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The hydration heat generated during the concreting of cast-in-place piles causes thermal disturbance to the surrounding permafrost, leading to its thawing. This further affects the stability of the pile foundation and degrades the construction progress. To explore the influence mechanisms of the concrete hydration heat on the permafrost temperature field around the pile, as well as that of different construction seasons on the pile-side boundary conditions and permafrost temperature field, monitoring results of on-site tests and numerical simulation were used to analyze the distribution law of the pile soil temperature field in space and time, and the pile-side boundary conditions and permafrost temperature field during construction seasons. The results show that the temperature trend of the pile foundation can be divided into three stages: a rapid rise phase (0∼2 d), a rapid decline phase (2∼10 d), and a slow decline and stabilization phase (10∼90 d). As the radial distance from the pile center decreases, there occur a corresponding acceleration in temperature increase and an elevated maximum temperature rise (MTR). The influence range of the molding temperature and the hydration heat is about 1∼2 times the pile diameter and less than 1.5 m in the depth direction. Compared to the atmospheric temperature, there is a lag in the change in the permafrost temperature caused by accumulation of ground temperature, and the significant difference between the two leads to an increased rate of heat exchange at the boundary condition. Conducting drilling operation and cast-in-place pile construction in the cold seasons is conducive to reducing the thermal disturbance to the permafrost around the pile in permafrost areas.

The challenge of effectively managing the formation and recovery of traffic cone robots (TCRs) is addressed by proposing a linear time-varying model predictive control (MPC) strategy. This problem involves coordinating multiple TCR formations within a work area to reach a target location, which is a huge challenge due to the complexity of dynamic coordination. Unlike conventional approaches, our method decomposes the formation control problem into two main components: leader TCR motion planning and follower formation tracking control. The motion planning component involves path and velocity planning to achieve leader trajectory control, which serves as a reference trajectory for the follower. The formation tracking task extends to formation control among multiple robots to achieve the traffic cone robot formation placement and recovery task. To address the TCR input limitation problem, input constraints are considered during the design process of the MPC controllers. The effectiveness and practicality of the proposed control strategy are validated through a series of numerical simulations and physical experiments with TCRs.

For a micro-indentation hardness test with non-destructivity, the Nix–Gao model is widely used to describe tested hardness or microhardness variation with an indentation depth induced by indentation size effect, in which tested hardness approaches the macrohardness when the indentation depth is large enough. Based on an analysis of hardness measurements on 10 body-centered cubic steels with diverse microstructure, this paper proposes an analytical relation between microhardness to macrohardness ratio and the indentation depth by explicitly linking characteristic indentation depth (a data-fitting parameter) to grain size and ferrite volume fraction using two different methods. In addition, the normal distribution theory is incorporated to consider the inevitable scatter of identical measurements resulting from material heterogeneity and machining/testing errors. Results show that the proposed model, with 96% reliability, can effectively predict microhardness variation with the indentation depth and its scatter.

The hydro-pneumatic suspension, known for enhancing vehicle ride comfort and stability, finds widespread use in engineering vehicles. Presently, the majority of mining trucks employ hydro-pneumatic suspension with a fixed damping hole, underscoring the critical importance of selecting appropriate damping hole parameters. Initially, an equilibrium mathematical model of the ¼ hydro-pneumatic suspension is established, and the influencing factors of the damping characteristics are analyzed. Subsequently, the simulation model and experimental bench for the hydro-pneumatic suspension are constructed. Sinusoidal signals with different frequencies and amplitudes serve as the excitation signals to analyze the variation trend of the force on the rod with displacement changes. The simulation and experimental results demonstrate a high degree of consistency, validating the rationality and validity of the simulation model. Building upon this foundation, various damping apertures are then selected to study the damping characteristics of the hydro-pneumatic suspension. The research indicates that as the damping aperture increases, the setting time of the hydro-pneumatic suspension system after excitation extends, accompanied by a decrease in the acceleration overshoot. As a result, a comprehensive evaluation index is developed, considering various factors, such as different weight setting times and peak longitudinal accelerations to assess the ride comfort of the suspension. This approach is then employed to determine the optimal damping aperture under both full-load and no-load conditions. The findings of this research offer valuable insights for the development of adaptive variable damping hydraulic suspensions, especially under variable load conditions.

The author retracts the article, ‘Drug Resistance and Molecular Characteristics of Car-bapenem-Resistant OXA-48-Producing Klebsiella pneumoniae Strains in Hainan, China’ [...]

The comprehensive performance of unmanned excavators is crucial for the development and optimization of the field of construction machinery. To effectively improve the unmanned excavator to meet the needs of the market, it is imperative to quantify the evaluation method of the comprehensive performance of unmanned excavators. In this study, an evaluation method combining a fuzzy analytic hierarchy process and multivariate image area analysis method is proposed. Firstly, based on the feature extraction of the signal stability of the unmanned excavators, fifteen evaluation indexes were proposed. Then, the case study is used to obtain the scores corresponding to these indexes. The fuzzy analytic hierarchy process is applied to determine the relative weight of the selected evaluation criteria, in which the uncertain and imprecise judgments of decision makers are converted into fuzzy numbers. At the same time, the braking performance of the three types of unmanned excavators was comprehensively evaluated and ranked using the multivariate image area analysis method as an empirical example. Finally, a weight analysis is performed to check the robustness of the ranking results. The results show that the proposed method is effective and feasible. It provides a reference for the performance improvement and efficiency optimization of unmanned excavators.

Non-viral vectors have been developing in gene delivery due to their safety and low immunogenicity. But their transfection effect is usually very low, thus limiting the application. Hence, we designed eight peptides (compounds 1–8). We compared their performances; compound 8 had the best transfection efficacy and biocompatibility. The transfection effect was similar with that of PEI, a most-widely-employed commercial transfection reagent. Atomic force microscope (AFM) images showed that the compound could self-assemble and the self-assembled peptide might encapsulate DNA. Based on these results, we further analyzed the inhibitory result in cancer cells and found that compound 8 could partially fight against Hela cells. Therefore, the compound is promising to pave the way for the development of more effective and less toxic transfection vectors.

Background: The emergence and global spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are of great concern to health services worldwide. These β-lactamases hydrolyze almost all β-lactams, are plasmid-encoded, and are easily transferable among bacterial species. They are mostly of the KPC types in CR-hvKp. OXA-48-producing hvKP strains have been rarely reported in the literature. Methods: OXA-48-producing hvKP strains were collected from clinical specimens at the First Affiliated Hospital of Hainan Medical University from January 2022 to March 2023. Hypervirulent strains were tested for virulence in a mouse lethality study and underwent whole genome sequencing to identify genomic features. Results: A total of 42 unique OXA-48-bearing K. pneumoniae strains were identified, including three CR-hvKP strains (KP2683-1, NCRE61, and KP2185), which were isolated from bacteremia, pulmonary abscess, and liver abscess separately. The three CR-hvKP strains belonged to two different clones of ST11 KL64 (KP2185 and NCRE61) and ST23 K1 (KP2683-1). The KP2683-1 strain had the highest virulence. Whole genome sequencing analysis indicated that NCRE61 and KP2185 acquired IncFIB-type plasmids with a set of virulence genes (iroBCDN, iucABCD, iutA, rmpA, and rmpA2), while KP2683-1 acquired an IncL-type blaOXA-48-harboring plasmid. Consecutive cultures showed that the blaOXA-48-harboring plasmids were highly stable in the three hvKP strains and could be transmitted to Escherichia coli J53 by conjugation. The drug susceptibility testing results show that Ceftazidime/avibactam is sensitive for OXA-48-producing hvKP. Conclusions: Our study highlighted the two evolutionary pathways of OXA-48-producing hvKP strains and confirmed their virulence through in vivo testing. Ceftazidime/avibactam may be a viable option for treating OXA-48-producing hvKP strains.

FinTech platforms are one of the most important elements in the rapidly digitized world’s economy. This study investigates the factors that affected individuals’ acceptance of FinTech services, especially on internet wealth management platforms. The current research extends the unified theory of acceptance and use of technology (UTAUT) published by MIS Quarterly with integrated financial consumption attributes (i.e., perceived value and perceived risk) alongside the core construct of UTAUT. Data were collected from an established survey company. The empirical results indicate that perceived value, perceived risk, and social influence are strongly related to individuals’ FinTech adoption intention, whereas performance expectancy, effort expectancy, and perceived risk affect individuals’ perceived value, which in turn influences adoption intention. The proposed FinTech adoption model could contribute to information technology (IT) adoption research by extending the UTAUT in which individuals’ performance expectancy and effort expectancy affect their adoption intention indirectly through perceived value. Finally, the implications of the proposed new model for future research and FinTech practice are discussed.

With the wide application of electric vehicles and the development of battery technology, pure electric construction machinery (PECM) has received more and more attention due to its high efficiency and no pollution. The working conditions of construction machinery are complex and accompanied by periodical working conditions and heavy load. For electric construction machinery, a heavy load represents an energy supply with a large current. To adapt to the working conditions of PECM, this paper proposes a robust controller to regulate the current of the hybrid energy system (HES) which include the battery and supercapacitor. The V-type operating conditions of a 5-ton pure electric loader are the research focus to analyze the working principles of the HES. The topology and energy flow patterns of the HES are proposed and analyzed. The model of the battery, supercapacitor, and DC/DC converter are depicted, and the robust control method is designed. An electric loader experiment platform is created to verify the effectiveness of the robust control method. Compared with the proportional integral control effect, the experiment results show that the proposed control method had good control performance and could better regulate the current. It can be used as a reference value for other dual energy source PECM.

The tuberous root of Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) is a traditional Chinese medicine with a wide range of clinical applications. However, the scarcity of its wild resources, its low yield, and the variable quality that results from its artificial cultivation leads to expensive market prices that are not conducive to the further industrial development of T. hemsleyanum. In this study, transcriptomic and non-targeted metabolomic analyses were integrated to explore the underlying molecular mechanisms and metabolite biosynthesis that occur during its root development. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were predominantly enriched for processes associated with flavonoid and phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Genes related to lignin were downregulated in tuberous roots (TRs), resulting in a decrease in lignification and the downregulation of metabolites related to flavonoids and phenylpropanoid biosynthesis. In addition, the expression levels of starch- and sucrose-related genes were upregulated in TRs. The root development of SYQ is also related to IAA, GA, ABA, and JA signaling pathways. Collectively, this study lays the foundation for analyzing the root development and quality-modulating mechanisms employed by T. hemsleyanum; this will be beneficial in conducting molecular-assisted breeding and controlling its secondary metabolite production.

To solve the demand for road damage object detection under the resource-constrained conditions of mobile terminal devices, in this paper, we propose the YOLO-LWNet, an efficient lightweight road damage detection algorithm for mobile terminal devices. First, a novel lightweight module, the LWC, is designed and the attention mechanism and activation function are optimized. Then, a lightweight backbone network and an efficient feature fusion network are further proposed with the LWC as the basic building units. Finally, the backbone and feature fusion network in the YOLOv5 is replaced. In this paper, two versions of the YOLO-LWNet, small and tiny, are introduced. The YOLO-LWNet was compared with the YOLOv6 and the YOLOv5 on the RDD-2020 public dataset in various performance aspects. The experimental results show that the YOLO-LWNet outperforms state-of-the-art real-time detectors in terms of balancing detection accuracy, model scale, and computational complexity in the road damage object detection task. It can better achieve the lightweight and accuracy requirements for object detection for mobile terminal devices.

Alcoholic liver disease (ALD) is a complicated disease which can lead to hepatocellular carcinoma; however, there is a lack of satisfactory therapeutics. Dehydroeburicoic acid (DEA) (1), a triterpenoid isolated from Antrodia cinnamomea, has been reported to act against ALD, but its mechanisms of action are still not clear. In this study, we report for the first time the use of DEA (1) as a dual inhibitor of the Keap1–Nrf2 protein–protein interaction (PPI) and GSK3β in an in vitro ALD cell model. DEA (1) engages Keap1 to disrupt the Keap1–Nrf2 PPI and inhibits GSK3β to restore Nrf2 activity in a Keap1-independent fashion. DEA (1) promotes Nrf2 nuclear translocation to activate downstream antioxidant genes. Importantly, DEA (1) restores the mitochondrial dysfunction induced by ethanol and generates antioxidant activity in the ALD cell model with minimal toxicity. We anticipate that DEA (1) could be a potential scaffold for the further development of clinical agents for treating ALD.

Methionine aminopeptidases (MetAPs) catalyze the cleavage of the N-terminal initiator methionine (iMet) in new peptide chains and arylamides, which is essential for protein and peptide synthesis. MetAP is differentially expressed in two diamondback moth (DBM; Plutella xylostella) strains: the G88 susceptible strain and the Cry1S1000 strain, which are resistant to the Bt toxin Cry1Ac, implicating that MetAP expression might be associated with Bt resistance. In this study, we identified and cloned a MetAP gene from DBMs, named PxMetAP1, which has a CDS of 1140 bp and encodes a 379 amino acid protein. The relative expression of PxMetAP1 was found to be ~2.2-fold lower in the Cry1S1000 strain compared to that in the G88 strain. PxMetAP1 presents a stage- and tissue-specific expression pattern, with higher levels in the eggs, adults, integument, and fatbody of DBMs. The linkage between PxMetAP1 and Cry1Ac resistance is verified by genetic linkage analysis. The knockout of PxMetAP1 in G88 by CRISPR/Cas9 leads to a ~5.6-fold decrease in sensitivity to the Cry1Ac toxin, further supporting the association between the PxMetAP1 gene and Bt tolerance. Our research sheds light on the role of MetAP genes in the development of Bt tolerance in P. xylostella and enriches the knowledge for the management of such a cosmopolitan pest.

The CRISPR/Cas9 system is an efficient tool for reverse genetics validation, and the application of this system in the cell lines provides a new perspective on target gene analysis for the development of biotechnology tools. However, in the cell lines of diamondback moth, Plutella xylostella, the integrity of the CRISPR/Cas9 system and the utilization of this cell lines still need to be improved to ensure the application of the system. Here, we stabilize the transfection efficiency of the P. xylostella cell lines at different passages at about 60% by trying different transfection reagents and adjusting the transfection method. For Cas9 expression in the CRIPSPR/Cas9 system, we identified a strong endogenous promoter: the 217–2 promoter. The dual-luciferase and EGFP reporter assay demonstrated that it has a driving efficiency close to that of the IE1 promoter. We constructed pB-Cas9-Neo plasmid and pU6-sgRNA plasmid for CRISPR/Cas9 system and subsequent cell screening. The feasibility of the CRISPR/Cas9 system in P. xylostella cell lines was verified by knocking out endogenous and exogenous genes. Finally, we generated a transgenic Cas9 cell line of P. xylostella that would benefit future exploitation, such as knock-in and multi-threaded editing. Our works provides the validity of the CRISPR/Cas9 system in the P. xylostella cell lines and lays the foundation for further genetic and molecular studies on insects, particularly favoring gene function analysis.

Due to the complexity of the sedimentary and diagenetic processes, natural rocks generally exhibit strong heterogeneity in mineral composition, physicochemical properties, and pore structure. Currently, 3D printed (3DP) rock analogs fabricated from sandy materials (silica sand) are widely applied to study the petrophysical and geomechanical characteristics of reservoir rocks, which provides an alternative and novel approach for laboratory tests to calibrate the environmental uncertainties, resolve up-scaling issues, and manufacture customized rock specimens with consistent structure and controllable petrophysical properties in a repeatable fashion. In this paper, silica sand with various grain sizes (GS) and Furan resin were used to fabricate rock analogs with different layer thicknesses (LTs) using the binder-jetting 3DP technique. A comprehensive experimental study was conducted on 3DP rock analogs, including helium porosity measurement, micro-CT scanning, SEM, and uniaxial compression. The results indicate that the LT and GS have a great influence on the physical properties, compression strength, and failure behavior of 3DP rock analogs. The porosity decreases (the difference is 7.09%) with the decrease in the LT, while the density and peak strength increase (showing a difference of 0.12 g/cm3 and 5.67 MPa). The specimens printed at the 200 and 300 μm LT mainly experience tensile shear destruction with brittle failure characteristics. The ductility of the 3DP rocks increases with the printing LT. The higher the content of the coarse grain (CG), the larger the density and the lower the porosity of the specimens (showing a difference of 0.16 g/cm3 and 8.8%). The largest peak compression strength with a mean value of 8.53 MPa was recorded in the specimens printed with CG (i.e., 100% CG), and the peak strength experiences a decrease with the increment in the content percentage of the fine grain (FG) (showing a difference of 2.01 MPa). The presented work helps to clarify the controlling factors of the printing process and materials characteristics on the physical and mechanical properties of the 3DP rock analogs, and allows for providing customizable rock analogs with more controllable properties and printing schemes for laboratory tests.

A foldable and cuttable sheet heater was fabricated using single-walled carbon nanotubes (SWCNTs) and aramid nanofibers (ANFs). SWCNTs are particularly well suited for Joule heating based on their high thermal stability, electrical properties, high current density, and aspect ratio. When the SWCNT/ANF composite reaches a high temperature during Joule heating, ANFs will endure this temperature due to their impressive thermal stability, derived from aramid fibers. With the aim of achieving a synergistic effect between the SWCNTs and ANFs, 0–100 wt% SWCNT/ANF composite sheets were fabricated by tip-type sonication and vacuum filtration. After assessing the thermal stability and electrical properties of the composite sheets, the Joule heating effect was analyzed. TGA showed that our sheet had high thermal stability in an air condition up to around 500 °C. The electrical conductivity of the composite sheet was improved as the amount of SWCNT added rose to 790.0 and 747.5 S/cm in the 75 and 100_SWCNTs/ANF, respectively. The maximum heating temperature, up to 280 °C, reached by Joule heating was measured as a function of SWCNT content and input voltage, and the relationship among SWCNT content, input voltage, heating temperature, and electric power was described. Mechanical properties were also measured in a temperature range similar to the heating temperature of 300 °C reached by Joule heating. Ultimately, we obtained a foldable and cuttable composite sheet with a stretchable structure, capable of being molded into a variety of shapes. This energy-efficient material can potentially be employed in any device in which a heater is required to deliver high temperatures.

In this study, CsPbBr3@SiO2 perovskite nanocrystal composites (CsPbBr3@SiO2 PNCCs) were synthesized by a benzyl bromide nucleophilic substitution strategy. Homogeneous halide exchange between CsPbBr3@SiO2 PNCCs and Cl− solution (aqueous phase) was applied to the determination of Cl− in sea sand samples. Fast halide exchange with Cl− in the aqueous phase without any magnetic stirring or pH regulation resulted in the blue shift of the photoluminescence (PL) wavelength and vivid PL color changes from green to blue. The results show that the PL sensing of Cl− in aqueous samples could be implemented by using the halide exchange of CsPbBr3@SiO2 PNCCs. A linear relationship between the PL wavelength shift and the Cl− concentration in the range of 0 to 3.0% was found, which was applied to the determination of Cl− concentration in sea sand samples. This method greatly simplifies the detection process and provides a new idea for further broadening PL sensing using the CsPbBr3 PNC halide.

In many organisms, cytochrome P450 enzymes are the primary detoxifying enzymes. Enhanced P450 activity can be mediated by the emergence of new genes, increased transcription due to mutations in the promoter regions, changes in enzyme structures and functions due to mutations in protein-coding regions, or changes in post-translational modifications; all of these changes are subject to insecticide selection pressure. Multiple signalling pathways and key effector molecules are involved in the regulation of insect P450s. Increased P450 activity is a key mechanism inducing insect resistance. Hence, downregulation of selected P450s is a promising strategy to overcome this resistance. Insect P450 inhibitors that act as insecticide synergists, RNA interference to induce P450 gene silencing, and the use of transgenic insects and crops are examples of strategies utilized to overcome resistance. This article reviews the latest advances in studies related to insect P450s-mediated agrochemical resistance, with focuses on the regulatory mechanisms and associated pest management strategies. Future investigations on the comprehensive regulatory pathways of P450-mediated detoxification, identification of key effectors, and downregulation strategies for P450s will ecologically, economically, and practically improve pest management.

To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were 691 DEGs and 16 mitochondria-related DEGs in the comparison of M-IVT vs. IM-IVT oocytes, and 2281 DEGs and 160 mitochondria-related DEGs in the comparison of M-IVT vs. M-IVO oocytes, respectively. The GO and KEGG analyses showed that most of them were involved in pathways such as oxidative phosphorylation, pyruvate metabolism, peroxisome, and amino acid metabolism, i.e., valine, leucine, isoleucine, glycine, serine, and threonine metabolism or degradation. During the progress of oocyte maturation, the metabolic pathway, which derives the main source of ATP, shifted from glucose metabolism to pyruvate and fatty acid oxidation in order to maintain a low level of damaging reactive oxygen species (ROS) production. Although the immature oocytes could be cultured to a mature stage by an in vitro technique (IVM), there were still some differences in mitochondria-related regulations, which showed that the mitochondria were regulated by nuclear genes to compensate for their developmental needs. Meanwhile, the results indicated that the current IVM culture medium should be optimized to compensate for the special need for further development according to this disclosure, as it was a latent strategy to improve the effectiveness of the IVM procedure.

The diamondback moth, Plutella xylostella, is a lepidopteran insect that mainly harms cruciferous vegetables, with strong resistance to a variety of agrochemicals, including Bacillus thuringiensis (Bt) toxins. This study intended to screen genes associated with Bt resistance in P. xylostella by comparing the midgut transcriptome of Cry1Ac-susceptible and -resistant strains together with two toxin-treated strains 24 h before sampling. A total of 12 samples were analyzed by BGISEQ-500, and each sample obtained an average of 6.35 Gb data. Additionally, 3284 differentially expressed genes (DEGs) were identified in susceptible and resistant strains. Among them, five DEGs for cadherin, 14 for aminopeptidase, zero for alkaline phosphatase, 14 for ATP binding cassette transport, and five heat shock proteins were potentially involved in resistance to Cry1Ac in P. xylostella. Furthermore, DEGs associated with “binding”, “catalytic activity”, “cellular process”, “metabolic process”, and “cellular anatomical entity” were more likely to be responsible for resistance to Bt toxin. Thus, together with other omics data, our results will offer prospective genes for the development of Bt resistance, thereby providing a brand new reference for revealing the resistance mechanism to Bt of P. xylostella.

We designed and tested a manufacturing process that resulted in the formation of composites with maximized electrical conductivity and optimized electromagnetic interference (EMI) shielding effectiveness (SE) properties. Single-walled carbon nanotube (SWCNT) paper, which is a microscopic aggregate of van der Waals force interaction, was impregnated with semi-cured epoxy to make SWCNT prepregs. These prepregs were completely cured into SWCNT/epoxy composites. Fabricating and curing processes were executed under proper temperature cycle depending on the time. We inspected SWCNT paper and the interfacial state between the SWCNTs and epoxy in the composite with a field emission-scanning electron microscopy and calculated the SWCNT weight fraction through thermogravimetric analysis measurements. Using these observations, electrical conductivity and EMI SE were investigated according to thickness which could be controlled by the suggested manufacturing process as 1-, 5- and 10-layer composites. Finally, we determined ideal composite thickness and the associated number of prepreg layers using skin depth theory.

Shengmaisan (SMS) is a famous traditional Chinese medicine (TCM) formula to treat coronary heart diseases. It has been developed into several TCM patent drugs to meet the demands of different patients. In this study, a research strategy was proposed to reveal the chemical variations among four SMS-based patent drugs, including Shengmai Oral Solution (Shengmaiyin, SMY), Shengmai Capsule (Shengmai Jiaonang, SMJN), Yiqi Fumai Injection (YQFMI), and Yiqi Fumai Capsule (Yiqi Fumai Jiaonang, YQJN). Firstly, 227 compounds were tentatively identified using an Orbitrap-MS in the full scan/dd-MS2 mode. Secondly, untargeted metabolomics analysis suggested that ginsenosides, steroidal saponins, and lignans were the main types of differential compounds for the four patent drugs. Finally, the contents of 25 compounds were simultaneously determined in 30 batches of samples in the parallel reaction monitoring (PRM) mode. Partial least squares discriminant analysis (PLS-DA) revealed the contents of ginsenosides Re, Rg1, Rb1, Ro, and Rg3, and schisandrin showed the highest intergroup variations. These compounds were chemical markers to differentiate the SMS-based patent drugs.

Angucyclinones are aromatic polyketides that possess impressive structural diversity and significant biological activities. The structural diversity of these natural products is attributed to various enzymatic or nonenzymatic modifications on their tetracyclic benz(a)anthracene skeleton. Previously, we discovered an unusual phenylamine-incorporated angucyclinone (1) from a marine Streptomyces sp. PKU-MA00218, and identified that it was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone (2) with phenylamine. In this study, we tested the nonenzymatic conversion of 2 with more phenylamine analogues, to expand the utility of this feasible conversion in unusual angucyclinones generation. The (3-ethynyl)phenylamine and disubstituted analogues including (3,4-dimethyl)phenylamine, (3,4-methylenedioxy)phenylamine, and (4-bromo-3-methyl)phenylamine were used in the conversion of 2, which was isolated from the fermentation of Streptomyces sp. PKU-MA00218. All four phenylamine analogues were incorporated into 2 efficiently under mild conditions, generating new compounds 3–6. The activation of 3–6 on nuclear factor erythroid 2-related factor 2 (Nrf2) transcription were tested, which showed that 4 possessing a dimethyl-substitution gave most potent activity. These results evidenced that disubstitutions on phenylamine can be roughly tolerated in the nonenzymatic reactions with 2, suggesting extended applications of more disubstituted phenylamines incorporation to generate new bioactive angucyclinones in the future.

In this paper, we study the phase transition property of an Ising model defined on a special random graph—the stochastic block model (SBM). Based on the Ising model, we propose a stochastic estimator to achieve the exact recovery for the SBM. The stochastic algorithm can be transformed into an optimization problem, which includes the special case of maximum likelihood and maximum modularity. Additionally, we give an unbiased convergent estimator for the model parameters of the SBM, which can be computed in constant time. Finally, we use metropolis sampling to realize the stochastic estimator and verify the phase transition phenomenon thfough experiments.

Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples’ transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp) were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp) inhibitor (verapamil) experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5) and log D (at pH 7.4) were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB.

Tanshinones are a class of abietane diterpene compound isolated from Salvia miltiorrhiza (Danshen or Tanshen in Chinese), a well-known herb in Traditional Chinese Medicine (TCM). Since they were first identified in the 1930s, more than 40 lipophilic tanshinones and structurally related compounds have been isolated from Danshen. In recent decades, numerous studies have been conducted to investigate the isolation, identification, synthesis and pharmacology of tanshinones. In addition to the well-studied cardiovascular activities, tanshinones have been investigated more recently for their anti-cancer activities in vitro and in vivo. In this review, we update the herbal and alternative sources of tanshinones, and the pharmacokinetics of selected tanshinones. We discuss anti-cancer properties and identify critical issues for future research. Whereas previous studies have suggested anti-cancer potential of tanshinones affecting multiple cellular processes and molecular targets in cell culture models, data from in vivo potency assessment experiments in preclinical models vary greatly due to lack of uniformity of solvent vehicles and routes of administration. Chemical modifications and novel formulations had been made to address the poor oral bioavailability of tanshinones. So far, human clinical trials have been far from ideal in their design and execution for the purpose of supporting an anti-cancer indication of tanshinones.

Based on the traditional regenerative braking electrical circuit, a novel energy recovery system for the main and auxiliary sources of electric vehicles (EVs) has been developed to improve their energy efficiency. The electrical circuit topology is presented in detail. During regenerative braking, the recovered mechanical energy is stored in both the main source and the auxiliary source at the same time. The mathematical model of the proposed system is derived step by step. Combining the merits and defects of H2 optimal control and H∞ robust control, a H2/H∞ controller is designed to guarantee both the system performance and robust stability. The perfect match between the simulated and experimental results validates the notion that the proposed novel energy recovery system is both feasible and effective, as more energy is recovered than that with the traditional energy recovery systems, in which recovered energy is stored only in the main source.

The genes encoding three coiled-coil regions in human pericentrin were gene synthesized with Escherichia coli codon-optimization, and the proteins were successfully over-produced in large quantities using E. coli expression. After verifying that the purified proteins were mostly composed of α-helices, one of the proteins was crystallized using polyethylene glycol 8000 as crystallizing agent. X-ray diffraction data were collected to 3.8 Å resolution under cryo-condition using synchrotron X-ray. The crystal belonged to space group C2 with unit cell parameters a = 324.9 Å, b = 35.7 Å, c = 79.5 Å, and β = 101.6˚. According to Matthews’ coefficient, the asymmetric unit may contain up to 12 subunits of the monomeric protein, with a crystal volume per protein mass (VM) of 1.96 Å3 Da−1 and a 37.3% solvent content.

Parkinson’s disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD.

As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics.

Periodontitis, characterized by inflammation and loss of periodontal tissue, is a significant health complication for individuals with diabetes mellitus (DM). Buildup of advanced glycation end-products (AGEs) in DM poses an increased risk of periodontitis via inflammaging. Ganoderma immunomodulatory protein (GMI) shows promise in suppressing inflammaging by mitigating oxidative stress and inflammation via Nrf2 modulation. However, its specific protective effects are not fully understood. Thus, this study aimed to investigate GMI’s anti-inflammaging properties and its underlying mechanism in diabetic-associated periodontitis (DP). We first simulated DP by culturing human gingival fibroblasts (HGFs) with AGEs and lipopolysaccharides from P. gingivalis (LPS). We then evaluated the impact of GMI on cell proliferation, migration and wound healing. Additionally, we assessed GMI’s effects on the components of inflammaging such as reactive oxygen species (ROS) formation, cellular senescence expression, IL-6 and IL-8 secretions, and NF-κB phosphorylation. Next, we explored whether GMI’s anti-inflammaging effects are mediated through the Nrf2 pathway by evaluating Nrf2 and HO-1, followed by the assessment of IL-6 and IL-8 post-Nrf2 knockdown. Our findings revealed that GMI treatment suppressed ROS production, cell senescence, IL-6 and IL-8 and NF-κB phosphorylation. Furthermore, GMI upregulated Nrf2/HO-1 expression and its protective effects were reversed when Nrf2 was knocked down. In conclusion, GMI exerts its anti-inflammaging effect via the modulation of the Nrf2/NF-κB signaling axis in DP in vitro, highlighting its potential as an effective adjunct treatment for diabetes-related periodontitis.

Cancer, also known as malignant tumour or neoplasm, is a leading cause of death worldwide. One distinct feature from normal cells is that cancerous cells often overexpress protein on the cell membrane—for instance, the overexpression of human epidermal growth factor receptor 2. The expression of a specific protein on the cancerous cell surface acts as a marker that differentiates the normal cell and facilitates the recognition of cancerous cells. An emerging anticancer treatment, Antibody–Drug Conjugates (ADCs), utilises this unique feature to kill cancerous cells. ADCs consist of an antibody linked with a cytotoxic payload, mainly targeting the antigen found on cancerous cells. This design can increase the specificity in delivering the cytotoxin to the drug target, thus increasing the drug efficacy and reducing the side effect of cancer treatment due to off-target toxicities. There are tremendous quantities of clinical trials conducted to evaluate the safety and effectiveness of this magic drug in treating different types of cancers. However, only 12 ADCs have been approved by the FDA until now. This review provides the principles of ADCs and highlights the ADCs that FDA has approved. In addition, some of the ADCs that undergo clinical trials are discussed in this review. The application of computational techniques in addressing ADCs’ challenges and neoantigen-targeted cancer vaccines is also highlighted. Although ADCs have been seen as promising magic drugs in cancer treatment, the problems such as toxicity, the stability of the linker, the specificity of an antibody with antigen, and so on, remain a challenge in developing ADCs.

Periodontitis is a significant health concern for individuals with diabetes mellitus (DM), characterized by inflammation and periodontium loss. Hyperglycaemia in DM exacerbates susceptibility to periodontitis by inducing inflammaging in the host immune system. The use of erbium-doped yttrium–aluminum–garnet laser (ErL) in periodontitis treatment has gained attention, but its impact on diabetic-associated periodontitis (DP) and underlying mechanisms remain unclear. In this study, we simulated DP by exposing human periodontal ligament fibroblasts (PDLFs) to advanced glycation end products (AGEs) and lipopolysaccharides from P. gingivalis (Pg-LPS). Subsequently, we evaluated the impact of ErL on the cells’ wound healing and assessed their inflammaging markers. ErL treatment promoted wound healing and suppressed inflammaging activities, including cell senescence, IL-6 secretion, and p65 phosphorylation. Moreover, the laser-targeted cells were observed to have upregulated expression of CTBP1-AS2, which, when overexpressed, enhanced wound healing ability and repressed inflammaging. Moreover, bioinformatic analysis revealed that CTBP1-AS2 acted as a sponge for miR155 and upregulated SIRT1. In conclusion, ErL demonstrated the ability to improve wound healing and mitigate inflammaging in diabetic periodontal tissue through the CTBP1-AS2/miR-155/SIRT1 axis. Targeting this axis could represent a promising therapeutic approach for preventing periodontitis in individuals with DM.

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.

Lactobacilli have been widely used as probiotics because of their benefits for intestinal health and physiological functions. Among a variety of Lactobacillus genera, Limosilactobacillus reuteri has been studied for its ability to exert anti-inflammatory functions and its role in controlling metabolic disorders, as well as the production of the antimicrobial compound reuterin. However, the effects and mechanisms of L. reuteri on enhancing immune responses in the immunosuppressed states have been relatively understudied. In this study, we isolated an immunomodulatory strain, namely, L. reuteri KBL346 (KBL346), from a fecal sample of a 3-month-old infant in Korea. We evaluated the immunostimulatory activity and hematopoietic function of KBL346 in macrophages and cyclophosphamide (CPA)-induced immunosuppressed mice. KBL346 increased the phagocytic activity against Candida albicans MYA-4788 in macrophages, and as biomarkers for this, increased secretions of nitric oxide (NO) and prostaglandin E2 (PGE2) were confirmed. Also, the secretions of innate cytokines (TNF-α, IL-1β, and IL-6) were increased. In CPA-induced immunosuppressed mice, KBL346 at a dosage of 1010 CFU/kg protected against spleen injury and suppressed levels of immune-associated parameters, including NK cell activity, T and B lymphocyte proliferation, CD4+ and CD8+ T cell abundance, cytokines, and immunoglobulins in vivo. The effects were comparable or superior to those in the Korean red ginseng positive control group. Furthermore, the safety assessment of KBL346 as a probiotic was conducted by evaluating its antibiotic resistance, hemolytic activity, cytotoxicity, and metabolic characteristics. This study demonstrated the efficacy and safety of KBL346, which could potentially be used as a supplement to enhance the immune system.

In osteoarthritis (OA), the articular cartilage covering the articular surface of the bone wears out, exposing the subchondral bone, and the synovial membrane surrounding the joint becomes inflamed, causing pain and deformity. OA causes pain, stiffness, and swelling, and discomfort in the knee when climbing stairs is a typical symptom. Although drug development studies are conducted to treat these inflammatory joint diseases, it is difficult to find conclusive research results which could reduce inflammation and slow cartilage tear. The development of drugs to relieve inflammatory pain often utilizes inflammatory triggers. Interleukins, one of the proteins in the limelight as pro-inflammatory factors, are immune-system-stimulating factors that promote the body’s fight against harmful factors such as bacteria. In this study, inflammation was induced in Chondrocytes cells (Chon-001 cells) with IL-1β and then treated with integrin αvβ3 to show anti-inflammatory and chondrogenesis effects. Integrin αvβ3 was not toxic to Chon-001 cells in any concentration groups treated with or without IL-1β. COX-2 and iNOS, which are major markers of inflammation, were significantly reduced by integrin αvβ3 treatment. Expressions of p-ERK, p-JNK, and p-p38 corresponding to the MAPKs signaling pathway and p-IκBα and p-p65 corresponding to the NF-κB signaling pathway were also decreased in a dose-dependent manner upon integrin αvβ3 treatment, indicating that inflammation was inhibited, whereas treatment with integrin αvβ3 significantly increased the expression of ALP, RUNX2, BMP2, BMP4, Aggrecan, SOX9, and COL2A1, suggesting that osteogenesis and chondrogenesis were induced. These results suggest that integrin αvβ3 in-duces an anti-inflammatory effect, osteogenesis, and chondrogenesis on IL-1β-induced Chon-001 cells.

Dermatitis is an inflammatory condition of the outer layer of the skin that causes itching, blisters, redness, swelling, and often exudation, scabs, and peeling. Among them, purulent inflammation is a symptom that often occurs on the skin and appears in the form of boils and acne. Various studies are being conducted to treat these inflammatory diseases. Accordingly, Lonicera japonica and Citri Reticulatae Pericarpium Polyphenolic Extract (LCPE), which uses herbal preparations such as Lonicera japonica, Citri Reticulatae Pericarpium, and Glycyrrhiza uralensis, has been used to suppress inflammation since ancient times, and its anti-inflammatory effect can be observed in skin keratinocytes after inducing inflammation. In this study, the major polyphenolic compounds in LCPE were quantitatively determined by analyzing the data through peak values using high-performance chromatography (HPLC-MS/MS) coupled with mass spectrometry. Additionally, bioactive compounds targeting 2,2-diphenyl-1-picrylhydrazyl (DPPH) were analyzed by ultrafiltration integrated with LC. Several compounds with the most significant effects were selected (chlorogenic acid, narirutin, and isorhamnetin). Skin keratinocytes induced by lipopolysaccharide (LPS) were treated with LCPE to show its anti-inflammatory effects. After LCPE treatment, inflammation-mediating cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were decreased. In addition, nuclear factor kappa (NF-кB) and mitogen-activated protein kinase (MAPK) were inhibited in important pathways related to inflammation. Lastly, molecular modeling was performed to determine binding scores with inflammation-related proteins using molecular docking for the selected compounds. According to these results, LCPE is effective in treating keratinocytes induced by LPS and reducing inflammation and has potential antioxidant effects, and the polyphenol components have been identified.

Hepatocellular carcinoma (HCC) has a poor prognosis and a low survival rate. Drugs without side effects are desperately needed since chemotherapy has a negative effect on the host cells. Previous research has firmly established that plant-based compounds have significant bioactivities without a negative impact on the host. Flavonoids, in particular, are a class of compounds with both anti-inflammatory and anti-cancer properties. Prunetrin (PUR) is a glycosyloxyisoflavone (Prunetin 4′-O-glucoside) derived from Prunus sp., and its other form, called prunetin, showed optimistic results in an anti-cancerous study. Hence, we aimed to discover the anti-cancer ability of prunetrin in liver cancer Hep3B cells. Our cytotoxicity results showed that PUR can decrease cell viability. The colony formation assay confirms this strongly and correlates with cell cytotoxicity results. Prunetrin, in a dose-dependent manner, arrested the cell cycle in the G2/M phase and decreased the expression of cyclin proteins such as Cyclin B1, CDK1/CDC2, and CDC25c. Prunetrin treatment also promoted the strong cleavage of two important apoptotic hallmark proteins called PARP and caspase-3. It also confirms that apoptosis occurs through the mitochondrial pathway through increased expression of cleaved caspase-9 and increased levels of the pro-apoptotic protein Bak. Bak was significantly increased with the declining expression of the anti-apoptotic protein Bcl-xL. Next, it inhibits the mTOR/AKT signaling pathways, proving that prunetrin includes apoptosis and decreases cell viability by suppressing these pathways. Further, it was also observed that the activation of p38-MAPK was dose-dependent. Taken together, they provide evidence that prunetrin has an anti-cancerous ability in Hep3B liver cancer cells by arresting the cell cycle via p38 and inhibiting mTOR/AKT.

Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.