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Microfluidics is characterized by the manipulation of fluids in submillimeter channels and has great application potential in encapsulation. To further extend the application of microfluidics in food industries, a 3D printed microfluidic device is used to encapsulate vitamin A and improve its stability. Two natural macromolecules, sodium alginate and gelatin, are added to water as the continuous phase to generate monodisperse emulsion. Under different flow rate ratios, the diameter of droplets decreases with the increase of continuous flow rate. However, at the same flow rate ratio, varying the dispersed and continuous flow rates does not significantly change the diameter and size distribution of emulsion collected. The prepared O/W (oil/water) single emulsion can form microgel particles and avoid degradation of vitamin A by simulated gastric acid; the encapsulated vitamin A will not be released until particles reach simulated intestinal tract. In the simulated digestion in vitro, no vitamin A is released for 2 h in the acidic environment; under an alkaline or neutral environment such as those in intestinal fluids, vitamin A can be released from the microgel particles within 2.5 h. Using the presented approach, emulsions encapsulating vitamin A have been prepared and can potentially be applied to encapsulate other oil-soluble substances in the food industry.

Human immunodeficiency virus type 1 (HIV-1) infection remains one of the worst crises in global health. The prevention of HIV-1 infection is a crucial task that needs to be addressed due to the absence of a licensed vaccine against HIV-1. DNA vaccines present a promising alternative approach to combat HIV-1 infection due to their excellent safety profile, lack of severe side effects, and relatively rapid fabrication. Traditional vaccines composed of a monomeric envelope or peptide fragments have been indicated to lack protective efficacy mediated by inducing HIV-1-specific neutralizing antibodies in clinical trials. The immunogenicity and protection against HIV-1 induced by DNA vaccines are limited due to the poor uptake of these vaccines by antigen-presenting cells and their ready degradation by DNases and lysosomes. To address these issues of naked DNA vaccines, we described the feasibility of CpG-functionalized silica-coated calcium phosphate nanoparticles (SCPs) for efficiently delivering DNA-based HIV-1 trimeric envelope vaccines against HIV-1. Vaccines comprising the soluble BG505 SOSIP.664 trimer fused to the GCN4-based isoleucine zipper or bacteriophage T4 fibritin foldon motif with excellent simulation of the native HIV-1 envelope were chosen as trimer-based vaccine platforms. Our results showed that SCP-based DNA immunization could significantly induce both broad humoral immune responses and potent cellular immune responses compared to naked DNA vaccination in vivo. To the best of our knowledge, this study is the first to assess the feasibility of CpG-functionalized SCPs for efficiently delivering DNA vaccines expressing a native-like HIV-1 trimer. These CpG-functionalized SCPs for delivering DNA-based HIV-1 trimeric envelope vaccines may lead to the development of promising vaccine candidates against HIV-1.

Hydrogen fuel cells are among the promising energy sources worldwide, which could accomplish cyclic production of energy and avoid the emission of green-house or contaminative byproducts. However, sulfur compounds (SCs) even at trace level (nmol/mol) are usually involved in cell construction and further H2 production, which would cause degradation of the catalysts and shorten the lifetime of the fuel cells. Moreover, the highly reactive SCs could cause varied species and concentrations of them in complex matrices, so online rather than offline analysis of SCs in H2 would be preferred. In this context, we developed a new system combining online cryogenic preconcentration of nine SCs and subsequent determination by GC-SCD (sulfur chemiluminescent detector), with the correlation coefficients of the calibration curves higher than 0.999, calculated limits of detection no higher than 0.050 nmol/mol, analytical time around 30 min per sample, and satisfactory precision and accuracy (RSD

Electrosynthesis has received great attention among researchers in both academia and industry as an ideal technique to promote single electron reduction without the use of expensive catalysts. In this work, we report the electrochemical reduction of Katritzky salts to alkyl radicals by sacrificing the easily accessible metal anode. This catalyst and electrolyte free platform has broad applicability to single electron transfer chemistry, including fluoroalkenylation, alkynylation and thiolation. The deaminative functionalization is facilitated by the rapid molecular diffusion across microfluidic channels, demonstrating the practicality that outpaces the conventional electrochemistry setups., Electrochemical transformations use electrons and electron holes instead of chemical oxidants and reductants as reagents. Here, the authors report an electrochemical reductive deaminative cross-coupling of Katrizky salts with various radical acceptors, including examples of fluoroalkenylation, alkynylation and thiolation.

Crystalline covalent organic frameworks (COFs) are porous polymeric semiconductors with network topologies, which are built from the integration of selected organic blocks with covalent bond linkages. They have shown great promise for artificial photosynthesis, owing to broad light harvesting, high crystallinity, and high carrier mobility. This Minireview introduces state-of-the-art COF photocatalysts based on different linkages and discusses the origin of photocatalytic activities for hydrogen evolution. Three typical COF photocatalysts, with linkages including imine (-C=N-), β-ketoenamine (O=C-C=C-NH-), and vinylene (-C=C-), are discussed with a particular focus on the advancements in synthetic methodologies and structural design, as well as photoelectronic properties that are relevant to photocatalytic performance. The Minireview is expected to elucidate their structure-property relationships and the way to design photoactive COFs with enhanced performances.

This work describes a general strategy for metal-catalyzed cross-coupling of fluoroalkyl radicals with aryl halides under electrochemical conditions. The contradiction between anodic oxidation of fluoroalkyl sulfinates and cathodic reduction of low-valent nickel catalysts can be well addressed by paired electrolysis, allowing for direct introduction of fluorinated functionalities into aromatic systems.

N-Dealkylation of amines by metal oxo intermediates (M Created by potrace 1.16, written by Peter Selinger 2001-2019 O) is related to drug detoxification and DNA repair in biological systems. In this study, we report the first example of N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex induced by visible light., The visible light-induced N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex has been investigated. We provide definitive evidence that these reactions occur via an ET/PT mechanism.

Background Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) and LABAs plus inhaled corticosteroids (ICS) for COPD, uncertainty remains regarding their comparative effects. Research Question Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD? Study Design and Methods We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vs three commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively. Results Patients with COPD initiating IND/GLY and VI/UMEC showed an 11% (incidence rate ratio [IRR], 0.89; 95% CI, 0.80-0.98) and 20% (IRR, 0.80; 95% CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vs FF/BDP, were associated with a 27% (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90) to 42% (HR, 0.58; 95% CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs. Interpretation Both LABA/LAMAs vs SAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

This work describes an electrochemically promoted nickel-catalyzed deoxygenative thiolation of alcohols and ketones under mild conditions. Excellent substrate tolerance and good chemical yields can be achieved by graphene/nickel foam electrodes in an undivided cell. Further study to gain mechanistic insight into this electrochemical cross-coupling has been carried out.

The main characteristic of skin aging is the change in the composition of the dermis, mainly resulting from fibroblast senescence. Mesenchymal stem cells derived from fetal dermis are defined as fetal dermal mesenchymal stem cells; they reportedly exert wound healing effects on the skin and regulate keloid fibroblast proliferation. D-Galactose is widely used in animal aging models. In this study, we confirmed that D-galactose inhibits adult dermal fibroblast proliferation, and the inhibitory effect gradually increased with increasing concentration. Finally, we chose a concentration of 40 g/L D-galactose to induce adult dermal fibroblast senescence. D-Galactose increased the intensity of senescence-associated β-galactosidase staining and the levels of reactive oxygen species in adult dermal fibroblasts. Furthermore, D-galactose increased the mRNA expression of p16, p21, and p53. The fetal dermal mesenchymal stem cell-conditioned medium improved the above-mentioned effects. Overall, fetal dermal mesenchymal stem cells exerted anti-aging effects against adult dermal fibroblasts induced by D-galactose via paracrine functions.

Fracture-type buried-hill reservoirs refer to dual media which have a fast breakthrough speed and a low sweep efficiency in the process of gas injection displacement. In order to overcome this problem, in this paper, a new profile control and oil displacement technology of pre-slug deep plugging by injection of different levels of nano-microspheres and natural gas was proposed. The mercury intrusion experiments were used to compare the fractal characteristics of the pore structures of the matrix and artificial fractured cores in the buried-hill reservoir. The results show that the heterogeneous characteristics of pores and fractures are the main factors leading to excessive gas breakthrough. Three nano-microsphere systems (WJ1, WJ2, and WJ3) with good temperature resistance, salt resistance, swelling properties, and stability were prepared using the inverse emulsion method. Core plugging performance tests show that WJ3 has the best plugging effect among the three nano-microsphere systems, followed by WJ2 and WJ1. According to the scanning electron microscopy observations, it was found that the sealing mechanism of nano-microspheres includes direct sealing, bridging sealing, adhesive sealing, direct pass, deformed pass, and crushing pass. Finally, the displacement experiments with a composite fractured core showed that compared with pure natural gas injection, the breakthrough time of the combined displacement process of nano-microspheres and natural gas was greatly extended, and the final oil displacement efficiency was increased to greater than 80%.

Highly sensitive and rapid detection of chloramphenicol antibiotics (CAPs) in aquatic products via lateral flow immunoassay (LFA) strips remains challenging. This study developed a surface-enhanced Raman scattering (SERS)–based LFA strip for ultrasensitive analysis of CAPs by using noble metal nanoparticles (NPs). A kind of core–shell Au@Ag NPs were employed to prepare SERS tags considering the stability and repeatability. In order to obtain higher stability and repeatability, we designed antibody-modified gold@silver core–shell nanoparticles (Au@Ag NPs) as SERS nanotags for quantitative Raman detection of the target in the LFA strip. Results showed that SERS-based LFA strip allowed quantified analysis of chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FFC) with the limits of detection of 0.36 ng/mL, 0.20 ng/mL, and 0.78 ng/mL, respectively. Furthermore, SERS-based LFA strip exhibited favorable sensitivity (IC50 values of CAP, TAP, and FFC were 12.94 ng/mL, 8.76 ng/mL, and 12.22 ng/mL, respectively). This SERS-based LFA strip was finally applied in the detection of CAP in chub and the recovery was 91.5 to 106.4%. This SERS-based LFA strip could be used as an effective tool for detecting CAPs in aquatic products.

The novel coronavirus (COVID-19) infections have adopted the shape of a global pandemic now, demanding an urgent vaccine design. The current work reports contriving an anti-coronavirus peptide scanner tool to discern anti-coronavirus targets in the embodiment of peptides. The proffered CoronaPep tool features the fast fingerprinting of the anti-coronavirus target serving supreme prominence in the current bioinformatics research. The anti-coronavirus target protein sequences reported from the current outbreak are scanned against the anti-coronavirus target data-sets via CORONAPEP which provides precision-based anti-coronavirus peptides. This tool is specifically for the coronavirus data, which can predict peptides from the whole genome, or a gene or protein's list. Besides it is relatively fast, accurate, userfriendly and can generate maximum output from the limited information. The availability of tools like CORONAPEP will immeasurably perquisite researchers in the discipline of oncology and structure-based drug design.

The current approaches remain insufficient for measuring chicken egg spoilage or present analytical limitations. This study aimed to complement the existing analyses and identify novel markers using liquid chromatography-high resolution mass spectrometry-based foodomics strategies. In the discovery set, comparative untargeted metabolomics was utilized to identify marker candidates in microbially inoculated chicken eggs. Markers were annotated by spectral matching with authentic standards, experimental libraries, or in silico fragmentation. In the validation set, targeted metabolomics was employed to verify the markers in stored chicken eggs from five farms. Statistical differences at a p-value < 0.001 revealed increases in lactic and 3-hydroxybutyric acids and decreases in phosphocholine, LPE(O-18:1), LPC(16:0), and LPC(18:0) in stored eggs. Receiver operating characteristic curve analysis of the six combined markers yielded an AUC of 0.956 and a sensitivity and specificity of ∼90%. Four phospholipids were highlighted as a novel class of spoilage markers. Our findings may contribute to further industrial implementation, benefiting the quality assurance and food safety of poultry egg production.

The difunctionalization of alkenes involving trifluoromethylthio group (SCF3) for the conversion of versatile and readily available olefins into more structurally complex molecules has been greatly studied. However, the disproportionate dithiolation of alkene is unknown. Herein, a transition-metal-free protocol is presented for vicinal trifluoromethylthio-thiolation of unactivated alkenes via a radical process under mild condition with broad substrate scope and excellent tolerance.

At present, cyclometalated iridium (Ir)(III) complexes are the most promising emitters for OLEDs. Contrary to well-developed Ir(III)-based red and green phosphorescent complexes, the efficient blue emitters are limited and the performances of blue OLEDs are still not satisfactory. Inspired by this, we designed two novel blue Ir(III) complexes employing 2-(2,4-difluoropyridyl)pyridine (dfpypy) and 2,6-difluoro-3-(pyridin-2-yl)benzonitrile (FCN) as the main ligands, respectively, and phenyl(pyridin-2-yl)phosphinate (ppp) as the ancillary ligand. The rational design of the molecular structure makes the two complexes achieve blue emission and possess good electron mobility simultaneously. The devices based on the Ir(III) phosphors exhibited good electroluminescence performances with low turn-on voltages, a peak current efficiency of 24.51 cd A−1, a maximum external quantum efficiency of 12.4%, a peak power efficiency of 21.99 lm W−1 and low efficiency roll-off. These results provide an effective strategy for the future molecular design of blue Ir(III) complexes with good electron transport property for OLEDs.

This work demonstrated the rational design and synthesis of donor–π–acceptor (D–π–A) linear vinylene-linked polymers for visible-light driven H2 production with high efficiency. Extending the in-plane conjugation, enhancing the electron push–pull interaction or/and lowering the steric hindrance of the D–π–A type linear conjugated polymer could broaden the visible-light absorption band, promote the photogenerated charge separation and transfer, and thus improve the photocatalytic performance.

High-performance chemiresistor gas sensor made of sulfide porous GaN decorated with Pt nanoparticles, which shows tunable sensor response and enhanced sensitivity. The fabricated gas sensors show detection of H2 down to 30 ppm at 23 °C after sulfide treatment and Pt decorated porous GaN. The response time and recovery time were equal to 47 s and 113 s, respectively. Density functional theory simulations were used to support the detection mechanism based on sulfide treatment. Adsorption energy calculations showed that H adsorption energy is lowered by the simultaneous presence of S and Pt on the GaN (0001) surface. The density of states (DOS) calculations revealed possibility of bond strengthening when Pt and S is adsorbed on GaN surface along with H, arising from the hybridization of d and p orbitals of Pt and S with that of H 1s orbitals.

Electrochemical fluorination (ECF) refers to the introduction of fluorine-containing moieties into organic molecules under electrochemical conditions. The primary objective of this review is to provide the reader with the highlights of electron-induced radical fluorinations in the past decade, comprising fluorination, difluoromethylation, trifluoromethylation and perfluoroalkylation. Some representative mechanisms are outlined for researchers to gain insight in the basic principles behind this technology.

In this study, nitrilotriacetic acid (NTA) was used to enhance UV/Fe0/H2O2 process for highly salty wastewater at neutral pH. The addition of Fe0 could not accelerate the UV/H2O2 process for salty wastewater treatment at neutral pH due to the precipitation of Fe ions. While NTA added into UV/Fe0/H2O2 process which could form complex with Fe ion, the tartrazine removal could increase from 45.7% to 84.7% within 60 min. The k-value of the UV/Fe0-NTA/H2O2 system to remove tartrazine is also 2.2 times higher than that in UV/Fe0/H2O2 system. Meanwhile, the UV/Fe0-NTA/H2O2 process could obtain good performance for salt wastewater treatment under a wide salt concentration level of 0–0.2 M. It can also expand the application range of pH to neutral pH. SEM and XPS characterization showed that the corrosion rate of Fe0 in salty system was faster, and the presence of NTA could accelerate the recirculation of Fe3+/Fe2+ on the Fe0 surface. EPR spectroscopic analysis and scavenge experiments showed that •OH was the main reactive radical for the removal of tartrazine in the UV/Fe0-NTA/H2O2 system. In addition, the k-value for removing tartrazine in various types of salt systems in the UV/Fe0-NTA/H2O2 system was 3.2–4.2 times that of the UV/Fe0/H2O2 system. It demonstrated UV/Fe0-NTA/H2O2 processes fits to different types of salt system. Therefore, this study will provide a new method for the treatment of saline wastewater at neutral pH.

Background: Because of the high affinity of these animal neurotoxin proteins for some special target site, they were usually used as pharmacological tools and therapeutic agents in medicine to gain deep insights into the function of the nervous system. Background and Objective: The animal neurotoxin proteins are one of the most common functional groups among the animal toxin proteins. Thus, it was very important to characterize and predict the animal neurotoxin proteins. Methods: In this study, the differences between the animal neurotoxin proteins and non-toxin proteins were analyzed. Results: Significant differences were found between them. In addition, the support vector machine was proposed to predict the animal neurotoxin proteins. The predictive results of our classifier achieved the overall accuracy of 96.46%. Furthermore, the random forest and k-nearest neighbors were applied to predict the animal neurotoxin proteins. Conclusion: The compared results indicated that the predictive performances of our classifier were better than other two algorithms.

Redox-active benzimidazolium sulfonamides as thiolating reagents have been developed for reductive C–S bond coupling. The IMDN-SO2R reagent provides a bench-stable cationic precursor to generate a portfolio of highly active N–S intermediates, which can be successfully applied in cross-electrophilic coupling with various organic halides. The employment of an electrophilic sulfur source solved the problem of catalyst deactivation and avoided odorous thiols, featuring practical conditions, broad substrate scope, and excellent tolerance., Redox-active benzimidazolium sulfonamides as thiolating reagents have been developed for reductive C–S bond coupling.

It is crucial to develop high-performance and cost-effective bifunctional electrocatalysts for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) toward overall water splitting. Herein, a unique heterostructure of reduced graphene oxide (rGO) and CoNiO2 nanosheets directly grown on nickel foam (NF) were successfully fabricated and applied as a kind of highly efficient bifunctional electrocatalyst. The optimum CoNiO2@rGO/NF electrode exhibits excellent electrocatalytic OER performance with an overpotential of only 272 mV to drive a current density of 100 mA·cm−2, and HER performance with an overpotential of 126 mV to achieve a current density of 10 mA·cm−2. Meanwhile, the electrodes also display outstanding long-term stability for OER and HER with negligible activity and morphology degradation after at least 40 h testing. Furthermore, when employed as both cathode and anode for overall water splitting, CoNiO2@rGO/NF electrode only requires 1.56 V at 10 mA·cm−2 and operates stably for over 40 h, which is among the best performing Co-based and Ni-based non-precious metal electrocatalysts. Detailed characterizations reveal that the extraordinary electrocatalytic performance should be attributed to the synergistic effect of the unique heterostructure of CoNiO2 nanosheets and rGO for increasing the electrode conductivity and integrity, ultrasmall primary particle size for providing larger electrode/electrolyte contact area and abundant active sites, and three-dimensional (3D) conductive networks for facilitating the electrochemical reaction.

Vinylboronates and alkylboronates are key components in variegated transformations in all facets of chemical science. The synthesis of vinylboronates and alkylboronates suffers from step-tedious and poor stereoselective procedures. We have developed a regulated radical difunctionalization strategy for the construction of fluorine-containing vinylboronates and alkylboronates with an integrated redox-active reagent IMDN-SO2RF. This bench-stable imidazolium sulfonate cationic salt offers a scalable and operational protocol for the fluoroalkylation-borylation of unsaturated hydrocarbons in a high regio- and stereoselective manner. The products can be further transformed into valuable fluorinated building blocks., The synthesis of vinylboronates and alkylboronates often suffers from step-tedious and poorly stereoselective procedures. Here, the authors report a bench-stable redox-active reagent for the radical difunctionalization of alkenes and alkynes affording fluorine-containing vinylboronates and alkylboronates.

The C-O bond cleavage for activation of alcohols is synthetically useful and practically challenging. This work describes carbazate as a new type of electrochemically activated alkylating agent derived from ubiquitous alcohols for direct functionalization of heteroarenes under mild electrolytic conditions. The simple undivided cell at low oxidative potentials with carbon/platinum electrode set-ups offers excellent substrate tolerance, affording a variety of primary, secondary and tertiary alkyl-decorated heterocycles in good chemical yields. Furthermore, the mechanism for this electrochemical deoxyalkylation reaction has been investigated.

Click chemistry focuses on the development of highly selective reactions using simple precursors for the exquisite synthesis of molecules. Undisputedly, the CuI -catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most valuable examples of click chemistry, but it suffers from some limitations as it requires additional reducing agents and ligands as well as cytotoxic copper. Here, we demonstrate a novel strategy for the azide-alkyne cycloaddition reaction that involves a photoredox electron-transfer radical mechanism instead of the traditional metal-catalyzed coordination process. This newly developed photocatalyzed azide-alkyne cycloaddition reaction can be performed under mild conditions at room temperature in the presence of air and visible light and shows good functional group tolerance, excellent atom economy, high yields of up to 99 %, and absolute regioselectivity, affording a variety of 1,4-disubstituted 1,2,3-triazole derivatives, including bioactive molecules and pharmaceuticals. The use of a recyclable photocatalyst, solar energy, and water as solvent makes this photocatalytic system sustainable and environmentally friendly. Moreover, the azide-alkyne cycloaddition reaction could be photocatalyzed in the presence of a metal-free catalyst with excellent regioselectivity, which represents an important development for click chemistry and should find versatile applications in organic synthesis, chemical biology, and materials science.

Purpose: To investigate the effect of bisleuconothine A (BA), alone and in combination with hyperbaric oxygen (HO), on traumatic brain injury (TBI) in rats. Methods: Traumatic brain injury (TBI) was induced by dropping a 200-g weight of steel on the left anterior frontal areas of Sprague-Dawley rats. The synergistic effect of BA and HO was determined by assessing neurological score, as well as parameters of oxidative stress and inflammation, expressions of P2X4 protein and other proteins, and levels of reactive oxygen species (ROS) in the brain tissues of TBI rats. Results: Neurological function score, levels of inflammatory mediators and oxidative stress parameters were significantly reduced in rats treated with BA alone, and in those treated with a combination of BA and HO, when compared with untreated TBI rats (p < 0.01). Moreover, treatment with BA alone, and BA-HO combination attenuated the altered protein expressions of P2X4, Akt, PI3K and TLR-4 in the TBI rats, and also upregulated the mRNA expression of P2X4 in the brain tissue, when compared with untreated TBI rats (p < 0.01). Conclusion: These results suggest that BA, when used alone or in combination with HO, reduces neuronal injury through upregulation of the protein expression of P2X4 in rats with traumatic brain injury. Thus, BA may be used clinically with HO therapy for the management of traumatic injury. Keywords: Bisleuconothine A, Hyperbaric oxygen, Neuronal injury, Oxidative stress, Inflammatory mediators

The V-shaped ketone ligand, benzophenone-2,4′-dicarboxylic acid (H2bpdc), was used as a long ditopic asymmetric linker to bridge mixed cobalt(II) clusters into a three-dimensional pcu network, namely [Co7(μ3–OH)2(bpdc)6(2,2′-bpy)4]·2H2O (1) (2,2′-bpy=2,2′-bipyridine), which was synthesized by methods of hydrothermal reaction and the crystal structure was determined. The linear trinuclear cluster [Co3(COO)6] and planar tetranuclear cluster [Co4(μ3–OH)2(COO)4] simultaneously appeared in the same compound for the first time. IR, elemental analysis and XRPD confirmed the phase purity of the bulk materials. Magnetic properties of 1 in the 300–2 K have been studied, which reveal the occurrence of antiferromagnetic interactions between Co(II) ions.

Myelin sheaths wrapping axons are key structures that help maintain the propagation speed of action potentials in both central and peripheral nervous systems (CNS and PNS). However, noninvasive, deep imaging technologies visualizing myelin sheaths in the digital skin in vivo are lacking in animal models. 3-photon fluorescence (3PF) imaging excited at the 1700-nm window enables deep imaging of myelin sheaths, but necessitates labeling by exogenous fluorescent dyes. Since myelin sheaths are lipid-rich structures which generate strong third-harmonic signals, in this paper, we perform a detailed comparative experimental study of both third-harmonic generation (THG) and 3PF imaging in the mouse digital skin in vivo. Our results show that THG imaging also enables visualization of myelin sheaths deep in the mouse digital skin, which shows colocalization with 3PF signals from labeled myelin sheaths. Besides its superior label-free advantage, THG does not suffer from photobleaching due to its 3PF property.

Motivation: The interactions of proteins with DNA, RNA, peptide, and carbohydrate play key roles in various biological processes. The studies of uncharacterized proteinmolecules interactions could be aided by accurate predictions of residues that bind with partner molecules. However, the existing methods for predicting binding residues on proteins remain of relatively low accuracies due to the limited number of complex structures in databases. As different types of molecules partially share chemical mechanisms, the predictions for each molecular type should benefit from the binding information with other molecules types. Results: In this study, we employed a multiple task deep learning strategy to develop a new sequence-based method for simultaneously predicting binding residues/sites with multiple important molecule types named MTDsite. By combining four training sets for DNA, RNA, peptide, and carbohydrate-binding proteins, our method yielded accurate and robust predictions with AUC values of 0.852, 0836, 0.758, and 0.776 on their respective independent test sets, which are 0.52 to 6.6% better than other state-of-the-art methods. To my best knowledge, this is the first method using multi-task framework to predict multiple molecular binding sites simultaneously. Availability: http://biomed.nscc-gz.cn/server/MTDsite/ Contact: yangyd25@mail.sysu.edu.cn

Background: Youguiyin (YGY) has been confirmed to treat osteoporosis (OP) in clinical trials, but its specific pharmacological mechanism remains unclear. This study aimed to explore the material basis and potential mechanism of YGY in the treatment of OP based on network pharmacology and molecular docking.Methods: Databases including TCMSP, SwissTargetPrediction database, OMIM, and TTD were used to predict the effective ingredients and relevant targets of YGY in the treatment of OP. The STRING database was used to reveal the relationship between each intersection target protein. Metascape database was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on the intersection targets. Cytoscape 3.6.0 software was used to show the complex network relationship of YGY in the treatment of OP. According to the results of network characteristics analysis, the core effective ingredients and the core targets were screened out. Autodock 4.0 was used for molecular docking and Pymol was used to visualize the docking results.Results: 290 effective ingredients, 1127 targets of the effective ingredients, 273 relevant targets of OP and 17 intersection targets were screened out in total by searching literature and databases. Intersection targets could affect biological processes including regulation of inflammatory response, ossification, negative regulation of post-transcriptional gene silencing, positive regulation of cytokine biosynthetic process and regulation of hormone levels by regulating signal pathways including TNF signaling pathway, osteoclast differentiation, apoptosis, MAPK signaling pathway and PI3K/Akt signaling pathway. Through screening, 14 core effective ingredients and 6 core targets were confirmed. The results of molecular docking showed that most of the core effective ingredients including α-humulene, cinnamaldehyde, denudatine, benzoylhypaconine and quercetin had good binding activity with the core targets including TNF-α, IL-1β and IL-6.Conclusion: Based on network pharmacology and molecular docking, the critical effective ingredients, key targets, important signal pathways and main biological processes of YGY in the treatment of OP were successfully screened out. This study revealed the material basis and the mechanism of YGY in the treatment of OP and provided a theoretical basis for follow-up experimental research and clinical application of YGY.

Reactive oxygen species (ROS)-induced vascular endothelial cell apoptosis is strongly associated with atherosclerosis progression. Herein, we aimed to examine whether Kansuinine A (KA), extracted from Euphorbia kansui L., prevents atherosclerosis development in a mouse model and inhibits cell apoptosis through oxidative stress reduction. Atherosclerosis development was analyzed in apolipoprotein E-deficient (ApoE−/−) mice fed a high-fat diet (HFD) using Oil Red O staining and H&amp, E staining. Human aortic endothelial cells (HAECs) were treated with KA, followed by hydrogen peroxide (H2O2), to investigate the KA-mediated inhibition of ROS-induced oxidative stress and cell apoptosis. Oil Red O staining and H&amp, E staining showed that atherosclerotic lesion size was significantly smaller in the aortic arch of ApoE−/− mice in the HFD+KA group than that in the aortic arch of those in the HFD group. Further, KA (0.1–1.0 μM) blocked the H2O2-induced death of HAECs and ROS generation. The H2O2-mediated upregulation of phosphorylated IKKβ, phosphorylated IκBα, and phosphorylated NF-κB was suppressed by KA. KA also reduced the Bax/Bcl-2 ratio and cleaved caspase-3 expression, preventing H2O2-induced vascular endothelial cell apoptosis. Our results indicate that KA may protect against ROS-induced endothelial cell apoptosis and has considerable clinical potential in the prevention of atherosclerosis and cardiovascular diseases.

Manganese complexes in +6 oxidation state are rare. Although a number of Mn(VI) nitrido complexes have been generated in solution via one-electron oxidation of the corresponding Mn(V) nitrido species, they are too unstable to isolate. Herein we report the isolation and the X-ray structure of a Mn(VI) nitrido complex, [MnVI(N)(TAML)]- (2), which was obtained by one-electron oxidation of [MnV(N)(TAML)]2- (1). 2 undergoes N atom transfer to PPh3 and styrenes to give Ph3P═NH and aziridines, respectively. A Hammett study for various p-substituted styrenes gives a V-shaped plot; this is rationalized by the ability of 2 to function as either an electrophile or a nucleophile. 2 also undergoes hydride transfer reactions with NADH analogues, such as 10-methyl-9,10-dihydroacridine (AcrH2) and 1-benzyl-1,4-dihydronicotinamide (BNAH). A kinetic isotope effect of 7.3 was obtained when kinetic studies were carried out with AcrH2 and AcrD2. The reaction of 2 with NADH analogues results in the formation of [MnV(N)(TAML-H+)]- (3), which was characterized by ESI/MS, IR spectroscopy, and X-ray crystallography. These results indicate that this reaction occurs via an initial "separated CPET" (separated concerted proton-electron transfer) mechanism; that is, there is a concerted transfer of 1 e- + 1 H+ from AcrH2 (or BNAH) to 2, in which the electron is transferred to the MnVI center, while the proton is transferred to a carbonyl oxygen of TAML rather than to the nitrido ligand.

Objective: Puerarin has been proven to treat diverse cancers, but its function on ovarian cancer (OC) is still blurry and needs further research.Methods: After OC cells were treated with 10, 20, 40, 80, or 160 μg/mL pue, cell vitality, colony number, apoptosis, the positive expression of P53, migration, and invasion were examined by cell function experiments, TUNEL staining, and immunofluorescence. P53, P21, PTEN, FGF1, GLI2, and ERK1/2-NF-κB pathway-related marker expressions were examined by western blot. Results: Pue weakened the OC cell vitality, colony number, and the positive expression of P53 but enhanced apoptosis in a dose-dependent manner. Next, we discovered that pue enhanced the P53, P21, PTEN, and GLI2 levels but restrained the FGF1 level. Pue also alleviated the OC cell migration and invasion activity. We also confirmed that pue weakened the ERK1/2-NF-κB pathway-related marker expressions.Conclusion: Puerarin restrained the OC progression via modulating P53 and PTEN expressions.

Simple Summary Circulating tumour cells (CTCs) have shown potential to act as markers of disease and prognosis in head and neck squamous cell carcinoma (HNSCC). However, there are a number of methods and devices reported to isolate and characterise CTCs. Translating CTC markers to clinical practice, for patient benefit, requires a reliable, reproducible and standardised approach. We report the benefit of the Parsortix microfluidic CTC enrichment platform in HNSCC. We demonstrate consistent cell capture rates between 10 and 100 cells/mL of whole blood. Analysis of gene expression with unfixed cells before and after Parsortix enrichment demonstrated a cell stress response and downregulation of key genes. We highlight the benefit of using a fixative blood collection tube (Transfix) to increase cell capture rate and preserve the CTC marker expression profile. Such evidence is crucial when designing sample processing protocols for large cohort multi-centre clinical trials investigating CTCs in any cancer type. Abstract Introduction: Research demonstrates strong evidence that circulating tumour cells (CTCs) can provide diagnostic and/or prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC) and a potential tool for therapeutic stratification. However, the question still remains as to the optimum method of CTC enrichment and how this can be translated into clinical practice. We aimed to evaluate the Parsortix microfluidic device for CTC enrichment and characterisation in HNSCC, seeking to optimise a sample collection and processing protocol that preserves CTC integrity and phenotype. Method: Spiking experiments of the FaDu and SCC040 HNSCC cell lines were used to determine the Parsortix capture rate of rare “CTC-like” cells. Capture rates of cancer cells spiked into EDTA blood collections tubes (BCTs) were compared to the Transfix fixative BCT and Cytodelics whole blood freezing protocol. The Lexogen Quantseq library preparation was used to profile gene expression of unfixed cells before and after microfluidic enrichment and enriched cell line spiked Transfix blood samples. An antibody panel was optimised to enable immunofluorescence microscopy CTC detection in HNSCC patient Transfix blood samples, using epithelial (EpCAM) and mesenchymal (N-cadherin) CTC markers. Results: Across a spiked cell concentration range of 9–129 cells/mL, Parsortix demonstrated a mean cell capture rate of 53.5% for unfixed cells, with no significant relationship between spiked cell concentration and capture rate. Samples preserved in Transfix BCTs demonstrated significantly increased capture rates at 0 h (time to processing) compared to EDTA BCTs (65.3% vs. 51.0%). Capture rates in Transfix BCTs were maintained at 24 h and 72 h timepoints, but dropped significantly in EDTA BCTs. Gene expression profiling revealed that microfluidic enrichment of unfixed cell lines caused downregulation of RNA processing/binding gene pathways and upregulation of genes involved in cell injury, apoptosis and oxidative stress. RNA was successfully extracted and sequenced from Transfix preserved cells enriched using Parsortix, demonstrating epithelial specific transcripts from spiked cells. In a proof-of-concept cohort of four patients with advanced HNSCC, CTCs were successfully identified and visualised with epithelial and epithelial-mesenchymal phenotypes. Conclusion: We have optimised a protocol for detection of CTCs in HNSCC with the Parsortix microfluidic device, using Transfix BCTs. We report a significant benefit, both in terms of cell capture rates and preserving cell phenotype, for using a fixative BCT- particularly if samples are stored before processing. In the design of large cohort multi-site clinical trials, such data are of paramount importance.