Preparation and Rheological Evaluation of Thiol-Maleimide/Thiol-Thiol Double Self-Crosslinking Hyaluronic Acid-Based Hydrogels as Dermal Fillers for Aesthetic Medicine.

This study presents the development of thiol-maleimide/thiol-thiol double self-crosslinking hyaluronic acid-based (HA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and HA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)-thiol as crosslinkers. The six resulting HA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties.

Composite Hydrogels of Ultrasound-Assisted-Digested Formic Acid-Decellularized Extracellular Matrix and Sacchachitin Nanofibers Incorporated with Platelet-Rich Plasma for Diabetic Wound Treatment.

In this study, an ultrasound-assisted digestion method of a formic acid-decellularized extracellular matrix (dECM) of porcine skin was developed and optimized to form UdECM hydrogels for diabetic wound healing. Results demonstrated that ultrasonication improved the extraction rate of collagen from dECM samples, preserved the collagen content of dECM, reduced residual cells, and extracted greater DNA contents. Scanning electron microscope (SEM) analyses were performed, which demonstrated the optimal porosity on the surface and density of the cross-section in the hydrogel structure, which could control the release of growth factors embedded in UdECM hydrogels at desirable rates to boost wound healing.

Distribution of Metallic Elements in Four Group Components of High-Temperature Coal Tar Pitch.

The metallic elements in high-temperature coal tar pitch (HCTP) will affect the properties of carbon materials produced from the HCTP. The study on the metallic elements in HCTP is essential for the quality improvement of its derived carbon materials. In this paper, the content of 15 metallic elements in HCTP and its four group components, including -heptane-soluble substance (HS), -heptane-insoluble-toluene-soluble substance (HI-TS), toluene-insoluble-quinoline-soluble substance (TI-QS), and quinoline-insoluble substance (QI), was determined.

Poloxamer sols endowed with in-situ gelability and mucoadhesion by adding hypromellose and hyaluronan for prolonging corneal retention and drug delivery.

The purpose of this study was to develop poloxamer (P407)-based in-situ thermogellable hydrogels with reducing concentration of P407 by adding hypromellose (HPMC) and with enhancing mucoadhesion of resulting hydrogels by adding hyaluronic acid (HA) for prolonging ocular delivery of hydroxypropyl-β-cyclodextrin (HPβCD)-solubilized testosterone (TES). Results demonstrated that 0.5% TES solution was successfully solubilized with adding 10% HPβCD.

Combined Docetaxel/Pictilisib-Loaded mPEGylated Nanocarriers with Dual HER2 Targeting Antibodies for Synergistic Chemotherapy of Breast Cancer.

Introduction: Approximately 15%~30% of breast cancers have gene amplification or overexpression of the human epidermal growth factor receptor 2 (HER2), resulting in the chemotherapy resistance, a more-aggressive phenotype and poor prognosis.

Methods: We propose a strategy of nanocarriers co-loaded with docetaxel (DTX) and pictilisib (PIC) at a synergistic ratio and non-covalently bound with dual anti-HER2 epitopes bispecific antibodies (BsAbs: anti-HER2-IV/methoxy-polyethylene glycol (mPEG) and anti-HER2-II/methoxy-PEG) for synergistic targeting to overcome the therapeutic dilemmas of the resistance for HER2-targetable chemodrugs. DTX/PIC-loaded nanocarriers (D/P_NCs) were prepared with single emulsion methods and characterized using dynamic light scattering analysis, and the drug content was assayed by high-performance liquid chromatographic method.

Topochemical synthesis of MnO/TiO and MnTiO/TiO nanocomposites as lithium-ion battery anodes with fast Li migration and giant pseudocapacitance the mesocrystalline effect.

Transition metal compounds are a promising substitute for graphite as lithium-ion battery (LIB) anodes. In this study, mesocrystalline MnO/TiO and MnTiO/TiO nanocomposites were synthesized using a layered titanic acid HTiO (HTO) precursor. The β-MnOOH layer is intercalated into the interlayer of HTO by Mn-exchange treatment of HO-intercalated HTO, which includes ion-exchange of Mn with H in the interlayer and oxidation of Mn to the β-MnOOH layer by HO in the interlayer space.

Bispecific T-cell engagers non-covalently decorated drug-loaded PEGylated nanocarriers for cancer immunochemotherapy.

Immunotherapy is blooming in recent years. However, this therapy needs to overcome off-target effects, cytokine release syndrome, and low responses in the 'cold' tumor environment. Herein, various combinations of immunotherapies and chemotherapies were proposed to transform 'cold' tumors into 'hot' tumors to enhance the efficacy of immunotherapies.

CPT11 with P-glycoprotein/CYP 3A4 dual-function inhibitor by self-nanoemulsifying nanoemulsion combined with gastroretentive technology to enhance the oral bioavailability and therapeutic efficacy against pancreatic adenocarcinomas.

Therapeutic efficacies of orally administrated hydrophobic chemodrugs are decreased by poor water solubilities and reduced oral bioavailabilities by P-glycoprotein (P-gp) and CYP450. In this study, CPT11 alone or combined with dual-function inhibitors (baicalein (BA) silymarin (SM), glycyrrhizic acid (GA), and glycyrrhetinic acid (GLA)) of P-gp and CYP450 loaded in a lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENP) to improve the solubility and inhibit the elimination by P-gp and CYP450. Results revealed that the LBSNENP composed of Capryol 90, lecithin/Tween 80/Cremophor EL, and propylene glycol at a weight ratio of 18:58:24 (designated PC90C10P0) was optimally selected.

Active Tumoral/Tumor Environmental Dual-Targeting by Non-Covalently Arming with Trispecific Antibodies or Dual-Bispecific Antibodies on Docetaxel-Loaded mPEGylated Nanocarriers to Enhance Chemotherapeutic Efficacy and Minimize Systemic Toxicity.

Purpose: This study was aimed at developing the trispecific antibodies (anti-EGFR/anti-FAP/anti-mPEG, TsAb) or dual bispecific antibodies (anti-EGFR/anti-mPEG and anti-FAP/anti-mPEG) docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micelles (mPEG-lsbPMs) for improving the targeting efficiency and therapeutic efficacy.

Methods: mPEG-lsbPMs were simply prepared via thin film method. The trispecific antibodies or bispecific antibodies bound the mPEG-lsbPMs by anti-mPEG Fab fragment.

Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity.

Ferroptosis, a form of regulated cell death triggered by lipid peroxidation, was recently identified as an important mechanism in radiotherapy (RT)-mediated tumor suppression and radioresistance, although the exact genetic contexts in which to target ferroptosis in RT remains to be defined. p53 is the most commonly mutated gene in human cancers and a major effector to RT. Here, we identify ferroptosis as a critical mechanism to mediate p53 function in tumor radiosensitivity.

mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation.

Glutathione peroxidase 4 (GPX4) utilizes glutathione (GSH) to detoxify lipid peroxidation and plays an essential role in inhibiting ferroptosis. As a selenoprotein, GPX4 protein synthesis is highly inefficient and energetically costly. How cells coordinate GPX4 synthesis with nutrient availability remains unclear.

H2A Monoubiquitination Links Glucose Availability to Epigenetic Regulation of the Endoplasmic Reticulum Stress Response and Cancer Cell Death.

Epigenetic regulation of gene transcription has been shown to coordinate with nutrient availability, yet the mechanisms underlying this coordination remain incompletely understood. Here, we show that glucose starvation suppresses histone 2A K119 monoubiquitination (H2Aub), a histone modification that correlates with gene repression. Glucose starvation suppressed H2Aub levels independently of energy stress-mediated AMP-activated protein kinase activation and possibly through NADPH depletion and subsequent inhibition of BMI1, an integral component of polycomb-repressive complex 1 (PRC1) that catalyzes H2Aub on chromatin.

Preparation and Characterization of a Novel Swellable and Floating Gastroretentive Drug Delivery System (sfGRDDS) for Enhanced Oral Bioavailability of Nilotinib.

Regarding compliance and minimization of side effects of nilotinib therapy, there is a medical need to have a gastroretentive drug delivery system (GRDDS) to enhance the oral bioavailability that is able to administer an optimal dose in a quaque die (QD) or daily manner. In this study, the influence on a swelling and floating () GRDDS composed of a polymeric excipient (HPMC 90SH 100K, HEC 250HHX, or PEO 7000K) and Kollidon SR was examined. Results demonstrated that PEO 7000K/Kollidon SR (P/K) at a 7/3 ratio was determined to be a basic GRDDS formulation with optimal swelling and floating abilities.

Stearyl polyethylenimine complexed with plasmids as the core of human serum albumin nanoparticles noncovalently bound to CRISPR/Cas9 plasmids or siRNA for disrupting or silencing PD-L1 expression for immunotherapy.

Purpose: In this study, a double emulsion method for complexing plasmids with stearyl poly-ethylenimine (PEI) as the core to form human serum albumin (HSA) (plasmid/PEI/HSA) nanoparticles (NPs) was developed for gene delivery by non-covalently binding onto plasmid/PEI/HSA nanoparticles with CRISPR/Cas9 or siRNA, which disrupts or silences the expression of programmed cell death ligand-1 (PD-L1) for immunotherapy.

Materials And Methods: Chemically synthesized stearyl-polyethyenimine (PEI)/plasmids/HSA nanoparticles were maded by double emulsion method. They were characterized by dynamic light scattering (DLS), transmission electron microscope and also evaluated by in vitro study on CT 26 cells.

MicroRNA-144-3p inhibits cell proliferation and induces cell apoptosis in prostate cancer by targeting CEP55.

Previous research reported that miR-144-3p functions as tumor suppressor in several tumors, including glioblastoma and hepatocelluar carcinoma, but the role of miR-144-3p in prostate cancer (PCa) remains unclear. In this study, we aimed to analyze the role of miR-144-3p in PCa. By RT-qPCR, we found that expression of miR-144-3p was markedly down-regulated in PCa tissues and cell lines compared with that in paired adjacent normal tissues and normal cell lines.

Collaborative Filtering Recommendation on Users' Interest Sequences.

As an important factor for improving recommendations, time information has been introduced to model users' dynamic preferences in many papers. However, the sequence of users' behaviour is rarely studied in recommender systems. Due to the users' unique behavior evolution patterns and personalized interest transitions among items, users' similarity in sequential dimension should be introduced to further distinguish users' preferences and interests.

Enhanced photoelectrocatalytic performance of α-Fe2O3 thin films by surface plasmon resonance of Au nanoparticles coupled with surface passivation by atom layer deposition of Al2O3.

The short lifetime of photogenerated charge carriers of hematite (α-Fe2O3) thin films strongly hindered the PEC performances. Herein, α-Fe2O3 thin films with surface nanowire were synthesized by electrodeposition and post annealing method for photoelectrocatalytic (PEC) water splitting. The thickness of the α-Fe2O3 films can be precisely controlled by adjusting the duration of the electrodeposition.

Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.

Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health and the current treatments for ESCC are frequently not effective. Recent epidemiological studies suggest that the anti-hyperglycemic agent metformin may reduce the risk of developing cancer, including ESCC, among diabetic patients. However, the antitumor effects of metformin on ESCC and the mechanisms underlying its cell cycle regulation remain elusive.

AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma.

AMP-activated protein kinase (AMPK) is a central metabolic sensor and plays an important role in regulating glucose, lipid and cholesterol metabolism. Therefore, AMPK is a key therapeutic target in diabetes. Recent pilot studies have suggested that diabetes drugs may reduce the risk of cancer by affecting the AMPK pathway.

Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells.

Hyperuricaemia is a disorder of purine metabolism, and is strongly associated with insulin resistance and abnormal glucose metabolism. As the producer of insulin, pancreatic β cells might be affected by elevated serum uric acid levels and contribute to the disregulated glucose metabolism. In this study, we investigated the effect of high uric acid on rat pancreatic β cell function.