Rearranging Spin Electrons by Axial-Ligand-Induced Orbital Splitting to Regulate Enzymatic Activity of Single-Atom Nanozyme with Destructive d-π Conjugation.

Most of the nanozymes have been obtained based on trial and error, for which the application is usually compromised by enzymatic activity regulation due to a vague catalytic mechanism. Herein, a hollow axial Mo-Pt single-atom nanozyme (H-MoN5@PtN4/C) is constructed by a two-tier template capture strategy. The axial ligand can induce Mo 4d orbital splitting, leading to a rearrangement of spin electrons (↑ ↑ → ↑↓) to regulate enzymatic activity. This creates catalase-like activity and enhances oxidase-like activity to catalyze cascade enzymatic reactions (H2O2 → O2 → O2•-), which can overcome tumor hypoxia and accumulate cytotoxic superoxide radicals (O2•-). Significantly, H-MoN5@PtN4/C displays destructive d-π conjugation between the metal and substrate to attenuate the restriction of orbitals and electrons. This markedly improves enzymatic performance (catalase-like and oxidase-like activity) of a Mo single atom and peroxidase-like properties of a Pt single atom. Furthermore, the H-MoN5@PtN4/C can deplete overexpressed glutathione (GSH) through a redox reaction, which can avoid consumption of ROS (O2•- and •OH). As a result, H-MoN5@PtN4/C can overcome limitations of a complex tumor microenvironment (TME) for tumor-specific therapy based on TME-activated catalytic activity.

CRISPR/Cas12a-Responsive Smart DNA Hydrogel for Sensitive Electrochemiluminescence Detection of the Huanglongbing Outer Membrane Protein Gene.

Citrus Huanglongbing (HLB) is known as the cancer of citrus, where Candidatus Liberibacter asiaticus (CLas) is the most prevalent strain causing HLB. In this study, we report a novel electrochemiluminescence (ECL) biosensor for the highly sensitive detection of the CLas outer membrane protein (Omp) gene by coupling rolling circle amplification (RCA) with a CRISPR/Cas12a-responsive smart DNA hydrogel. In the presence of the target, a large number of amplicons are generated through RCA. The amplicons activate the trans-cleavage activity of CRISPR/Cas12a through hybridizing with crRNA, triggering the response of smart DNA hydrogel to release the encapsulated AuAg nanoclusters (AuAg NCs) on the electrode and therefore leading to a decreased ECL signal. The ECL intensity change (I0 - I) is positively correlated with the concentration of the target in the range 50 fM to 5 nM, with a limit of detection of 40 fM. The performance of the sensor has also been evaluated with 10 samples of live citrus leaves (five HLB negative and five HLB positive), and the result is in excellent agreement with the gold standard qPCR result. The sensing strategy has expanded the ECL versatility for detecting varying levels of dsDNA or ssDNA in plants with high sensitivity.

Effects of ultrasonic power on drying kinetics and product quality of licorice extract during ultrasound-assisted vacuum drying.

BACKGROUND: Licorice extract is an important raw material for food additives and medicine. The quality of licorice extract is dictated by the drying process. The commonly used drying methods of licorice extract are not efficient in obtaining high-quality products so alternative techniques need to be developed and researched. In this study, ultrasound-assisted vacuum drying (UAVD) was first utilized to improve drying efficiency and produce a higher-quality product. The changes in water mobility of licorice extract during drying were characterized using low-field nuclear magnetic resonance. In addition, the effects of ultrasonic power on the drying dynamics, the contents of liquiritin and glycyrrhizic acid, the antioxidant capacity and the microstructure formation of licorice extract during the whole drying process were investigated. RESULTS: The drying times for licorice extract to reach equilibrium moisture content were reduced by 9.09-69.70% with UAVD at 40-200 W compared with that without ultrasonic treatment (0 W). Moreover, the proportions of bound water and semi-bound water in fresh concentrate were 3.75% and 96.25%. It was also found that high ultrasonic power promoted the flow of water and the formation of porous structure in licorice extract, which led to the improvement of drying efficiency. The contents of liquiritin (2.444%) and glycyrrhizic acid (6.514%) were retained to a large degree in the dried product at an ultrasonic power of 80 W. The DPPH inhibition rate of UAVD samples with different ultrasonic powers ranged from 84.07 ± 0.46% to 90.65 ± 0.22%. CONCLUSION: UAVD has the advantages of high efficiency and low energy consumption, which may be an alternative technology for vacuum drying widely used in industry. © 2024 Society of Chemical Industry.

[Scientific connotation of temperature control in processing of Chinese medicinal materials based on theory of quality evaluation through morphological identification].

Processing of Chinese medicinal materials is an important part in the Chinese medicine heritage, and the temperature control in the processing has a direct impact on the quality and efficacy of traditional Chinese medicines. However, the processing of Chinese medicinal materials has the problems of subjective temperature judgement, determination of the end point based on experience, unclear processing mechanism, unstable quality of products, and inconsistent processing standards. The temperature control in the processing is reflected in the appearance and internal quality of Chinese medicinal materials. The theory of quality evaluation through morphological identification is developed based on the comprehensive evaluation of the shape, color, taste, and components, which is associated with the temperature control in the processing. To solve the problems above, this paper puts forward the following solutions. The first is literature mining. By review of the ancient medical works and pharmaceutical experience, the temperature control in processing and the evolution of processing methods can be revealed. Second, according to the ancient method, the processing principle can be explored, on the basis of which the processing technology can be innovated. Third, the standard operating procedure(SOP) should be established to quantify the fire temperature, providing a theoretical basis for the formulation of Chinese medicinal material processing standards. Moreover, it provides a basis for improving the quality of processed products and increasing the safety and effectiveness of traditional Chinese medicines.

Tunable Interband Transitions in Twisted h-BN/Graphene Heterostructures.

In twisted h-BN/graphene heterostructures, the complex electronic properties of the fast-traveling electron gas in graphene are usually considered to be fully revealed. However, the randomly twisted heterostructures may also have unexpected transition behaviors, which may influence the device performance. Here, we study the twist-angle-dependent coupling effects of h-BN/graphene heterostructures using monochromatic electron energy loss spectroscopy. We find that the moiré potentials alter the band structure of graphene, resulting in a redshift of the intralayer transition at the M point, which becomes more pronounced up to 0.22 eV with increasing twist angle. Furthermore, the twisting of the Brillouin zone of h-BN relative to the graphene M point leads to tunable vertical transition energies in the range of 5.1-5.6 eV. Our findings indicate that twist-coupling effects of van der Waals heterostructures should be carefully considered in device fabrications, and the continuously tunable interband transitions through the twist angle can serve as a new degree of freedom to design optoelectrical devices.

Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent.

This study evaluated the subacute toxicity and toxicokinetics of a potential anti-cancer drug candidate, pterostilbene, in rats. Animals were orally administered at two repeated doses of 200 and 500 mg/kg for 28 days. No mortality was observed during the 28 days of continuous administration of pterostilbene. Body weight and food consumption in each group increased steadily, while no significant difference was found. Liver weight in the 500 mg/kg female, but not male group increased with mild cytoplasmic vacuoles observed in histopathological study. Toxicokinetics was assessed by measuring plasma concentrations of pterostilbene on the first and 28th day of administration using UPLC-MS/MS. Toxicokinetic parameters showed that AUC0-t significantly increased in all animals, while the increase in females was greater than males. System exposure of pterostilbene appeared to be linear within the administrated dose range. In conclusion, our findings suggested a minimal subacute toxicity profile of pterostilbene, which could strongly support further development of this compound as a novel anti-cancer agent.

Structure of Amorphous Two-Dimensional Materials: Elemental Monolayer Amorphous Carbon versus Binary Monolayer Amorphous Boron Nitride.

The structure of amorphous materials has been debated since the 1930s as a binary question: amorphous materials are either Zachariasen continuous random networks (Z-CRNs) or Z-CRNs containing crystallites. It was recently demonstrated, however, that amorphous diamond can be synthesized in either form. Here we address the question of the structure of single-atom-thick amorphous monolayers. We reanalyze the results of prior simulations for amorphous graphene and report kinetic Monte Carlo simulations based on alternative algorithms. We find that crystallite-containing Z-CRN is the favored structure of elemental amorphous graphene, as recently fabricated, whereas the most likely structure of binary monolayer amorphous BN is altogether different than either of the two long-debated options: it is a compositionally disordered "pseudo-CRN" comprising a mix of B-N and noncanonical B-B and N-N bonds and containing "pseudocrystallites", namely, honeycomb regions made of noncanonical hexagons. Implications for other nonelemental 2D and bulk amorphous materials are discussed.

[Conversion of traditional Chinese medicine (TCM) into nanomedicine:application of theory of unification of medicines and excipients].

In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.

[Application and problems analysis of traditional Chinese medicine volatile oil preparation technology based on ionic liquids].

Ionic liquids(ILs) are salts composed entirely of anions and cations in a liquid state at or near room temperature, which have a variety of good physicochemical properties such as low volatility and high stability. This paper mainly reviewed the research overview of ILs in the application of traditional Chinese medicine(TCM) volatile oil preparation technology. Firstly, it briefly introduced the application of TCM volatile oil preparation technology and composition classification and physicochemical properties of ILs, and then summarized the application of ILs in the extraction, separation, analysis, and preparation of TCM volatile oil. Finally, the problems and challenges of ILs in the application of TCM volatile oil were explained, and the application of ILs in TCM volatile oil in the future was prospected.

ADAMTS8 inhibited lung cancer progression through suppressing VEGFA.

BACKGROUND: ADAMTS8 expression has been identified to be low in many cancers including lung cancer. However, the specific functions and regulatory system of ADAMTS8 remain to be unveiled. PURPOSE: To study the potential modulatory mechanism of ADAMTS8 in lung cancer in cell and xenograft mice models. METHODS: Differential expression of ADAMTS8 in lung cancer was analyzed on online tools. So was the overall survival curve in association with ADAMTS8/VEGFA expression in lung cancer patients. RT-qPCR was applied to validate the ADAMTS8 expression in lung cancer cell lines H460 and A549, with the normal lung epithelial cell Beas-2b as a control. Thereafter, overexpressed and knockdown plasmids were constructed for transfection. Colony and flow cytometry methods were used for cell proliferation and apoptosis. RT-qPCR and Western blot methods validated the changes in VEGFA after ADAMTS8 regulation in cells. Tube formation and Transwell methods were applied to observe the changes in tube formation and migration in HUVECs induced by tumor conditioned medium (TCM). Stable-transfected cells were injected subcutaneously into nude mice. H&E and Immunohistochemistry were applied to analyze the pathological differences and protein changes of ADAMTS8, VEGFA and CD31. RESULTS: High ADAMTS8 was correlated with high overall survival rate in lung cancer patients. ADAMTS8 was also abnormally downregulated in NSCLC cells. Upregulation of ADAMTS8 suppressed cell proliferation and enhanced apoptosis while downregulation of ADAMTS8 promoted cell proliferation and decreased apoptosis. VEGFA was negatively correlated with ADAMTS8 in lung cancer tissues. Upregulation of ADAMTS8 inhibited VEGFA in mRNA and protein levels. Further, knockdown of ADAMTS8 induced tube formation and migration of HUVECs and upregulation of ADAMTS8 inhibited this. In addition, upregulation of ADAMTS8 in nude mice inhibited tumor growth and also suppressed VEGFA and CD31 in tumors. CONCLUSION: ADAMTS8 inhibited lung cancer progression through suppressing VEGFA in lung cancer.

Genome-wide association study of serum tumor markers in Southern Chinese Han population.

BACKGROUND: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. METHODS: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. RESULTS: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. CONCLUSION: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.

[Stability improvement of Chinese medicinal essential oils based on delivery systems and their application in medical field].

Essential oils from Chinese medicine are popular in the fields such as medicine, food, and cosmetics because of their unique biological characteristics. However, since essential oils are lipophilic compounds with high volatility, poor stability, and strong irritation, various preparation technologies need to be employed to improve stability, reduce irritation, and increase bioavailability. At present, a variety of preparation technologies have been applied to the encapsulation of essential oils. Various encapsulation strategies are formed because of different delivery systems featured with multiple principles and characteristics and are widely used to improve the stability of essential oils. Essential oils of Chinese medicine are widely used in the medical field, and they are under continuous innovation and development in clinical research, the pharmaceutical industry, medical products, etc. The present study summarized various delivery systems that could improve the stability of essential oils and reviewed the applications of essential oils encapsulated in the delivery systems in the medical field to provide re-ferences for the improvement of stability of essential oils and their safety, efficiency, and wide use in the medical field.

[Quality control mode based on engineering quality view of Chinese medicine pharmacy].

Due to the characteristics of confusing varieties of Chinese medicinal materials, different sources, complex chemical composition, non-standard preparation process, and non-standard pharmaceutical equipment, the quality of Chinese medicinal preparations is difficult to be controlled and evaluated effectively under the current quality control mode and method of Chinese medicinal preparation. The present study proposed an engineering quality view of Chinese medicine pharmacy and a strategy to control the quality of Chinese medicinal preparations based on the current situation. The "overall, dialectical, and dynamic" multi-factor engineering quality view, covering original medicinal materials, preparation technologies, pharmaceutical equipment, and Chinese medicinal preparations, ensures the traceable process, measurable procedures, and feedback quality. The quality control mode of Chinese medicinal preparation with controllable sources, standardized preparation technologies, green pharmaceutical equipment, and intelligent manufacturing is built up.

LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. METHODS: Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: LINC01414 rs699467 (OR = 0.73, 95% CI 0.56-0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31-0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31-6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). CONCLUSION: Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Robust autofocusing method for multi-wavelength lensless imaging.

Lensless imaging based on multi-wavelength phase retrieval becomes a promising technology widely used as it has simple acquisition, miniaturized size and low-cost setup. However, measuring the sample-to-sensor distance with high accuracy, which is the key for high-resolution reconstruction, is still a challenge. In this work, we propose a multi-wavelength criterion to realize autofocusing modulation, i.e., achieving much higher accuracy in determining the sample-to-sensor distance, compared to the conventional methods. Three beams in different spectrums are adopted to illuminate the sample, and the resulting holograms are recorded by a CCD camera. The patterns calculated by performing back propagation of the recorded holograms, with exhaustively searched sample-to-sensor distance value, are adopted to access the criterion. Image sharpness can be accessed and the optimal sample-to-sensor distance can be finely determined by targeting the valley of the curve given by the criterion. Through our novel multi-wavelength based autofocusing strategy and executing further phase retrieval process, high-resolution images can be finally retrieved. The applicability and robustness of our method is validated both in simulations and experiments. Our technique provides a useful tool for multi-wavelength lensless imaging under limited experimental conditions.

Eremophilane Sesquiterpenes and Polyketones Produced by an Endophytic Guignardia Fungus from the Toxic Plant Gelsemium elegans.

A cultured endophytic fungus, Guignardia mangiferae, isolated from the toxic plant Gelsemium elegans yielded five new sesquiterpenes (1-5), two new polyketones (6 and 7), and two known terpene polyketones (8 and 9). Their structures were elucidated using spectroscopic methods. On the basis of circular dichroism, the absolute configurations of the new compounds were determined. Compounds 1, 3, 4, and 9 inhibited lipopolysaccharide-induced NO production in BV2 cells with IC50 values of 15.2, 6.4, 4.2, and 4.5 µM, respectively (positive control curcumin, IC50 = 3.9 µM).

EENdb: a database and knowledge base of ZFNs and TALENs for endonuclease engineering.

We report here the construction of engineered endonuclease database (EENdb) (http://eendb.zfgenetics.org/), a searchable database and knowledge base for customizable engineered endonucleases (EENs), including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). EENs are artificial nucleases designed to target and cleave specific DNA sequences. EENs have been shown to be a very useful genetic tool for targeted genome modification and have shown great potentials in the applications in basic research, clinical therapies and agricultural utilities, and they are specifically essential for reverse genetics research in species where no other gene targeting techniques are available. EENdb contains over 700 records of all the reported ZFNs and TALENs and related information, such as their target sequences, the peptide components [zinc finger protein-/transcription activator-like effector (TALE)-binding domains, FokI variants and linker peptide/framework], the efficiency and specificity of their activities. The database also lists EEN engineering tools and resources as well as information about forms and types of EENs, EEN screening and construction methods, detection methods for targeting efficiency and many other utilities. The aim of EENdb is to represent a central hub for EEN information and an integrated solution for EEN engineering. These studies may help to extract in-depth properties and common rules regarding ZFN or TALEN efficiency through comparison of the known ZFNs or TALENs.

Genomic deletion induced by Tol2 transposon excision in zebrafish.

Genomic deletions induced by imprecise excision of transposons have been used to disrupt gene functions in Drosophila. To determine the excision properties of Tol2, a popular transposon in zebrafish, we took advantage of two transgenic zebrafish lines Et(gata2a:EGFP)pku684 and Et(gata2a:EGFP)pku760, and mobilized the transposon by injecting transposase mRNA into homozygous transgenic embryos. Footprint analysis showed that the Tol2 transposons were excised in either a precise or an imprecise manner. Furthermore, we identified 1093-bp and 1253-bp genomic deletions in Et(gata2a:EGFP)pku684 founder embryos flanking the 5' end of the original Tol2 insertion site, and a 1340-bp deletion in the Et(gata2a:EGFP)pku760 founder embryos flanking the 3' end of the insertion site. The mosaic Et(gata2a:EGFP)pku684 embryos were raised to adulthood and screened for germline transmission of Tol2 excision in their F(1) progeny. On average, ∼42% of the F(1) embryos displayed loss or altered EGFP patterns, demonstrating that this transposon could be efficiently excised from the zebrafish genome in the germline. Furthermore, from 59 founders, we identified one that transmitted the 1093-bp genomic deletion to its offspring. These results suggest that imprecise Tol2 transposon excision can be used as an alternative strategy to achieve gene targeting in zebrafish.

EVCSeer: An Exploratory Study on Electric Vehicle Charging Stations Utilization via Visual Analytics.

Promoting the development of electric vehicles requires the widespread deployment of charging infrastructure, which poses numerous technical and financial constraints. Despite extensive research focusing on optimizing charging station locations, few studies have accounted for charging station utilization and the factors that influence it. This study aims to evaluate charging station operations and explore charging station utilization to inform planning and facilitate better utilization of funds for expanding charging infrastructure. We present EVCSeer, a visual analytics system that utilizes representative predictive models and well-designed visualizations to analyze factors affecting charging station utilization, compare deployment strategies, and optimize utilization. The system also enables "what-if" analysis of charging station deployments. Two case studies, expert interviews, and a qualitative user study support the validity and usefulness of EVCSeer.

MARLens: Understanding Multi-Agent Reinforcement Learning for Traffic Signal Control Via Visual Analytics.

The issue of traffic congestion poses a significant obstacle to the development of global cities. One promising solution to tackle this problem is intelligent traffic signal control (TSC). Recently, TSC strategies leveraging reinforcement learning (RL) have garnered attention among researchers. However, the evaluation of these models has primarily relied on fixed metrics like reward and queue length. This limited evaluation approach provides only a narrow view of the model's decision-making process, impeding its practical implementation. Moreover, effective TSC necessitates coordinated actions across multiple intersections. Existing visual analysis solutions fall short when applied in multi-agent settings. In this study, we delve into the challenge of interpretability in multi-agent reinforcement learning (MARL), particularly within the context of TSC. We propose MARLens, a visual analytics system tailored to understand MARL-based TSC. Our system serves as a versatile platform for both RL and TSC researchers. It empowers them to explore the model's features from various perspectives, revealing its decision-making processes and shedding light on interactions among different agents. To facilitate quick identification of critical states, we have devised multiple visualization views, complemented by a traffic simulation module that allows users to replay specific training scenarios. To validate the utility of our proposed system, we present three comprehensive case studies, incorporate insights from domain experts through interviews, and conduct a user study. These collective efforts underscore the feasibility and effectiveness of MARLens in enhancing our understanding of MARL-based TSC systems and pave the way for more informed and efficient traffic management strategies.