verifies the effectiveness of the method and provides a useful reference for improving cross-domain learning and model generalization capability in the field of target detection.

Plants are subjected to abiotic stresses throughout their developmental period. Abiotic stresses include drought, salt, heat, cold, heavy metals, nutritional element and oxidative stresses. Improving plant response to various environmental stresses is critical for plant survival and perpetuation. The WRKY transcription factors have special structure (WRKY structural domains), which enable WRKY transcription factors to have different transcriptional regulatory functions. The WRKY transcription factors can not only regulate abiotic stresses response and plant growth and development by regulating phytohormone signalling pathways, but also promote or suppress the expression of downstream genes by binding to the W-box [TGACCA/TGACCT] in the promoters of their target genes. In addition, WRKY transcription factors not only interact with other families of transcription factors to regulate plant defence responses in abiotic stresses, but also self-regulate by recognizing and binding to W-boxes in their own target genes to regulate their defence responses to abiotic stresses. However, in recent years, research reviews on the regulatory roles of WRKY transcription factors in higher plants are scarce and shallow. In this review, we focus on the structure and classification of WRKY transcription factors, as well as the identification of their downstream target genes and molecular mechanisms involved in the response to abiotic stresses, which can improve the tolerance ability of plants in abiotic stress and we also look forward to their future research directions, with a view to providing theoretical support for the genetic improvement of crop abiotic stresses tolerance.

Space instable target simulator (SITS) is a vital actuator for ground verification of on-orbital capture technology, the motion performance of which directly affects simulation credibility. Different delays reduce the stability of SITS and ultimately lead to its divergence. In order to achieve high fidelity simulation, the impact of force measurement delay, discrete control cycle, and simulator response delay on stability is analyzed firstly. Then, the dynamic equation and transfer function identification model of hybrid simulator is constructed, and the necessary and sufficient conditions of its stability and convergence are obtained using the Routh criterion. After that, a switching compensator with variable gain is proposed, the compensation principle diagram of which is build, and its mathematical model including the energy observer and tracking differentiator is also established. Finally, three sets of numerical simulations are conducted to validate the correctness of the stability analysis and effectiveness of proposed compensation method. Simulation results show that all three types of delay can cause SITS to lose stability under critical stable motion state, and the delay in force measurement has the greatest impact, followed by the influence of control cycle. Compared with the force applied to simulated target, velocity and its recovery coefficient of space instable target using fixed gain and linear gain compensation, the proposed compensator has significantly better performance.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. SREBPs are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). We review the mechanisms by which SREBPs regulate lipogenesis, the alterations in these processes associated with liver diseases, and therapeutic strategies to target these pathways.

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with aggressive phenotype and represents a poor prognostic factor. Here, we focus on mechanisms by which LOXL2 orchestrates multiple oncogenic functions in HCC development. We are reviewing current knowledge about the roles of LOXL2 in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial-mesenchymal transition. Also, we are highlighting the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize current LOXL2 inhibitors and discuss their potential in HCC precision treatment.

Huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare reagent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical reagents.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.

Autonomous aerial refueling technology is an effective solution to extend flight duration of unmanned aerial vehicles, and also a great challenge due to its high risk. For autonomous probe-and-drogue refueling tasks, relative navigation to provide relative position between the receiver aircraft and the refueling drogue is the first and essential step, and vision-based method is the most frequently used. A new monocular vision navigation sensor with image processing strategy consisting of the drogue detection method and the tracking method is developed for autonomous aerial refueling in this paper. In the drogue detection method, thresholding and mathematical morphology method are adopted to eliminate image interference, and contours extraction method is applied to obtain all contours, which are then subsequently checked to achieve target contour of drogue. In the tracking method, a rectangle of interest (ROI) of current frame image is determined by positioning results of last frame, and then processed by the previous drogue detection method. Finally, the proposed image processing strategy in monocular vision navigation sensor is validated using real flight images, which are captured from an autonomous aerial refueling testbed using a micro six-rotor aircraft as receiver aircraft.

For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named interacting multiple model fifth-degree spherical simplex-radial cubature filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and fifth-degree spherical simplex-radial cubature filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with IMMUKF, IMMCKF and IMM5thCKF.

The proliferation of cloud computing has given rise to challenges in security that established perimeter-based models cannot easily adapt to. The new buzzword Zero Trust, which is based on the principle of "never trust, always verify," has been looked up as one of the promising solutions. Is Zero Trust a certainty or pie in the sky for security in the cloud? This is discussed further in this paper. This philosophical approach leads us through the earlier work and scientific literature available on the subject, presenting Zero Trust's capabilities, advantages when introduced into cloud security architecture, and obstacles about its incorporation. The study finds that Zero Trust holds the potential to enhance cloud security significantly, but it is no silver bullet and demands careful implementation and further studies to understand its intricacies as well as pitfalls.

This article reviews the contemporary understanding of the functional role of connexins in intercellular communications, their involvement in maintaining cellular and tissue homeostasis, and in aging-associated respiratory disease pathogenesis. Connexins are discussed as potential therapeutic targets. The review particularly focuses on the involvement of gap junctions connexins and hemichannels in the transfer of calcium ions, metabolite molecules, ATP and mitochondria through the cell membrane. Various disorders in the regulation of intercellular communication can heavily contribute to the pathogenesis of multiple diseases, including respiratory system diseases. A deeper understanding of molecular mechanisms underlying the activities of various connexins in gap junction channels will enable the prospective development of therapeutic approaches using either inhibiting or stimulating the activities of a certain connexin, considering its critical functions in intercellular communications on the whole.

Hyperspectral small target detection (HSTD) is a promising pixel-level detection task. However, due to the low contrast and imbalance number between the target and background spatially and high dimensions spectrally, it is a challenging one. To address these issues, this work proposes a representation learning-based graph and generative network for hyperspectral small target detection. The model builds a fusion network through frequency representation for HSTD, where the novel architecture incorporates irregular topological data and the spatial-spectral feature to improve its representation ability. Firstly, a graph convolutional network (GCN) module better models the non-local topological relationship between samples to represent the hyperspectral scene’s underlying data structure. The mini-batch-training pattern of the GCN decreases the high computational cost of building an adjacency matrix for high-dimensional data sets. In parallel, the generative model enhances the differentiation reconstruction and the deep feature representation ability with respect to the target spectral signature. Finally, a fusion module compensates for the extracted different types of HS features and integrates their complementary merits for hyperspectral data interpretation while increasing detection and background suppression capabilities. Experiments on different hyperspectral data sets demonstrate the advantages of the proposed architecture.

Drug-target affinity (DTA) prediction is crucial for understanding molecular interactions and aiding drug discovery and development. While various computational methods have been proposed for DTA prediction, their predictive accuracy remains limited, failing to delve into the structural nuances of interactions. With increasingly accurate and accessible structure prediction of targets, we developed a novel deep learning model, named S2DTA, to accurately predict DTA by fusing sequence and structural knowledge of drugs, targets, and pockets using heterogeneous models based on graph and semantic networks. Experimental findings underscored that complex feature representations imparted negligible enhancements to the model’s performance. However, the integration of heterogeneous models demonstrably bolstered predictive accuracy. In comparison to three state-of-the-art methodologies, the supremacy of S2DTA became strikingly apparent. It showcased a noteworthy 25.2% reduction in Mean Absolute Error (MAE) and an impressive 20.1% decrease in Root Mean Square Error (RMSE). Furthermore, S2DTA exhibited substantial advancements in other pivotal metrics, including Pearson Correlation Coefficient (PCC), Spearman, Concordance Index (CI), and R2. These metrics experienced remarkable increments of at least 19.6%, 17.5%, 8.1%, and a remarkable 49.4%, respectively. Finally, we conducted interpretability analysis on the effectiveness of S2DTA by bidirectional self-attention mechanism, fully proving that S2DTA is a valuable and accurate tool for predicting DTA. For further exploration, the source data and code repository can be accessed at https://github.com/dldxzx/S2DTA.

Underwater robotics equipped with visual detection systems have the function of detecting un-derwater artifacts, which is of great significance to deep-sea archaeology. Underwater artifacts are located in complex environments with poor imaging conditions, and the targets have chal-lenging problems such as breakage, stacking, and sediment burial, which causes the marine cul-tural target detection failures. To solve these problems, this paper proposes an underwater cul-tural target detection algorithm based on the deformable deep aggregation network model for underwater robotics exploration. To fully extract the target feature information of underwater targets in complex environments, this paper designs a multi-scale deep aggregation network with deformable convolutional layers. Besides, the BAM attention module is designed for fea-ture optimization, which enhances the potential feature information of the target while weak-ening the background interference information. Finally, the target prediction is achieved through feature fusion at different scales. The proposed algorithm has been extensively validat-ed and analyzed on the collected underwater artifact datasets, and the precision, recall, and mAP of the algorithm have reached 93.1%, 91.4%, and 92.8%, respectively. In addition, the present al-gorithm has been practically deployed on the underwater robotics. In the deep-sea tests, the ar-tifact detection frame rate reaches up to 19 fps, which satisfies the real-time target detection。

This paper presents an optimized energy management strategy for Li-ion power batteries used on electric vehicles (EVs) at low temperatures. Under low-temperature environments, EVs suffer a sharp driving range loss resulted from the energy and power capability reduction of the battery. Simultaneously, because of Li plating, battery degradation becomes an increasing concern as temperature drops. All these factors could greatly increase the total vehicle operation cost. Prior to battery charging and vehicle operating, preheating battery to a battery-friendly temperature is an approach to promote energy utilization and reduce total cost. Based on the proposed LiFePO4 battery model, the total vehicle operation cost under certain driving cycles is quantified in the present paper. Then given a certain ambient temperature, a target temperature of preheating is optimized under the principle of minimizing total cost. As for the preheating method, a liquid heating system is also implemented on an electric bus. Simulation results show that the preheating process becomes increasingly necessary with a decreasing ambient temperature; however, the preheating demand declines as driving range grows. Vehicle tests verify that the preheating management strategy proposed in this paper is able to save total vehicle operation cost.

The effectiveness of a hybrid technique for identifying seismic damage in planar, multistory, steel X or V-braced frames is demonstrated here through an example of a six-story frame. This proposed technique, referred to as “M and P”, combines the instrumental Monitoring (M) with Pushover analysis (P). According to the methodology, the diagram of stepping eigenfrequencies of the frame in the inelastic region is initially plotted against seismic roof displacement. The fundamental natural frequency detected via the monitoring process is then utilized in this key diagram to reveal the inelastic roof displacement that corresponds to the damage state of the steel braced frame. This displacement is subsequently used as the target in the pushover analysis, facilitating the identification of seismic damage in the existing steel braced frame. Finally, the damage image is correlated with the damage stiffness matrix of the frame at the same inelastic roof displacement. The investigation results indicate that combining instrumental monitoring with pushover analysis enables accurate identification of seismic damage potential in existing steel braced frames.

With prosperous development and successful application of deep learning technologies in the field of remote sensing, numerous deep-learning based methods have emerged for synthetic aperture radar (SAR) automatic target recognition (ATR) tasks over the past few years. Generally, most deep-learning based methods can achieve outstanding recognition performance in condition that an abundant of labeled samples are available to train the model. However, in real application scenarios, it is difficult and costly to acquire and to annotate abundant SAR images due to the imaging mechanism of SAR, which poses a big challenge to existing SAR ATR methods. Thereby, SAR target recognition under the situation of few-shot, where only a scarcely few of labeled samples are available, is a fundamental problem that needs to be solved. In this paper, we put forward a new method named enhanced prototypical network with customized region-aware convolution (CRCEPN) to specially tackle the few-shot SAR ATR tasks. To be specific, We first develop a feature extraction network based on a customized and region-aware convolution, which can adaptively adjust convolutional kernels and their receptive fields according to each SAR image’s own characteristics as well as the semantical similarity among spatial regions, thus augmenting its capability to extract more informative and discriminative features. To achieve accurate and robust target identity prediction under the few-shot condition, we then propose an enhanced prototypical network which can improve the representation ability of the class prototype by properly making use of training and test samples together, thus effectively raising the classification accuracy. Meanwhile, a new hybrid loss is designed to learn a feature space with both inter-class separability and intra-class tightness as much as possible, which can further upgrade the recognition performance of the proposed method. Experiments performed on the moving and stationary target acquisition and recognition (MSTAR) dataset and the OpenSARShip dataset demonstrate that the proposed method is competitive with some state-of-the-art methods for few-shot SAR ATR tasks.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

U-Net, based on a deep convolutional neural network (CNN), has been clinically used to au-to-segment normal organs and potentially target volumes. However, CNNs with local geometric dependencies may limit the accuracy of segmentation. Additionally, the performance of CNNs can vary depending on the selection of network hyper-parameters, which was mitigated by the proposition of nnU-Net. We chose a vision transformer architecture called VT U-Net, which features a self-attention excluding the convolution layer, to overcome the limitations of CNNs by utilizing global geometric information of images. The VT U-Net v.2 became more powerful thanks to the adaptive hyper-parameter optimizer embedded in nnU-Net. However, despite leveraging the benefits of nnU-Net, VT U-Net v.2 still had additional network hyper-parameters that needed to be optimally chosen. Accordingly, among various hyper-parameters, this study attempted to find the optimal combination of the patch size and the embedded dimension regarding the transformer. From the 4-fold cross-validation, the modified VT U-Net v.2 showed the highest average performance for planning target volume (PTV) segmentation among the investigated networks. Though nnU-Net was based on convolution layers, the adaptive hyper-parameter optimizers turned out to enhance the performance. It was also confirmed that network hyper-parameters affected the segmentation accuracy of vision transformers.

Parasitic diseases are among the most serious public health problems in developing countries, causing high mortality and economic burdens. The Trypanosomatidae family includes Leishmania spp. and Trypanosoma cruzi, which cause leishmaniasis and Chagas disease, respectively. Both these parasites are among the major agents of neglected tropical diseases (NTDs). Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization (WHO) records approximately 0.7-1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000-30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Despite the similarity of the parasites, the evolution of the disease and the clinical indexes are explicitly different in African, Asian, and American forms of infection. Clinical therapies are associated with drug resistance and side effects. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Peptide-based drugs are an attractive class of therapeutic agents. They are recognized for being highly selective and effective, as well as safe and well tolerated. Moreover, they are now being explored in the development of novel therapeutics for a variety of health disorders, including oncology, endocrinology, metabolic, cardiovascular, and bone diseases. In addition, they are being explored in tropical diseases such as leishmaniasis and Chagas disease. We will discuss current knowledge regarding the parasite life cycle, signs and symptoms, diagnosis, and treatment options for leishmaniasis and Chagas disease.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

The Sugarcane yellow leaf virus (SCYLV) is associated with sugarcane yellow leaf disease (SCYLD) and is considered to be the most economically deleterious emerging pathogen that represents a potential threat and danger to sugarcane cultivation in China. Over the last two decades, high genetic diversity in the SCYLV genotypes was observed worldwide, with a greater chance of YLD incidence for sugarcane injury. SCYLV infection has significantly damaged its economic traits and is responsible for substantial losses in biomass production in sugarcane cultivars. This study aims to identify and comprehensively analyze sugarcane microRNAs (miRNAs) as therapeutic targets against SCYLV using plant miRNA prediction tools. Mature sugarcane miRNAs are retrieved and are used for hybridization of the SCYLV. A total of seven common sugarcane miRNAs were selected based on consensus genomic positions. The biologically significant, top ranked ssp-miR528 was consensually predicted to have a potentially unique hybridization site at nucleotide position 4162 for targeting the ORF5 of the SCYLV genome; this was predicted by all the algorithms used in this study. Then, the miRNA–mRNA regulatory network was generated using the Circos algorithm, which was used to predict novel targets. There are no acceptable commercial SCYLV-resistant sugarcane varieties available at present. Therefore, the predicted biological data offer valuable evidence for the generation of SCYLV-resistant sugarcane plants.

With the increasing demand for security surveillance, assisted driving, and remote sensing, target detection networks with rich environmental perception capabilities and high detection accuracy have become a research hotspot. However, detection techniques based on single-modality images face limitations in environmental adaptability, as they are easily affected by lighting conditions, as well as obstacles such as smoke, rain, and vegetation, leading to information loss and failing to meet the required accuracy. To address these issues, we propose a target detection network—IV-YOLO, which integrates features from both visible and infrared images. We built a dual-branch fusion network based on YOLOv8 (You Only Look Once v8) that combines infrared and visible images for target detection. On this foundation, we designed a Bidirectional Pyramid Feature Fusion structure (Bi-Fusion) to fully integrate complementary features from different modalities, reducing detection errors caused by feature redundancy and extracting fine-grained features of small targets through dual-modal fusion. Additionally, we developed the Shuffle-SPP structure, which combines channel and spatial attention mechanisms to enhance focus on deep features and further aggregate upsampling, extracting richer features. To improve the model’s expressive power, we designed a loss function tailored for multi-scale target detection boxes, accelerating the network’s convergence during training. Experimental results show that the proposed IV-YOLO network achieves an average precision (mAP) of 74.6% on the UAV remote sensing dataset, 75.4% on the KAIST pedestrian dataset, and 84.8% on the FLIR dataset. While ensuring detection accuracy, our model significantly reduces computational load, making it well-suited to meet real-time requirements. This architecture is expected to find broad application in fields such as autonomous driving, public safety, and others.

Cancer is one of the most dreaded illnesses of the 20th century, cancer is continuing to spread and is becoming more common in the 21 st century.As of right now, breast cancer seems to be the most common cancer worldwide and the leading cause of cancer-related fatalities.In present study we used different network pharmacology tools for identification of target that involved in breast cancer that network pharmacology tool used target identification and validation process in drug discovery.In present study we used UniprotKB as text mining tool for identification of breast cancer gene in that we got the 2,658 gene in that we take the 165 in study the we done the GO and KEGG enrichment analysis in that we take pathways related to the breast cancer further we used STRING for determination protein-protein interaction in that we got the interaction between NDUFA1 with NDUFA3 and EREG,MYO1B with ACTN4 and XRCC3 with XRCC2.The interaction network was drawn and the network was analyzed by Cytoscape.