A quick paster type of soluble nanoparticle microneedle patch for the treatment of obesity.

Obesity is a major public burden on the working population and induces chronic diseases. Its treatment often requires long-term medication, which makes patient compliance difficult. In this study, we reported the value of HORN-MN, which comprised a fast-soluble hyaluronic acid microneedle matrix and a weak acid-degradable oleanolic acid dimer of rosiglitazone nanoparticles. The results showed that the microneedles easily punctured the stratum corneum and dissolved in the dermis of the abdominal wall within 5 min, followed by the release of rosiglitazone nanoparticles. Thereafter, the nanoparticles were endocytosed by macrophages and white adipocytes, then degraded to oleanolic acid in the lysosomes, thereby, releasing rosiglitazone. Oleanolic acid significantly improved the inflammatory status of obese adipose tissue and promoted white adipocyte browning, and rosiglitazone significantly potentiated WAC browning. Accordingly, the patch demonstrated a remarkable obesity-reducing efficacy in mice. In conclusion, this study developed a quick paster type of soluble rosiglitazone nanoparticle microneedle for the treatment of obesity. This patch can be suitable for working people, with an evident obesity-reducing efficacy but no effect on skin integrity despite multiple administrations.

A Retrospective Study on Predicting Recurrence of Intermediate-Stage Hepatocellular Carcinoma After Radical Therapy.

Purpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease. Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients' RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91). Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.

A PVDF/g-C3N4-Based Composite Polymer Electrolytes for Sodium-Ion Battery.

As one of the most promising candidates for all-solid-state sodium-ion batteries and sodium-metal batteries, polyvinylidene difluoride (PVDF) and amorphous hexafluoropropylene (HFP) copolymerized polymer solid electrolytes still suffer from a relatively low room temperature ionic conductivity. To modify the properties of PVDF-HEP copolymer electrolytes, we introduce the graphitic C3N4 (g-C3N4) nanosheets as a novel nanofiller to form g-C3N4 composite solid polymer electrolytes (CSPEs). The analysis shows that the g-C3N4 filler can not only modify the structure in g-C3N4CSPEs by reducing the crystallinity, compared to the PVDF-HFP solid polymer electrolytes (SPEs), but also promote a further dissociation with the sodium salt through interaction between the surface atoms of the g-C3N4 and the sodium salt. As a result, enhanced electrical properties such as ionic conductivity, Na+ transference number, mechanical properties and thermal stability of the composite electrolyte can be observed. In particular, a low Na deposition/dissolution overpotential of about 100 mV at a current density of 1 mA cm-2 was found after 160 cycles with the incorporation of g-C3N4. By applying the g-C3N4 CSPEs in the sodium-metal battery with Na3V2(PO4)3 cathode, the coin cell battery exhibits a lower polarization voltage at 90 mV, and a stable reversible capacity of 93 mAh g-1 after 200 cycles at 1 C.

Enhanced Electrochemical Performance of PEO-Based Composite Polymer Electrolyte with Single-Ion Conducting Polymer Grafted SiO2 Nanoparticles.

In order to enhance the electrochemical performance and mechanical properties of poly(ethylene oxide) (PEO)-based solid polymer electrolytes, composite solid electrolytes (CSE) composed of single-ion conducting polymer-modified SiO2, PEO and lithium salt were prepared and used in lithium-ion batteries in this work. The pyridyl disulfide terminated polymer (py-ss-PLiSSPSI) is synthesized through RAFT polymerization, then grafted onto SiO2 via thiol-disulfide exchange reaction between SiO2-SH and py-ss-PLiSSPSI. The chemical structure, surface morphology and elemental distribution of the as-prepared polymer and the PLiSSPSI-g-SiO2 nanoparticles have been investigated. Moreover, CSEs containing 2, 6, and 10 wt% PLiSSPSI-g-SiO2 nanoparticles (PLi-g-SiCSEs) are fabricated and characterized. The compatibility of the PLiSSPSI-g-SiO2 nanoparticles and the PEO can be effectively improved owing to the excellent dispersibility of the functionalized nanoparticles in the polymer matrix, which promotes the comprehensive performances of PLi-g-SiCSEs. The PLi-g-SiCSE-6 exhibits the highest ionic conductivity (0.22 mS·cm-1) at 60 °C, a large tLi+ of 0.77, a wider electrochemical window of 5.6 V and a rather good lithium plating/stripping performance at 60 °C, as well as superior mechanical properties. Hence, the CSEs containing single-ion conducting polymer modified nanoparticles are promising candidates for all-solid-state lithium-ion batteries.

Supercarriers of antibiotic resistome in a world's large river.

BACKGROUND: Antibiotic resistome has been found to strongly interact with the core microbiota in the human gut, yet little is known about how antibiotic resistance genes (ARGs) correlate with certain microbes in large rivers that are regarded as "terrestrial gut." RESULTS: By creating the integral pattern for ARGs and antibiotic-resistant microbes in water and sediment along a 4300-km continuum of the Yangtze River, we found that human pathogen bacteria (HPB) share 13.4% and 5.9% of the ARG hosts in water and sediment but contribute 64% and 46% to the total number of planktonic and sedimentary ARGs, respectively. Moreover, the planktonic HPB harbored 79 ARG combinations that are dominated by "natural" supercarriers (e.g., Rheinheimera texasensis and Noviherbaspirillum sp. Root189) in river basins. CONCLUSIONS: We confirmed that terrestrial HPB are the major ARG hosts in the river, rather than conventional supercarriers (e.g., Enterococcus spp. and other fecal indicator bacteria) that prevail in the human gut. The discovery of HPB as natural supercarriers in a world's large river not only interprets the inconsistency between the spatial dissimilarities in ARGs and their hosts, but also highlights the top priority of controlling terrestrial HPB in the future ARG-related risk management of riverine ecosystems globally. Video Abstract.

A Systematic Review of Population Pharmacokinetic Models of Methotrexate.

BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among individuals, and they could be predicted by its pharmacokinetics. Many population pharmacokinetic models have been published to describe MTX pharmacokinetics. The objective of this systematic review was to summarize and discuss covariates with significant influence on MTX pharmacokinetics. METHODS: We searched PubMed and EMBASE databases from their inception to April 2021 for population pharmacokinetic of MTX. The articles were screened by inclusion and exclusion criteria. The characteristics of studies and information for model construction and validation were extracted, summarized and discussed. RESULTS: Thirty-five articles were included. The two-compartment model well described the pharmacokinetic behavior of MTX. For inter-individual variability, an exponential distribution error model was usually used for high-dose MTX population pharmacokinetic models, while a proportional distribution error model was used for low-dose MTX population pharmacokinetic models. Proportional and combined proportional and additive error models were used to describe residual error. Renal function was an independent indicator of MTX clearance. Body weight, age, gene polymorphisms (SLCO1B1, ABCC2, ABCB1, ABCG2 and MTHFR) and co-medications (proton pump inhibitors, non-steroidal anti-inflammatory drug, dexamethasone, vancomycin, penicillin and salicylic acid) could influence MTX clearance. Body weight, body surface area, age and dosage regimen have significant influence on MTX central compartment volume. Internal bootstrap test, external validation and visual predictive check were used to evaluate model predictive ability. CONCLUSIONS: Various covariates could affect MTX pharmacokinetics, and their relationships have been summarized and discussed. This review will be helpful for researchers to develop their own population pharmacokinetic models and select appropriate models for individualized therapy of MTX.

Graphene Composite via Bacterial Cellulose Assisted Liquid Phase Exfoliation for Sodium-Ion Batteries.

One of the most critical challenges for commercialization of sodium-ion battery (SIB) is to develop carbon anodes with high capacity and good rate performance. Graphene would be an excellent SIB anode candidate due to its success in various kinds of batteries. Liquid-phase exfoliation (LPE) method is an inexpensive, facile and potentially scalable method to produce less-defected graphene sheets. In this work, we developed an improved, dispersant-assisted LPE method to produce graphene composite materials from raw graphite with high yield and better quality for SIB anode. Here, bacterial cellulose (BC) was used as a green dispersant/stabilizer for LPE, a "spacer" for anti-restacking, as well as a carbon precursor in the composite. As a result, the carbonized BC (CBC)/LPE graphene (LEGr) presented improved performance compared to composite with graphene prepared by Hummers method. It exhibited a specific capacity of 233 mAh g-1 at a current density of 20 mA g-1, and 157 mAh g-1 after 200 cycles at a high current density of 100 mA g-1 with capacity retention rate of 87.73%. This method not only provides new insight in graphene composites preparation, but also takes a new step in the exploration of anode materials for sodium-ion batteriesSIBs.

Ultraflexible and Mechanically Strong Polymer/Polyaniline Conductive Interpenetrating Nanocomposite via In Situ Polymerization of Vinyl Monomer.

Simultaneous enhancement of conductivity and mechanical properties for polyaniline/polymer nanocomposite still remains a big challenge. Here, a reverse approach via in situ polymerization (RIP) of vinyl monomers in waterborne polyaniline dispersion was raised to prepare conductive polyaniline (GPANI)/polyacrylate (PMB) interpenetrating polymer (GPANI-PMB) nanocomposite. GPANI/PMB physical blend was simultaneously prepared as reference. The conductive GPANI-PMB nanocomposite film with compact pomegranate-shape morphology is homogeneous, ultraflexible and mechanically strong. With incorporating a considerable amount of PMB into GPANI via the RIP method, only a slight decrease from 3.21 to 2.80 S/cm was detected for the conductivity of GPANI-PMB, while the tensile strength significantly increased from 25 to 43.5 MPa, and the elongation at break increased from 40% to 234%. The water absorption of GPANI-PMB3 after 72 h immersion decreased from 24.68% to 10.35% in comparison with GPANI, which is also higher than that of GPANI/PMB. The conductivity and tensile strength of GPANI-PMB were also much higher than that of GPANI/PMB (0.006 S/cm vs. 5.59 MPa). Moreover, the conductivity of GPANI-PMB remained almost invariable after folding 200 times, while that of GPANI/PMB decreased by almost half. This RIP approach should be applicable for preparing conventional conductive polymer nanocomposite with high conductivity, high strength and high flexibility.

Methotrexate Polyglutamates Analysis by Chromatography Methods in Biological Matrices: A Review.

Methotrexate (MTX) is used as an immunosuppressant and antineoplastic drug in clinical practice. MTX is a parent drug and converts to MTX polyglutamates (MTXPGs) to exhibit its biological activity. Clinical studies found that MTXPG levels were associated with MTX response and toxicities, especially at low doses. Due to huge variance of MTX response and toxicities between individuals, therapeutic drug monitoring is necessary for its use in individualized therapy. Various chromatography methods coupled with ultraviolet-visible detector, fluorescence detector and mass spectrometry have been reported for MTXPG analysis in various biological matrices. The aim of this paper is to review the chromatographic based methods for the measurement of total and/or individual MTXPGs. We searched Embase, Science Direct and PubMed databases using "methotrexate polyglutamate" and "chromatography" as search terms, and found 745 articles. Of those, 14 articles were extracted for this study. The key steps for method development (sample pretreatment, parameter optimization of liquid chromatography and mass spectrometry, selection of internal standard) and validation (lower limit of quantitation, accuracy, precision, recovery, matrix effect and stability) were analyzed and summarized, which might be helpful for researchers to develop their own methods.

Facile approach to fabricate waterborne polyaniline nanocomposites with environmental benignity and high physical properties.

Waterborne polyaniline (PANI) dispersion has got extensive attention due to its environmental friendliness and good processability, whereas the storage stability and mechanical property have been the challenge for the waterborne PANI composites. Here we prepare for waterborne PANI dispersion through the chemical graft polymerisation of PANI into epichlorohydrin modified poly (vinyl alcohol) (EPVA). In comparison with waterborne PANI dispersion prepared through physical blend and in situ polymerisation, the storage stability of PANI-g-EPVA dispersion is greatly improved and the dispersion keeps stable for one year. In addition, the as-prepared PANI-g-EPVA film displays more uniform and smooth morphology, as well as enhanced phase compatibility. PANI is homogeneously distributed in the EPVA matrix on the nanoscale. PANI-g-EPVA displays different morphology at different aniline content. The electrical conductivity corresponds to 7.3 S/cm when only 30% PANI is incorporated into the composites, and then increases up to 20.83 S/cm with further increase in the aniline content. Simultaneously, the tensile strength increases from 35 MPa to 64 MPa. The as-prepared PANI-g-EPVA dispersion can be directly used as the conductive ink or coatings for cellulose fibre paper to prepare flexible conductive paper with high conductivity and mechanical property, which is also suitable for large scalable production.