Platelike carbon-encapsulated nickel nanocrystals for efficient electrooxidation of 5-hydroxymethylfurfural.

Platelike carbon-encapsulated nickel nanocrystals (Ni@C) were engineered as a high-performance electrocatalyst for the conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). This electrocatalyst demonstrated remarkable electrocatalytic performance in oxidizing HMF at a low potential, achieving 100% HMF conversion, 97.7% FDCA yield, and 97.4% Faraday efficiency (FE).

Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury.

Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

Photozyme-Catalyzed ATP Generation Based on ATP Synthase-Reconstituted Nanoarchitectonics.

We demonstrate that ATP synthase-reconstituted proteoliposome coatings on the surface of microcapsules can realize photozyme-catalyzed oxidative phosphorylation. The microcapsules were assembled through layer-by-layer deposition of semiconducting graphitic carbon nitride (g-C3N4) nanosheets and polyelectrolytes. It is found that electrons from polyelectrolytes are transferred to g-C3N4 nanosheets, which enhances the separation of photogenerated electron-hole pairs. Thus, the encapsulated g-C3N4 nanosheets as the photozyme accelerate oxidation of glucose into gluconic acid to yield protons under light illumination. The outward transmembrane proton gradient is established to drive ATP synthase to synthesize adenosine triphosphate. With such an assembled system, light-driven oxidative phosphorylation is achieved. This indicates that an assembled photozyme can be used for oxidative phosphorylation, which creates an unusual way for chemical-to-biological energy conversion. Compared to conventional oxidative phosphorylation systems, such an artificial design enables higher energy conversion efficiency.

A two-photon fluorescent probe for formaldehyde detection and regeneration in living cells.

A two-photon excited fluorescent probe CMB-1 has been rationally developed for the detection and regeneration of formaldehyde based on a novel nucleophilic addition of a secondary amine to FA and subsequential alcoholysis reactivity mechanism. It enables a specific turn-on response towards formaldehyde and facilitates the monitoring of exogenous and endogenous formaldehyde in living cells via both one- and two-photon microscopy, with minimal influence on its native homeostasis and local concentration.

Engineering Poly(ethylene glycol) Nanoparticles for Accelerated Blood Clearance Inhibition and Targeted Drug Delivery.

Surface modification with poly(ethylene glycol) (PEGylation) is an effective strategy to improve the colloidal stability of nanoparticles (NPs) and is often used to minimize cellular uptake and clearance of NPs by the immune system. However, PEGylation can also trigger the accelerated blood clearance (ABC) phenomenon, which is known to reduce the circulation time of PEGylated NPs. Herein, we report the engineering of stealth PEG NPs that can avoid the ABC phenomenon and, when modified with hyaluronic acid (HA), show specific cancer cell targeting and drug delivery. PEG NPs cross-linked with disulfide bonds are prepared by using zeolitic imidazolate framework-8 NPs as templates. The reported templating strategy enables the simultaneous removal of the template and formation of PEG NPs under mild conditions (pH 5.5 buffer). Compared to PEGylated liposomes, PEG NPs avoid the secretion of anti-PEG antibodies and the presence of anti-PEG IgM and IgG did not significantly accelerate the blood clearance of PEG NPs, indicating the inhibition of the ABC effect for the PEG NPs. Functionalization of the PEG NPs with HA affords PEG NPs that retain their stealth properties against macrophages, target CD44-expressed cancer cells and, when loaded with the anticancer drug doxorubicin, effectively inhibit tumor growth. The innovation of this study lies in the engineering of PEG NPs that can circumvent the ABC phenomenon and that can be functionalized for the improved and targeted delivery of drugs.

Confined microemulsion sono-polymerization of poly(ethylene glycol) nanoparticles for targeted delivery.

Confined sono-polymerization is developed to prepare poly(ethylene glycol) nanoparticles within water-in-oil microemulsion, followed by post-functionalization with a bispecific antibody (anti HER2 and anti PEG) for targeted delivery of photosensitizers (i.e., indocyanine green). The nanoparticles could specifically target to breast cancer cells (i.e., SKBR3) that overexpress HER2 receptors for the inhibition of cancer cell growth under 808 nm laser irradiation. This study highlights a facile and controllable method to fabricate therapeutic nanoparticles capable of targeted delivery.

Oxidation stability enhanced MXene-based porous materials derived from water-in-ionic liquid Pickering emulsions for wearable piezoresistive sensor and oil/water separation applications.

HYPOTHESIS: Stemming from their unique superiorities, Ti3C2-MXenes have emerged as versatile 2D materials for a myriad of appealing applications. However, two crucial issues are detrimental to maximize the inherent properties of MXenes for further specific developments, i.e. restacking problem and environmental instability. EXPERIMENTS: Herein, we develop an effective strategy, constructing water-in-ionic liquid (W/IL) Pickering emulsions with further polymerization of the continuous phase, to fabricate oxidation stability enhanced Ti3C2-MXene based porous materials. It is the first time to utilize a brand new platform between the immiscible IL and water for MXene nanosheets to assemble with guest species serving as building blocks for macromonoliths. FINDINGS: The prepared porous materials can provide elastic hollow-sphere structures derived from emulsion template, for wearable piezoresistive sensor with high sensitivity, excellent accuracy and favorable reproducibility. Intriguingly, ILs as dispersion and surface modification with polymeric ionic liquids (PILs) play indispensable roles in ameliorating oxidation stability of MXenes in porous materials, by virtue of quenching reactive oxygen species (ROS) and forming protective layer through the capping effect. Furthermore, the processed aerogels after supercritical drying can selectively absorb several organic solvents owing to their high hydrophobicity, abundant porosity and sufficient mechanical strength. All results indicate that the innovative strategy can simultaneously circumvent two major drawbacks of MXenes for the first time, and shed light on the opportunity to further enrich their practical applications by constructing multifunctional platform.

Patient selection for ambulatory laparoscopic cholecystectomy: A systematic review.

Background: Currently, there is no consensus on patient selection for ambulatory laparoscopic cholecystectomy (LC). This study is a systematic review of previously published patient selection for ambulatory LC. Methods: A comprehensive search was done in PubMed, Web of Science, Embase and Google Scholar Database up to March 2020 to summarise previously reported medical or surgical selection criteria used for inclusion and exclusion of patients, as well as successful same-day discharge rates and readmission rate after discharge. Results: Fifty-nine studies with a total of 13,219 patients were included in this systematic review. In total, the median same-day discharge rate was 90% (range: 63%-99.4%), and median readmission rate was 2.22% (range: 0%-16.9%). The most considered medical criteria were American Society of Anesthesiologists classification I and II, age <70, and body mass index <35. Surgical criteria varied greatly. The top three accessible exclusion variables were (1) common bile duct stones, cholangitis, or jaundice (27 publications, 45.8%); (2) history of abdominal surgery (12 publications, 20.3%) and (3) history of pancreatitis (9 publications, 15.3%). Conclusion: The results of the current study showed the variable patient selection in different centres, the medical aspect criteria may be expanded under adequate pre-anaesthetic assessment and preparation and the surgical aspect criteria should include more laboratory or imaging parameters to ensure the surgical safety.

Risk factors for patient selection in ambulatory laparoscopic cholecystectomy: A Single-centre experience.

Backgrounds: Ambulatory laparoscopic cholecystectomy (LC) reduces healthcare cost and increases hospital bed capacity. Currently, there is no consensus on patient selection for ambulatory LC. Evaluation of risk factors for ambulatory discharge is essential. Materials and Methods: Consecutive patients who underwent LC in our centre throughout 2019 were collected. We evaluated the discharge fitness using the Post-Anaesthetic Discharge Scoring System at 8 h after the operation. The relations between pre-operative variables and dischargeable possibilities were analysed for screening risk factors. Furthermore, we performed a literature review to summarise all published information. Results: Six hundred and forty-one cases were included in this study. American Society of Anaesthesiologist (ASA) grading (odds ratio OR = 0.415, P = 0.001) and leucocytes (OR = 0.80, P < 0.001) significantly predicted the fitness of discharge. ASA contributed to lower activity (P = 0.002) and intake/output (P = 0.006) scores. Leucocytes influence the vital sign (P < 0.001) and pain or post-operative nausea and vomiting (PONV) (P < 0.001) scores. The prolonged operation could predict the inabilities of discharge with a cut-off value of 55 min by dropping vital signs (P = 0.011), activity (P < 0.001) and pain or PONV (P = 0.012) scores. Male sex (OR: 1.702, P = 0.010), body mass index (BMI) (OR: 1.087, P = 0.008), leucocytes (OR: 1.075, P = 0.017) and C-reactive protein (CRP) (OR: 1.018, P = 0.003) were predictors for prolonged operation (>55 min). Conclusions: We suggest that pre-operative ASA grading III and leucocytes are risk factors for the fitness of ambulatory discharge after LC and intraoperative time. Male, BMI and CRP predict complicated surgery, and they should be considered preoperatively.

Hot Melt Super Glue: Multi-Recyclable Polyphenol-Based Supramolecular Adhesives.

The rapid and facile synthesis of hot melt super glue (HMSG) via the formation of adhesive supramolecular networks between catechol or pyrogallol hydroxyl groups (-OH) of polyphenols and repeat units (-CH2 CH2 O-) of poly(ethylene glycol) (PEG) based on hydrogen bonds is reported. The adhesion strength of HMSG, processed by heating-cooling of polyphenols and PEG without additional solvents, can be tuned up to 8.8 MPa via changing the molecular weight of PEG and the ratio of hydrogen bonding donors and receptors. The advantages of the reported HMSG lie in the ease and scalability of the assembly process, rapid adhesion on various substrates with excellent processability, resistance of low temperature and organic solvents, and recyclable adhesion strength. The solvent-free HMSG represents a promising adhesive supramolecular network to expand the versatility and application of polyphenol-based materials.

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma.

BACKGROUND: Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients. METHODS: Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567). RESULTS: The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells. CONCLUSIONS: In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. TRIAL REGISTRATION: DRKS00013567.

Photovoltaic Energy Conversion and Storage of Micro-Supercapacitors Based on Emulsion Self-Assembly of Upconverting Nanoparticles.

With the rapid need for new kinds of portable and wearable electronics, we must look to develop flexible, small-volume, and high-performance supercapacitors that can be easily produced and stored in a sustainable way. An integrated system simultaneously converting recyclable energy to electricity and storing energy is sought after. Here we report photovoltaic energy conversion and storage integrated micro-supercapacitors (MSCs) with asymmetric, flexible, and all-solid-state performances constructed from thousands of close-packed upconverting nanoparticles (UCNPs) via an emulsion-based self-assembly process using oleic acid (OA)-capped upconverting nanoparticles. The carbonated-UCNPs supraparticles (CSPs) are further coated with polypyrrole (PPy) to improve their electrochemical performance. Such a design can develop CSPs@PPy as electrode materials with high gravimetric capacitance, 308.6 F g-1 at 0.6 A g-1. The fabricated MSCs exhibit excellent areal capacitance, C s = 21.8 mF cm-2 at 0.36 A cm-2 and E = 0.00684 mWh cm-2, and have superior flexibility and cycling ability. The MSC devices have a sensitive near-infrared ray (NIR) photoelectrical response capability, which can capture the NIR of sunlight to convert it into electrical energy and store the electric energy due to an excellent capacitive performance. We propose a method for multifunctional integration of energy conversion and storage, and provide future research directions and potential applications of self-powered flexible wearable photonic electronics.

Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with an extremely poor prognosis. Minichromosome maintenance 8 homologous recombination repair factor (MCM8) is a helicase involved in the elongation step of DNA replication and tumorigenesis. In the present study, the clinical significance and biological function of MCM8 in CCA were investigated. The expression levels of MCM8 in CCA and paracancerous tissues were analyzed using immunohistochemical staining. The potential mechanisms underlying MCM8 and the biological effects of MCM8 in CCA cells were explored using in vitro assays and in vivo mouse xenograft models. The high expression levels of MCM8 in CCA has important clinical significance in predicting disease progression. Knockdown of MCM8 decreased proliferation, promoted apoptosis and suppressed migration of CCA cells. MCM8 knockdown also suppressed tumor growth in vivo. Mechanistically, MCM8 knockdown led to the abnormal downregulation of survivin, XIAP, HSP27, IGF­1sR, sTNF­R1, sTNF­R2, TNF­α and TNF­ß. Furthermore, downregulation of MCM8 expression inhibited the PI3K/Akt signaling pathway and induced the MAPK9 signaling pathway. MCM8 promoted the malignant progression of CCA, indicating that inhibition of MCM8 may have the potential to serve as a novel molecular targeted therapy.

Encapsulation of Enzymes in Metal-Phenolic Network Capsules for the Trigger of Intracellular Cascade Reactions.

Nanoengineered capsules encapsulated with functional cargos (e.g., enzymes) are of interest for various applications including catalysis, bioreactions, sensing, and drug delivery. Herein, we report a facile strategy to engineer enzyme-encapsulated metal-phenolic network (MPN) capsules using enzyme-loaded zeolitic imidazolate framework nanoparticles (ZIF-8 NPs) as templates, which can be removed in a mild condition (e.g., ethylenediaminetetraacetic acid (EDTA) solution). The capsule size (from 250 nm to 1 µm) and thickness (from 9.8 to 33.7 nm) are well controlled via varying the template size and coating time, respectively. Importantly, MPN capsules encapsulated with enzymes (i.e., glucose oxidase) can trigger the intracellular cascade reaction via the exhaustion of glucose to produce H2O2 and subsequently generate toxic hydroxyl radicals (•OH) based on the Fenton reaction via the reaction between H2O2 and iron ions in MPN coatings. The intracellular cascade reaction for the generation of •OH is efficient to inhibit cancer cell viability, which is promising for the application in chemodynamic therapy.

Sono-Fenton Chemistry Converts Phenol and Phenyl Derivatives into Polyphenols for Engineering Surface Coatings.

We report a sono-Fenton strategy to mediate the supramolecular assembly of metal-phenolic networks (MPNs) as substrate-independent coatings using phenol and phenyl derivatives as building blocks. The assembly process is initiated from the generation of hydroxyl radicals (. OH) using high-frequency ultrasound (412 kHz), while the metal ions synergistically participate in the production of additional . OH for hydroxylation/phenolation of phenol and phenyl derivatives via the Fenton reaction and also coordinate with the phenolic compounds for film formation. The coating strategy is applicable to various phenol and phenyl derivatives and different metal ions including FeII , FeIII , CuII , and CoII . In addition, the sono-Fenton strategy allows real-time control over the assembly process by turning the high-frequency ultrasound on or off. The properties of the building blocks are maintained in the formed films. This work provides an environmentally friendly and controllable method to expand the application of phenolic coatings for surface engineering.

The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis.

BACKGROUND: For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS). MATERIAL AND METHODS: A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3+, CD8+, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis. RESULTS: Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3+, CD8+, NK-cell infiltration predicted better survival (OS, DFS and RFS; p < 0.05). Higher Treg and Neutrophil infiltration predicted lower OS and DFS. For Macrophages and B cells no difference in survival could be found. DISCUSSION: As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.

Poly(ethylene glycol)-Mediated Assembly of Vaccine Particles to Improve Stability and Immunogenicity.

We report the one-step assembly of vaccine particles by encapsulating ovalbumin (OVA) and cytosine-phosphate-guanine oligodeoxynucleotides (CpG) into poly(ethylene glycol) (PEG)-mediated zeolitic imidazolate framework-8 nanoparticles (OVA-CpG@ZIF-8 NPs), where PEG improves the stability and dispersity of ZIF-8 NPs and the NPs protect the encapsulated OVA and CpG to circumvent the cold chain issue. Compared with free OVA and OVA-encapsulated ZIF-8 (OVA@ZIF-8) NPs, OVA-CpG@ZIF-8 NPs can enhance antigen uptake, cross-presentation, dendritic cell (DC) maturation, production of specific antibody and cytokines, and CD4+ T and CD8+ T cell activation. More importantly, the vaccine particles retain their bioactivity against enzymatic degradation, elevated temperatures, and long-term storage at ambient temperature. The study highlights the importance of PEG-mediated ZIF-8 NPs as a vaccine delivery system for the promising application of effective and cold chain-independent vaccination against diseases.

Amphiphilic Au Nanoclusters Modulated by Magnetic Gemini Surfactants as a Cysteine Chemosensor and an MRI Contrast Agent.

Cationic magnetic Gemini surfactants (mag-G-surfs), [C14H29(CH3)2N(CH2)2N(CH3)2C14H29]2+·2[XCl3Br]- (14-2-14·2X, X = Ce, Gd, or Ho), efficiently induce the aggregation of glutathione-protected Au nanoclusters (NCs) (GSH-Au NCs). These magnetic luminescent aggregates not only possess aggregation-induced emission (AIE) behavior but also display aggregation-induced magnetic enhancement. In particular, 14-2-14·2Ce and 14-2-14·2Gd have a better effect on boosting the luminescence intensity, quantum yield (QY), and luminescence lifetime (τ). The luminescent aggregates of GSH-Au NCs triggered by 14-2-14·2Gd or 14-2-14·2Ho exhibit more favorable paramagnetic behavior. Other Au NCs containing a Au(I)-thiolate complex shell also exhibit the obvious AIE phenomenon after introducing 14-2-14·2Gd, demonstrating the luminescence enhancement effect of mag-G-surfs. The luminescent aggregate 14-2-14·2Ce@GSH-Au NCs can serve as a "light up" fluorometric probe to detect cysteine selectively with the detection limit (DL) of 36 µM, and the magnetic luminescent aggregate 14-2-14·2Gd@GSH-Au NCs has the potential to be a novel contrast agent in T1-weighted magnetic resonance (MR) imaging due to its satisfactory contrasting ability.

Leukocytes infiltration correlates intratumoral microvessel density and influence overall and late-phase disease-free survival in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a severe type of primary liver cancer with high postoperative recurrence. The prognosis predictability of tumor-infiltrating leukocytes (TILs) for patients who underwent HCC resection has been widely reported. However, limited information is available about TIL trafficking, which is also crucial for HCC patients.We included tumor tissue samples and clinical data from 89 HCC patients in this study and performed immunohistochemistry for CD3, CD8, FoxP3, and CD31. TILs were measured using an algorithm for quantification of tumor immune stroma (QTiS). Intratumoral microvessels were counted using Weidner's method. We first examined correlations among them and analyzed their relationships with clinical and survival data.Intratumoral microvessel density (iMVD) was significantly correlated with infiltration of CD3+ (r = 0.338, P = .001) and CD8+ (r = 0.320, P = .002) cells, but not FoxP3+ (r = 0.153, P = .152) cells. After multivariate analysis, higher infiltration of CD3+ (P = .038) independently showed significant predictability on better overall survival after resection of HCC. Although no influence of CD3+ (P = .386) and CD8+ (P = .648) cells were found on general disease-free survival, infiltration of CD3+ (P = .012), tumor size (P = .032) and albumin (P = .007) cells independently predicted late-phase disease-free survival. No significant relationships regarding iMVD, and infiltration of FoxP3+ cells with overall and disease-free survival were found.Our data suggest that increased iMVD could enrich tumor-infiltrating CD3+ cells. Infiltrated CD3+ cells could help to better predict both the overall and late-phase disease-free survival after resection of HCC.