Four New Furofuran Lignans from Phryma leptostachya Inhibit the Accumulation of Molting Hormones in Armyworm.

Furofuran lignans have been identified as the main substances responsible for the biological activities of the plant genus Phryma. Here, four new phrymarolin-type leptolignans A-D (7-10) and eight previously known lignans were isolated from P. leptostachya. Of these, nine exhibited significant antifeedant activity against armyworm (Mythimna separata) through a dual-choice bioassay, with the EC50 values ranging from 0.58 to 10.08 µg/cm2. In particular, the newly identified lignan leptolignan A (7) showed strong antifeedant activity, with an EC50 value of 0.58 ± 0.34 µg/cm2. Further investigation found that leptolignan A can inhibit the growth and nutritional indicators in the armyworm M. separata. The concentrations of two molting hormones, 20-hydroxyecdysone and ecdysone, were also found to decrease significantly following the treatment of the armyworms with the lignan, implying that the target of the P. leptostachya lignan may be involved in 20-hydroxyecdysone and ecdysone synthesis. These results enrich our knowledge of P. leptostachya metabolite structural diversity, and provide a theoretical basis for the control of armyworm using lignans.

How AI and Robotics Will Advance Interventional Radiology: Narrative Review and Future Perspectives.

The rapid advancement of artificial intelligence (AI) and robotics has led to significant progress in various medical fields including interventional radiology (IR). This review focuses on the research progress and applications of AI and robotics in IR, including deep learning (DL), machine learning (ML), and convolutional neural networks (CNNs) across specialties such as oncology, neurology, and cardiology, aiming to explore potential directions in future interventional treatments. To ensure the breadth and depth of this review, we implemented a systematic literature search strategy, selecting research published within the last five years. We conducted searches in databases such as PubMed and Google Scholar to find relevant literature. Special emphasis was placed on selecting large-scale studies to ensure the comprehensiveness and reliability of the results. This review summarizes the latest research directions and developments, ultimately analyzing their corresponding potential and limitations. It furnishes essential information and insights for researchers, clinicians, and policymakers, potentially propelling advancements and innovations within the domains of AI and IR. Finally, our findings indicate that although AI and robotics technologies are not yet widely applied in clinical settings, they are evolving across multiple aspects and are expected to significantly improve the processes and efficacy of interventional treatments.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Design, synthesis and evaluation of carbamate-bridged amino acid prodrugs of cycloicaritin with improved antitumor activity, aqueous solubility and phase II metabolic stability.

Cycloicaritin (CICT), a bioactive flavonoid derived from the genus Epimedium, exhibits a variety of beneficial biological activities, including promising anticancer effects. However, its poor oral bioavailability is attributed to its extremely low aqueous solubility and rapid elimination via phase II conjugative metabolism. To overcome these limitations, we designed and synthesized a series of carbamate-bridged prodrugs, protecting the hydroxyl group at the 3-position of cycloicaritin by binding with the N-terminus of a natural amino acid. The optimal prodrug 4b demonstrated a significant increase in aqueous solubility as compared to CICT, as well as improved stability in phase II metabolism, while allowing for a rapid release of CICT in the blood upon gastrointestinal absorption. The prodrug 4b also facilitated oral absorption through organic anion-transporting polypeptide 2B1-mediated transport and exhibited moderate cytotoxicity. Importantly, the prodrug enhanced the oral bioavailability of CICT and displayed dose-dependent antitumor activity with superior safety. In summary, the prodrug 4b is a novel potential antitumor drug candidate, and the carbamate-bridged amino acid prodrug approach is a promising strategy for the oral delivery of CICT.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Classification of a Massive Number of Viral Genomes and Estimation of Time of Most Recent Common Ancestor (tMRCA) of SARS-CoV-2 Using Phylodynamic Analysis.

Estimating the time of most recent common ancestor (tMRCA) is important to trace the origin of pathogenic viruses. This analysis is based on the genetic diversity accumulated in a certain time period. There have been thousands of mutant sites occurring in the genomes of SARS-CoV-2 since the COVID-19 pandemic started; six highly linked mutation sites occurred early before the start of the pandemic and can be used to classify the genomes into three main haplotypes. Tracing the origin of those three haplotypes may help to understand the origin of SARS-CoV-2. In this article, we present a complete protocol for the classification of SARS-CoV-2 genomes and calculating tMRCA using Bayesian phylodynamic method. This protocol may also be used in the analysis of other viral genomes. Key features • Filtering and alignment of a massive number of viral genomes using custom scripts and ViralMSA. • Classification of genomes based on highly linked sites using custom scripts. • Phylodynamic analysis of viral genomes using Bayesian evolutionary analysis sampling trees (BEAST). • Visualization of posterior distribution of tMRCA using Tracer.v1.7.2. • Optimized for the SARS-CoV-2.

Flexible Humidity Sensor Based on a Graphene Oxide-Carbon Nanotube-Modified Co3O4 Nanoparticle-Embedded Laser-Induced Graphene Electrode.

To meet evolving humidity monitoring needs, the development of flexible, high-performance humidity sensors is crucial. This study introduces an innovative flexible humidity sensor using a single-step laser scribing technique to fabricate a flexible in situ Co3O4 nanoparticle-embedded laser-induced graphene (Co3O4-LIG) composite electrode. Compared to conventional LIG electrodes, the Co3O4-LIG electrode exhibits improved conductivity and hydrophilicity, enhancing charge transfer and water molecule affinity. The unique two-dimensional structure and exceptional water permeability of graphene oxide (GO) combine with the rapid water response and high specific surface area of carboxylated multiwalled carbon nanotubes (MWCNTs), thereby assuming a crucial function in the modification and optimization of the performance of humidity sensors. Through the application of a homogenously blended aqueous solution comprising GO and MWCNTs in precise proportions onto the Co3O4-LIG composite electrode, an excellent humidity-responsive layer is established, culminating in the realization of a cutting-edge GO-MWCNTs@Co3O4-LIG flexible humidity sensor. Noteworthy attributes of this sensor include a heightened sensitivity [959.1% (ΔR/R0)], rapid response and recovery times (within 5 and 26 s, respectively), and a noteworthy linearity (R2 = 0.994) across a relative humidity range of 14 to 95%. The findings presented herein offer valuable insights and a practical blueprint for the design and production of flexible humidity sensors.

Hyperglycemia Inhibits Hepatic SHBG Synthesis Through the NGBR-AMPK-HNF4 Pathway in Rats with Polycystic Ovary Syndrome Induced by Letrozole in Combination with a High-Fat Diet.

SCOPE: Polycystic ovary syndrome (PCOS) is closely related to non-alcoholic fatty liver disease (NAFLD), and sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis. METHODS AND RESULTS: This study establishes a rat model of PCOS complicated by NAFLD using a high-fat diet in combination with letrozole and performs transcriptomic analysis of the liver. Transcriptomic analysis of the liver shows that the expression of neurite growth inhibitor-B receptor (NgBR), hepatocyte nuclear factor 4α (HNF4α), and SHBG is low. Meantime, HepG2 cells are treated with palmitic acid (PA) to model NAFLD in vitro, which causes decreases in the expression of NgBR, HNF4α, and SHBG. However, the expression of HNF4α and SHBG is restored by treatment with the AMP-activated protein kinase (AMPK) agonist AICAR. CONCLUSIONS: NgBR regulates the expression of HNF4α by activating the AMPK signaling pathway, thereby affecting the synthesis of SHBG in the liver. Further mechanistic studies regarding the effect of liver fat on NGBR expression are warranted.

A Visible Light-Responsive TiO2 Photocathode Achieved by a Rh Dopant.

Developing an efficient and stable photocathode material for photoelectrochemical solar water splitting remains challenging. Herein, we demonstrate the potential of rutile TiO2 as a photocathode by Rh doping with visible light absorption up to 640 nm and an onset potential of 0.9 V versus the reversible hydrogen electrode. The dopant transforms the rutile host from an n-type semiconductor to a p-type one, as confirmed by the Mott-Schottky curve and kelvin probe force microscopy. Physical and photoelectrochemical analyses further suggest that the doping mechanism is dependent on concentration. Lower levels of dopants generate localized Rh3+, while higher levels favor Rh4+ that interacts more strongly with the O 2p orbitals. The latter is found not only to extend the visible light absorption range but also to facilitate charge transport. This work elucidates the role of the Rh dopant in adjusting the photoelectrochemical behavior of TiO2, and it provides a promising photocathode material for solar energy conversion.

Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.

AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. AURKA is located on chromosome 20 and is amplified or overexpressed in many human cancers, such as breast cancer. AURKA regulates some basic cellular processes, and this regulation is realized via the phosphorylation of downstream substrates. AURKA can function in either the cytoplasm or the nucleus. It can promote the transcription and expression of oncogenes together with other transcription factors in the nucleus, including FoxM1, C-Myc, and NF-κB. In addition, it also sustains carcinogenic signaling, such as N-Myc and Wnt signaling. This article will focus on the role of AURKA in the nucleus and its carcinogenic characteristics that are independent of its kinase activity to provide a theoretical explanation for mechanisms of resistance to kinase inhibitors and a reference for future research on targeted inhibitors.

AURKA plays an important role in the control of the proliferation, invasion, cell cycle regulation and self-renewal of cancer stem cells.Small molecule kinase inhibitors targeting AURKA have been developed, but the overall response rate of patients in clinical trials is not ideal, prompting us to pay attention to the non-kinase activity of AURKA.This review focuses on the nuclear function of AURKA and its oncogenic properties independent of kinase activity, demonstrating that the nuclear substrate of AURKA and the remote allosteric site of the kinase may be targets of anticancer therapy.

eDNA reveals spatial homogenization of fish diversity in a mountain river affected by a reservoir cascade.

One of the main reasons for the decline in global freshwater biodiversity can be attributed to alterations in hydrological conditions resulting from dam construction. However, the majority of current research has focused on single or limited numbers of dams. Here, we carried out a seasonal fish survey, using environmental DNA (eDNA) method, on the Wujiang River mainstream (Tributaries of the Yangtze River, China) to investigate the impact of large-scale cascade hydropower development on changes in fish diversity patterns. eDNA survey revealed that native fish species have decreased in contrast to alien fish. There was also a shift in fish community structure, with declines of the dominant rheophilic fish species, an increase of the small-size fish species, and homogenization of species composition across reservoirs. Additionally, environmental factors, such as temperature, dissolved oxygen and reservoir age, had a significant effect on fish community diversity. This study provides basic information for the evaluation of the impact of cascade developments on fish diversity patterns.

Accuracy assessment between computer-guided surgery planning and actual tooth position during tooth autotransplantation.

BACKGROUND/AIM: This study aims to evaluate the precision and efficacy of utilizing computer-aided design (CAD) in combination with three-dimensional printing technology for tooth transplantation. MATERIAL AND METHODS: This study analysed 50 transplanted teeth from 48 patients who underwent tooth transplantation surgery with the aid of CAD and positional guides. A consistent coordinate system was established using preoperative and postoperative cone-beam computed tomography images. Linear displacements and angular deviations were calculated by identifying key regions in both virtual designs and actual transplanted teeth. Additionally, an analysis was conducted to explore potential factors influencing these deviations. RESULTS: The mean cervical deviation, apical deviation, and angular deviation among the 50 transplanted teeth were 1.16 ± 0.57 mm, 1.80 ± 0.94 mm, and 6.82 ± 3.14°, respectively. Cervical deviation was significantly smaller than apical deviation. No significant difference in deviation was observed among different recipient socket locations, holding true for both single-root, and multi-root teeth. However, a significant difference was noted in apical deviation between single-root and multi-root teeth. Our analysis identified a correlation between apical deviation and root length, leading to the development of a prediction model: Apical deviation = 0.1390 × (root length) + 0.2791. CONCLUSIONS: The postoperative position of the donor teeth shows discrepancies compared to preoperative simulation when utilizing CAD and 3D printed templates during autotransplantation procedures. Continual refinement of preoperative design is a crucial endeavour.

Relationship between Ambient Temperature and Reasonable Heat Dissipation Coefficient of Mass Concrete Pouring Blocks.

In engineering practice, similar surface insulation measures are typically applied to different parts of mass concrete surfaces. However, this can lead to cracking at the edges of the concrete surface or the wastage of insulation materials. In comparison to flat surfaces, the edges of mass concrete structures dissipate heat more rapidly, leading to more pronounced stress concentration phenomena. Therefore, reinforced insulation measures are necessary. To reduce energy consumption and enhance overall insulation effectiveness, it is essential to study the specific insulation requirements of both the flat surfaces and edges of concrete separately and implement targeted surface insulation measures. Taking the bridge abutment planned for pouring in Nanjing City as the research object, this study established a finite element model to explore the effects of different ambient temperatures and different surface heat dissipation coefficients on the early-age temperature and stress fields of different parts of the abutment's surface. Based on simulation results, reasonable heat dissipation coefficients that meet the requirements for crack prevention on both the structure's plane and edges under different ambient temperatures were obtained. The results indicate that under the same conditions, the reasonable heat dissipation coefficient at the edges was smaller than that on the flat surfaces, indicating the need for stronger insulation measures at the edges. Finally, mathematical models correlating ambient temperature with reasonable heat dissipation coefficients for the structure's plane and edges at these temperatures were established, with high data correlation and determination coefficients (R2) of 0.95 and 0.92. The mathematical models were validated, and the results from finite element calculations were found to be consistent with those from the mathematical models, validating the accuracy of the mathematical models. The conclusions drawn can provide references for the insulation of similar engineering concrete planes and edges.

Tensile and High Cycle Fatigue Performance at Room and Elevated Temperatures of Laser Powder Bed Fusion Manufactured Hastelloy X.

The application potential of additive manufacturing nickel-based superalloys in aeroengines and gas turbines is extensive, and evaluating their mechanical properties is crucial for promoting the engineering application in load-bearing components. In this study, Hastelloy X alloy was prepared using the laser powder bed fusion process combined with solution heat treatment. The tensile and high cycle fatigue properties were experimentally investigated at room temperature as well as two typical elevated temperatures, 650 °C and 815 °C. It was found that, during elevated-temperature tensile deformation, the alloy exhibits significant serrated flow behavior, primarily observed during the initial stage of plastic deformation at 650 °C but occurring throughout the entire plastic deformation process at 815 °C. Notably, when deformation is small, sawtooth fluctuations are significantly higher at 815 °C compared to 650 °C. Irregular subsurface lack of fusion defects serve as primary sources for fatigue crack initiation in this alloy including both single-source and multi-source initiation mechanisms; moreover, oxidation on fracture surfaces is more prone to occur at elevated temperatures, particularly at 815 °C.

Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections.

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

Thermal performance and experimental analysis of stainless steel flat plate solar collector with full-flow channels.

The thermal performance of a flat plate solar collector (FPSC) is a critical indicator that depends on the environment, operational parameters, and dimensions. This study examines the impact of size on thermal performance improvement mechanisms. Firstly, numerical simulation models are introduced as the foundation for optimization research. This involves analyzing the flow resistance of microchannels and defining their structural parameters. Furthermore, experimental tests were conducted on a stainless steel flat plate solar collector (S/S FPSC) with the best design parameters to validate the accuracy of the mathematical model during the design phase. The results indicate that increasing the width of the microchannel and the height of corrugations can effectively enhance the thermal performance of the S/S FPSC. The momentary efficiency is projected to reach a remarkable 86.10% under ideal circumstances. Additionally, a mathematical expression was proposed to establish the relationship between the surrounding conditions and the momentary efficiency of the S/S FPSC. Moreover, the microchannel comprises S/S material, maintaining a homogeneous temperature distribution to maximize heat absorption. The use of stainless steel also extends the lifespan of the FPSC.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

Rapid, Massive, and Green Synthesis of Polyoxometalate-Based Metal-Organic Frameworks to Fabricate POMOF/PAN Nanofiber Membranes for Selective Filtration of Cationic Dyes.

Developing high-efficiency membrane materials for the rapid removal of organic dyes is crucial but remains a challenge. Polyoxometalates (POMs) clusters with anionic structures are promising candidates for the removal of cationic dyes via electrostatic interactions. However, their shortcomings, such as their solubility and inability to be mass-produced, hinder their application in water pollution treatment. Here, we propose a simple and green strategy utilizing the room temperature stirring method to mass produce nanoscale polyoxometalate-based metal-organic frameworks (POMOFs) with porous rhomboid-shaped dodecahedral and hexagonal prism structures. The products were labeled as POMOF1 (POMOF-PW12) and POMOF2 (POMOF-PMo12). Subsequently, a series of x wt% POMOF1/PAN (x = 0, 3, 5, and 10) nanofiber membranes (NFMs) were prepared using electrospinning technology, where polyacrylonitrile (PAN) acts as a "glue" molecule facilitating the bonding of POMOF1 nanoparticles. The as-prepared samples were comprehensively characterized and exhibited obvious water stability, as well as rapid selective adsorption filtration performance towards cationic dyes. The 5 wt% POMOF1/PAN NFM possessed the highest removal efficiency of 96.7% for RhB, 95.8% for MB, and 86.4% for CV dyes, which realized the selective separation over 95% of positively charged dyes from the mixed solution. The adsorption mechanism was explained using FT-IR, SEM, Zeta potential, and adsorption kinetics model, which proved that separation was determined via electrostatic interaction, hydrogen bonding, and π-π interactions. Moreover, the POMOF1/PAN membrane presented an outstanding recoverable and stable removal rate after four cycles. This study provides a new direction for the systematic design and manufacture of membrane separation materials with outstanding properties for contaminant removal.

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.