Advancements in nanoscale delivery systems: optimizing intermolecular interactions for superior drug encapsulation and precision release.

Nanoscale preparations, such as nanoparticles, micelles, and liposomes, are increasingly recognized in pharmaceutical technology for their high capability in tailoring the pharmacokinetics of the encapsulated drug within the body. These preparations have great potential in extending drug half-life, reducing dosing frequency, mitigating drug side effects, and enhancing drug efficacy. Consequently, nanoscale preparations offer promising prospects for the treatment of metabolic disorders, malignant tumors, and various chronic diseases. Nevertheless, the complete clinical potential of nanoscale preparations remains untapped due to the challenges associated with low drug loading degrees and insufficient control over drug release. In this review, we comprehensively summarize the vital role of intermolecular interactions in enhancing encapsulation and controlling drug release within nanoscale delivery systems. Our analysis critically evaluates the characteristics of common intermolecular interactions and elucidates the techniques employed to assess them. Moreover, we highlight the significant potential of intermolecular interactions in clinical translation, particularly in the screening and optimization of preparation prescriptions. By attaining a deeper understanding of intermolecular interaction properties and mechanisms, we can adopt a more rational approach to designing drug carriers, leading to substantial advancements in the application and clinical transformation of nanoscale preparations. Moving forward, continued research in this field offers exciting prospects for unlocking the full clinical potential of nanoscale preparations and revolutionizing the field of drug delivery.

"Machine replacement" or "job creation": How does artificial intelligence impact employment patterns in China's manufacturing industry?

Artificial intelligence (AI), as an important engine for promoting high-quality economic development, should not be overlooked in terms of its impact on the employment of the labor force while promoting the digital and intelligent transformation of industries. In the face of the complex international environment and non-systemic shocks, it is of great significance to explore whether it is "machine replacement" or "job creation" in the process of the integration of AI and industry, as well as the impact of technological progress on the employment pattern of the labor force, in order to promote the economic development, respond to and solve the employment problem. It is of great significance to promote economic development and cope with and solve the employment problem. Based on the task model, this paper analyses the mechanism of the impact of AI on the employment pattern of manufacturing industry. Meanwhile, based on the provincial panel data of China's manufacturing industry from 2011 to 2020, it empirically examines the impact of AI on the total employment, employment structure and employment quality of the labor force, and analyses the multiple responses of AI on the employment pattern of the manufacturing industry. The study shows that: Firstly, the level of development of AI and the total amount of employment is a positive U-shaped relationship, the short term is dominated by the substitution effect, and the long term is dominated by the creation effect; Secondly, with regard to the employment structure, low-skilled labor is more likely to be replaced. The financial, accommodation and catering industries are relatively less affected by the spillover effects of the manufacturing industry; Third, with regard to the employment quality, the gap between urban and rural incomes has eased, with per capita net income of rural residents rising to a higher degree than per capita disposable income of urban residents. Thus, in order to further address the impact of AI on the employment patterns of the labor force, the level of AI development should be increased while expanding employment channels, paying attention to labor force skills training, reinforcing the leading role of developed regions, and accelerating regional integration and urban-rural integration, so as to share the dividends of technological progress.

Nanoparticle surface decoration mediated efficient protein and peptide co-encapsulation with precise ratiometric control for self-regulated drug release.

Accuratly controlling drug release from a smart "self-regulated" drug delivery system is still an ongoing challenge. Herein, we developed a surface decoration strategy to achieve an efficient drug encapsulation with precise ratiometric control. Thanks to the surface decoration with cationic carrier materials by electrostatic attraction, the surface properties of different protein and peptide nanoparticles were uniformed to those adsorbed carrier materials. These carrier materials endowed protein and peptide nanoparticles with good dispersity in the oil phase and significantly inhibited the drug transfer from oil to water. With uniform surface properties, we realized the co-encapsulation of multiple types of proteins and peptides with precise ratiometric control. The encapsulation efficiency was higher than 87.8% for insulin. After solidification, the adsorbed materials on the surface of nanoparticles formed a solid protection layer, which prolonged the mean residence time of insulin from 3.3 ± 0.1 h (for insulin solution) to 47.5 ± 1.3 h. In type 1 diabetes, the spermine-modified acetalated dextran microparticle co-loaded with insulin, glucose oxidase and catalase maintained the blood glucose level within the normal range for 7 days.

Colloidal Jamming by Interfacial Self-Assembled Polymers: A Robust Route for Ultrahigh Efficient Encapsulation.

The control of cargo phase-transfer is of interest for many applications in science and technology. Herein, we report a simple, versatile and robust method to block the phase-transfer of cargo colloids by interfacial self-assembled amphiphilic polymer molecules. After simply increasing the concentration of amphiphilic polymers, the orientation of interfacial polymer molecules changed from flat to upright, forming a thick three-dimensional polymer layer at the oil-water interface. Even under fierce external force, this thick interfacial layer robustly prevented the phase-transfer of cargo colloids, resulting in an ultrahigh encapsulation efficiency (up to 97.1 %) for proteins and peptides. One single injection of high insulin-loaded microcomposites (58.3 wt%) kept the blood glucose level within the normoglycemic state for 10 days in type 1 diabetic rats. The mass of administrated amphiphilic polymers was 1889 times smaller than that of microcomposites prepared with non-amphiphilic ones.

Prediction of drug capturing by lipid emulsions in vivo for the treatment of a drug overdose.

Despite the successful treatment of drug intoxications, little information is available to quantitively predict the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules. We defined two new parameters, drug accommodation capacity and drug capture kinetics, to characterize the drug capture capability of lipid emulsions. By precisely characterizing their drug capture capability, the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules was quantitively described. This quantitative description enabled an accurate prediction of the reducing extent on the half-life and area under drug concentration-time curve, which was verified by the successful treatment of overdosed propafenone. Moreover, the capture effect prediction using drug capture capability was more accurate than that of directly using logP. Overall, the developed capture capability accurately described the effect of lipid emulsions on drug pharmacokinetic features, which can guide the clinical application of lipid emulsions for the treatment of drug overdose.

Targeted Polymeric Nanoparticles Based on Mangiferin for Enhanced Protection of Pancreatic ß-Cells and Type 1 Diabetes Mellitus Efficacy.

Mangiferin (MGF) is found in many natural plants, such as Rhizoma Anemarrhenae, and has anti-diabetes effects. However, its clinical applications and development are limited by poor solubility and low-concentration enrichment in pancreatic islets. In this paper, targeted polymeric nanoparticles were constructed for MGF delivery with the desired drug loading content (6.86 ± 0.60%), excellent blood circulation, and missile-like delivery to the pancreas. Briefly, Glucagon-like peptide 1 (GLP-1) as an active targeting agent to the pancreas was immobilized on the block copolymer polyethyleneglycol-polycaprolactone (PEG-PCL) to obtain final GLP-1-PEG-PCL amphiphiles. Spherical MGF-loaded polymeric nanoparticles were acquired from the self-assembly of the targeted GDPP nanoparticles and MGF with a homogeneous size of 158.9 ± 1.7 nm and a negative potential for a good steady state in circulation. In this drug vehicle, GLP-1 acts as the missile vanguard via the GLP-1 receptor on the surface of the pancreas for improving the accumulation and efficiency of MGF in the pancreas, the hypoglycemic effect of MGF, and the restorative effect on pancreatic islets, which were investigated. As compared to free MGF, MGF/GDPP nanoparticles appeared to be more concentrated in the pancreas, with better blood glucose and glucose tolerance, enhanced insulin levels, increased ß-cell proliferation, reduced ß-cell apoptosis, and islet repair in vivo. This targeted drug delivery system provided a novel strategy and hope for enhancing MGF delivery and anti-diabetes efficacy.

Integrated Metalloproteinase, pH and Glutathione Responsive Prodrug-Based Nanomedicine for Efficient Target Chemotherapy.

Prodrug self-assembled nanomedicines with cleavable moieties sensitive to intracellular stimuli have attracted great interest to pharmacists. In this paper, a docetaxel-hyaluronic acid (DTX-HA) conjugate with peptide, hydrazone bonds and disulfide in sequence, which were cleavable catalyzed by metalloproteinase (MMP), weak acidity and glutathione (GSH), respectively, were involved in a moiety as the linker to immobilize DTX on HA chains, the prodrugs were self-assembled into nanoparticles and utilized for cancer chemotherapy. The synthesis of conjugate was characterized by 1H NMR, ESI-TOF and GPC. The self-assembly of the conjugates was investigated via DLS and TEM. The release profiles revealed that the nanomedicine was disassociated to trigger the drug release in the simulated intracellular conditions of MMP, pH value and GSH, respectively. The in vitro anticancer activity of the nanomedicine with IC50 test, cytometry and confocal laser scanning microscopy exhibited efficient cellular uptake and apoptosis of cancer cells. The in vivo anticancer study of the nanomedicine in tumor-bearing nude mice showed promising therapeutic efficacy in magnificent inhibition tumor growth, long circulation time in pharmacokinetic and low toxicity to organs.

Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.

OBJECTIVE: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China. DESIGN: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses. METHODS: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool. RESULTS: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/µl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses. CONCLUSION: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

Fluorescence Resonance Energy Transfer Visualization of Molecular Delivery from Polymeric Micelles.

Polymeric micelles are important carriers for anticancer drug delivery. However, rare papers focused on the dynamic of drug in the core of micelles. In this paper, we used fluorescence resonance energy transfer (FRET) technique to investigate the dynamic diffusion of drug from polymeric micelles. mPEG-PCL diblock copolymers were used as carriers. A pair of fluorescence molecules Cy3 and Cy5 was selected to evoke the FRET phenomenon. Cy5 was immobilized on the terminal group of PCL segments, Cy3 was encapsulated in the Cy5 modified polymeric micelles as the model drug. The drug loaded polymeric micelles were incubated with 4T1 breast cancer cells. The FRET was observed to explore the dynamic of Cy3 in the micelles. The results showed that the Cy3 loaded micelles were stable in aqueous solution as the energy-transfer efficiency (ETE, I660/I565) rarely decreased even when the time was as long as 120 h. The ETE increased with the content of encapsulated Cy3. The FRET spectra showed that the ETE of the Cy3 loaded polymeric micelles lowered with the release of Cy3 in PBS. The intracellular tracking of the Cy3 loaded micelles found more than 60% loaded drug was release within 12 h with the calculation of ETE in FRET spectra and it was same to confocal laser scanning and flow cytometry results.

Viral Capsids Mimicking Based on pH-Sensitive Biodegradable Polymeric Micelles for Efficient Anticancer Drug Delivery.

Bio-inspired supramolecular self-assembly have been widely explored in biomedical engineering, especially in the field of drug delivery. Here, viral capsid analogue pH-Sensitive polymeric micelles HA-Hyd-DOX were reported, where natural polysacarrides hyaluronic acid (HA) and anticancer drug doxorubicin (DOX), were linked through a hydrazone bond with a high drug loading content of 33.09 wt%. The polymeric micelles look like artificial virus capsids from "core-shell" structures. In addition, the polymeric backbone HA and hydrazone bonds were destroyed in the presence of hyaluronidase in cancer cells and under the acidic conditions of pH = 5 respectively, thereby prodrug-based polymeric micelles could penetrate into the tumor and DOX could be released in lysosomes to enhance anticancer efficacy. With the comparison of typical prodrug-based polymeric micelles mPEG-Hyd-DOX system where DOX was linked to methoxy poly(ethylene glycol) with a hydrazone bond linkage, HA-Hyd-DOX showed greater inhibition to cancer cells due to the better penetration. Such viral capsids mimicking polymeric micelles provided some remarkable benefits for drug delivery, including, high drug loading efficiency, controlled drug release and excellent biodegradable.

Identification of a New HIV-1 Circulating Recombinant Form CRF65_cpx Strain in Jilin, China.

This study reported a new HIV-1 circulating recombinant form CRF65_cpx virus isolated from a man who have sex with men (MSM) in Jilin, China. The near full-length genome of this virus was composed of 14 mosaic gene fragments derived from CRF01_AE, subtype B' (Thai B) and subtype C, highly similar to the CRF65_cpx viruses recently identified in Yunnan and Anhui of China. Phylogenetic tree analysis suggested that this CRF65_cpx strain was not generated among MSM in Jilin, but originated in southern regions of China and spread to Jilin by MSM population. The emergence of CRF65_cpx in Jilin indicated HIV-1 epidemic in this area was more and more complicated and the MSM population has become the important source for generation of new recombinant viruses. Real-time surveillance of new HIV-1 infections among MSM population is quite required.

Identification of a Novel HIV-1 Unique Recombinant Form Comprising CRF01_AE, Subtype B', and CRF65_cpx Among Men Who Have Sex with Men in Jilin, China.

The current HIV-1 epidemic in China is featured by diverse subtypes and continual emergence of new recombinant viruses. This study identified a novel unique recombinant form (URF), JL16013, among men who have sex with men (MSM) in Jilin, China. The JL16013 virus was different from all known subtypes and set up a distinct branch on the phylogenetic tree. This virus had a CRF01_AE backbone with two subtype B' fragments and one CRF65_cpx fragment inserted into gag, pol, env, and nef regions, suggesting that this novel URF might have originated from the CRF01_AE, subtype B', and CRF65_cpx viruses that were cocirculating in Jilin province. This was the first report of the CRF01_AE/B'/CRF65_cpx recombinant in China. Identification of this URF indicated the severity and complexity of the HIV-1 epidemic among MSM in Jilin province. Timely surveillance of new HIV-1 infections and new recombinants among the MSM population is urgently required.

Mongoliibacter ruber gen. nov., sp. nov., a haloalkalitolerant bacterium of the family Cyclobacteriaceae isolated from a haloalkaline lake.

A novel haloalkalitolerant, rod-shaped bacterium, designated strain YIM 4-4T, was isolated from the surface water of the Dugerno lake, a haloalkaline lake in Inner Mongolia. The taxonomy of strain YIM 4-4T was investigated by a polyphasic approach. Strain YIM 4-4T was Gram-stain-negative, strictly aerobic, non-motile and formed red colonies. Optimal growth conditions were 28 °C, pH 8.0-11.0 and 0.5-2 % NaCl. The major respiratory quinone was menaquinone-7 (MK-7). The polar lipid profile was composed predominantly of phosphatidylethanolamine, six unidentified polar lipids, one phospholipid and one aminolipid. The predominant cellular fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 1I/anteiso-C17 : 1B, iso-C16 : 1G, iso-C17 : 0 3-OH, C16 : 1ω7c/C16 : 1ω6c and iso-C16 : 1. The genomic DNA G+C content was 43.0 mol%. 16S rRNA gene sequence analysis indicated that the members of the genera Cecembia, Fontibacter, Aquiflexum and Indibacter of the family Cyclobacteriaceae (phylum Bacteroidetes) were the most closely related, with 16S rRNA gene sequence similarities ranging from 93.6 to 94.2 %. Other members of the family Cyclobacteriaceae showed sequence similarities < 93.0 %. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain YIM 4-4T represents a novel species of a new genus, for which the name Mongoliibacter ruber gen. nov., sp. nov. is proposed. The type strain is YIM 4-4T ( = CCTCC AB 2012966T = DSM 27929T).