Self-Assembled DNA Microflowers for Platelet-Derived Extracellular Vesicle Isolation and Infected Wound Healing.

Platelet-derived extracellular vesicles (PEVs) showing great potential in wound healing have attracted increasing attention recently. Nondestructive isolation and effective utilization strategies are highly conducive for PEVs developing into recognized therapeutic entities. Here, we present an efficient strategy for PEV isolation and bacterial infected wound healing based on self-assembled DNA microflowers. First, DNA microflowers are prepared using rolling circle amplification. Then, the hydrophobic interaction between cholesteryl modified on DNA microflowers and the phospholipid bilayer membrane of PEVs leads to the formation of a network structure with improved mechanical strength and the separation of PEVs from biological samples. Finally, controlled release of PEVs is achieved through bacterial-induced hydrogel degradation. In vitro experiments demonstrate the obtained DNA hydrogel with good cytocompatibility and therapeutic potential. Taken together, the DNA microflower-based hydrogels with bioadhesive, self-healing, tunable mechanical properties and bacteria-responsive behavior offer substantial potential for EV isolation and wound healing.

Palladium-Catalyzed Defluorinative Coupling of Difluoroalkenes and Aryl Boronic Acids for Ketone Synthesis.

The transition-metal-catalyzed carbonylation reaction is a useful approach for ketone synthesis. However, it is often problematic to use exogenous carbonyl reagents, such as gaseous carbon monoxide. In this manuscript, we report a novel palladium-catalyzed coupling reaction of gem-difluoroalkenes and aryl boronic acids that yields bioactive indane-type ketones with an all-carbon α-quaternary center. Characterization and stoichiometric reactions of the key intermediates RCF2 PdII support a water-induced defluorination and cross-coupling cascade mechanism. The vinyl difluoromethylene motif serves as an in situ carbonyl precursor which is unprecedented in transition-metal-catalyzed coupling reactions. It is expected to raise broad research interest from the perspectives of ketone synthesis, fluoroalkene functionalization, and rational design of new synthetic protocols based on the unique reactivity of difluoroalkyl palladium(II) species.

Cyclo(RGD) peptide-decorated silver nanoparticles with anti-platelet potential for active platelet-rich thrombus targeting.

The development of integrated nanomedicine for prevention and early diagnosis of thrombosis is highly significant. Platelet plays a vital role in thrombotic disorders, offering an ideal target for thromboprophylaxis and imaging of thrombi. We herein fabricated cyclo(RGD) peptide-decorated AgNPs (designated cRGD-AgNPs) for active targeting platelet-rich thrombi. In vitro cytotoxicity and hemolysis assays demonstrated that cRGD-AgNPs have acceptable biocompatibility pattern. Both PEG-AgNPs (non-targeted version) and cRGD-AgNPs can inhibit agonist-mediated platelet aggregation, whereas the latter exhibited significant attenuation on platelet activation and adhesion onto collagen and fibrinogen matrix. Furthermore, the superior binding ability of cRGD-AgNPs with platelet-rich thrombus was demonstrated in static/dynamic condition in vitro. In vivo studies revealed that cRGD-AgNPs could actively target thrombi in a mouse model of carotid artery thrombi with favorable safety. Our results here suggest that cRGD-AgNPs with intrinsic anti-platelet potential might be promising nano theranostics for thromboprophylaxis and active thrombus targeting.

An Electrospun Scaffold Loaded with an Enteromorpha Polysaccharide for Accelerated Wound Healing in Diabetic Mice.

The design and development of innovative multifunctional wound dressing materials in engineered biomaterials is essential for promoting tissue repair. In this study, nanofibrous wound dressing materials loaded with anti-inflammatory ingredients were manufactured by a promising electrospinning strategy, and their capability for treating diabetic wounds was also investigated. A scaffold blend consisting of an Enteromorpha polysaccharide and polyvinyl alcohol (PVA) was fabricated. The in vitro and in vivo studies confirmed the efficacy of PVA/EPP1 fiber. We found that PVA/EPP1 fiber accelerated the repair of a full-thickness skin wound in diabetic mice. The results suggest that this scaffold could effectively shorten the wound healing time by inhibiting inflammatory activity, which makes it a promising candidate for the treatment of hard-to-heal wounds caused by diabetes.

The Role of FOXP3 on Tumor Metastasis and Its Interaction with Traditional Chinese Medicine.

Forkhead box protein 3 (FOXP3) is an important transcription factor for regulatory T cells (Tregs) and plays an important role in their immunosuppressive function. In recent years, studies have found that FOXP3 is expressed in many kinds of tumors and plays different roles in tumors' biological behaviors, including tumor proliferation, metastasis, drug resistance, and prognosis. However, the effects of FOXP3 on tumor metastasis and its interaction with traditional Chinese medicine (TCM) remain unclear. Therefore, in this review, we focus on the effects of FOXP3 on tumor metastasis and its relationship with TCM, which can provide evidence for further research and therapy in clinical settings.

Iron-Catalyzed Fluoroalkylation of Arylborates with Sulfone Reagents: Beyond the Limitation of Reduction Potential.

The iron-catalyzed alkyl-aryl coupling reaction between sulfones and arylboron compounds has remained a challenge. We report the first iron-catalyzed radical difluoroalkylation of arylborates with N-heteroaryl sulfones. The coordination between the iron catalyst and the nitrogen atom of N-heteroaryl sulfones was identified to be important in overcoming the reduction potential limitation of sulfones in the intermolecular single-electron-transfer process, which enables both fluoroalkyl N-heteroaryl sulfones (with relatively high reduction potentials) and nonfluorinated alkyl N-heteroaryl sulfones (with low reduction potentials) to serve as powerful alkylation reagents.

Fluoroalkylation of Various Nucleophiles with Fluoroalkyl Sulfones through a Single Electron Transfer Process.

The fluoroalkylation of various nucleophilic reagents with (phenylsulfonyl)difluoromethyl (PhSO2CF2)-substituted phenanthridines was achieved to give fluorinated phenanthridine derivatives, which enables the construction of both carbon-heteroatom and carbon-carbon bonds via the substitution of the phenylsulfonyl group. Mechanistic studies indicated that these reactions proceed through a unimolecular radical nucleophilic substitution (SRN1) mechanism. It is worthwhile noting that in the cases of O-nucleophiles ( t-BuO- and PhO-), the addition of t-BuOK/PhCHO could significantly promote the reactions, due to the in situ formation of a highly reactive electron donor species through the interaction of t-BuOK, PhCHO, and the solvent DMF, which can effectively initiate the single electron transfer process.

Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2-Pyridyl Sulfone.

We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C-S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the involvement of radical species in this iron-catalyzed difluoromethylation process.

Black Pigment Gallstone Inspired Platinum-Chelated Bilirubin Nanoparticles for Combined Photoacoustic Imaging and Photothermal Therapy of Cancers.

Bilirubin (BR), a bile pigment that exerts potent antioxidant and anti-inflammatory effects, is also a major constituent of black pigment gallstones found in bile ducts under certain pathological conditions. Inspired by the intrinsic metal-chelating power of BR found in gallstones, herein we report a cisplatin-chelated BR-based nanoparticle (cisPt@BRNP) for use as a new photonic nanomedicine for combined photoacoustic imaging and photothermal therapy of cancers. The cisPt@BRNPs were prepared by simply mixing cisplatin with BRNPs, yielding ca. 150-nm-size NPs. Upon near-IR laser irradiation at 808 nm, cisPt@BRNPs generated considerable heat and induced clear death of cancer cells in vitro. Following intravenous injection into human colon cancer-bearing mice, cisPt@BRNPs allowed effective tumor visualization by photoacoustic imaging and remarkable antitumor efficacy by photothermal therapy, suggesting their potential for use as a new photonic nanomedicine for cancer therapy.

Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide "on-demand" drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers.

Stereoselective nucleophilic fluoromethylation of aryl ketones: dynamic kinetic resolution of chiral α-fluoro carbanions.

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions.

Photodynamic black phosphorus nanosheets functionalized with polymyxin B for targeted ablation of drug-resistant mixed-species biofilms.

Biofilms, particularly those formed by multiple bacterial species, pose significant economic and environmental challenges, especially in the context of medical implants. Addressing the urgent need for effective treatment strategies that do not exacerbate drug resistance, we developed a novel nanoformulation, Ce6&PMb@BPN, based on black phosphorus nanosheets (BPN) for targeted treatment of mixed-species biofilms formed by Acinetobacter baumannii (A. baumannii) and methicillin-resistant Staphylococcus aureus (MRSA).The formulation leverages polymyxin B (PMb) for bacterial targeting and chlorin e6 (Ce6) for photodynamic action. Upon near-infrared (NIR) irradiation, Ce6&PMb@BPN efficiently eliminates biofilms by combining chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), reducing biofilm biomass significantly within 30 min. In vivo studies on mice infected with mixed-species biofilm-coated catheters demonstrated the formulation's potent antibacterial and biofilm ablation effects. Moreover, comprehensive biosafety evaluations confirmed the excellent biocompatibility of Ce6&PMb@BPN. Taken together, this intelligently designed nanoformulation holds potential for effectively treating biofilm-associated infections, addressing the urgent need for strategies to combat antibiotic-resistant biofilms, particularly mixed-species biofilm, in medical settings.

Photodynamic chitosan sponges with dual instant and enduring bactericidal potency for treating skin abscesses.

The emergence of multidrug-resistant (MDR) bacteria has made wound infection treatment difficult, calling for novel strategies for effective elimination of bacteria in wounds and promoting their recovery. Herein, we report a novel chitosan antibacterial sponge combining zinc oxide particles (ZnO) and the photosensitizer chlorin e6 (Ce6), named CS-ZnO/Ce6 sponge for combating multidrug-resistant bacteria and treating skin abscesses. The fabricated CS-ZnO/Ce6 sponge had porous structure with high porosity, conducive to absorbing the wound exudate. Meanwhile, the hemostatic property of this sponge enabled it to stop the continuous bleeding of the wound. Upon 660 nm light irradiation, the CS-ZnO/Ce6 sponge exhibited an instant photodynamic bactericidal effect against several typical MDR strains, and the presence of ZnO could continuously inhibit bacterial growth. In addition, local remedy of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice with CS-ZnO/Ce6 sponge with light irradiation caused a potent immediate bacterial killing effect and prolonged bacteriostasis in mice with skin abscesses, leading to the rapid recovery of the wound. The biocompatibility of the CS-ZnO/Ce6 sponge in mice was also verified by histological examination of the main organs. Collectively, the CS-ZnO/Ce6 sponge with broad-spectrum antibacterial activity and long-term bacterial inhibition potential could be useful for treating microbial infections and accelerating wound healing.

Physicochemical Properties and In Vivo Hepatoprotective Effect of Polysaccharides from Grape Pomace.

Here, the polysaccharides from grape pomace, a by-product in the wine industry, were characterized and evaluated in vitro and in vivo. The polysaccharides were extracted and studied using spectroscopic and chemical methods. The results revealed that GPPs are rich in arabinose, galactose and glucuronic acid and are heteropolysaccharides without protein and nucleic acid, containing α-glycoside bonds with irregular clusters on the surface. In vitro antioxidant activity assays indicated that GPPs have concentration-dependent antioxidant activity. In vivo, GPPs markedly decreased the levels of TNF-a, IL-6, ALT, AST and MDA in serum and liver tissues and restored the levels of SOD, CAT and GSH. Additionally, further histopathological examination confirmed that GPPs could mitigate the injury of liver induced by CCl4. Our results demonstrate that GPPs had antioxidant and hepatoprotective effects, and they are expected to be a potential ingredient for functional foods or hepatoprotective drugs.

Physicochemical characteristics and biological activities of grape polysaccharides collected from different cultivars.

In this study, four wine grape polysaccharides were extracted and optimized by using an efficient ultrasound-assisted extraction. A three-level, three-factor Box Behnken Design (BBD) combining with response surface methodology (RSM) was employed to optimize the extraction conditions including ultrasonic power, ultrasonic time and liquid-to-solid ratio. Furthermore, their physicochemical structures, antioxidant and liver protective activity were investigated and compared. Results revealed that the functional groups and monosaccharide compositions of these grape polysaccharides collected from different varieties were similar. Nevertheless, their molecular weights, molar ratios of monosaccharide compositions and surface morphological features were different. And the antioxidant activities of these polysaccharides were screened by free radical scavenging test. 'Beichun' (BC) and 'Benni fuji' (BF) polysaccharides possessed better antioxidant function. Further, the in vivo evaluation indicated that the polysaccharides of BC and BF have a protective effect against myocardial I/R injury in mice by inhibiting myocardial necroptosis mediated by mitochondrial ROS generation. Therefore, BC and BF grapes have potential applications in the medical and food industries.

Chloroplast-boosted photodynamic therapy for effective drug-resistant bacteria killing and biofilm ablation.

Due to the misuse of various antibiotics, the problem of bacterial resistance has become more serious worldwide, and the associated diseases have significantly increased the medical burden of society. Antimicrobial photodynamic therapy (PDT) has received widespread attention because of its safety, efficiency, and facile implementation. Here, we report an oxygen-supply antibacterial agent (Ce6@CS/CP), which could enhance the efficacy of antibacterial PDT via photosynthesis of O2. Ce6@CS/CP displayed a robust interaction with bacteria, hence facilitating the delivery efficiency of Ce6. In vitro experiments demonstrated that the photodynamic bactericidal potency of Ce6@CS/CP was remarkably greater than that of free Ce6. Furthermore, Ce6@CS/CP also exhibited superior significant antibiofilm activity to free Ce6. As a live oxygen-supply antibacterial agent, Ce6@CS/CP possesses excellent bacteria delivery ability of Ce6 and could enhance the potency of antibacterial PDT by photosynthesis, offering a new strategy for fighting against drug-resistant bacteria.

Comparison of physicochemical characteristics, antioxidant and immunomodulatory activities of polysaccharides from wine grapes.

In this study, an efficient ultrasonic-assisted extraction method was used for the extraction and optimization of four wine grape polysaccharides. A three-level, three-factor Box Behnken Design combined with the response surface approach was used to optimize the extraction conditions. Their physicochemical properties, molecular structure, antioxidant activity, immunomodulatory activity and hepatoprotective effects were examined and compared. These findings suggest that the four wine grape polysaccharides share similar basic structural features and monosaccharide composition. Furthermore, four wine grape polysaccharides exhibited antioxidant and immunomodulatory activities in a concentration-dependent manner. Moldova (MD) polysaccharide displayed better antioxidant activity and immunomodulatory ability. Furthermore, MD polysaccharide has a significant therapeutic effect on CCl4-induced rat liver injury by improving the antioxidant defense system and inhibiting oxidative stress, indicating that MD has a hepatoprotective effect. Taken together, the MD wine grape polysaccharide may have potential applications in prevention of liver disease in the functional food and pharmaceutical industries.

Photodynamic nano hydroxyapatite with biofilm penetration capability for dental plaque eradication and prevention of demineralization.

Dental caries represents one of the most prevalent diseases worldwide, characteristic of the growth of dental plaque and demineralization of tooth enamel. Current medications for eradication of dental plaques and prevention of demineralization suffer from several limitations to overcome, calling for novel strategies with great potency in eliminating cariogenic bacteria and dental plaque that forms, as well as in inhibiting the demineralization of enamel, into an integrated system. Considering the potency of photodynamic therapy in bacteria inactivation and the composition of enamel, we herein report that the novel photodynamic nano hydroxyapatite (nHAP), named Ce6 @QCS/nHAP, was useful for this purpose. Ce6 @QCS/nHAP, comprised of quaternary chitosan (QCS)-coated nHAP loaded with chlorin e6 (Ce6), exhibited good biocompatibility and non-compromised photodynamic activity. In vitro studies revealed that Ce6 @QCS/nHAP could effectively associate with cariogenic Streptococcus mutans (S. mutans), leading to a significant antibacterial effect through photodynamic killing and physical inactivation against the planktonic microbe. Three-dimensional fluorescence imaging suggested that Ce6 @QCS/nHAP exhibited a superior S. mutans biofilm penetration capacity to free Ce6, resulting in effective dental plaque eradiation when light irradiation was applied. The number of surviving bacteria in biofilm was at least 2.8 log units lower in the Ce6 @QCS/nHAP group compared to that in the free Ce6 group. Further, in the S. mutans biofilm-infected artificial tooth model, treatment with Ce6 @QCS/nHAP also resulted in the significant prevention of hydroxyapatite disks from demineralization, with lower percentage of fragmentation and weight loss These data suggest that our photodynamic nanosystem can effectively eradicate dental plaque while also significantly protecting artificial tooth from demineralization, opening up new possibilities in treating bacterium-associated dental caries.

Polydopamine-coated thalidomide nanocrystals promote DSS-induced murine colitis recovery through Macrophage M2 polarization together with the synergistic anti-inflammatory and anti-angiogenic effects.

High levels of proinflammatory cytokines, macrophage polarization status and immune-mediated angiogenesis play pivotal roles in the pathogenesis of inflammatory bowel disease (IBD). Thalidomide, an anti-inflammatory, immunomodulatory and antiangiogenic agent, is used off-label for treatment of IBD. The therapeutic potential of thalidomide is limited by its poor solubility and side effects associated with its systemic exposure. To address these issues and promote its therapeutic effects on IBD, thalidomide nanocrystals (Thali NCs) were prepared and coated with polydopamine (PDA), a potential macrophage polarization modulator, to form PDA coated Thali NCs (Thali@PDA). Thali@PDA possessed a high drug loading and displayed average particle size of 764.7 ± 50.30 nm. It showed a better anti-colitis effect than bare thalidomide nanocrystals at the same dose of thalidomide. Synergistic effects of polydopamine on anti-inflammatory and anti-angiogenic activities of thalidomide were observed. Furthermore, PDA coating could direct polarization of macrophages towards M2 phenotype, which boosted therapeutic effects of Thali@PDA on IBD. Upon repeated dosing of Thali@PDA for one week, symptoms of IBD in mice were significantly relieved, and histomorphology of the colitis colons were normalized. Key proinflammatory cytokine levels in the inflamed intestines were significantly decreased. Toxicity study also revealed that Thali@PDA is a safe formulation.

Development and validation of an artificial neural network model for non-invasive gastric cancer screening and diagnosis.

Non-invasive and cost-effective diagnosis of gastric cancer is essential to improve outcomes. Aim of the study was to establish a neural network model based on patient demographic data and serum biomarker panels to aid gastric cancer diagnosis. A total of 295 patients hospitalized in Nanjing Drum Tower hospital diagnosed with gastric cancer based on tissue biopsy, and 423 healthy volunteers were included in the study. Demographical information and tumor biomarkers were obtained from Hospital Information System (HIS) as original data. Pearson's correlation analysis was applied on 574 individuals' data (training set, 229 patients and 345 healthy volunteers) to analyze the relationship between each variable and the final diagnostic result. And independent sample t test was used to detect the differences of the variables. Finally, a neural network model based on 14 relevant variables was constructed. The model was tested on the validation set (144 individuals including 66 patients and 78 healthy volunteers). The predictive ability of the proposed model was compared with other common machine learning models including logistic regression and random forest. Tumor markers contributing significantly to gastric cancer screening included CA199, CA125, AFP, and CA242 were identified, which might be considered as important inspection items for gastric cancer screening. The accuracy of the model on validation set was 86.8% and the F1-score was 85.0%, which were better than the performance of other models under the same condition. A non-invasive and low-cost artificial neural network model was developed and proved to be a valuable tool to assist gastric cancer diagnosis.