A Berry geometrical phase is identified in a strongly metastable system containing dynamically responsive clathrate hydrate structures within a crystal-fluid material. High energy degeneracy in the associated chemistry produces local stability and false vacuum conditions that lead to non-extensive and non-additive contributions in the fundamental thermodynamic relation. Application of Ginzburg-Landau theory and the scaling laws reveals a coherence length and a penetration depth for a macro-scale dual superconductor. The coherence length determines non-extensive volume changes whilst its inverse gives the Higgs mass. The penetration depth determines the extent of QCD vacuum suppression whilst its inverse gives the vector boson mass together with indirect manifestation as non-additive hyperbolic curvature. Simultaneous emergence of the Ginzburg-Landau superconducting phase transition is consistent with gauge-invariant coupling of the scalar field to the Yang-Mills action in QCD. The discovery of an energy gap in the gradient energy term of the system Lagrangian is associated with a critical correlation length revealed in the transition from a gapped to a gapless superconducting state. Together with the emergence and absorption of the Higgs-like scalar field, a mechanism for describing a renormalized QCD mass gap arises.

Asymmetric lithium salts, such as Lithium (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI), have been demonstrated to surpass traditional symmetric lithium salts with improved Li+ conductivity and the capacity to generate stable solid electrolyte interphase (SEI) while maintaining compatibility with aluminum (Al0) current collector. However, the intrinsic reductive mechanism through which LiDFTFSI influences battery performance remains unclear and under debate. Herein, the detailed SEI reactions of LiDFTFSI-based electrolytes were investigated by combining density functional theory and molecular dynamics, aiming to clarify the formation process and atomic structure of SEI. Our results show that asymmetric DFTFSI– weakens the interaction between carbonate solvents and Li+, and substantially alter the solvation structure, exhibiting a well-balanced coordination capacity to bis(trifluoromethanesulfonyl)imide (TFSI–). Nanoseconds hybrid molecular dynamics simulation further reveals that the preferential decomposition of LiDFTFSI produces sufficient LiF and Li2O to facilitate a robust SEI. Moreover, the abundant F– generated from LiDFTFSI decomposition accumulates on the Al surface and subsequently combines with Al3+ from the current collector to form AlF3, potentially inhibiting corrosion of the current collector. Overall, these findings elucidate how LiDFTFSI regulates the solvation sheath and SEI structure, advancing the development of high-performance electrolytes compatible with current collector.

Astragalus plants belong to the legume family and have obvious rhizosphere effect. The northwestern area of Yunnan China is the main distribution region of Astragalus plants with high application value, but low recognition and resource reserves. The aim of this research is to explore the species diversity of cultivable rhizosphere fungi derived from A. acaulis, A. forrestii, and A. ernestii growing in special high-cold environment of northwest Yunnan, and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fungus Aspergillus calidoustus AA12 from A. acaulis fermentation substance showed a broad antibacterial spectrum and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species of A. calidoustus, including a sesterterpine 6-epi-ophiobolin G (1), two sesquiterpenes penicisochroman A (2), pergillin (3) and 7-methyl-2-(1-methylethylethlidene)-furo[3,2-H]isoquinoline-3-one (4), and three polyketides trypacidin (5), 1,2-seco-trypacidin (6) and questin (7). Compound 1 exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL, and prominent inhibitory effect on the biofilm of Streptococcus agalactiae at MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizosphere fungi Astragalus-derived in special high-cold environment and further increased the library of fungi available for natural anti-infectious products screening.

This investigation explores the potential of enhancing aqueous zinc-ion batteries (AZIBs) through the introduction of a novel cathode material, NH4V4O10 (NVO), combined with reduced graphene oxide (rGO). Utilizing Density Functional Theory (DFT), it was hypothesized that the incorpora-tion of rGO would increase the interlayer spacing of NVO and diminish the charge transfer in-teractions, thus promoting enhanced diffusion of Zn2+ ions. These theoretical predictions were substantiated by experimental data acquired from hydrothermal synthesis, which indicated a marked increase in interlayer spacing. Significantly, the NVO-rGO composite exhibits remarkable cyclic durability, maintaining 95% of its initial specific capacity of 507 mAh g−1 after 600 cycles at a current density of 5 A g−1. The electrochemical performance of NVO-rGO not only surpasses that of pristine NVO but also outperforms the majority of existing vanadium oxide cathode materials reported in the literature. This study underscores the effective integration of theoretical insights and experimental validation, contributing to the advancement of high-performance energy storage technologies.

This study explores the enhancement of aqueous zinc-ion batteries (AZIBs) using ammonium-enhanced vanadium oxide cathodes. Density Functional Theory (DFT) calculations reveal that NH₄⁺ incorporation into V₆O₁₆ lattices significantly facilitates Zn²⁺ ion diffusion by reducing electrostatic interactions, acting as a structural lubricant. Subsequent experimental validation using (NH₄)₂V₆O₁₆ cathodes synthesized via a hydrothermal method corroborates the DFT findings, demonstrating remarkable electrochemical stability with a capacity retention of 90% after 2000 cycles at 5 A g⁻¹. These results underscore the potential of NH₄⁺ in improving the performance and longevity of AZIBs, providing a pathway for sustainable energy storage solutions.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

Using density functional theory (DFT), the density of states of NH4V3O8 (NVO) was analyzed pre and post-oxygen defects (Od) formation. The findings revealed a reduced bandgap in NVO after Od introduction, emphasizing the role of Od in enhancing conductivity of the material, thus improving its electrochemical attributes. Through the water bath method, both NVO and its oxygen-deficient counterpart, (NH4)2V10O25⸱8H2O (NVOd), were synthesized as potential cathode materials for aqueous zinc-ion batteries (AZIBs). Experimental outcomes resonated with DFT predictions, highlighting the beneficial role of oxygen defects in boosting electrical conductivity. Notably, the refined material displayed a remarkable capacity of 479.3 mAh g-1 at 0.1 A g-1, underscoring its promise for advanced energy storage solutions.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

This study reports on the development of bio-based hydrophobic coatings for packaging papers through deposition of polyhydroxybutyrate (PHB) particles in combination with nanofibrillated cellulose (NFC) and plant wax. In a first approach, PHB particles in micrometer range (PHB-MP) were prepared through a phase-separation technique providing internally nanosized structures. The particles were transferred as a coating by dip-coating filter papers in the particle suspension, followed by sizing with a carnauba wax solution. This approach allowed partial to almost full surface coverage of PHB-MP over the paper surface resulting in static water contact angles of 105° to 122° and 129° to 144° after additional wax coating. In a second approach, PHB particles with submicron sizes (PHB-SP) were synthesized by an oil-in-emulsion (o/w) solvent evaporation method, and mixed in aqueous suspensions with 0 to 7 wt% NFC. After dip-coating filter papers in PHB-SP/NFC suspensions and sizing with a carnauba wax solution, static water contact angles of 112° to 152° were obtained. The intrinsic properties of the particles were analyzed by scanning electron microscopy, thermal analysis and infrared spectroscopy, indicating higher crystallinity for PHB-SP than PHB-MP. The chemical interactions between the more amorphous PHB-MP particles and paper fibers were identified as an esterification reaction, while the morphology of the NFC fibrillar network was playing a key role as binding agent in the retention of more crystalline PHB-SP at the paper surface, hence contributing to higher hydrophobicity.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

This work presents a novel approach for the study of the movement of droplets on inclined surfaces under the influence of gravity and chemical heterogeneities. The developed numerical methodology uses data-driven modeling to extend the applicability limits of an analytically derived reduced-order model for the contact line velocity. More specifically, while the reduced-order model is able to capture the effects of the chemical heterogeneities to a satisfactory degree, it does not account for gravity. To alleviate this shortcoming, datasets generated from direct numerical simulations are used to train a data-driven model for the contact line velocity, which is based on the Fourier neural operator and corrects the reduced-order model predictions to match the reference solutions. This hybrid surrogate model, which comprises of both analytical and data-driven components, is then integrated in time to simulate the droplet movement, offering a speedup of five orders of magnitude compared to direct numerical simulations. The performance of this hybrid model is quantified and assessed in different wetting scenarios, by considering various inclination angles and values for the Bond number, demonstrating the accuracy of the predictions as long as the adopted parameters lie within the ranges considered in the training dataset.

As a member of smart materials, electrorheological elastomers (EREs) formed by pre-treating active electrorheological particles are attracting more and more attention. In this work, four Mg-doped strontium titanate particles with spherical, dendritic, flake-like and pinecone-like morphorlogies were obtained by hydrothermal and low-temperature co-precipitation. XRD, SEM, Raman and FT-IR were used to characterize the obtained products. The results showed that the sizes of Mg-doped strontium titanates are about 1.5‒2.0 μm, and the phase structure are dominated by cubic crystal. These Mg-doped strontium titanates were dispersed in a hydrogel composite elastic medium. Then, Mg-doped strontium titanate/glycerol/gelatin electrorheological composite hydrophilic elastomers were obtained with or without electric field. The electric field response properties of Mg-doped strontium titanate composite elastomers were investigated. It concluded that dendritic Mg-doped strontium titanate composite elastomers is high-performance EREs. And the maximum value of energy storage modulus of Mg-doped strontium titanate composite elastomers has achieved 8.70 MPa. This high electrorheological performance of the products is helpful for their applications in vibration control, force transducers, smart structures, dampers, and other fields.

This paper numerically investigates a 3D mesh independency study of a straight blade horizontal axis tidal turbine modelled using Computational Fluid Dynamics (CFD). The solution was produced by employing two turbulence models, the standard k-ε model and Shear Stress Transport (SST) in ANSYS CFX. Three parameters were investigated: mesh resolution, turbulence model, and power coefficient in the initial CFD, analysis. It was found that the mesh resolution and the turbulence model affect the power coefficient results. The power coefficients obtained from the standard k-ε model are 15% to 20% lower than the accuracy of the SST model. It can also be demonstrated that the torque coefficient increases with the increasing Tip Speed Ratio (TSR), but drops drastically after TSR = 5 and k-ε model failing to capture the non-linearity in the torque coefficient with the increasing TSR.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

The ergosterol pathway is a prime antifungal target. The minimum inhibitory concentration (MIC) assay is a simple research tool that determines the lowest concentration at which a novel antimicrobial with limited scope to determine the mechanism of action for a drug. In this study, we show that by adding hydrogen peroxide, an oxidative stressor, or glutathione (GSH), an antioxidant, to modify a commonly performed MIC assay allowed us to screen selectively for new antifungal drugs that target ergosterol biosynthesis in fungi. A human pathogen, Microsporum gypseum, was used as a test organism. When exposed to ergosterol targeting drugs, the hydrogen peroxide treatment significantly decreased fungal survival by reducing ergosterol in the cell wall, whereas GSH increased survival of M. gypseum. Further, by performing a series of experiments with M. gypseum, it was determined that the oxidative stress from hydrogen peroxide causes cell death at different developmental stages. These findings allow us to describe a simple, high-throughput method for simultaneously screening new antifungal drugs for activity and effects on the ergosterol pathway. By using this tool, two isoquinoline alkaloids were discovered to be potent inhibitors of ergosterol biosynthesis by reducing the amount of ergosterol without affecting the expression of 1,3-β-glucan.

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.

In the ground-based infrared optical remote sensing system, the target signal is very weak due to the dynamic strong light background and the movement of small and small targets. In order to improve the limit detection capability, the background suppression and target enhancement methods are required to be more suitable for this scene. To solve this problem, we first analyze the image features in the current scene, and propose a more perfect point target and noise model. Then, we propose a new WY distribution function based on the Fermi Dirac distribution function, and propose an anisotropic filtering method based on this function, and further suppress the back-ground through the difference results of two steps. Then, based on the distribution function, we further designed an energy concentration accumulation strategy in 9 scale directions, through which the SNR of the target is effectively improved and the suppression ability of the background is enhanced. Through quantitative and qualitative experimental analysis, compared with the same type of algorithms, the proposed method has better robustness against extremely weak targets and dynamic backgrounds.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Synthetic Aperture Radar (SAR) is an active sensor that uses microwave for sense, it is unrestricted by weather and illumination conditions, and it can observe targets all day and weather. Aircraft targets are important monitoring objects in military and civilian fields, and how to efficiently detect and recognize aircraft targets is an important topic in the field of SAR image interpretation. Based on the features of SAR images, such as complex background, high resolution, and multi-scale, we proposed an improved method based on YOLOv5s. Firstly, this paper proposed the structure of the multi-scale receptive field and channel attention fusion, which is applied to the shallow layer of the backbone of YOLOv5s, it can adjust the weights of the multi-scale receptive field during the training process to enhance the extraction ability of feature information. Secondly, we proposed four de-coupled detection heads to replace the original part in YOLOv5s, which can improve the efficiency and accuracy of SAR image interpretation for small targets. Thirdly, in the case of the limited amount of SAR images, this paper proposed multi methods of data augmentation, which can enhance the diversity and generalization of the network. Fourthly, this paper proposed the K-means++ to re-place the original K-means to improve the network convergence speed and detection accuracy. Finally, Experiments demonstrate that the improved YOLOv5s can enhance the accuracy of SAR image interpretation by 9.3%, and the accuracy of small targets is improved more obviously, reaching 13.1%.

Portfolio weights solely based on risk avoid estimation error from the sample mean, but they are still affected from the misspecification in the sample covariance matrix. To solve this problem, we shrink the covariance matrix towards the Identity, the Variance Identity, the Single-index model, the Common Covariance, the Constant Correlation and the Exponential Weighted Moving Average target matrices. By an extensive Monte Carlo simulation, we offer a comparative study of these target estimators, testing their ability in reproducing the true portfolio weights. We control for the dataset dimensionality and the shrinkage intensity in the Minimum Variance, Inverse Volatility, Equal-risk-contribution and Maximum Diversification portfolios. We find out that the Identity and Variance Identity have very good statistical properties, being well-conditioned also in high-dimensional dataset. In addition, the these two models are the best target towards to shrink: they minimise the misspecification in risk-based portfolio weights, generating estimates very close to the population values. Overall, shrinking the sample covariance matrix helps reducing weights misspecification, especially in the Minimum Variance and the Maximum Diversification portfolios. The Inverse Volatility and the Equal-Risk-Contribution portfolios are less sensitive to covariance misspecification, hence they benefit less from shrinkage.

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.

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hgb A2 that is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. RBC indices were analyzed using mathematical formulas and the sensitivity and negative predictive value (NPV) calculated. Among 1334 blood counts suspected α-thal analyzed, only the Shine&Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33% and NPV 98.93 and 99.93%, respectively. Molecular defects were found in 291, 81 had normal α genes. Molecular analysis was not performed in 962. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results and increase the awareness of the primary physicians about the carrier risk and send an alert with a recommendation for further testing.

Online speech enhancement is of great interest, because of its diverse areas of application. The Demucs architecture has been recently shown to achieve a high level of performance, even with small audio segments, while requiring a relatively small amount of computational resources. However, an issue that it bears, as well as most of state-of-the-art speech enhancement techniques, is that of target speech selection: it is assumed that only one speech source is present. However, in real-life scenarios, more than one speech source may be present, in it is uncertain which speech source within the fed mixture should be enhanced. Thus, it is of interest to complement speech enhancement techniques (such as Demucs-based) with a target selection scheme, so as to ensure that only the source of interest is enhanced. In this work, two target selection strategies are explored: 1) an embedding-based strategy, using a codified sample of the target speech, and 2) a location-based strategy, using a beamforming-based pre-filter to select the target that is in front of a 2-microphone array. It is shown that while both strategies improve the performance of the Demucs-based technique when one or more speech interferences are present, they both have their pros and cons. Specifically, while the beamforming-based strategy achieves overall a better performance compared to the embedding-based strategy, it is sensitive against the location variation of the target speech source which the embedding-based strategy does not suffer from.

When ground-penetrating radar is used to detect targets within concrete, the location of the targets, the identification of different shapes, properties and less obvious echoes all greatly increase the interpretation time of the staff and can easily cause misjudgment of the echo images. In this paper, the ground-penetrating radar echo images (B-scan) after processing are mean filtered to eliminate the direct waves that interfere greatly with the echoes. The RFB-s structure is added to the YOLOv3-SPP network structure, while the Anchor value is optimized and the EIOU loss function is introduced. For four types of data with different shapes and properties at random target locations, three models, YOLOv3, YOLOv3-SPP and the improved YOLOv3-SPP, are used for classification and identification, and the proposed algorithm models are comprehensively evaluated using model evaluation metrics. The experimental results show that the algorithm models proposed in this paper have good recognition effect in ground-penetrating radar echo image target detection.

The Doppler band compensated by the keystone transform (KT) is limited. Therefore, it needs to be used in conjunction with the Doppler ambiguity compensation function to correct the range migration (RM) caused by maneuvering targets with Doppler ambiguity. However, the KT implemented by sinc interpolation suffers from significant performance loss at boundaries of compensation Doppler bands. Additionally, in a multi-target scenario, KT implementation methods occupy high complexity when the Doppler range of targets spans over two compensation Doppler bands. To address aforementioned issues, this study presents a variable Doppler starting point keystone transform (VDSPKT) method, where a new form of ambiguity compensation function is constructed, turning the Doppler starting point of the compensation band in KT variable. Firstly, the position of the compensation Doppler band is changed from fixed to adjustable as needed, enhancing the flexibility of KT. Crucially, the connection points of the compensation Doppler bands in sinc interpolation are reset, avoiding the performance loss at their boundaries. Also, the compensation band is adjusted to cover the narrow Doppler frequency range caused by targets, significantly improving the computational efficiency. Finally, the simulation results demonstrate that the proposed approach effectively addresses the performance degradation and high computational complexity of KT in the aforementioned scenarios, resulting in a computational load reduced by approximately 50% compared to traditional methods.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

The dynamic factors in the environment violate the static environment assumption of the SLAM algorithm, leading to a decrease in the accuracy of camera positioning. In recent years, many studies have attempted to address dynamic objects by combining semantic constraints and geometric constraints, but issues such as poor real-time performance, the potential for mistakenly treating humans as rigid objects, and subpar performance in high-dynamic scenes still persist. This paper proposes a dynamic scene visual SLAM algorithm called Dynamic SLAM based on target tracking and multi-view geometry (TKG-SLAM), based on object detection, Kalman filters, and multi-view geometry. This algorithm takes into consideration both real-time performance and algorithm accuracy. It combines semantic constraints and multi-view geometry constraints, selectively running the algorithm in different scenarios, filtering and preserving static points for camera pose estimation. Experimental results demonstrate that, compared to current state-of-the-art dynamic SLAM methods, our approach achieves optimal performance in some scenarios and exhibits stronger real-time capabilities.

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.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

An appearance model plays a crucial rule in multi-target tracking. In traditional approaches, the two steps of appearance modeling i.e visual representation and statistically similarity measure are modeled separately. Visual representation is achieved either through hand-crafted features or deep features and statically similarity is measure through a cross entropy loss function. A loss function based on cross-entropy (KL-divergence, mutual information) find closely related probability distribution for the targets. However, if the targets have similar visual representation, it ends up mixing the targets. To tackle this problem, we come up with a synergetic appearance model named Single Shot Appearance Model based on Siamese neural network. The network is trained with a contrastive loss function for finding the similarity between different targets in a single shot. The input to the network is two target patches and based on their similarity, a contrastive score is output by the network. The proposed model is evaluated on accumulative dissimilarity metric on three datasets. Quantitatively, promising results are achieved against three baseline methods.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

In this paper, inspired by Jleli and Samet [journal of inequalities and applications 38 (2014) 2 1–8] we introduce two new classes of auxiliary functions and utilize the same to define (q, y)R-weak 3 contractions. Utilizing (q, y)R-weak contractions, we prove some fixed point theorems in the setting 4 of relational metric spaces. We employ some examples to substantiate the utility of our newly proved 5 results. Finally, we apply one of our newly proved results to ensure the existence and uniqueness of 6 solution of a Volterra-type integral equation.

Macrophages as a source and target of GDF-15

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

Synthetic Aperture Radar has been extensively used in numerous fields and can gather a wealth of information about the area of interest. This large-scene data-intensive technology puts a high value on automatic target recognition (ATR) which can free the utilizers and boost the efficiency. Recent advances in artificial intelligence have made it possible to create a deep learning-based SAR ATR that can automatically identify target features from massive input data. In the last 6 years, intensive research has been conducted in this area, however, most papers in the current SAR ATR field used recurrent neural network (RNN) and convolutional neural network (CNN)-varied models to deepen the regime’s understanding of the SAR images. To equip SAR ATR with updated deep learning technology, this paper tries to apply a lightweight vision transformer (LViT)-based model to classify SAR images. The entire structure was verified by an open- accessed SAR data set and recognition results show that the final classification outcomes are robust and more accurate in comparison with referred traditional network structures without even using any convolutional layers.

The burden of hypertension remains unacceptably high globally, particularly in low- and middle-income countries (LMICs). Workplace offer enormous potential as an idea setting for early detection and treatment of hypertension among the working class. Analysis of such a Workplace Screening Programme can reveal information about its potential impact. Machine learning techniques such as k-Means Clustering are untapped tools for such analyses. We set out to deploy this tool for the analysis of our university annual medical screening of workforce for hypertension. An anonymized dataset containing the demography and blood pressure measurements values obtained from staffs of different departments/units in an academic institution was obtained. The total number of samples or data points are 1, 723 in which the input dataset contains six features, including year category (2018, 2019, 2021,2022), Department/Unit (academic and non-academic), gender (male and female), while the target output is the blood pressure status (low, normal and high) respectively. Analysis of the dataset was carried out using machine learning techniques. In this retrospective analysis, it was observed that the mean age for this working class is 42 years old. Similarly, it was discovered that hypertension was prevalent among members of staff above the age of 40 irrespective of their gender or professional category (academic or non-academic). The analysis also revealed that there was a steady decline in the prevalence of hypertension from 2018 to 2022. From the research, it is evident that the adoption of machine learning techniques for periodic analyses of workplace health status screening initiative (especially for hypertension) is effective, feasible, and sustainable to diagnose and control hypertension among the working class.

Abstract: Background: The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of the screening campaign, and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. Methods: We initiated an HCV patients recall program to identify the HCV participants who might not be treated after the HCV screening campaign. A program staff recalled HCV participants who lost to follow-up through the telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Result: Among 185 HCV-infected participants, 109 (58.9%) HCV-infected participants had obtained LTC. Compared with those who had LTC, those without LTC were older, lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6 %) persons had liked to care. The proportion of LTC increased by 8.7 %. 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of 82 patients with viremia, 78 (95.1%) received antiviral therapy. 76 (97.4 %) of them achieved a sustained virological response. Conclusion: After a community screening campaign, 59 % of participants with anti-HCV positive had LTC. The recall program can increase by 9 %. However, there were still 32% of HCV participants who couldn't be linked to care. Outreach care for non-LTC patients is a way worth trying to achieve micro-elimination of HCV in the rural community.

Genetic engineering and directed evolution are effective methods to address the low yield and poor industrialization level of microbial target products. The current research focus is on how to efficiently and rapidly screen beneficial mutants from constructed large-scale mutation libraries. Traditional screening methods such as plate screening and well plate screening are severely limited in their development and application due to their low efficiency and high costs. In the past decade, microfluidic technology has become an important high-throughput screening technology due to its fast speed, low cost, high automation, and high screening throughput, and it has developed rapidly. Droplet-based microfluidic high-throughput screening has been widely used in various fields such as strain/enzyme activity screening, pathogen detection, single-cell analysis, drug discovery, and chemical synthesis, and has been widely applied in industries such as materials, food, chemicals, textiles, and biomedicine. In particular, in the field of enzyme research, droplet-based microfluidic high-throughput screening has shown excellent performance in discovering enzymes with new functions, improved catalytic efficiency or stability, acid-base tolerance, etc. Currently, droplet-based microfluidic high-throughput screening technology has achieved high-throughput screening of enzymes such as glycosidase, lipase, peroxidase, protease, amylase, oxidase, and transaminase, as well as high-throughput detection of products such as riboflavin, coumarin, 3-dehydroquinate, lactic acid, and ethanol. This article reviews the application of droplet-based microfluidics in high-throughput screening, with a focus on high-throughput screening strategies based on UV, visible, and fluorescence spectroscopy, including labeled optical signal detection screening, as well as label-free electrochemical detection, mass spectrometry, Raman spectroscopy, nuclear magnetic resonance, etc. Furthermore, the research progress and development trends of droplet-based microfluidic technology in enzyme modification and strain screening are also introduced.

A method is developed to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC). A structurally heterogeneous set of compounds active against MTBC was used to obtain a structural pattern model based on structural invariants. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets and was also able to select new active chemical structures in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.

The images captured by UAVs during inspection often contain numerous small targets related to transmission lines, which are critical and vulnerable elements for ensuring the safe operation of these lines. However, due to various factors such as the small size of the targets, low resolution, complex background, and potential line aggregation, achieving accurate and real-time detection becomes challenging. To address these issues, this paper proposes a detection algorithm called P2-ECA-EIOU-YOLOv5 (P2E-YOLOv5). Firstly, in order to address the challenges posed by the complex background and environmental interference that impact small targets, an ECA attention module is integrated into the network. This module effectively enhances the network's focus on small targets while concurrently mitigating the influence of environmental interference. Secondly, considering the characteristics of small target size and low resolution, a new high-resolution detection head is introduced, which is more sensitive to small targets. Lastly, the network utilizes the EIOU-Loss as the regression Loss function to improve the positioning accuracy of small targets, as they tend to aggregate. Experimental results demonstrate that the proposed P2E-YOLOv5 detection algorithm achieves an accuracy P of 96.0% and an average accuracy (mAP) of 97.0% for small target detection in transmission lines.

Infrared detection plays an important role in the military, aerospace, and other fields, which has the advantages of all-weather, high stealth, and strong anti-interference. However, infrared dim small target detection suffers from complex backgrounds, low signal-to-noise ratio, blurred targets with small area percentages, and other challenges. In this paper, we proposed a multiscale YOLOv5-AFAM algorithm to realize high-accuracy and real-time detection. Aiming at the problem of target intra-class feature difference and inter-class feature similarity, the Adaptive Fusion Attention Module - AFAM was proposed to generate feature maps that are calculated to weigh the features in the network and make the network focus on small targets. This paper proposed a multiscale fusion structure to solve the problem of small and variable detection scales in infrared vehicle targets. In addition, the downsampling layer is improved by combining Maxpool and convolutional downsampling to reduce the number of model parameters and retain the texture information. For multiple scenarios, we constructed an infrared dim and small vehicle target detection dataset, ISVD. The multiscale YOLOv5-AFAM was conducted on the ISVD dataset, compared to YOLOv7, [email protected] achieves a small improvement while the parameters are only 17.98% of it. By contrast with the YOLOv5s model, [email protected] was improved by 4.3% with a 6.6% reduction in the parameters. Experiments results demonstrate that the multiscale YOLOv5-AFAM has a higher detection accuracy and detection speed on infrared dim and small vehicles.

Compared to wide-field telescopes, small-field detection systems have higher spatial resolution, resulting in stronger detection capabilities and higher positioning accuracy. When detecting by small-field in synchronous orbit, both space debris and fixed stars are imaged as point targets, making it difficult to distinguish them. In addition, with the improvement of detection capabilities, the number of stars in the background rapidly increases, which puts higher requirements on recognition algorithms. Therefore, star detection is indispensable for identifying and locating space debris in complex backgrounds. To address these difficulties, this paper proposes a real-time star extraction method based on adaptive filtering and multi frame projection. We use bad point repair and background suppression algorithms to preprocess star image. Afterwards, we analyze and enhance the target signal-to-noise ratio(SNR). Then, we use multi frame projection to fuse information. Subsequently, adaptive filtering, adaptive morphology, and adaptive median filtering algorithms are proposed to detect trajectories. Finally, the projection is released to locate the target. Our recognition algorithm has been verified by real star images, and the images were captured using small-field telescope. The experimental results demonstrate the effectiveness of the algorithm proposed in this paper. We successfully extracted hip-27066 star, which has magnitudes about 12 and SNR about 1.5. Compared with existing methods, our algorithm has advantages in both recognition rate and false-alarm rate, and can be used as real time target recognition algorithm for space-based synchronous orbit detection payload.

Multiply-accumulate calculations using a memristor crossbar array is an important method to realize neuromorphic computing. However, the memristor array fabrication technology is still immature, and it is difficult to fabricate large-scale arrays with high-yield, which restricts the development of memristor-based neuromorphic computing technology. Therefore, cascading small-scale arrays to achieve the neuromorphic computational ability that can be achieved by large-scale arrays, which is of great significance for promoting the application of memristor-based neuromorphic computing. To address this issue, we present a memristor-based cascaded framework with some basic computation units, several neural network processing units can be cascaded by this means to improve the processing capability of the dataset. Besides, we introduce a split method to reduce pressure of input terminal. Compared with VGGNet and GoogLeNet, the proposed cascaded framework can achieve 93.54% Fashion-MNIST accuracy under the 4.15M parameters. Extensive experiments with Ti/AlOx/TaOx/Pt we fabricated are conducted to show that the circuit simulation results can still provide a high recognition accuracy, and the recognition accuracy loss after circuit simulation can be controlled at around 0.26%.

Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still poses a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, we report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.

Spray penetration into citrus canopies is critical for adequate coverage and deposition to ensure effective pest control. However, mismatch of air assistance to target canopy characteristics can lead to unintended spray loss through over penetration. To evaluate the effect of air assistance on on-target deposition, two sprayers (surrogates for airflow rates) were used to apply a fluorescent tracer dye solution @ target concentration of 300 ppm to 16 medium foliage density tree blocks in a commercial mandarin orchard. The complete factorial experiment in three replications comprised two ground speeds (1.6 and 4.8 km/h), two disc-core nozzles (TeeJet® D3-25 and D6-45), and either one or two nozzle rows to obtain a wide range of application rates (496 to 9,719 L/ha). Dye deposition significantly decreased with canopy depth (p=&lt;0.001) by nearly 7 times across the 3.4-m-wide canopies but was not significant over 1.2 to 2.2 m sampling height (p=0.867). Deposition obtained with the low airflow rate sprayer was significantly greater (p=&lt;0.001) than that obtained with the high airflow rate sprayer over the dose range likely due to too much air pushing out spray droplets. This study underscores the importance of matching the air assistance of orchard sprayers to the target canopy.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

As a typical visual positioning system, monocular ranging is widely used in various fields. However, when the distance increases, there is a greater error. YOLOv8 network has the advantages of fast recognition speed and high accuracy. This paper proposes a method by combining YOLOv8 network recognition with a monocular ranging method to achieve target localization and grasping for the NAO robots. By establishing a visual distance error compensation model and applying it to correct the estimation results of the monocular distance measurement model, the accuracy of the NAO robot's long-distance monocular visual positioning is improved. Additionally, a grasping control strategy based on pose interpolation is proposed. Throughout, the proposed method's advantage in measurement accuracy was confirmed via experiments, and the grasping strategy has been implemented to accurately grasp the target object.

In autonomous driving systems, high-speed and real-time image processing, along with object recognition, are crucial technologies. This paper builds upon the research achievements in in-dustrial item sorting systems and proposes an object recognition and sorting system for auton-omous driving. In industrial sorting lines, goods sorting robots often need to work at high speeds to efficiently sort large volumes of items. This poses a challenge to the robot's real-time vision and sorting capabilities, making it both practical and economically viable to implement a real-time and low-cost sorting system in a real-world industrial sorting line. Existing sorting systems have limitations such as high cost, high computing resource consumption, and high power consump-tion. These issues lead to the fact that existing sorting systems are typically used only in large industrial plants. In this paper, we design a high-speed, low-cost, low-resource-consumption FPGA (Field-Programmable Gate Array) based item sorting system that achieves similar perfor-mance to current mainstream sorting systems at a lower cost and consumption than existing sorting systems. The recognition part employs a morphological recognition method, which segments the image using a frame difference algorithm and then extracts the color and shape features of the items. To handle sorting, a six-degree-of-freedom robotic arm is introduced in the sorting segment. The improved cubic B-spline interpolation algorithm is employed to plan the motion trajectory and consequently control the robotic arm to execute the corresponding actions. Through a series of experiments, this system achieves an average recognition delay of 25.26ms, ensures smooth operation of the gripping motion trajectory, minimizes resource consumption, and reduces implementation costs.

Plant phenotype plays an important role in crop breeding and planting. Leaf phenotype is an important part of plant phenotype. In order to analyze the leaf phenotype, the target leaf is required to be segmented from the complex background image. In this paper, an automatic soybean leaf segmentation method based on object detection and interactive segmentation models is proposed. Firstly, the Libra R-CNN object detection algorithm is used to detect all soybean leaves in the image. Then, based on the idea that the target soybean leaf is located in the center of the image and the area is large, the detection bounding box of the target leaf is selected. In order not to destroy the segmentation result, the bounding box is optimized to completely enclose the whole leaf. Finally, according to the optimized bounding box, the prior channels of foreground and background are constructed using Gaussian model. The two channels together with the original image are as the input of the interactive object segmentation with inside-outside guidance model to segment the target soybean leaf. A large number of qualitative and quantitative experimental results show that the method has high segmentation accuracy and strong generalization capacity.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

With the development of educational technology, machine learning and deep learning provide technical support for traditional classroom observation assessment. However, in real classroom scenarios, the technique faces challenges such as lack of clarity of raw images, complexity of datasets, multi-target detection errors and complexity of character interactions.Based on the above problems, a student classroom behavior recognition network incorporating super-resolution and target detection is proposed. To cope with the problem of unclear original images in the classroom scenario, SRGAN (Super Resolution Generative Adversarial Network for Images) is used to improve the image resolution and thus the recognition accuracy.To address the dataset complexity and multi-targeting problems, feature extraction is optimized and multi-scale feature recognition is enhanced by introducing AKConv and LASK attention mechanisms into the Backbone module of YOLOv8s algorithm. To improve the character interaction complexity problem, the CBAM attention mechanism is integrated to enhance the recognition of important feature channels and spatial regions. Experiments show that it can detect six behaviors of students raising their hands, reading, writing, playing cell phones, looking down, and lying on the table in high-definition images. And the accuracy and robustness of this network are verified.Compared with small target detection algorithms such as Faster R-CNN, YOLOv5, and YOLOv8s, this network has better detection performance and can efficiently deal with the behavior recognition of multiple students.

Hydrogen is the lightest atom and composes roughly half of the atomic content in macromolecules, yet their location can only be inferred or predicted in most macromolecular structures. This is because hydrogen can rarely be directly observed by the most common structure determination techniques (such as X-ray crystallography and electron cryo-microscopy). However, knowledge of hydrogen atom positions, especially for enzymes, can reveal protonation states of titratable active site residues, hydrogen bonding patterns, and the orientation of water molecules. Though we know they are present, this vital layer of information, which can inform a myriad of biological processes, is frustratingly invisible to us. The good news is that, even at modest resolution, neutron crystallography (NC) can reveal this layer and has emerged this century as a powerful tool for elucidating enzyme catalytic mechanisms. Due to its strong and coherent scattering of neutrons, incorporation of deuterium into the protein crystal amplifies the power of NC. This is especially true when solvation and the specific participation of key water molecules are crucial for catalysis. Neutron data allow the modeling of all three atoms in water molecules and have even revealed previously unobserved and unique species such as hydronium (D3O+) and deuteroxide (OD-) ions as well as lone deuterons (D+). Herein, we briefly review why neutrons are ideal probes for identifying catalytically important water molecules and these unique water-like species, limitations in interpretation, and four vignettes of enzyme success stories from disparate research groups. One of these groups was that of Dr. Chris G. Dealwis, who died unexpectedly in 2022. As a memorial appreciation of his scientific career, we will also highlight his interest and contributions to the neutron crystallography field. As both the authors were mentored by Chris, we feel we have a unique perspective on his love of molecular structure and admiration for neutrons as a tool to query those structures.

In the field of maneuvering target tracking, the combined observations of azimuth and Doppler may cause weak observation or non-observation in the application of traditional target tracking algorithms. Additionally, traditional target-tracking algorithms require pre-defined multiple mathematical models to accurately capture the complex motion states of targets, while model mismatch and unavoidable measurement noise lead to significant errors in target state prediction. To address those above challenges, in recent years, the target-tracking algorithms based on neural networks, such as recurrent neural networks (RNNs), long short-term memory (LSTM) networks, and Transformer architectures, have been widely used for their unique advantages to achieve accurate predictions. To better model the nonlinear relationship between the observation time series and the target state time series, as well as the contextual relationship among time series points, we present a deep learning algorithm called recursive downsample-convolve-interact neural network (RDCINN) based on convolutional neural network (CNN) that downsamples time series into sub-sequences and extracts multi-resolution features to enable the modeling of complex relationships between time series, which overcomes the shortcomings of traditional target-tracking algorithms in using observation information inefficiently due to weak observation or non-observation. The experimental results show that our algorithm outperforms other existing algorithms in the scenario of strong maneuvering target tracking with the combined observations of azimuth and Doppler.

Reliable prediction of sustainable energy consumption is the key to designing environmental friend buildings. In this study, two novel hybrid intelligent methods, namely grasshopper optimization algorithm (GOA), wind-driven optimization (WDO), and biogeography-based optimization (BBO) is employed to optimize the multitarget prediction of heating loads (HLs) and cooling loads (CLs) in heating ventilation and air conditioning (HVAC) systems. Concerning the optimization of applied hybrid algorithms, a series of swarm-based iteration is performed, and the best structure for the abovementioned methods are proposed. Besides, through sensitivity analyzing the relationship between the HLs and CLs and influential factors are highlighted. In other words, the GOA, WDO, and BBO algorithm are mixed with a class of feedforward artificial neural networks (ANN), which called MLP (multi-layer perceptron) to predict the HLs and CLs. According to the provided sensitivity analysis, the WDO with swarm size = 500 proposes the most proper-fitted terms after it has been combined with optimized MLP. The proposed WDO-MLP (training (R2 correlation=0.977 and RMSE error=0.183) and testing (R2 correlation=0.973 and RMSE error=0.190)) provided accurate prediction in the heating load and (training (R2 correlation=0.99 and RMSE error=0.147) and testing (R2 correlation=0.99 and RMSE error=0.148)) presents the most-fit prediction in the cooling load.

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/.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity &lt; 80%, but both values &gt; 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

The number of visible navigation satellites in a multi-constellation system increases exponentially compared to a single constellation, significantly increasing the complexity of the system state equations in the data fusion algorithm of a tightly coupled navigation system. This results in an exponential increase in the computation volume for navigation and positioning, seriously affecting real-time performance. To address this, a low-cost, low-computation satellite screening algorithm is proposed. It adaptively changes the number of constellation satellites by setting different screening thresholds and adjusting the number of remaining satellites. The algorithm then sorts and differentiates the azimuth and elevation angles of the screened satellites to form a selection strategy that divides the space region multiple times, enabling fast satellite selection. This approach greatly reduces the calculation amount while ensuring positioning accuracy. Experimental results show that the proposed algorithm maintains positioning differences within 5 meters compared to traditional satellite selection algorithms, and the time consumed for selecting a single epoch is greatly reduced. This indicates that the algorithm is suitable for low-cost multi-constellation satellite positioning systems.

Plasmodium species that cause malaria, a disease responsible for about half a million deaths per annum despite concerted efforts to combat it. The causative agent depends on type III beta phosphatidylinositol 4-kinase (PPI4K) during the development of merozoite. PPI4K is the only clinically validated Plasmodium kinase so far and its inhibitors are effective both in vitro and in vivo. In this work, a small library of ~22 000 fragments was virtually screened using PPI4K homology model to discover potential ligands of the enzyme. 16 virtual hits were selected based on ≤ -9.0 kcal/mol binding energy cut off and were subjected to similarity and substructure searching after they had passed PAINS screening. The derivatives obtained showed improved binding energies, which ranged from -10.00 to -13.80 kcal/mol. Moreover, the topmost ranking compound 31, with interesting drug-like quality was stable within the protein’s binding cavity during the 10 ns molecular dynamics simulation period. In addition, analysis of its binding pose revealed some unique binding interactions with PPI4K active site residues as the basis for the observed improved binding affinity. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a healthy isocitrate dehydrogenase 1, a mutant that results in cancer, using the recently developed web tool PredictSNP^Onco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

A novel coronavirus called 2019-nCoV was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. 2019-nCoV spreads more rapidly than SARS-CoV. Unfortunately, there is no drug to combat the virus. It is of high significance to develop a drug that can combat the virus effectively before the situation gets worse. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In this paper, we first collected virus RNA sequences from the GISAID database, translated the RNA sequences into protein sequences, and built a protein 3D model using homology modeling. Coronavirus main protease is considered to be a major therapeutic target, thus this paper focused on drug screening based on the modeled 2019-nCov_main_protease structure. The deep learning based method DFCNN, developed by our group, can identify/rank the protein-ligand interactions with relatively high accuracy. DFCNN is capable of performing virtual screening quickly since no docking or molecular dynamic simulation is needed. DFCNN identifies potential drugs for 2019-nCoV protease by performing drug screening against 4 chemical compound databases. Also, we performed drug screening for all tripeptides against the binding site of 2019-nCov_main_protease since peptides often show better stability, more bio-availability and negligible immune responses. In the end, we provided the list of possible chemical ligands and peptide drugs for experimental validation.

The incidence of Severe Combined Immunodeficiency (SCID) in Manitoba, (1/15,000), is at least three to four times higher than the national average and that reported from other jurisdictions. It is overrepresented in two population groups: Mennonites (ZAP70 founder mutation) and First Nations of Northern Cree ancestry (IKBKB founder mutation). We have previously demonstrated that in these two populations the most widely utilized T-cell receptor excision circle (TREC) assay is an ineffective newborn screening test to detect SCID as these patients have normal numbers of mature T-cells. We have developed a semi-automated, closed tube, high resolution DNA melting procedure to simultaneously genotype both of these mutations from the same newborn blood spot DNA extract used for the TREC assay. Parallel analysis of all newborn screening specimens utilizing both TREC analysis and the high resolution DNA procedure should provide as complete ascertainment as possible of SCID in the Manitoba population.

Molten salt electrolysis stands as an indispensable technique for the production of rare earth metals, where the judicious distribution of the electric field within the electrolytic cell is paramount for ensuring the seamless operation of the electrolysis process. This study introduces a pioneering approach by integrating the Nernst-Planck equation with the Butler-Volmer equation, thereby devising a holographic electric field model tailored for the electrolysis of the NdF3-LiF molten salt system. The paper presents pioneering experimental measurements concerning the potential distribution and voltage drop characteristics within a 6kA rare earth electrolytic cell, elucidating the interplay between decomposition voltage and current density, which substantiates the model's precision. Our findings unveil that, under operational conditions of 4010 amperes, the 6kA electrolytic cell incurs a total voltage drop of 6.3 volts, delineating a melt voltage drop of 4.43 volts, an ohmic voltage drop of 0.248 volts, and an interfacial voltage drop of 1.622 volts at the electrode-electrolyte junction. The discrepancy in error is confined to within 0.3% of the actual measured voltage of 6.28 volts.The simulation outcomes from the holographic electric field model have been confirmed to precisely and comprehensively reflect the characteristics of the electric field distribution during the rare earth molten salt electrolysis process, offering valuable theoretical insights for practical manufacturing applications.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

As the number of publications is quickly growing in any area of science, the need to efficiently find relevant information amidst a large number of similarly themed articles becomes very important. Semantic searching through text documents has the potential to overcome the limits of keyword-based searches, especially since the introduction of attention-based transformers, which can capture contextual nuances of meaning in single words, sentences or whole documents. The deployment of these computational tools has been made simpler and accessible to investigators in every field of research thanks to a growing number of dedicated libraries, but a knowledge of how meaning representation strategies work is crucial to make the most out of these instruments. The present work aims at introducing the technical evolution of the meaning representation systems, from vectors to embeddings and transformers tailored to life science investigators with no previous knowledge of natural language processing.

The marine region of the Zhongjieshan Islands is an essential component and location for enhancement and release in Zhoushan Fishing Ground. The scientific assessment of the target species' ecological carrying capacity serves as the foundation for augmentation and release efforts. Based on data from the 2021-2022 survey of biological resources in the waters of Zhongjieshan islands, the Ecopath model was built to analyze the trophic structure, energy flow, and overall characteristics of the ecosystem, as well as the ecological carrying capacity of the main enhancement and releasing species, Larimichthys crocea and Sepiella maindroni. The ecosystem's functional groups had trophic levels ranging from 1 to 3.48, with an average energy transfer efficiency of 8.11% and total flow of 2125.905 t·km-2. The ratio of total primary output to total respiration is 1.713. Zhongjieshan Islands' ecosystem was currently at an embryonic stage. The ecological carrying capacity of Larimichthys crocea and Sepiella maindroni was calculated to be 0.2325 t·km-2 and 0.1617 t·km-2, separately or individually. Larimichthys crocea and Sepiella maindroni showed enormous potential for development and release. The findings offered essential data for ecological studies on the waters of Zhongjieshan Islands, as well as a reference for enhancement and release efforts in this area.

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.

Underwater target detection is widely used in various applications such as underwater search and rescue, underwater environment monitoring, and Marine resources survey. However, the visibility of the underwater environment and the accuracy of target detection can be affected by complex underwater light changes and unpredictable background noise. To address these issues, we propose an improved underwater target detection algorithm based on YOLOv8n. Our algorithm focuses on three aspects. Firstly, we replace the original C2f module with Deformable Convnets v2 to enhance the adaptive ability of the target region in the convolution check feature map and extract the target region's features more accurately. Secondly, we introduce SimAm, a non-parametric attention mechanism, which can deduce and assign three-dimensional attention weights without adding network parameters. Lastly, we optimize the loss function by replacing the CIOU loss function with the Wise-IOU loss function. To conduct our experiments, we create our own dataset of underwater target detection for experimentation. Meanwhile, we also utilized the Pascal VOC dataset to evaluate our approach. The [email protected] and [email protected]:0.95 of the original YOLOv8n algorithm on the underwater target detection were 88.6% and 51.8%, respectively, and the improved algorithm [email protected] and [email protected]:0.95 can reach 91.8% and 55.9%. The original YOLOV8n algorithm was 62.2% and 45.9% [email protected] and [email protected]:0.95 on the Pascal VOC dataset, respectively. The improved YOLOV8n algorithm [email protected] and [email protected]:0.95 were 65.7% and 48.3%, respectively. The floating-point computation volume of the model is reduced by about 6%. The above experimental results prove the effectiveness of our method.

We develop an interactive likelihood (ILH) for sequential Monte-Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, AFL, and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (OSPA and CLEAR MOT). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

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.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

Prevalence estimates of Parkinson’s disease (PD) – the fastest growing neurodegenerative disease – are underestimated due to issues surrounding diagnostic accuracy, symptomatic undiagnosed cases, suboptimal prodromal monitoring, and limited screening access. Remotely monitored wearable devices and sensors provide precise, objective, and frequent measures of motor and non-motor symptoms. Here, we used consumer-grade wearable device and sensor data from the WATCH-PD study to develop a PD screening tool aimed at eliminating gaps between patient symptoms and diagnosis. Early-stage PD (n=82) and age-matched comparison (n=50) participants completed a multidomain assessment battery during a one-year longitudinal multicenter study. Using disease- and behavior-relevant feature engineering and multivariate machine learning modeling of early-stage PD status, we developed a highly accurate (92.3%), sensitive (90.0%), and specific (100%) Random Forest classification model (AUC=0.92) that performed well across environmental contexts. These findings provide robust support for further exploring consumer-grade wearable devices and sensors for global population-wide PD screening and surveillance.

The oxidative coupling of methane (OCM) to produce ethane and ethylene (C2 compounds) as platform chemicals involves complex chemistry with reactions both in the gas phase and on the catalyst surface, resulting in a distribution of products at the expense of C2 selectivity. This work uses experimental data from a variety of mixed metal oxides on supports at different reaction conditions (temperature, contact time, and reactant flow rates) to train a random forest regressor that predicts methane conversion and C2 selectivity (key performance indicators (KPIs)), and deploys it to locate optimal conditions that maximize C2 yield for a catalyst. Investigating the regressor interpretability via feature importance reveals that the choice of metals and support are crucial to C2 selectivity predictions, while the predictions of methane conversion are driven by the reaction conditions. The machine learning (ML) regressor is used as a surrogate to develop performance curves for each of the catalysts via a multi-objective optimization routine that seeks to maximize the KPIs in the decision space of reaction conditions, is seen to locate optimal conditions at which the maximum C2 yields for catalysts are predicted to be 15%, higher on average. Analyzing the catalysts in the space of their performance curves with respect to a popular OCM catalyst, Mn-Na2WO4/SiO2, reveals distinct patterns based on intrinsic properties of metals and supports. Further, the decision space with catalyst descriptors and reaction conditions is optimized for high C2 yields using the ML surrogate, in a static multi-objective optimization routine, and an adaptive Bayesian routine, where the latter was found to have a wider field focus in proposing catalyst formulations and conditions. Transition metal oxides on a variety of supports were proposed but not their lanthanide oxide counterparts.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Malnutrition is a serious problem with negative impact on the quality of life and the evolution of our patients, contributing to an increase in morbidity, hospital stay, mortality and health spending. Early identification is fundamental to implement the necessary therapeutic actions involving adequate nutritional support to prevent or reverse malnutrition. This review presents two complementary methods of fighting malnutrition: nutritional screening and nutritional assessment. Nutritional risk screening is conducted using simple, quick-to-perform tools and is the first line of action in detecting at-risk patients. It should be implemented systematically and periodically on admission to hospital or residential care, as well as on an outpatient basis for patients with chronic conditions. Once patients with a nutritional risk have been detected they should undergo a more detailed nutritional assessment to identify and quantify the type and degree of malnutrition. This should include health history and clinical examination, dietary history, anthropometric measurements, evaluation of the degree of aggression determined by the disease, functional assessment and, whenever possible, some method of measuring body composition.

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.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

Rapid advances in the screening, diagnosis, and treatment of genetic disorders has increased the number of conditions that could be detected through universal newborn screening (NBS). However, addition of conditions to the Recommended Uniform Screening Panel (RUSP) and implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders. NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases have utilized NBSTRN’s tools, and in turn contributed research data to further expand and refine these this resource. Additionally, we discuss ongoing tool development to facilitate expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.

Due to the convenience of implementing without additional transmitter, radar communication integrated systems using conventional communication signals have become an effective means of monitoring unmanned aerial vehicles and other aircraft. However, the non-ideal radar signal form causes the strong signal to cover the weak signal, and the clutter suppression is required to expose the target. As the target signal is extremely low, and the performance of conventional clutter suppression methods is limited, the residual clutter remains after the time-varying clutter is suppressed, which leads to many false alarm points on the processed RD spectrum. The two-dimensional distribution of these false alarms in range-Doppler is very similar to the target and difficult to be distinguished, which seriously affects the target detection and tracking. To reduce false alarm points and improve the performance of target detection, the difference of spatial-temporal stationarity between target signal and clutter in a short time is discussed in this paper, a radar false alarm suppression method based on target spatial-temporal stationarity is proposed by using the difference of stationarity between target signal and false alarm points in range, Doppler, energy and azimuth. In this algorithm, to ensure the short-time stationarity of the target, the RD spectrum of sub-frames with short time interval is obtained by using the sliding matching filtering method and extract the peak points. Then, the Mahalanobis distance between the peak points of each sub-frame is used to eliminate false alarm points. Finally, false alarm points are further eliminated through the target tracking and retain the real target information, so as to improve the radar target detection performance. The simulation experiments show that this method can eliminate more than 90% false alarms points while maintaining the detection performance of the target. The processing of actual data in the field experiment shows that the after suppression false alarm by this algorithm can obtain more ideal target detection results, and realize the tracking of the UAV and other aircraft track.

In order to meet the national energy saving goals set in the Vietnam National Energy Efficiency Program in the period of 2019 – 2030 (VNEEP), the Vietnamese government has adopted a series solutions and policies to improve energy efficiency. The Vietnam’s 63 provinces will be as main actor for the national achievement in energy efficiency. Thus, understanding the province’s potentiality of energy efficiency is useful for the harmonious and sustainable development between the economy and energy systems. In this study, provincial and national data from General Statistic Office are analyzed in terms of the energy efficiency levels. With the trends of economic development and energy consumption in both national and regional levels, the Lorenz curve between Vietnamese energy consumption and GDP is investigated. The Lorenz coefficient shows the energy allocation is nether reasonable nor balanced. By using clustering method, the 63 provinces of Vietnam clustered into 7 groups that the provinces in the cluster has the similar indexes of energy efficiency i.e. ability, responsibility, potential and difficulty. The energy consumption and GDP are predicted in the period of 2019 – 2025. Based on the difference of GDP development and energy consumption levels, the target of energy efficiency for each province through clustering is set. The results show that 33 provinces included in the cluster 1, 2, 3, 4 and 6 are heavy contribution. Among them, the provinces in the cluster 2 and 3 need to focus on the industry sector in their energy saving policy. The cluster 7 included the under-developed provinces can learn development’s experiences of the provinces in the cluster 1, 2, 3 and 4 to find the best way of their future development.

The node position information is critical in the wireless sensor network (WSN). However, the existing positioning algorithms commonly have low positioning accuracy because of noise interferences in communication. To solve this problem, this paper presents an iterative positioning model based on distance correction to improve the positioning accuracy of the target node in WSN. First, the log-distance distribution model of received signal strength indication (RSSI) ranging is built and the noise impact factor is derived based on the model. Second, the initial position coordinates of the target node are obtained based on the triangle centroid localization algorithm, thereby calculating the distance deviation coefficient under the influence of noise. Then, the ratio of the distance measured by the log-normal distribution model to the median distance deviation coefficient is taken as the new distance between the anchor node and the target node. Based on the new distance, the triangular centroid positioning algorithm is used again to calculate the target node coordinates. Finally, the iterative positioning model is constructed, and the distance deviation coefficient is updated repeatedly to update the positioning result until the set number of iterations is reached. Experiment results show that the proposed iterative positioning model can improve positioning accuracy effectively.

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. For this, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epider-mal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), Serine/threonine-protein kinase mTOR (mTOR) and Poly [ADP-ribose] polymerase-1 (PARP1). Then, mapped single nucleotide polymorphisms and designed target mutations, and performed molecular docking with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Close to half (45.4%) of 2.3 million breast cancers (BC) diagnosed in 2020 were from Asia. While the burden of breast cancer has been examined on the level of broad geographic regions, literature on more in-depth coverage of the individual countries and subregions of the Asian continent is lacking. This review examines the breast cancer burden in 47 Asian countries. Breast cancer screening guidelines and risk-based screening initiatives are discussed.

At present, there are no hardware or biochemical systems allow to assess the severity of post-COVID syndrome in vivo. The hardware of the proposed biotechnical system is based on routine transthoracic electrical impedance rheography, which makes it possible to register the frequency characteristics of the patient's bioimpedance response to controlled stress stimulation, thereby simultaneously fixing the characteristics of his productive heart, the state of the hemomicrocirculatory bed, the efficiency of the gas transport function of his blood, and also reliably assess personal reactivity and adaptive potential. Subsequent mathematical approximation of the obtained biometric data by an original neural network makes it possible to rank the results obtained and automatically generate a program of medical rehabilitation for a particular patient, depending on the severity of his post-COVID syndrome. The study results proved two reliable physiological signs confirming the presence of latent post-COVID complications: a decrease in the base impedance value for light exercise and an increase in the length of the systolic arc of the rheocardiogram.

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proved to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in treatment of HCC. This review summarizes impact of hypoxia on HCC tumor biology, adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

New dimers of selected dipyridothiazines with an m-xylene linker have been designed, synthesized and characterized. Their structure was identified using 1H and 13C NMR as well as 2D NMR techniques (COSY, ROESY, HSQC and HMBC experiments) and HR MS spectrometry. The compounds were subjected to preliminary in silico biological profile tests using the Way2Drug server and analysis of the probable cytotoxic effect on various cancer cell lines. Preliminary in vitro cytotoxicity tests were performed against normal cell lines (HaCaT) and five cancer cell lines (SW480, SW620, MDA-MB-231, A-549, LN-229) showing moderate activity. An analysis of the structure-activity relationship was performed.