Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes.

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

Interaction of microorganisms with carbonates from the micro to the macro scales during sedimentation: Insights into the early stage of biodegradation.

The assembly process of Organic Matter (OM) from single molecules to polymers and the formation process of Ca-CO3 ion-pairs are explored at the micro-scale, and then the relationship between OM and carbonate based on the results of microbially-induced carbonate precipitation (MICP) laboratory experiments is established at the macro-scale. Molecular dynamics (MD) is used to model the assembly of OM (a) in an aqueous solution, (b) on surfaces of calcite (10 1‾ 4) crystals and (c) on defective calcite (101‾ 4) crystal surfaces. From the MICP experiments, carbonate minerals containing abundant OM were precipitated and were characterized by Scanning Electron Microscopy (SEM), X-Ray Diffractometry (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The results of the MD show that OM is assembled into polymers in all three simulation systems. Although the Ca-CO3 ion-pairs and OM were briefly combined, the aggregation assembly of OM molecules and the precipitation of carbonate calcium are not related in the long run. The highly specific surface area of the defective calcite shows an increase in the adsorption of OM. The van der Waals forces, which are primarily responsible for controlling the assembly of OM molecules, increase with the degree of aggregation. According to the MICP experiments, OM is enriched on the mineral surfaces, and more OM is found at the steps of defective crystals with their larger surface areas. Through MD and MICP laboratory experiments, this work systematically describes the interaction of OM and carbonate minerals from the micro to the macro scales, and this provides insight into the interaction between OM and carbonates and biogeochemical processes related to the accumulation of OM in sediments.

HBV DNA and HBsAg: Early Prediction of Response to Peginterferon α-2a in HBeAg-Negative Chronic Hepatitis B.

Objective: The proportion of hepatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients in China has increased rapidly. However, the response of these patients to peginterferon (peg-IFN) treatment is poor, and the antiviral treatment strategies are inconsistent. This study aimed to investigate the role of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in early prediction of response in HBeAg-negative CHB patients receiving peg-IFN α-2a. Patients and Methods: Treatment-naïve HBeAg-negative patients were involved in this prospective study during 2014-2018. The HBV DNA and HBsAg were quantified at baseline and during treatment (weeks 12, 24 and 48) in sera. The factors associated with HBV DNA undetectable and HBsAg <100 IU/ml at treatment 48 weeks were assessed. Results: This study involved 45 patients. There was HBV DNA undetectable in 36 cases (80%), including 19 (52.8%) with HBsAg <100 IU/ml at week 48. The HBV DNA <2.0 log10IU/ml at week 24 (PPV = 96.9%, NPV = 66.7%, P = 0.018) was an independent predictor of HBV DNA undetectable at week 48. The HBsAg <800 IU/ml at baseline (PPV = 92.1%, NPV = 69.7%, P = 0.054) and HBsAg decline >5.00-fold at week 24 (PPV = 83.3%, NPV = 77.8%, P = 0.038) were independent predictors of HBsAg <100 IU/ml and HBV DNA undetectable at week 48. Conclusion: Early on-treatment quantification of HBV DNA and HBsAg in patients with HBeAg-negative CHB treated with peg-IFN α-2a may help identify those likely to be cured by this method and optimize therapy strategies.

Polydopamine-capped AgNPs as a novel matrix overcoming the ion suppression of phosphatidylcholine for MALDI MS comprehensive imaging of glycerophospholipids and sphingolipids in impact-induced injured brain.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a powerful tool for the characterization and localization of analytes without the need for extraction, purification, separation or labeling of samples. However, in tissue sections the most abundant lipids, phosphatidylcholines (PCs), could suppress the signals of other classes of coexisting lipids. In this work, polydopamine (PDA)-capped AgNPs (AgNPs@PDA) were synthesized as a matrix of MALDI MSI to analyze lipids in both positive and negative ion modes. By adjusting the thickness of the PDA layer, the signal of silver cluster ions of AgNPs@PDA was effectively controlled, and the ability of AgNPs@PDA serving as a matrix was optimized. More interestingly, using AgNPs@PDA as a matrix, the sensitivity of PCs was dramatically decreased, and the PC signals were greatly suppressed, while for other lipids (including PE, HexCer, PS, PI, PIP, and ST), they were just the opposite. The reason, we believe, is related to the positively charged surface of AgNPs@PDA, and the polyhydroxy and amino groups of PDA. Benefitting from the suppression of the signals of PCs and the improvement of detection sensitivity of other lipids, 58 glycerophospholipids and 25 sphingolipids in brain tissue sections could be imaged in one run with AgNPs@PDA as a matrix by MALDI MSI, much better than when using traditional organic matrices 2,5-dihydroxybenzoic acid and 9-aminoacridine.

Characterization of a novel thermostable GH45 endoglucanase from Chaetomium thermophilum and its biodegradation of pectin.

A novel thermostable endoglucanase (CTendo45) encoding gene was cloned from Chaetomium thermophilum and heterologously expressed in Pichia pastoris. Sequence alignment indicated that the CTendo45 enzyme belonged to glycoside hydrolase family 45. The recombinant enzyme was purified by Ni2+ affinity chromatography, and its apparent molecular mass was estimated to be 32 kDa by SDS-PAGE. The purified enzyme displayed maximum activity at 70°C and pH 4. CTendo45 was stable at 60°C for 1 h, and residual activities of 78.9% and 65.6% were estimated after 1 h at 70°C and 80°C, respectively. Ca2+, Zn2+, Mg2+, Cu2+ and Mn2+ were found to have beneficial effects on the enzyme activity to different degrees. The specific activity of purified CTendo45 was 1.52 IU mg-1 and the Km value was 59.6 µg ml-1 with a sodium carboxymethyl cellulose substrate. Moreover, CTendo45 exhibited high hydrolysis activity towards pectin, and the hydrolysis products were mainly galacturonic acid oligosaccharides. CTendo45 is the first reported bifunctional enzyme in glycoside hydrolase family 45 from C. thermophilum that is able to hydrolyze both cellulose and pectin. The biochemical properties of this recombinant CTendo45 make it a potentially effective glycoside hydrolase for industrial applications.

Polypyrrole nanoprobes with low non-specific protein adsorption for intracellular mRNA detection and photothermal therapy.

In this work, we discovered that polypyrrole nanoparticles (PPy NPs) displayed a low non-specific protein adsorption. We herein present the first PPy NP-based biosensing platform for intracellular mRNA detection in living cells. We also demonstrate that PPy NPs exhibit high NIR absorbance and can be utilized for cancer photothermal therapy.

Optofluidic ultrahigh-throughput detection of fluorescent drops.

This paper describes an optofluidic droplet interrogation device capable of counting fluorescent drops at a throughput of 254,000 drops per second. To our knowledge, this rate is the highest interrogation rate published thus far. Our device consists of 16 parallel microfluidic channels bonded directly to a filter-coated two-dimensional Complementary Metal-Oxide-Semiconductor (CMOS) sensor array. Fluorescence signals emitted from the drops are collected by the sensor that forms the bottom of the channel. The proximity of the drops to the sensor facilitates efficient collection of fluorescence emission from the drops, and overcomes the trade-off between light collection efficiency and field of view in conventional microscopy. The interrogation rate of our device is currently limited by the acquisition speed of CMOS sensor, and is expected to increase further as high-speed sensors become increasingly available.

Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles.

Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co-glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins to investigate the effect of PLGA on the formulation of the SLN. The results showed that PLGA was essential for the primary w/o emulsification. In addition, the stability of the w/o emulsion, the encapsulation efficiency and loading capacity of the nanoparticles were enhanced with the increase of PLGA concentration. Furthermore, increasing PLGA concentration decreased zeta potential significantly but had no influence on particle size of the SLN. In vitro release study showed that PLGA significantly affected the initial burst release, i.e. the higher the content of PLGA, the lower the burst release. The released proteins maintained their integrity and bioactivity as confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and biological assay. These results demonstrated that PLGA was an effective emulsifier for the preparation of hydrophilic protein-loaded SLN.

[Three-dimensional finite element initial analysis on the structure defect restoration of mandibular first molar under static and impact loads].

OBJECTIVE: To make a mechanical analysis on three-dimensional finite element models of the mandibular first molar with the maximum distal occlusal (DO) structure defect after the root canal therapy and filling and crown restoration under static and impact loads and to provide a guideline for planning restoration for the clinic. METHODS: The research adopted reverse engineering technology to build the model of three-dimensional finite element. The form of the intercuspal occlusion and cusp to cusp occlusion during the circulation of posterior teeth occlusion movement were simulated. Half-sine pulse/impact was chosen for the impact dynamic. The impact ratio was indicated to the stress change between impact loads and static loads. RESULTS: Under the two kinds of loads, the maximum Mohr stress values of the metal crowns were shown in all models. The restoration effects between the two kinds of models were compared, the maximum Mohr stress value of the crown metal and dentin was not obviously difference. The maximum Mohr stress values of dentin were all obviously smaller than the stretch limit strength of dentin. The impact ratio closed to 1. CONCLUSION: The impact loads accorded with the oral actual situation more than the static loads, but the suitable analysis of the static loads could be accepted. The restoration of metal crown is necessary. The effects between the amalgam filling and full crown restoration and composite resin filling and full crown restoration is not difference obviously.