Electrocatalytic Hydrogenation of 5-Hydroxymethylfurfural Promoted by a Ru1 Cu Single-Atom Alloy Catalyst.

Electrochemical reduction of biomass-derived 5-hydroxymethylfurfural (HMF) represents an elegant route toward sustainable value-added chemicals production that circumvents the use of fossil fuel and hydrogen. However, the reaction efficiency is hampered by the high voltage and low activity of electrodes (Cu, Bi, Pb). Herein, we report a Ru1 Cu single-atom alloy (SAA) catalyst with isolated Ru atoms on Cu nanowires that exhibits an electrochemical reduction of HMF to 2,5-dihydroxymethylfuran (DHMF) with promoted productivity (0.47 vs. 0.08 mmol cm-2 h-1 ) and faradic efficiency (FE) (85.6 vs. 71.3 %) at -0.3 V (vs. RHE) compared with Cu counterpart. More importantly, the FE (87.5 %) is largely retained at high HMF concentration (100 mM). Kinetic studies by using combined electrochemical techniques suggest disparate mechanisms over Ru1 Cu and Cu, revealing that single-atom Ru promotes the dissociation of water to produce H* species that effectively react with HMF via an electrocatalytic hydrogenation (ECH) mechanism.

The effects of periodontitis associated microbiota on the development of oral squamous cell carcinoma.

Epidemiological data have shown that periodontal bacterial infection, periodontitis, and oral squamous cell carcinoma have close relationship on the disease progress and risk. However, the specific role of periodontal microbes and their mechanism in the development of oral squamous cell carcinoma is not yet clear. In our previous work, metagenomic Illumina Mi-seq analysis was used to identify tstructure and abundance of periodontital microbiome. Accoding to the results, we used Porphyromonas.spp. and Fusobacterium.spp. as the periodontitis positive microbiota; Neisseria.spp and Corynebacterium.spp as periodontitis negative microbiota (their average relative abundance were >5%). These representative strains of the above genus were used to infect OSCC cells to explore their effect on tumor cell biology behavior, and detect the expression level of the gene in related to inflammation, migration, invasion and cell cycle. We find that periodontitis positive correlated microbiota had a promoting effect on the development of oral squamous cell carcinoma in vitro by regulating mRNA and protein expression of IL-6, IL-8, MMP-9 and Cyclin-D1. Periodontitis negative correlated microbiota had suppression effect on the development of oral squamous cell carcinoma in vitro analysis.

Activation and Disproportionation of Zr2Fe Alloy as Hydrogen Storage Material.

As a hydrogen storage material, Zr2Fe alloy has many advantages such as fast hydrogen absorption speed, high tritium recovery efficiency, strong anti-pulverization ability, and difficulty self-igniting in air. Zr2Fe alloy has lower hydrogen absorption pressure at room temperature than LaNi5 alloy. Compared with the ZrVFe alloy, the hydrogen release temperature of Zr2Fe is lower so that the material can recover hydrogen isotopes at lower hydrogen concentration efficiently. Unfortunately, the main problem of Zr2Fe alloy in application is that a disproportionation reaction is easy to occur after hydrogen absorption at high temperature. At present, there is little research on the generation and influencing factors of a disproportionation reaction in Zr2Fe alloy. In this paper, the effects of temperature and hydrogen pressure on the disproportionation of Zr2Fe alloy were studied systematically. The specific activation conditions and experimental parameters for reducing alloy disproportionation are given, which provide a reference for the specific application of Zr2Fe alloy.

Formation of Twisted ß-Sheet Tapes from a Self-Complementary Peptide Based on Novel Pillararene-GCP Host-Guest Interaction with Gene Transfection Properties.

Small peptides capable of assembling into well-defined nanostructures have attracted extensive attention due to their interesting applications as biomaterials. This work reports the first example of a pillararene functionalized with a guanidiniocarbonyl pyrrole (GCP)-conjugated short peptide segment. The obtained amphiphilic peptide 1 spontaneously self-assembles into a supramolecular ß-sheet in aqueous solution based on host-guest interaction between pillararene and GCP unit as well as hydrogen-bonding between the peptide strands. Interestingly, peptide 1 at low concentration shows transitions from small particles to "pearl necklace" assemblies, and finally to branched fibers in a time-dependent process. At higher concentration, it directly assembles into twisted ß-sheet tapes. Notably, without pillararene moiety, the control peptide A forms α-helix structure with morphology changing from particles to bamboo-like assemblies depending on concentration, indicating a significant role of the pillararene-GCP host-guest interaction for the secondary structure formation. Moreover, peptide 1 can serve as an efficient gene transfection vector.

Taxonomic and Functional Analyses of the Supragingival Microbiome from Caries-Affected and Caries-Free Hosts.

Caries is one of the most prevalent and costly infectious diseases affecting humans of all ages. It is initiated by cariogenic supragingival dental plaques forming on saliva-coated tooth surfaces, yet the etiology remains elusive. To determine which microbial populations may predispose a patient to caries, we report here an in-depth and comprehensive view of the microbial community associated with supragingival dental plaque collected from the healthy teeth of caries patients and healthy adults. We found that microbial communities from caries patients had a higher evenness and inter-individual variations but simpler ecological networks compared to healthy controls despite the overall taxonomic structure being similar. Genera including Selenomonas, Treponema, Atopobium, and Bergeriella were distributed differently between the caries and healthy groups with disturbed co-occurrence patterns. In addition, caries and healthy subjects carried different Treponema, Atopobium, and Prevotella species. Moreover, distinct populations of 13 function genes involved in organic acid synthesis, glycan biosynthesis, complex carbohydrate degradation, amino acid synthesis and metabolism, purine and pyrimidine metabolism, isoprenoid biosynthesis, lipid metabolism, and co-factor biosynthesis were present in each of the healthy and caries groups. Our results suggested that the fundamental differences in dental plaque ecology partially explained the patients' susceptibility to caries, and could be used for caries risk prediction in the future.

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells.

Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe3O4 NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe3O4 nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM.

Curcumin attenuates opioid tolerance and dependence by inhibiting Ca2+/calmodulin-dependent protein kinase II α activity.

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug's poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1-10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity.

Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion.

The homotypic fusion of endoplasmic reticulum (ER) membranes is mediated by atlastin (ATL), which consists of an N-terminal cytosolic domain containing a GTPase module and a three-helix bundle followed by two transmembrane (TM) segments and a C-terminal tail (CT). Fusion depends on a GTP hydrolysis-induced conformational change in the cytosolic domain. Here, we show that the CT and TM segments also are required for efficient fusion and provide insight into their mechanistic roles. The essential feature of the CT is a conserved amphipathic helix. A synthetic peptide corresponding to the helix, but not to unrelated amphipathic helices, can act in trans to restore the fusion activity of tailless ATL. The CT promotes vesicle fusion by interacting directly with and perturbing the lipid bilayer without causing significant lysis. The TM segments do not serve as mere membrane anchors for the cytosolic domain but rather mediate the formation of ATL oligomers. Point mutations in either the C-terminal helix or the TMs impair ATL's ability to generate and maintain ER morphology in vivo. Our results suggest that protein-lipid and protein-protein interactions within the membrane cooperate with the conformational change of the cytosolic domain to achieve homotypic ER membrane fusion.

Synthesis of Mono-PEGylated Growth Hormone Releasing Peptide-2 and Investigation of its Biological Activity.

The purpose of this study was to investigate an efficient synthetic route to the mono-PEGylated growth hormone releasing peptide-2 (GHRP-2) and its biological activity in vivo. The commercially available key PEGylating reagent, mPEG-NHS ester, was successfully utilized to the synthesis of mono-PEGylated GHRP-2, during which the PEGylation profiles of GHRP-2 were monitored by high-performance liquid chromatography (HPLC). The product was purified by cation exchange chromatography, and its biological activity was conducted in rats. The desired mono-PEGylated GHRP-2 as the major product was readily obtained in anhydrous aprotic solvent, such as dimethyl formamide (DMF) and dimethylsulfoxide (DMSO), when the molar ratio of mPEG-NHS ester to GHRP-2 was fixed to be 0.8:1. The products were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The evaluation of the biological activity for the products showed that the mono-PEGylated GHRP-2 gave a more stable activity than GHRP-2, suggesting that PEGylation led to the increase in the half-life of GHRP-2 in plasma without greatly impairing the biological activity. PEGylation of the GHRP-2 is a good choice for the development of the GHRP-2 applications.

Hyaluronan degradation by HYAL2 is essential for odontoblastic differentiation and migration of mouse dental papilla cells.

The coordination between odontoblastic differentiation and directed cell migration of mesenchymal progenitors is necessary for regular dentin formation. The synthesis and degradation of hyaluronan (HA) in the extracellular matrix create a permissive niche that directly regulates cell behaviors. However, the role and mechanisms of HA degradation in dentin formation remain unknown. In this work, we present that HA digestion promotes odontoblastic differentiation and cell migration of mouse dental papilla cells (mDPCs). Hyaluronidase 2 (HYAL2) is responsible for promoting odontoblastic differentiation through degrading HA, while hyaluronidase 1 (HYAL1) exhibits negligible effect. Silencing Hyal2 generates an extracellular environment rich in HA, which attenuates F-actin and filopodium formation and in turn inhibits cell migration of mDPCs. In addition, activating PI3K/Akt signaling significantly rescues the effects of HA accumulation on cytodifferentiation. Taken together, the results confirm the contribution of HYAL2 to HA degradation in dentinogenesis and uncover the mechanism of the HYAL2-mediated HA degradation in regulating the odontoblastic differentiation and migration of mDPCs.

Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.

We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality.

Enhancing bowel preparation quality and tolerability in a low health literacy population in Western China: a multicenter randomized trial.

BACKGROUND AND AIMS: Insufficient bowel preparation (BP) presents substantial challenges to the effectiveness of outpatient colonoscopy for colorectal cancer screening, particularly within populations characterized by low health literacy and poor adherence. METHODS: We conducted a prospective, randomized, blinded, endoscopic controlled study involving 474 colonoscopy outpatients aged 18-80 years hailing from a low health literacy population with convenient access to WeChat. These patients were subsequently randomized into three groups: the control group, WeChat group, and the automatic reminder group (ARG). All people were administered 3 L of polyethylene glycol. The Boston Bowel Preparation Scale (BBPS) score of 6 or a segmental score of 2 was used as the primary outcome to evaluate BP quality. Secondary outcomes included polyp detection rate (PDR) and adverse events, etc. RESULTS: Our findings revealed that both the WeChat group (n = 158) and ARG (n = 158) exhibited significantly higher rates of adequate BP compared to the control group (n = 158) (WeChat vs. control, 79.1% vs. 61.4%; ARG vs. control, 74.7% vs. 61.4%; p < 0.001). Furthermore, these educationally reinforced groups displayed improved BP compliance (p < 0.05). According to the Hospital Anxiety and Depression Scale (HADS), patients in the reinforced education groups exhibited lower overall anxiety levels (p = 0.001) and experienced fewer adverse reactions (p = 0.019). Compared to the control group, the PDR in the right hemi-colon was significantly greater in the WeChat group (11.4%) (2.5%), and a similar trend was observed in the ARG (7.6%). Additionally, individuals in the WeChat group reported higher levels of satisfaction with their colonoscopy experience (p = 0.043). In a multivariate analysis, adjusting for potential confounding factors, WeChat-based re-education ([OR] 1.496, 95% CI 1.154-1.939; p = 0.002)) emerged as a protective factor for achieving adequate BP. CONCLUSION: Enhanced education through WeChat can improve BP quality, and ARG applies equally to low health literacy populations.

A Protein-Like Nanogel for Spinning Hierarchically Structured Artificial Spider Silk.

Spider dragline silk is draw-spun from soluble, ß-sheet-crosslinked spidroin in aqueous solution. This spider silk has an excellent combination of strength and toughness, which originates from the hierarchical structure containing ß-sheet crosslinking points, spiral nanoassemblies, a rigid sheath, and a soft core. Inspired by the spidroin structure and spider spinning process, a soluble and crosslinked nanogel is prepared and crosslinked fibers are drew spun with spider-silk-like hierarchical structures containing cross-links, aligned nanoassemblies, and sheath-core structures. Introducing nucleation seeds in the nanogel solution, and applying prestretch and a spiral architecture in the nanogel fiber, further tunes the alignment and assembly of the polymer chains, and enhances the breaking strength (1.27 GPa) and toughness (383 MJ m-3 ) to approach those of the best dragline silk. Theoretical modeling provides understanding for the dependence of the fiber's spinning capacity on the nanogel size. This work provides a new strategy for the direct spinning of tough fiber materials.

Non-leaching antibacterial cellulose triacetate reverse osmosis membrane via covalent immobilization of quaternary ammonium cations.

A novel procedure to fabricate quaternized cellulose triacetate reverse osmosis (QCTA-RO) membranes via the etherification procedure between partially hydrolyzed CTA-RO membrane and 3-chloro-2-hydroxypropyl-trimethyl ammonium chloride (CHPTAC) in alkaline solutions (pH=9-11) for different reaction time (1, 2, 3 and 4h) was proposed. The structure and performances of the obtained QCTA-RO membranes were characterized and their antibacterial performances against E. coli and S. aureus were evaluated through colony counting method. The results showed that quaternary amine group was successfully grafted on the surface of membrane via covalently bond without significant damage to morphology, mechanical performance and thermal stability. The permeation flux values increased with prolonging modification time to 3h, while the salt rejection decreased slightly but remained above 92%. QCTA-RO membranes displayed good antibacterial activity against Gram-negative E. coli and Gram-positive S. aureus and their bactericidal rates were 78.7-89.0% and 64.7-76.6% respectively at the optimized modification time of 2-3h.

PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

Near-Infrared-Triggered Azobenzene-Liposome/Upconversion Nanoparticle Hybrid Vesicles for Remotely Controlled Drug Delivery to Overcome Cancer Multidrug Resistance.

Overcoming multidrug resistance is achieved by developing a novel drugdelivery-system paradigm based on azobenzene liposome and phosphatidylcholine-modified upconversion nanoparticle (UCNP) hybrid vesicles for controlled drug release using a nearinfrared (NIR) laser. Upon 980 nm light irradiation, the reversible photoisomerization of the azobenzene derivatives by simultaneous UV and visible light emitted from the UCNPs makes it possible to realize NIR-triggered release of the chemotherapeutic drug doxorubicin.

[Analysis of causes and whole microbial structure in a case of rampant caries].

OBJECTIVE: To analyze the whole microbial structure in a case of rampant caries to provide evidence for its prevention and treatment. METHODS: Clinical samples including blood, supragingival plaque, plaque in the caries cavity, saliva, and mucosal swabs were collected with the patient's consent. The blood sample was sent for routine immune test, and the others samples were stained using Gram method and cultured for identifying colonies and 16S rRNA sequencing. DNA was extracted from the samples and tested for the main cariogenic bacterium (Streptococcus mutans) with qPCR, and the whole microbial structure was analyzed using DGGE. RESULTS: The patient had a high levels of IgE and segmented neutrophils in his blood. Streptococci with extremely long chains were found in the saliva samples under microscope. Culture of the samples revealed the highest bacterial concentration in the saliva. The relative content of hemolytic bacterium was detected in the samples, the highest in the caries cavity; C. albicans was the highest in the dental plaque. In addition, 33 bacterial colonies were identified by VITEK system and 16S rDNA sequence phylogenetic analysis, and among them streptococci and Leptotrichia wade were enriched in the dental plaque sample, Streptococcus mutans, Fusobacterium nucleatum, and Streptococcus tigurinus in the caries cavity, and Lactobacillus in the saliva. S. mutans was significantly abundant in the mucosal swabs, saliva and plaque samples of the caries cavity as shown by qPCR. Compared to samples collected from a healthy individual and another two patients with rampant caries, the samples from this case showed a decreased bacterial diversity and increased bacterial abundance shown by PCR-DGGE profiling, and multiple Leptotrichia sp. were detected by gel sequencing. CONCLUSION: The outgrowth of such pathogenic microorganisms as S. mutans and Leptotrichia sp., and dysbiosis of oral microbial community might contribute to the pathogenesis of rampant caries in this case.

FRET-capable supramolecular polymers based on a BODIPY-bridged pillar[5]arene dimer with BODIPY guests for mimicking the light-harvesting system of natural photosynthesis.

AA/BB-type and A2/B3-type FRET-capable supramolecular polymers based on a BODIPY-bridged pillar[5]arene dimer and two BODIPY derivative guests have been successfully constructed and their application in mimicking the light-harvesting system of natural photosynthesis was studied.

Monte Carlo simulation of pore blocking phenomena in cross-flow microfiltration.

An off-lattice Monte Carlo method was developed to examine the pore blocking phenomena in cross-flow microfiltration. Membranes were generated by randomly distributed pores with a given pore size distribution on a two-dimensional plane. The permeability of particles through the membrane pores was calculated, and the effects of crucial factors on the reduction of permeability were discussed. Reasonable fouling rules for simulations were examined and selected. At the initial stage the flux decreases sharply as the filtration time increases and then a steady state is reached. The results fit the pore blocking mechanism well. The simulation model developed in this study can be effectively used for analyzing a number of factors influencing physical fouling of membranes.

Survey of phthalate pollution in arable soils in China.

The problem of pollution by phthalates is of global concern due to their widespread occurrence, toxicity and endocrine disruption properties. The contamination by phthalates such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) in 23 arable soils throughout China was investigated to evaluate the present pollution situation. The survey results demonstrated that phthalates were ubiquitous pollutants in soils in China. The total concentrations of phthalates differed from one location to another, and ranged from 0.89 to 10.03 mg kg(-1) with a median concentration of 3.43 mg kg(-1). Among the phthalates, DEHP was dominant and detected in all 23 soils. DEP and DBP were also in abundance, and DMP was rarely detected. Similar contamination patterns were observed in all 23 soils. A distinct feature of phthalate pollution in China was that the average concentration in northern China was higher than that in southern China. In addition, a close relationship was observed between the concentration of phthalates in soils and the consumption of agricultural film. The correlation showed that the application of agriculture film might be a significant pollution source of phthalates in arable soils of China. The potential risk of phthalates in soils was assessed on the basis of current guide values and limits.