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Dental caries is one of the most prevalent non-communicable diseases worldwide, mediated by a multispecies biofilm that consists of high levels of acidogenic bacteria which ferment sugar to acid and cause teeth demineralization. Current treatment practice remains insufficient in addressing 1) rapid clearance of therapeutic agents from the oral environment 2) destroying bacteria that contribute to the healthy oral microbiome. In addition, increasing concerns over antibiotic resistance calls for innovative alternatives. In this study, we developed a pH responsive nano-carrier for delivery of polycationic silver nanoparticles. Branched-PEI capped silver nanoparticles (BPEI-AgNPs) were encapsulated in a tannic acid - Fe (III) complex-modified poly(D,L-lactic-co-glycolic acid) (PLGA) particle (Fe(III)-TA/PLGA@BPEI-AgNPs) to enhance binding to the plaque biofilm and demonstrate "intelligence" by releasing BPEI-AgNPs under acidic conditions that promote dental caries The constructed Fe(III)-TA/PLGA@BPEI-AgNPs (intelligent particles - IPs) exhibited significant binding to an axenic S. mutans biofilm grown on hydroxyapatite. Ag + ions were released faster from the IPs at pH 4.0 (cariogenic pH) compared to pH 7.4. The antibiofilm results indicated that IPs can significantly reduce S. mutans biofilm volume and viability under acidic conditions. Cytotoxicity on differentiated Caco-2 cells and human gingival fibroblasts indicated that IPs were not cytotoxic. These findings demonstrate great potential of IPs in the treatment of dental caries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Extending covalent organic frameworks (COFs) into crystalline carbon-free covalent backbones is an important strategy to endow these materials with more exotic functions. Integrating metal-free inorganic and organic components into one covalent framework is an effective way to address the issue of poor thermal/solvent stability in the field of nonlinear optics (NLO). However, constructing such structures is very challenging. Here, we linked 3-connected nods (BO3) and 2-connected organic building blocks (Te(Ph)2) together to produce colorless single crystals (size up to 400 µm) of a three-dimensional (3D) chiral covalent framework (CityU-22). The single-crystal X-ray diffraction (SCXRD) analysis reveals that CityU-22 has a non-carbon Te-O-B-O bond-based network with the srs topology. The chiral CityU-22 displays good stability under the treatment of different common solvents or heat (the decomposition temperature above 300 °C). Due to its non-π-conjugated backbone (-Te-O-B-O-), CityU-22 shows an ultraviolet NLO behavior with a second-harmonic generation (SHG) response similar to KH2PO4 (KDP)., (© 2024 Wiley‐VCH GmbH.)

The push-pull osmotic pump tablet is a promising drug delivery approach, offering advantages over traditional dosage forms in achieving consistent and predictable drug release rates. In the current study, the drug release process of push-pull osmotic pump tablets is modelled for the first time using the discrete element method (DEM) incorporated with a microscopic diffusion-induced swelling model. The effects of dosage and formulation design, such as delivery orifice size, drug-to-polymer ratio, tablet surface curvature, friction between particles and cohesion of polymer particles, on the drug release performance are systematically analysed. Numerical results reveal that an enlarged delivery orifice significantly increases both the total drug release and the drug release rate. Moreover, the larger the swellable particle component in the tablet, the higher the drug release rate. Furthermore, the tablet surface curvature is found to affect the drug release profile, i.e. the final drug release percentage increases with the increasing tablet surface curvature. It is also found that the drug release rate could be controlled by adjusting the inter-particle friction and the cohesion of polymer particles in the formulation. This DEM study offers valuable insights into the mechanisms governing drug release in push-pull osmotic pump tablets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Porous copper (Cu), with varying porosities, has been made using carbamide as a space holder through the powder metallurgy route. Two shapes of carbamide particles were used, (i) needlelike and (ii) spherical, in order to investigate the effect of the space holder shape on the pore structure and mechanical properties of porous Cu. The compressive deformation behavior of porous Cu was studied under a compression test. The pores' structural characteristics and mechanical properties of the porous Cu varied significantly with the shape of the space holder. Although the effect of the space holder shape on the porosity was not regular, the effect on the mechanical properties was regular. The stress increased monotonically with the increase in the strain, and strain hardening occurred at the plastic yield stage. The elastic modulus and yield strength followed the power law, with the relative density irrespective of the space holder shape. The empirical constants associated with different empirically developed power law relations were different, according to the shape of space holder. A quantitative relationship between the elastic modulus and yield strength and the spacer content was obtained to control the mechanical properties of the present porous Cu or other porous metals and metal foams using the well-known space holder method.

Objectives: The preoperative classification of pleomorphic adenomas (PMA) and Warthin tumors (WT) in the parotid gland plays an essential role in determining therapeutic strategies. This study aims to develop and validate an ultrasound-based ensemble machine learning (USEML) model, employing nonradiative and noninvasive features to differentiate PMA from WT., Methods: A total of 203 patients with histologically confirmed PMA or WT who underwent parotidectomy from two centers were enrolled. Clinical factors, ultrasound (US) features, and radiomic features were extracted to develop three types of machine learning model: clinical models, US models, and USEML models. The diagnostic performance of the USEML model, as well as that of physicians based on experience, was evaluated and validated using receiver operating characteristic (ROC) curves in internal and external validation cohorts. DeLong's test was used for comparisons of AUCs. SHAP values were also utilized to explain the classification model., Results: The USEML model achieved the highest AUC of 0.891 (95% CI, 0.774-0.961), surpassing the AUCs of both the US (0.847; 95% CI, 0.720-0.932) and clinical (0.814; 95% CI, 0.682-0.908) models. The USEML model also outperformed physicians in both internal and external validation datasets (both p < 0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of the USEML model and physician experience were 89.3%/75.0%, 87.5%/54.2%, 87.5%/65.6%, and 89.3%/65.0%, respectively., Conclusions: The USEML model, incorporating clinical factors, ultrasound factors, and radiomic features, demonstrated efficient performance in distinguishing PMA from WT in the parotid gland., Clinical Relevance Statement: This study developed a machine learning model for preoperative diagnosis of pleomorphic adenoma and Warthin tumor in the parotid gland based on clinical, ultrasound, and radiomic features. Furthermore, it outperformed physicians in an external validation dataset, indicating its potential for clinical application., Key Points: • Differentiating pleomorphic adenoma (PMA) and Warthin tumor (WT) affects management decisions and is currently done by invasive biopsy. • Integration of US-radiomic, clinical, and ultrasound findings in a machine learning model results in improved diagnostic accuracy. • The ultrasound-based ensemble machine learning (USEML) model consistently outperforms physicians, suggesting its potential applicability in clinical settings., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect., Methods: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)., Results: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus , and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii ( L. johnsonii ) and Lactobacillus reuteri ( L. reuteri ) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii , and L. reuteri can significantly increase SCFA content in SHR feces., Conclusion: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus ., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

NADPH-cytochrome P450 reductase (CPR) is essential for the detoxification of endogenous and exogenous substances mediated by cytochrome P450. While several insect CPRs have been found to be associated with insecticide resistance, the CPR of Aphis gossypii has not been characterized, and its functional role in insecticide resistance remains undefined. In this study, we cloned and characterized the full-length sequence of A. gossypii CPR (AgCPR). The deduced amino acid sequence of AgCPR contains all conserved domains of CPR, which shows high similarity to other insect CPRs and was clustered into a same branch of aphids according to phylogenetic analysis. The transcript of AgCPR was present in all developmental stages, with the highest expression in the adult stage. Furthermore, the expression of AgCPR could be induced by sulfoxaflor, a commonly used insecticide, in a time- and dose-dependent manner. Further silencing of AgCPR by feeding dsRNA significantly increased the susceptibility of A. gossypii to this insecticide. These findings suggest that AgCPR may play a significant role in the susceptibility of A. gossypii to sulfoxaflor and in the development of P450-mediated resistance to sulfoxaflor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tribolium castaneum (Herbst) is a worldwide grain storage pest controlled by chemical control methods of phosphine fumigation, which results in many hazards, damages human health, makes pests resistant to pesticides, and pollutes the environment. In recent years, the popularity of botanical insecticides has continued to rise, and plant essential oils (EO) are considered potential alternatives for developing insecticides. In the current study, we selected the Chamaecyparis obtusa EO to determine its insecticidal effects and component analysis on T. castaneum. Through gas chromatography-ion mobility spectrometry (GC-IMS) technology, cedrol was the most obvious compound in the signal peak of the volatile components detected in the C. obtusa EO. The results of the bioassay showed that the C. obtusa EO had certain contact activity against T. castaneum, and the LD 50 was 52.54 μg/adult. At three concentrations (0.41,1.62, 2.83 uL/cm 2 ), the repellent rates of C. obtusa EO against T. castaneum were all above 80% at 15, 30, 60, and 120 min, respectively, indicating that the repellent effect was strong. Meanwhile, the C. obtusa EO exhibited fumigant toxicity against T. castaneum with LC 50 values of 7.09 μg/L air. In addition, C. obtusa EO significantly increased the activity of AChE, CarE, POD, CAT, T-SOD, and chitinase in T. castaneum. Finally, the mechanism of C. obtusa EO on T. castaneum adults was explored based on transcriptome sequencing. We found that the DEGs focused on the chitin metabolic process and some aging genes in T. castaneum. Therefore, C. obtusa EO could be used as potential eco-friendly candidates for stored grain pest management., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Effective triage of high-risk human papillomavirus (hrHPV)+ women is warranted to avoid unnecessary referral and overtreatment. Molecular triage tests have recently begun to impact cervical intraepithelial neoplasia grade 3 (CIN3) or cervical cancer (CC), termed CIN3+, detection. We find that zinc finger protein 671 methylation (ZNF671 m ) test has superior performance for CIN3+ detection in all single molecular triage tests, including HPV16/18 genotyping, paired box gene 1 methylation (PAX1 m ), and ZNF671 m , in the training set. Using ZNF671 m test instead of Thinprep cytologic test (TCT) as a single triage strategy or as a combined triage strategy with HPV16/18 genotyping has achieved comparable sensitivity but higher specificity for CIN3+ detection among 391 hrHPV+ women in the validation set. Little attention has been paid to the women with hrHPV- status but detected CIN3+. We find that the CIN3+ risk after a negative result could be reduced further by triage using ZNF671 m in hrHPV- patients., Competing Interests: Declaration of interests Q.L., H.Z., P.Z., Y.C., Y.A., and L.Y. are inventors on a patent related to the detection of ZNF671 gene methylation (publication number: CN112941189A, publication date: June 11, 2021)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aiming at the problem of large measurement error and phase shift in resistance voltage dividers under high-frequency conditions in the field of power measurement, such as power harmonics, an error correction method is proposed for an alternating current (AC) resistance voltage divider based on the equivalence principle. Firstly, the frequency error model of the AC resistance voltage divider precision is established, and the angle difference of the continuous spectrum ratio difference from 50 Hz to 100 kHz is corrected by determining the shielding structure and the resistance parameters and fine-tuning the shielding potential correction method to reduce the capacities error of the AC resistance voltage divider design precision. At the same time, the performance parameters such as the direction and magnitude of the shielding potential compensation capacitive error are investigated. Finally, the precision voltage divider (the maximum voltage applied is 480 V) calibration experiments verify that the important characteristic judgment factor of the voltage divider is independent of the frequency and the equivalent capacitance value, which effectively solves the phase correction problem of harmonic power measurement.

A simple and sensitive fluorometric assay based on nitrogen-doped carbon dots (N-CDs) was developed for the determination of thrombin (TB) activity in human serum samples and living cells. The novel N-CDs were prepared by a facile one-pot hydrothermal method using 1,2-ethylenediamine and levodopa as precursors. Such N-CDs exhibited green fluorescence with excitation/emission peaks at 390/520 nm and a high fluorescence quantum yield of approximately 39.2%. H-D-Phenylalanyl-L-pipecolyl-Larginine-p-nitroaniline-dihydrochloride (S-2238) was hydrolyzed by TB to produce p-nitroaniline which was capable of quenching the fluorescence of N-CDs due to an inner filter effect. This assay was used to detect TB activity with a low detection limit of 11.3 fM. The proposed sensing method was then expanded to the TB inhibitor screening and exhibited excellent applicability. As a typical TB inhibitor, argatroban was determined in a concentration as low as 1.43 nM. The method has also been successfully employed for the determination of TB activity in living HeLa cells. This work showed significant potential for TB activity assay in clinical and biomedicine applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be amplified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors' views for the future of the field are also presented.

Radix arnebiae oil (RAO) is a clinically useful traditional Chinese medical formula with outstanding curative effects on burns. However, the mechanism of the effect of RAO on wound healing remains unclear. The present study investigates the molecular mechanisms of the potential curative effect of RAO on wound healing. The concentrations of the main constituents, shikonin, imperatorin, and ferulic acid in RAO detected by HPLC were 24.57, 3.15, and 0.13 mg/mL, respectively. A rat burn model was established, and macroscopic and histopathological studies were performed. RAO significantly accelerated wound closure and repair scarring, increased superoxide dismutase activities, and reduced malondialdehyde. RAO also downregulated interleukin (IL)-6, IL-1 β and tumor necrosis factor- α in wound tissues and increased secretion of vascular endothelial growth factor, epidermal growth factor, and transforming growth factor (TGF)- β 1. RAO increased the gene expression of TGF- β 1, type I and III collagen, and increased the protein expression of TGF- β 1 and phosphorylation of PI3K and Akt. In conclusion, RAO likely promotes wound healing via antioxidant and anti-inflammatory activities and increases re-epithelization. Activation of the TGF- β 1/PI3K/Akt pathway may play an important role in the healing efficacy of RAO. These findings suggest that RAO could be a promising alternative local treatment for burn wound healing., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The abuse of sulfameter (SME) in animal husbandry can cause drug resistance and toxic or allergic reactions in humans. Therefore, it is very important to establish a simple, inexpensive, and efficient method for detecting SME in food. In this work, we propose a single fluorescent aptamer/graphene oxide (GO)-based biosensor to detect SME residues in milk. Aptamers that specifically bind to SME were screened using capture-SELEX and a ssDNA library immobilized on magnetic beads. The 68 active candidate aptamers were chemically synthesized for specificity and affinity characterization. Among the aptamers, the aptamer sulf-1 revealed the highest affinity (K d  = 77 ± 15 nM) to SME and was selected to construct a GO-based fluorescent biosensor for real milk sample detection. Under optimal conditions, the single fluorescent aptasensor had a wide linear range (R 2 was 0.997) from 7 to 336 ng/ml and a low detection limit of 3.35 ng/ml that was calculated with a 3SD/slope. The single fluorescent method was also validated using SME-fortified milk samples, showing average recoveries ranging from 99.01% to 104.60% with a relative standard deviation of less than 3.88%. These results demonstrate that this novel aptamer sensor provides an opportunity for sensitive, convenient, and accurate detection of SME residues in milk., (© 2023 John Wiley & Sons Ltd.)

Optical diffraction tomography (ODT) has gradually become a popular label-free imaging technique that offers diffraction-limited resolution by mapping an object's three-dimensional (3D) refractive index (RI) distribution. However, there is a lack of comprehensive quantitative image assessment metrics in ODT for studying how various experimental conditions influence image quality, and subsequently optimizing the experimental conditions. In this Letter, we propose to standardize the image assessment in ODT by proposing a set of metrics, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and structural distinguishability (SD). To test the feasibility of the metrics, we performed experiments on angle-scanning ODT by varying the number of illumination angles, RI contrast of samples, sample feature sizes, and sample types (e.g., standard polystyrene beads and 3D printed structures) and evaluated the RI tomograms with SNR, CNR, and SD. We further quantitatively studied how image quality can be improved, and tested the image assessment metrics on subcellular structures of living cells. We envision the proposed image assessment metrics may greatly benefit end-users for assessing the RI tomograms, as well as experimentalists for optimizing ODT instruments.

Micromanipulation is a powerful technique to measure the mechanical properties of microparticles including microcapsules. For microparticles with a homogenous structure, their apparent Young's modulus can be determined from the force versus displacement data fitted by the classical Hertz model. Microcapsules can consist of a liquid core surrounded by a solid shell. Two Young's modulus values can be defined, i.e., the one is that determined using the Hertz model and another is the intrinsic Young's modulus of the shell material, which can be calculated from finite element analysis (FEA). In this study, the two Young's modulus values of microplastic-free plant-based microcapsules with a core of perfume oil (hexyl salicylate) were calculated using the aforementioned approaches. The apparent Young's modulus value of the whole microcapsules determined by the classical Hertz model was found to be E A = 0.095 ± 0.014 GPa by treating each individual microcapsule as a homogeneous solid spherical particle. The previously obtained simulation results from FEA were utilised to fit the micromanipulation data of individual core-shell microcapsules, enabling to determine their unique shell thickness to radius ratio ( h/r ) FEA = 0.132 ± 0.009 and the intrinsic Young's modulus of their shell ( E FEA = 1.02 ± 0.13 GPa). Moreover, a novel theoretical relationship between the two Young's modulus values has been derived. It is found that the ratio of the two Young's module values ( E A / E FEA ) is only a function on the ratio of the shell thickness to radius ( h/r ) of the individual microcapsule, which can be fitted by a third-degree polynomial function of h/r . Such relationship has proven applicable to a broad spectrum of microcapsules (i.e., non-synthetic, synthetic, and double coated shells) regardless of their shell chemistry.

Single-frame off-axis holographic reconstruction is promising for quantitative phase imaging. However, reconstruction accuracy and contrast are degraded by noise, frequency spectrum overlap of the interferogram, severe phase distortion, etc. In this work, we propose an iterative single-frame complex wave retrieval based on an explicit model of object and reference waves. We also develop a phase restoration algorithm that does not resort to phase unwrapping. Both simulation and real experiments demonstrate higher accuracy and robustness compared to state-of-the-art methods, for both complex wave estimation and phase reconstruction. Importantly, the allowed bandwidth for the object wave is significantly improved in realistic experimental conditions (similar amplitudes for object and reference waves), which makes it attractive for large field-of-view and high-resolution imaging applications.

Rhyzopertha dominica is one of the most important stored grain pests that seriously damage rice and wheat. At present, the method of controlling stored grain pests mainly relies on insecticide fumigation. However, the excessive use of pesticides not only leaves pesticide residues, with harmful effects on human health and the environment, but also induces insect resistance. Ozone is a strong oxidant with the characteristics of easy decomposition and without residue. Although ozone has been widely used in the food industry in recent years, research on the control of stored grain pests is limited. In this research, we used ozone treatment to control R . dominica adults and explore the molecular mechanisms that affect them. Here, we found that ozone treatment on R . dominica adults could decrease life span and increase malondialdehyde (MDA) content, as well as reduce activity of total superoxide dismutase (SOD) and catalase (CAT). Using RNA-seq technology, we identified 641 genes that were differentially expressed between ozone-treated and control R . dominica adults [fold-change of ≥ 2 ( q -value < 5%)]. When comparing ozone treatment with control R . dominica adults, 330 genes were significantly upregulated and 311 were downregulated. RT-qPCR confirmed that 11 genes were differentially expressed in ozone-treated and control R . dominica adults. These genes were involved in insect cuticle protein and antioxidant system. This research showed that ozone treatment could reduce the lifespan of R . dominica through antioxidant system. It is an environmentally benign method for the control of stored grain pests and has great development potential., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Liquid-liquid phase separation (LLPS) forms biomolecular condensates or coacervates in cells. Metabolic enzymes can form phase-separated subcellular compartments that enrich enzymes, cofactors, and substrates. Herein, we report the construction of synthetic multienzyme condensates that catalyze the biosynthesis of a terpene, α-farnesene, in the prokaryote E. coli. RGGRGG derived from LAF-1 was used as the scaffold protein to form the condensates by LLPS. Multienzyme condensates were then formed by assembling two enzymes Idi and IspA through an RIAD/RIDD interaction. Multienzyme condensates constructed inside E. coli cells compartmentalized the cytosolic space into regions of high and low enzyme density and led to a significant enhancement of α-farnesene production. This work demonstrates LLPS-driven compartmentalization of the cytosolic space of prokaryotic cells, condensation of a biosynthetic pathway, and enhancement of the biosynthesis of α-farnesene., (© 2022 Wiley-VCH GmbH.)

Microparticles are widely used in many industrial sectors. A micromanipulation technique has been widely used to quantify the mechanical properties of individual microparticles, which is crucial to the optimization of their functionality and performance in end-use applications. The principle of this technique is to compress single particles between two parallel surfaces, and the force versus displacement data are obtained simultaneously. Previously, analysis of the experimental data had to be done manually to calculate the rupture strength parameters of each individual particle, which is time-consuming. The aim of this study is to develop a software package that enables automatic analysis of the rupture strength parameters from the experimental data to enhance the capability of the micromanipulation technique. Three algorithms based on the combination of the "three-sigma rule", a moving window, and the Hertz model were developed to locate the starting point where onset of compression occurs, and one algorithm based on the maximum deceleration was developed to identify the rupture point where a single particle is ruptured. Fifty microcapsules each with a liquid core and fifty porous polystyrene (PS) microspheres were tested in order to produce statistically representative results of each sample, and the experimental data were analysed using the developed software package. It is found that the results obtained from the combination of the "3 σ + window" algorithm or the "3 σ + window + Hertz" algorithm with the "maximum-deceleration" algorithm do not show any significant difference from the manual results. The data analysis time for each sample has been shortened from 2 to 3 h manually to within 20 min automatically.

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose ( Rosa rugosa ), white chrysanthemum ( Chrysanthemum morifolium ), and Daidaihua ( Citrus aurantium ). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats., Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein-protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD., Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ , SREBP , AKT , and RELA , were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats., Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

The excellent performance and safety of direct formic acid fuel cells (DFAFCs) promote them as potential power sources for portable electronic devices. However, their real application is still highly challenging due to the poor power performance and high complexity in the fabrication of catalyst electrodes. In this work, we demonstrate a new gas diffusion electrode (GDE) with ultrathin PtCu alloy nanowire (NW) arrays in situ grown on the carbon paper gas diffusion layer surface. The growing process is achieved by a facile template- and surfactant-free self-growth assisted reduction method at room temperature. A finely controlled ion reduction process tunes the nucleation and crystal growth of Pt and Cu leading to the formation of alloy nanowires with an average diameter of about 4 nm. The GDE is directly used as the anode for DFAFCs. The results in the half-cell GDE measurement indicate that the introduction of Cu in PtCu NWs boosts the direct oxidation pathway for formic acid. The Pt 3 Cu 1 NW GDE shows a 2.4-fold higher power density compared to the Pt NW GDE in the membrane electrode assembly test in single cells.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Background: The aim of this retrospective study was to evaluate the risk factors for central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC), according to the guidelines of the 2017 Thyroid Imaging Report and Data System (TI-RADS) published by the American College of Radiology (ACR)., Methods: This study included a retrospective analysis of 844 patients with PTC who were pathologically diagnosed, treated with central lymph node dissection, and divided into CLNM and nonmetastatic groups. Univariate and multivariate analyses were performed to determine the relationship between the TI-RADS score and CLNM., Results: Among 844 patients, 439 developed CLNM, with a metastasis rate of 52% and a TI-RADS score of 9.42 ± 2.262, which were higher than those of the non-CLNM group ( P < 0.05). Univariate analysis demonstrated that the sex, location, maximum diameter of the nodule, multifocality, margin, shape, calcification, and TI-RADS score were related to CLNM ( P < 0.05 for all). However, multivariate logistic regression analysis demonstrated that female, maximum diameter of the nodule, multifocality, a taller-than-wide shape, and high TI-RADS score were the independent risk factors for CLNM ( P < 0.05 for all)., Conclusion: The TI-RADS score combined with sex, nodule size, shape, and multifocality has a certain predictive effect on CLNM, which can provide a reference to the clinicians for further treatment strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Minying Zhong et al.)

The high mobility group AT‑hook 2 (HMGA2) protein has been found to be upregulated in the majority of tumor types and is associated with a poor prognosis. Previous studies have suggested the oncogenic role of HMGA2 in gallbladder cancer (GBC). The present study aimed to investigate the effects of HMGA2 on the invasion, migration and angiogenesis of GBC cells. To achieve this aim, HMGA2 was overexpressed or silenced in the GBC cell line, EH‑GB1, and then the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) abilities of EH‑GB1 cells were investigated using Cell Counting Kit‑8, wound healing, Transwell and western blotting assays. In addition, the expression levels of VEGFA were determined in EH‑GB1 cells using western blotting and reverse transcription‑quantitative PCR following HMGA2 overexpression or silencing. Furthermore, HMGA2‑silenced EH‑GB1 cells were transfected with VEGFA overexpression plasmids to evaluate the tube formation ability of HUVECs using tube formation assay. The results demonstrated that HMGA2 silencing inhibited GBC cell proliferation, migration, invasion and EMT, as evidenced by the downregulated expression of Ki67, proliferating cell nuclear antigen, MMP2, MMP9, N‑cadherin, snail family transcriptional repressor 2 and zinc finger E‑box‑binding homeobox 1, and attenuated cell migration and invasion. However, the opposite results were obtained following HMGA2 overexpression. Moreover, HMGA2 knockdown and overexpression downregulated and upregulated VEGFA expression, respectively. In addition, the tube formation ability of HUVECs and the expression levels of CD31, VEGFR1 and VEGFR2 were downregulated following HMGA2 silencing. However, these effects were partially rescued by simultaneous VEGFA overexpression. In conclusion, the findings of the present study revealed that HMGA2 may promote GBC cell migration, invasion, EMT and angiogenesis. Therefore, inhibiting HMGA2 expression could be considered as a possible therapeutic approach for GBC.

Thiazole orange (TO), an asymmetric cyanine dye, has been widely used in biomolecular detection and imaging of DNA/ RNA in gels, due to its unique fluorogenic behavior: fluorescence of free dye in aqueous solution is very weak but emission can be significantly enhanced in nucleic-acid-bound dye. Herein we describe the ultrafast excited-state dynamics of free TO in aqueous solution by exploiting both a femtosecond upconversion spectrophotofluorometer and a picosecond time-correlated single-photon counting (TCSPC) apparatus. For the first time, the fluorescence lifetime of TO monomer in water was found to be ∼1 ps, mixed with concurrent solvent relaxation (which was confirmed by the experimental results of TO in DMSO). Even at moderate concentration, this lifetime has an amplitude (a measure of molecular fraction) that significantly dominates other lifetimes, and this is the origin of weak steady state fluorescence of free TO in water. We also found a novel slower decay component around 34 ps. Interestingly and in addition, the lifetime component on the 30-40 ps timescale was also found in TO- γ -Cyclodextrin (CD) complexes. The fraction of this component increased with the addition of γ -CD. Cyclodextrin has been reported to promote the aggregation of TO. Thus, although a very coincidental match of this time constant by one for a torsional process within the cavity can not be ruled out, we ascribe the shared 30-40 ps component to the lifetime of a highly quenched TO dimer experiencing intra-and inter-molecular rearrangement., Competing Interests: The authors declare no competing financial interest.

There is no consensus on the effect of the probiotics on postoperative adaptive immunity in patients undergoing surgical resection for CRC. We aimed to systematically evaluate the effect of probiotics on postoperative adaptive immunity in perioperative CRC patients. The main end points were postoperative serum IgG, IgA, IgM, CD4 + T-cells, CD8 + T-cells and CD4 + -to-CD8 + ratio. Meta-analysis was performed with a fixed or random effects model. We included six randomized controlled trials (RCTs) with 492 perioperative CRC patients. The use of enteral probiotics significantly increased the levels of peripheral blood IgG (MD: 1.33; 95% CI: 0.88 - 1.77; I 2 = 41%), IgA (MD: 0.20; 95% CI: 0.10 - 0.30; I 2 = 53%), IgM (MD: 0.18; 95% CI: 0.13 - 0.24; I 2 = 41%), CD4 + T-cells (MD: 2.79; 95% CI: 2.34 - 3.24; I 2 = 0) and CD4 + -to-CD8 + ratio (MD: 0.09; 95% CI: 0.04 - 0.13; I 2 = 7%). In conclusion, w e report that the use of enteral probiotics improves postoperative humoral and cellular immunity in patients with CRC.

Gastric cancer is a common tumor of the digestive system, which can occur in any part of the stomach. Kallikrein 6 (KLK6) is a trypsin-like serine protease and has been found to be involved in extracellular matrix remodeling, tumor invasion and nervous system plasticity. Our previous study reported that KLK6 suppressed HGC-27 gastric cancer cell growth by inhibiting epithelial-mesenchymal transition; however, the mechanism of action underlying the effect of KLK6 still remains unclear. The aim of the present study was to investigate the effect and the underlying mechanism of KLK6 on stem cell-like properties and metabolism in gastric carcinoma cells. The HGC-27 cell line was transfected with KLK6 overexpression (OV-KLK6) and interference (short hairpin-KLK6) vectors, then the transfection efficiency was confirmed using western blot analysis and reverse transcription-quantitative PCR. The percentage of CD133 + and CD44 + cells was detected using flow cytometry, while the protein expression levels of the stem-associated genes, Nanog, Oct-4, SOX2 and Notch1, the metabolic markers, hexokinase (HK)1, HK2, GLUT1, and the proteins within the PI3K signaling pathway, phosphorylated (p)-PI3K, p-AKT and p-mTOR, were determined using western blot analysis. Biochemical kits were used to measure ATP production, lactic acid content and glucose uptake. A tumorigenicity assay was performed with nude mice to detect gastric tumor volume, and the protein expression level of Oct-4, Nanog, HK1, HK2 and GLUT1, and the mRNA expression level of KLK6 was also determined in gastric tumor tissues of mice. Compared with that in the control group, KLK6 protein and mRNA expression levels were significantly decreased in the four sh-RNA groups (P<0.05). Among them, sh-RNA-3 induced the lowest KLK6 expression and was used to silence KLK6 in subsequent experiments. Compared with that in the control and negative control groups, the percentage of CD133 + and CD44 + cells, the protein expression level of Oct-4, Nanog, HK1, HK2, GLUT1, p-PI3K, p-AKT and p-mTOR, and ATP content, lactic acid production, glucose uptake and gastric tumor volume were significantly decreased by sh-KLK6 (P<0.05), whereas KLK6 overexpression induced the opposite effect (P<0.05). In conclusion, KLK6 modulated stemness properties and cell metabolic profile in gastric carcinoma cells and the mechanism may be associated with the PI3K/AKT/mTOR signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021, Spandidos Publications.)

Lithium-sulfur (Li-S) batteries are deemed to have great prospects in the next generation advanced energy storage systems and have been considered in recent years. However, the majority of substrates with both high electronic conductivity and full coverage of adsorption-catalysis synergy are difficult to achieve. Herein, nitrogen functionalized porous carbon nanofibers assembled with nickel ferrite nanoparticles (NFO/NCFs) are successfully prepared by electrospinning combined with hydrothermal treatment, which were applied to current collector containing Li 2 S 6 catholyte and binder-free for Li-S batteries. With its abundant active sites, the NFO/NCFs have a vital role in the adsorption and catalysis of the polysulfides, which further accelerate the redox kinetics. Consequently, Li 2 S 6 catholyte impregnated NFO/NCFs electrode (sulfur loading: 5.09 mg cm -2 ) exhibits the first discharge capacity of 997 mAh g -1 and maintains at 637 mAh g -1 after 350 cycles at 0.2C, which is superior cycling performance than NCFs. Even at 10.2 mg cm -2 sulfur loading, the composite electrode shows a high area capacity of 8.35 mAh cm -2 at 0.1C and retains 6.01 mAh cm -2 after 150 cycles. The results suggest the multifunction NFO/NCFs that anchor effectively and catalysis are beneficial to realize the goal of the large-scale application for Li-S batteries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, we carried out an amplified luminescent proximity homogeneous assay (AlphaLISA) to detect sulfonamides (SAs) antibiotic residues in plasma, milk, pork, chicken, and fish. The SAs AlphaLISA method can detect 13 SAs with half-inhibitory concentration (IC 50 ) 2.11-29.77 ng/ml. The detection level of those SAs was 0.3-41.12 ng/ml in matrices, which satisfied the maximum residue limit (MRL) of the European Union, United States, and China. Our recoveries are in the range of 88% to 116.8% with a coefficient of variation less than 9.3% for different spiked food samples. We observed a good correlation between the AlphaLISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) with blood samples from injected rabbits. The established AlphaLISA method provided a no-washing, rapid, high-throughput screening tool for SAs in food quality control, which is suitable for small-volume samples., Competing Interests: 1No conflict of interest declared., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Metabolism-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and the use of traditional Chinese medicines (TCMs) to treat this disease has attracted increasing attention. The Qing Gan San (QGS) formula comprises Polygonatum sibiricum, the peel of Citrus reticulata Blanco, the leaves of Morus alba L, Cichorium intybus, Glycyrrhiza uralensis Fisch, and Cirsium setosum. The present study aimed to uncover the anti-hyperlipidaemic effects, hepatic fat accumulation-lowering effects and mechanisms of QGS in high-fat diet-induced MAFLD rats. QGS significantly reduced the levels of total cholesterol and triglycerides in both serum and liver tissue and partially protected hepatic function. Additionally, QGS significantly ameliorated hepatic lipid accumulation with histopathology observation, as demonstrated by H&E and oil red O staining. RNA sequencing was used to further investigate the key genes involved in the development and treatment of MAFLD. Hierarchical clustering analysis showed that the gene expression profiles in rats with MAFLD were reversed to normal after QGS treatment. QGS had 222 potential therapeutic targets associated with MAFLD. Enrichment analysis among these targets revealed that QGS affected biological functions/pathways such as the regulation of lipid metabolic processes (GO: 0019216) and the non-alcoholic fatty liver disease pathway (hsa04932), and identified Srebp-1 as a key regulator in the synthesis of cholesterol and triglycerides. Subsequently, both immunofluorescence and Western blot analyses demonstrated that QGS suppressed the transfer of Srebp-1 to the nucleus from the cytoplasm, suggesting that the activation of Srebp-1 was inhibited. Our study reveals the effects and mechanisms of QGS in the treatment of MAFLD and provides insights and prospects to further explore the pathogenesis of MAFLD and TCM therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Sun, Liang, Wu, Lv, He, Li, Sun and Song.)

Kallikrein-related peptidase 6 (KLK6), a member of the kallikrein-related peptidase family, is involved in the regulation of epithelial-mesenchymal transition (EMT) in cancer cells and is highly expressed in gastric cancer tissues. The aim of the present study was to investigate the effect of KLK6 on the proliferation, migration and invasion of gastric cancer cells and to determine the underlying mechanism of its actions. The expression of KLK6 was measured in metastatic gastric cancer cells using western blotting and reverse transcription-quantitative PCR, and KLK6 was overexpressed or inhibited in HGC-27 cells using plasmid transfection. Cell proliferation, migration, invasion and EMT were also evaluated using Cell Counting Kit 8, Transwell and western blot analysis, respectively. In addition, a mouse xenograft model was constructed by injection of HGC-27 cells. The xenograft was treated with KLK6 interference or overexpression plasmids to study the in vivo effects of KLK6 on tumor development. The results demonstrated that KLK6 was highly expressed in HGC-27 cells and that KLK6 inhibition attenuated cell proliferation, migration and invasion and prevented gastric cancer tumor development. In addition, KLK6 inhibition reduced the expression of epithelial cell adhesion molecule and vimentin, reduced the phosphorylation of SMAD2 and SMAD3 and upregulated epithelial-cadherin expression. In conclusion, KLK6 inhibition suppressed the proliferation, migration and invasion of gastric cancer cells both in vitro and in vivo through the inhibition of EMT. These findings indicate that KLK6 a potential therapeutic target for gastric cancer therapy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Bacterial infections caused by biofilms are severe clinical problems, resulting in high drug resistance by limiting the penetration of antibiotics. Herein, a near-infrared (NIR)-activated chem/photodynamic/photothermal combined therapeutic agent is proposed by loading fluorescein isothiocyanate (FITC), ultrasmall copper sulfide nanoparticles (Cu 2- x SNPs), and ε-polylysine (PLL) onto mesoporous silica nanoparticles (MSNs) through a layer-by-layer self-assembly approach. FITC-doped MSNs are prepared to monitor the permeability and accumulation of nanocomposites into biofilms. MSNs can also act as hosts for the synthesis of ultrasmall Cu 2- x SNPs, which has effective photodynamic and photothermal ablation against bacteria under NIR light irradiation. Moreover, biodegradable PLL introduced can not only enhance adhesion toward the bacterial surface to increase the effectiveness of phototherapy but also damage bacteria through electrostatic interaction. As a result, the prepared nanocomposites could not only penetrate biofilms but also ablate biofilms through combined chem/photodynamic/photothermal effects under NIR light irradiation. Furthermore, the nanocomposites could treat bacterial infections in vivo with negligible tissue toxicity. Overall, the finely designed nanocomposites are anticipated to display promising applications in imaging-guided chem/photodynamic/photothermal combined therapy for bacterial infections.

Background: Parkinson's disease is the second major neurodegenerative diseases secondarily to Alzheimer's disease. Rapamycin is a fermentation product, which derived from Streptomyces hygroscopius. The aim of this study is to investigate the effect of rapamycin and its potential mechanisms on the acute attack of 1-methyl-4-phenyl-1,2,3,6-four hydrogen pyridine (MPTP) induced Parkinson's disease (PD) in mice., Methods: PD model was established by intraperitoneal injection of MPTP for 5 days. The effect of intraperitoneal injection of rapamycin for treating the symptoms caused by PD was evaluated by behavior observation and HE pathological section. In order to understand the possible mechanism, immunofluorescence and immune precipitation mainly analyzes were used to measure the expression of critical protein p-4ebp1 in mammalian target of rapamycin (mTOR) signaling pathways in the striatum and substantia nigra., Results: Rapamycin can effectively alleviate symptoms of PD. The levels of key protein p-4EBP1 in the striatum and substantia nigra were both significantly higher in PD group compared with control group (P<0.01), while being pretreated with rapamycin, the expression of p-4EBP1 in the striatum and substantia nigra were both decreased obviously (P<0.01)., Conclusions: p-4EBP1 protein may be involved in the pathogenesis of PD via mTOR signaling pathway. Inhibited mTOR-4EBP1 pathways could make a certain protective effect for the acute attack of PD induced by MPTP.

The aim of this work was to study an improved solvent evaporation method to prepare poly (lactic acid) (PLA) microspheres via foam-transfer. Since the foaming process and its transfer were critical to the improved method, they have been studied. Additionally, the delivery capability of foams was studied as a function of the oil/water ratio, the stirring rate, the concentration of polyvinyl alcohol (PVA) and ethanol (EtOH) in the aqueous phase (ω PVA, ω EtOH ). It was found that foaming varied during the preparation process and it influenced the properties of PLA microspheres. When the oil/water ratio (w/w) ≥ 3:10, stirring rate ≥ 600 r/min, ω PVA  ≥ 1 wt%, and ω EtOH  = 0 wt%, solvent evaporation was able to produce enough foams for foam-transfer, which helped to deliver more than 89 wt% PLA microspheres to the receiving vessel. However, ω PVA  ≤ 0.3 wt% and ω EtOH  = 20 wt% were unfavorable for maintaining the spherical shape of PLA microspheres and caused the aggregation. The methodology was further used to prepare azoxystrobin-loaded PLA microspheres successfully with a high encapsulation efficiency of 86.54%. This work is meaningful since it enables an efficient and continuous route to prepare functional biodegradable polymer microspheres., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new optical microscopy technique, termed high spatial and temporal resolution synthetic aperture phase microscopy (HISTR-SAPM), is proposed to improve the lateral resolution of wide-field coherent imaging. Under plane wave illumination, the resolution is increased by twofold to around 260 nm, while achieving millisecond-level temporal resolution. In HISTR-SAPM, digital micromirror devices are used to actively change the sample illumination beam angle at high speed with high stability. An off-axis interferometer is used to measure the sample scattered complex fields, which are then processed to reconstruct high-resolution phase images. Using HISTR-SAPM, we are able to map the height profiles of subwavelength photonic structures and resolve the period structures that have 198 nm linewidth and 132 nm gap (i.e., a full pitch of 330 nm). As the reconstruction averages out laser speckle noise while maintaining high temporal resolution, HISTR-SAPM further enables imaging and quantification of nanoscale dynamics of live cells, such as red blood cell membrane fluctuations and subcellular structure dynamics within nucleated cells. We envision that HISTR-SAPM will broadly benefit research in material science and biology.

Aim: Previously, we constructed a novel anti-p21Ras single-chain antibody fragment, KGH-R1-single-chain fragment variant (ScFv). However, the immunoreactivity of this antibody toward p21Ras is still unclear. Materials & methods: ELISAs, immunohistochemistry, western blotting and immunofluorescence were used to identify the immunoreactivity of KGH-R1-ScFv toward p21Ras. An in silico approach was used to determine the protein structures of KGH-R1-ScFv and p21Ras and then to predict the site involved in the binding of KGH-R1-ScFv to p21Ras. Results: KGH-R1-ScFv had a specific immune reaction with prokaryotically expressed p21Ras, human tumor cells and tumor tissues with RAS mutations or overexpression of RAS . Molecular docking showed that KGH-R1-ScFv could stably interact with wild-type and mutant p21Ras and the binding sites were in the complementarity-determining regions of KGH-R1-ScFv. Conclusion: KGH-R1-ScFv shows specific immunoreactivity toward wild-type and mutant p21Ras as well as the corresponding tumors, which suggests that KGH-R1-ScFv shows potential as a therapeutic antibody for therapy of RAS -driven tumors.

In this study, vacuum low-pressure carburizing heat treatments were carried out on 18Cr2Ni4WA case-carburized alloy steel. The evolution and phase transformation mechanism of the microstructure of the carburized layer during low-temperature tempering and its effect on the surface hardness were studied. The results showed that the carburized layer of the 18Cr2Ni4WA steel was composed of a large quantity of martensite and retained austenite. The type of martensite matrix changed from acicular martensite to lath martensite from the surface to the core. The hardness of the carburized layer gradually decreased as the carbon content decreased. A thermodynamic model was used to show that the low-carbon retained austenite was easier to transform into martensite at lower temperatures, since the high-carbon retained austenite was more thermally stable than the low-carbon retained austenite. The mechanical stability-not the thermal stability-of the retained austenite in the carburized layer dominated after carburizing and quenching, and cryogenic treatment had a limited effect on promoting the martensite formation. During low-temperature tempering, the solid-solution carbon content of the martensite decreased, the compressive stress on the retained austenite was reduced and the mechanical stability of the retained austenite decreased. Therefore, during cooling after low-temperature tempering, the low-carbon retained austenite transformed into martensite, whereas the high-carbon retained austenite still remained in the microstructure. The changes in the martensite matrix hardness had a far greater effect than the transformation of the retained austenite to martensite on the case hardness of the carburized layer.

A series of 2-(((5-akly/aryl-1 H -pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3 H )-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC 50 values in the range of 0.0038-0.4759 μmol/L. Among those compounds, I-11 had an EC 50 value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. In vitro anti-HIV-1 activity and resistance profile studies suggested that compounds I-11 and I-12 displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (EC 50 s range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC 50 values of 2.77 and 4.87 μmol/L for HIV-1A 17 (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both I-11 and I-12 obtained sub-micromolar IC 50 values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound I-11 has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Objective: In this study, we aimed to determine the effects of physical therapy intervention on mental function in patients with stroke., Methods: In this retrospective experimental study, we included 134 patients previously diagnosed with anxiety and depression who presented to our outdoor physical therapy clinic with hemiplegia owing to stroke during 2016 to 2018. The main interventions were neurodevelopmental techniques, strength training, stationary cycling, and shoulder wheel exercise. The treatment duration was 6 months, 5 days a week. Key outcome measurement tools included the Patient Health Questionnaire-9 (PHQ-9), Disability Rating Scale (DRS), and Functional Independent Measure (FIM). Baseline and post-interventional measurements were compared using a paired-sample t -test., Results: Baseline scores on the PHQ-9, DRS, and FIM were 24.77±1.24, 19.67±1.25, and 20.77±1.74, respectively; post-intervention scores on these three scales were 9.08±0.49, 7.78±1.49, and 82.52±10.03 respectively. In the comparison, significant differences were observed between baseline and post-interventional scores., Conclusion: We found that physiotherapy interventions improved motor function in patients with stroke as well as their mental function. Patients with stroke with impaired mental function can improve by participating in a physiotherapy treatment program.

Cardiogenic shock is the most severe form of acute heart failure. The aim of the current study was to investigate correlations between diagnostic parameters and the estimated ejection fraction in patients with cardiogenic shock. A total of 2,445 patients with acute myocardial infarction were subjected to coronary angiograms and standard 2D transthoracic echocardiography. Information for culprit vessel(s) and mitral regurgitation were collected. The Spearman's correlation test was used to assess the correlation between diagnostic parameters and estimated ejection fractions at a 95% confidence level. The angiographically-derived numbers of culprit vessels had a significant correlation with mitral regurgitation (r=0.907; P=0.034). The echocardiographically-derived mitral regurgitation was significantly correlated with the numbers of culprit vessels (r=0.896; P=0.04). Positive correlation was established between angiographically- and echocardiographically-measured left ventricular ejection fraction (r=0.356; P=0.045). The numbers of culprit vessels (P=0.058) and mitral regurgitation (r=0.99; P=0.001) were similar for angiography and echocardiography. Echocardiography- and angiography-derived results were correlated with the estimated ejection fractions of patients with cardiogenic shock. However, there is a substantial difference in the procedures of the two operational techniques., (Copyright: © Chen et al.)

Fluorescent metal sensors based on DNA often rely on changes in end-to-end distance or local environmental near fluorophore labels. Because metal ions can also nonspecifically interact with DNA through various mechanisms, such as charge screening, base binding, and increase or decrease in duplex stability, robust and specific sensing of metal ions has been quite challenging. In this work, a side-by-side comparison of two signaling strategies on a Na + -specific DNAzyme that contained a Na + -binding aptamer was performed. The duplex regions of the DNAzyme was systematically shortened and its effect was studied by using a 2-aminopurine (2AP)-labeled substrate strand. Na + binding affected the local environmental of the 2AP label and increased its fluorescence. A synergistic process of Na + binding and forming the duplex on the 5'-end of the enzyme strand was observed, and this end was close to the aptamer loop. Effective Na + binding was achieved with a five base-pair stem. The effect on the 3'-end is more continuous, and the stem needs to form first before Na + can bind. With an optimized substrate binding arm, a FRET-based sensor has been designed by labeling the two ends of a cis form of the DNAzyme with two fluorophores. In this case, Na + failed to show a distinct difference from that of Li + or K + ; thus indicating that probing changes to the local environment allows more robust sensing of metal ions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, a few RNA-cleaving DNAzymes have been isolated with excellent specificity for Na + , and some of them contain a Na + -binding aptamer. This metal recognition mechanism is different from that of most previously reported DNAzymes. When using 2-aminopurine (2AP) as a probe, interesting local folding induced by Na + was recently observed. In this work, FRET was used to probe the global folding of the Ce13d DNAzyme; one of the Na + -specific DNAzymes. FRET pairs were at different locations, which yielded a total of five constructs to probe the three-way junction structure with a large loop. With endlabeled DNAzymes, the global structure appears to be quite rigid with little folding upon adding up to 200 mm monovalent metal ions, although some minor differences were observed between Li + , Na + , and K + . This lack of significant conformational change is also consistent with circular dichroism spectroscopy data. The loop was then labeled with an internal tetramethylrhodamine fluorophore at the G14 position, and its cleavage activity was partially retained. A clear Na + -dependent folding was observed with spectral crossover. From a biosensing standpoint, global folding based sensors are unlikely to work due to the overall rigid structure of the DNAzyme. Therefore, the best way to use this DNAzyme to discriminate Na + from K + is based on cleavage activity, followed by probing local folding, whereas global folding is the least effective for metal discrimination., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, the excellent Na+ selectivity of a few RNA-cleaving DNAzymes was exploited, where Na+ can be around 3000-fold more effective than K+ for promoting catalysis. By using a double mutant based on the Ce13d DNAzyme, and by lowering the temperature, increased 2-aminopurine (2AP) fluorescence was observed with addition of both Na+ and K+. The fluorescence increase was similar for these two metals at below 10 mM, after which K+ took a different pathway. Since 2AP probes its local base stacking environment, K+ can be considered to induce misfolding. Binding of both Na+ and K+ was specific, since single base mutations could fully inhibit 2AP fluorescence for both metals. The binding thermodynamics was measured by temperature-dependent experiments revealing enthalpy-driven binding for both metals and less coordination sites compared to G-quadruplex DNA. Cleavage activity assays indicated a moderate cleavage activity with 10 mM K+, while further increase of K+ inhibited the activity, also supporting its misfolding of the DNAzyme. For comparison, a G-quadruplex DNA was also studied using the same system, where Na+ and K+ led to the same final state with only around 8-fold difference in Kd. This study provides interesting insights into strategies for discriminating Na+ and K+.

Polymeric microspheres with different internal structures have been widely used because of their characteristics in the structures. This paper reports a method of controlling the internal structures of polymeric microspheres via the introduction of a water-soluble organic solvent to the continuous phase in the foam phase preparation of porous polymeric microspheres. The introduction of a water-soluble organic solvent enables the control of polymeric microspheres' internal structures, from porous to hollow. Because a water-soluble organic solvent is introduced, the organic solvent may be diffused toward the interface because of the affinity between the organic solvent and the oil droplets, resulting an accumulation of organic solvent molecules at the interface to form an organic solvent layer. The presence of this layer may decrease the evaporation rate of the internal organic solvent in an oil droplet, which extends the time for the mingling of porogen droplets to form a few large pores or even an extremely large single pore inside. This method is also capable of altering the thickness of hollow microspheres' shells in a desired way, with improved efficiency, yield and the capacity for continuous use on an industrial scale.

The open reading frames of 19 cytochrome P450 monooxygenase (CYP) genes were sequenced from Chironomus tentans, a commonly used freshwater invertebrate model. Phylogenetic analysis of the 19 CYPs along with a previously reported CYP (CtCYP4G33) revealed that they belong to three different clans, including 3 in CYP4, 15 in CYP3, and 2 in mitochondria clan. When third-instar larvae were exposed to atrazine at 5000 μg/L, the transcription of CtCYP6EX3, CtCYP6EV3, CtCYP9AT1 and CtCYPEX1 was significantly up-regulated. To examine whether CtCYP6EX3 played a role in oxidative activation of chlorpyrifos to chlorpyrifos-oxon, we evaluated larval susceptibility to chlorpyrifos after CtCYP6EX3 transcript was suppressed by RNAi. The larvae fed chitosan/dsCtCYP6EX3 nanoparticles showed a significantly decreased CtCYP6EX3 transcript (53.1%) as compared with the control larvae fed chitosan/dsGFP nanoparticles. When the CtCYP6EX3-silenced larvae were exposed to chlorpyrifos at 6 μg/L or its binary mixture with atrazine (chlorpyrifos at 3 μg/L and atrazine at 1000 μg/L), the larvae became less susceptible to the pesticides as their mortalities decreased by 24.1% and 20.5%, respectively. These results along with our previous findings suggested that the increased toxicity of chlorpyrifos was likely due to an enhanced oxidative process from chlorpyrifos to chlorpyrifos-oxon by CtCYP6EX3 as RNAi of CtCYP6EX3 led to decreased susceptibility of C. tentans larvae to chlorpyrifos alone and the binary mixture of atrazine and chlorpyrifos. However, further study would be necessary to validate our results by functional assays using heterologously expressed CtCYP6EX3 enzyme., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Compound Arnebiae radix oil has been clinically applied to treat burns and scalds for a long time. However, it is unstable and inconvenient to use. The aim of this study was to prepare a compound Arnebiae radix microemulsion gel for transdermal delivery system and evaluate its characteristics., Materials and Methods: Based on the solubility of Shikonin, the active component of Arnebiae radix and the results of phase studies, adequate ratio of each component in microemulsion was determined. The optimized microemulsion gel was prepared using Carbomer 940. The gels were characterized in terms of appearance, preliminary stability test and the content of Shikonin in the compound Arnebiae radix microemulsion gel with HPLC analysis., Results: The optimized conditions for preparing microemulsion were Tween-80, glycerin, isopropyl myristate (IPM) with the ratio of 6:3:2. The optimal microemulsion gel was obtained with Carbomer 940 (1.0%)., Conclusion: The prepared compound Arnebiae radix microemulsion gel showed good stability over time. It is more convenience in application than the previous used formulations.

Some cytochrome P450 (CYP) genes are known for their rapid up-regulation in response to insecticide exposures in insects. To date, however, limited information is available with respect to the relationships among the insecticide type, insecticide concentration, exposure duration and the up-regulated CYP genes. In this study, we examined the transcriptional response of eight selected CYP genes, including CYP4G7, CYP4Q4, CYP4BR3, CYP12H1, CYP6BK11, CYP9D4, CYP9Z5 and CYP345A1, to each of four insecticides in the red flour beetle, Tribolium castaneum. Reverse transcription quantitative PCR (RT-qPCR) revealed that CYP4G7 and CYP345A1 can be significantly up-regulated by cypermethrin (1.97- and 2.06-fold, respectively), permethrin (2.00- and 2.03-fold) and lambda-cyhalothrin (1.73- and 1.81-fold), whereas CYP4BR3 and CYP345A1 can be significantly up-regulated by imidacloprid (1.99- and 1.83-fold) when 20-day larvae were exposed to each of these insecticides at the concentration of LC20 for 24 h. Our studies also showed that similar levels of up-regulation can be achieved for CYP4G7, CYP4BR3 and CYP345A1 by cypermethrin, permethrin, lambda-cyhalothrin or imidacloprid with approximately one fourth of LC20 in 6 h. Our study demonstrated that up-regulation of these CYP genes was rapid and only required low concentrations of insecticides, and the up-regulation not only depended on the CYP genes but also the type of insecticides. Our results along with those from previous studies also indicated that there were no specific patterns for predicting the up-regulation of specific CYP gene families based on the insecticide classification.

The retention and adhesion of melamine formaldehyde (MF) microcapsules on a model fabric surface in aqueous solution were investigated using a customised flow chamber technique and atomic force microscopy (AFM). A cellulose film was employed as a model fabric surface. Modification of the cellulose with chitosan was found to increase the retention and adhesion of microcapsules on the model fabric surface. The AFM force-displacement data reveal that bridging forces resulting from the extension of cellulose chains dominate the adhesion between the microcapsule and the unmodified cellulose film, whereas electrostatic attraction helps the microcapsules adhere to the chitosan-modified cellulose film. The correlation between results obtained using these two complementary techniques suggests that the flow chamber device can be potentially used for rapid screening of the effect of chemical modification on the adhesion of microparticles to surfaces, reducing the time required to achieve an optimal formulation.