Methoxyl-modulated high-performance ratiometric fluorescent probe with AIE properties for hypochlorite detection and live cell imaging.

In recent years, the mechanism concerning fluorescence can be modulated by intramolecular charge transfer (ICT) effect has been widely used in the creation of ratiometric fluorescent probes. However, on this basis, further studies on the structure-activity relationship between molecular constitution of probes and their photophysical characteristics, as well as sensing performance remained less comprehensive. In this work, with triphenylamine (TPA) and methylthio as typical fluorophore and recognition groups respectively, an ICT-based hypochlorite (ClO) fluorescent probe named Probe A was initially constructed, and then through ingenious molecular design, the second probe defined as Probe B was successfully prepared by introducing methoxyls as electron donors.

Quaternized antimicrobial peptide mimics based on harmane as potent anti-MRSA agents by multi-target mechanism covering cell wall, cell membrane and intracellular targets.

Infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA) seriously threatens public health. The design of antimicrobial peptide mimics (AMPMs) based on natural products (NPs) is a new strategy to kill MRSA and slow the development of drug resistance recently. Here, we reported the design and synthesis of novel AMPMs based on harmane skeleton.

An inulin-based glycovesicle for pathogen-targeted drug delivery to ameliorate salmonellosis.

The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study.

Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells.

The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico.

Analysis of Methylome, Transcriptome, and Lipid Metabolites to Understand the Molecular Abnormalities in Polycystic Ovary Syndrome.

Purpose: This study aimed to identify differentially methylated genes (DMGs) and differentially expressed genes (DEGs) to investigate new biomarkers for the diagnosis and treatment of polycystic ovary syndrome (PCOS).

Methods: To explore the potential biomarkers of PCOS diagnosis and treatment, we performed methyl-binding domain sequencing (MBD-seq) and RNA sequencing (RNA-seq) on ovarian granulosa cells (GCs) from PCOS patients and healthy controls. MBD-seq was also performed on the ovarian tissue of constructed prenatally androgenized (PNA) mice.

Hydrogen sulfide-sensitive Chitosan-SS-Levofloxacin micelles with a high drug content: Facile synthesis and targeted infection therapy.

The delivery system of antibiotics plays an important role in increasing the drug efficacy and reducing the risks of off-target toxicities and antibiotic resistance. The pathophysiology of bacterial infections is similar to that of tumor tissues, but only a few delivery systems have been able to target and release antibiotics on demand. Herein, we designed and developed a robust Chitosan-SS-Levofloxacin (CS-SS-LF) micelles for targeted antibiotic delivery, in which disulfide bond can be reduced by hydrogen sulfide (HS), a typical product of , and subsequently released antibiotic to eradicate infection.

Substance P&dimethyloxallyl glycine-loaded carboxymethyl chitosan/gelatin hydrogel for wound healing.

Recent efforts have focused on preparing drug-loaded hydrogel for wound healing. In order to obtain an ideal hydrogel dressing for skin wound repair, a carboxymethyl chitosan-gelatin hydrogel was prepared for co-delivery of SP (substance P) and DMOG (dimethyloxallyl glycine) by a chemical cross-linking method using genipin as the cross-linking agent. The synthesized hydrogels have good biocompatibility and physicochemical properties due to the low toxicity of the hydrogel material.

Encapsulation of in Hyaluronic Acid-Based Hydrogel for Pathogen-Targeted Delivery to Ameliorate Enteritis.

Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens. However, biological challenges encountered during oral delivery have greatly limited their potential health benefits. Here, a model probiotic () was encapsulated in an intestinal-targeted hydrogel to alleviate bacterial enteritis in a novel mode.

Hyaluronic acid-coated ZIF-8 for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital infection. Here, we showed that hyaluronic acid modified organic metal framework material ZIF-8 could be a Trojan horse of vancomycin (Van) for effective treatment of MRSA infections. The Van-loaded nanoparticles were readily up-taken by macrophages via a CD44-mediated process and collapsed in the acidic condition of endosome/lysosome, as a consequence, it could eradicate MRSA with high efficiency in macrophages.

Hyaluronic acid-based levofloxacin nanomicelles for nitric oxide-triggered drug delivery to treat bacterial infections.

Antibiotics are powerful weapons to fight against bacterial infections, while most of them lack of selective targeting towards pathological site which could restrict their antibacterial efficacy. To overcome this challenge, an antimicrobial levofloxacin(LF)was conjugated onto hyaluronic acid (HA) moieties via an o-phenylenediamine linker to prepare a NO-sensitive nanosystem (HA-NO-LF) in this study. The HA-NO-LF nanomicelles could enter host cells via a CD44 mediated endocytosis and release drug gradually upon exposure to endogenous NO.

Pathogen-targeting glycovesicles as a therapy for salmonellosis.

Antibiotic therapy is usually not recommended for salmonellosis, as it is associated with prolonged fecal carriage without reducing symptom duration or severity. Here we show that antibiotics encapsulated in hydrogen sulfide (HS)-responsive glycovesicles may be potentially useful for the treatment of salmonellosis. The antibiotics are released in the presence of Salmonella, which is known to produce HS.

Versatile Chlorin e6-based magnetic polydopamine nanoparticles for effectively capturing and killing MRSA.

Bacterial infections are a growing global challenge for public health as antibiotic resistance could cause the failure of anti-infective treatment eventually. So, it is urgent to develop new potential antibacterial materials. Herein, a multifunctional chitosan (CS) functionalized magnetic Chlorin e6 (CS-MP-Ce6) was constructed to combat methicillin-resistant Staphylococcus aureus (MRSA) infection by integrating bacterial conjugation and enrichment, and near-infrared (NIR)-triggered photodynamic sterilization.

Synergistic clearance of intracellular pathogens by hyaluronan-streptomycin micelles encapsulated with rapamycin.

Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize inside, which protects them from the attack by host immune system and antibiotics. A novel amphiphilic molecule was synthesized through conjugation of streptomycin and decylamine to hyaluronan. Rapamycin was encapsulted by the spontaneous self-assembly of hyaluronan-based amphiphilic molecules.

A photo-controlled hyaluronan-based drug delivery nanosystem for cancer therapy.

In this paper, a novel photo-controlled drug-loaded nanomicelles were self-assembled by the amphiphile of hyaluronan-o-nitrobenzyl-stearyl chain (HA-NB-SC) with doxorubicin (DOX) encapsulated within the hydrophobic core. DOX-loaded HA-NB-SC nanomicelles are ∼139 nm in diameter. CD44-overexpressed HeLa cells can easily take up HA-NB-SC micelles through recognition of HA moiety.

Light controllable chitosan micelles with ROS generation and essential oil release for the treatment of bacterial biofilm.

Bacterial biofilms are widely associated with persistent infections and food contamination. High resistance to conventional antimicrobial agents resulted in an urgent need for novel formulation to eliminate these bacterial communities. Herein we fabricated light controllable chitosan micelles loading with thymol (T-TCP) for elimination of biofilm.

Inulin based glutathione-responsive delivery system for colon cancer treatment.

Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells.

A tanshinone I derivative enhances the activities of antibiotics against Staphylococcus aureus in vitro and in vivo.

Infections caused by Staphylococcus aureus are prevalent. The dramatically reduced discovery of new antibiotics, as well as the persistent emergence of resistant bacteria, represents a major health problem in both hospital and community settings. Using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy.

N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids and derivatives: synthesis, evaluation as a class of novel analgesics, and 3D QSAR analysis.

Via a five-step-reaction procedure for the preparation of 19 known N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (6a-s) and successive removal of 9-(tetrahydropyran-2-yl) and benzylester groups 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (7a-s) and 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids (8a-s) were provided. On tail-flick mouse model the in vivo analgesic activities of these 38 novel compounds were measured and most of them were defined as good analgesics. Based on Molecular Field Analysis of the pain threshold variations of the mice receiving 48 compounds in terms of the descriptors proton and methyl an equation was established.