Carbazole-based mitochondria-targeted fluorescent probes for in vivo viscosity and cyanide detection in cells and zebrafish.

Cells of most eukaryotic species contain mitochondria, which play a role in physiological processes such as cellular senescence, metabolism, and autophagy. Viscosity is considered a key marker for many illnesses and is involved in several crucial physiological processes. Cyanide (CN-) can target cytochrome-c oxidase, disrupting the mitochondrial electron transport chain and causing cell death through asphyxiation. In this study, a fluorescent probe named HL-1, which targets mitochondria and measures viscosity and CN- levels, was designed and synthesized. HL-1 is viscosity-sensitive, with a linear correlation coefficient of up to 0.992. In addition, HL-1 was found to change color substantially during a nucleophilic addition reaction with CN-, which has a low detection limit of 47 nM. HL-1 not only detects viscosity and exogenous CN- in SKOV-3 cells and zebrafish but also monitors viscosity changes during mitochondrial autophagy in real time. Furthermore, HL-1 has been used successfully to monitor changes in mitochondrial membrane potential during apoptosis. Endogenous CN- in plant samples was quantified. HL-1 provides new ideas for studying viscosity and CN-.

HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA.

PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.

High S-doped amorphous carbon/carbon quantum dots coupled micro-frame for highly efficient potassium storage.

Anode materials with excellent rate capability, capacity, and cycle life have been a challenge in obtaining cost-effective K-ion batteries (KIBs). Based on the concept of waste recycling, we prepared the S-doped (21.5%) amorphous carbon/carbon quantum dots coupled micro-frame (SCMF) by combining chemical exfoliation and S/Se-assisted carbonization. SCMF exhibited the advantages of integrating amorphous carbon and carbon quantum dots (CQDs). The CQDs serve as fast electron channels, while amorphous carbon can accommodate more large-size K-ions and mitigate volume expansion. In KIBs, SCMF maintained a high reversible capacity (414.0 mAh g-1, after 100 cycles at 100 mA g-1), a good rate capability (224.0 mAh g-1, 2000 mA g-1), and excellent capacity retention (208.9 mAh g-1, after 2000 cycles at 1000 mA g-1). The molecular dynamic simulation revealed that CQDs provided fast electron transport channels and that C, O and S atoms had suitable interactions with K, facilitating potassium storage. Moreover, the potassium-ion capacitor (PIC) assembled from SCMF and activated carbon exhibited stable electrochemical performance, proving its potential for application. The research provided valuable insights into the reuse of biomass waste in new secondary batteries.

Research progress on post-translational modification of proteins and cardiovascular diseases.

Cardiovascular diseases (CVDs) such as atherosclerosis, myocardial remodeling, myocardial ischemia-reperfusion (I/R) injury, heart failure, and oxidative stress are among the greatest threats to human health worldwide. Cardiovascular pathogenesis has been studied for decades, and the influence of epigenetic changes on CVDs has been extensively studied. Post-translational modifications (PTMs), including phosphorylation, glycosylation, methylation, acetylation, ubiquitination, ubiquitin-like and nitrification, play important roles in the normal functioning of the cardiovascular system. Over the past decade, with the application of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an increasing number novel acylation modifications have been discovered, including propionylation, crotonylation, butyrylation, succinylation, lactylation, and isonicotinylation. Each change in protein conformation has the potential to alter protein function and lead to CVDs, and this process is usually reversible. This article summarizes the mechanisms underlying several common PTMs involved in the occurrence and development of CVDs.

Emerging roles of ferroptosis in cardiovascular diseases.

The mechanism of cardiovascular diseases (CVDs) is complex and threatens human health. Cardiomyocyte death is an important participant in the pathophysiological basis of CVDs. Ferroptosis is a new type of iron-dependent programmed cell death caused by excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS) and abnormal iron metabolism. Ferroptosis differs from other known cell death pathways, such as apoptosis, necrosis, necroptosis, autophagy and pyroptosis. Several compounds have been shown to induce or inhibit ferroptosis by regulating related key factors or signalling pathways. Recent studies have confirmed that ferroptosis is associated with the development of diverse CVDs and may be a potential therapeutic drug target for CVDs. In this review, we summarize the characteristics and related mechanisms of ferroptosis and focus on its role in CVDs, with the goal of inspiring novel treatment strategies.

Isomerization energies and surface electrostatic potential analyses on nitriles and isocyanides.

Isocyanide-nitrile rearrangement has long been a continuing and interesting topic. A series of nitriles and isocyanides with the substituents of R = -AlH2, -BeH, -BH2, -C≡CH, -CF3, -CH3, -Cl, -C≡N, -COOH, -F, -H, Li, -MgH, -Na, -NH2, -NO2, -OH, -PH2, -SH, -SiH3, and -CH = CH2 were investigated systematically based on full optimization at B3LYP-D3(BJ)/def2-QZVP level, and the isomerization energies from R-C≡N to:C = N-R were estimated. The substituent effect and bonding characters were analyzed by surface ESP colored van der Waals surfaces in conjunction with the global and local electrostatic extrema.

Triazole-directed fabrication of polyoxovanadate-based metal-organic frameworks as efficient multifunctional heterogeneous catalysts for the Knoevenagel condensation and oxidation of alcohols.

By introducing 4-amino-1,2,4-triazole (4-NH2-trz), three new polyoxovanadate-based metal-organic frameworks (PMOFs) [Ni3(4-NH2-trz)6][V6O18]·3H2O (1), [Co3(4-NH2-trz)6][V6O18]·3H2O (2) and [Cu3OH(4-NH2-trz)3H2O][VO3]5·H2O (3) have been synthesized and thoroughly characterized by single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), infrared spectroscopy (FT-IR), thermogravimetric (TG) analysis and elemental analysis (EA). Among them, PMOFs 1 and 2 had similar structures containing [V6O18]6- clusters; however, PMOF 3 was isolated as a structure containing a [VO3]55- cluster when the amount of the 4-NH2-trz ligand was reduced to half with the other synthesis conditions being the same as those of PMOFs 1 and 2 except for the transition-metal chlorides. Furthermore, the negative charges of polyoxovanadate [V6O18]6- and [VO3]55- anions were balanced by trinuclear complex cations [Ni3(4-NH2-trz)6]6- for 1, [Co3(4-NH2-trz)6]6- for 2 and [Cu3OH(4-NH2-trz)3H2O]5- for 3, respectively. PMOFs 1-3 were further used as heterogeneous catalysts in the Knoevenagel condensation under solvent-free conditions and showed high catalytic activity. PMOF 1 showed moderate catalytic activities in the oxidation of various aromatic alcohols using H2O2 as an oxidant. Moreover, PMOF 1 could be reused at least three times without losing its activity.

High-Yield and High-Efficiency Conversion of HMF to Levulinic Acid in a Green and Facile Catalytic Process by a Dual-Function Brønsted-Lewis Acid HScCl4 Catalyst.

Lignocellulosic biorefineries have received considerable attention for the purpose of producing high-value chemicals and materials. Levulinic acid (LA) is an important biomass-derived platform chemical that is produced from sugar-based biomass. Unfortunately, the catalysts reported thus far have shortcomings, such as expensive starting materials, complicated synthesis or purification operations, and a low LA yield under harsh reaction conditions. Herein, we develop a novel dual-functional catalyst, HScCl4, by combining Brønsted acid (HCl) and Lewis acid (ScCl3) sites. The as-prepared HScCl4 catalyst shows high efficiency and high selectivity for converting 5-hydroxymethylfurfural (HMF) to LA in a biphasic system consisting of methyl isobutyl ketone (MIBK) and water. The density functional theory (DFT) results show that the synergistic catalytic effect, originating from the Brønsted and Lewis acidic sites of HScCl4, significantly decreases the energy barriers of reactants and intermediates, thus facilitating the conversion of HMF to LA. Moreover, the efficient separation of LA in the water-MIBK biphasic system by extracting LA to the MIBK phase minimizes the side reactions of LA and thus the formation of humins while significantly improving the LA yield. The conversion of HMF and the selectivity for LA are 100 and 95.6% at 120 °C for 35 min, respectively. The free energy (ΔG) and activation energy (E a) of the reaction are -30 kcal mol-1 and 13.7 kJ mol-1, respectively. The developed process provides a green, sustainable, and efficient pathway to produce LA from biomass-derived HMF under mild conditions.

Integrated Chinese and western medicine for SLE: A protocol for systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of integrated Chinese and western medicine in the treatment of Systemic Lupus Erythematosus (SLE) have not been systematically evaluated. METHODS: This systematic review and meta-analysis will be performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will search PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP, and China National Knowledge Infrastructure (CNKI) for potentially eligible studies from their inception to Dec. 2020, and we will select all the eligible randomized controlled trials (RCTs) of the integrated Chinese and western medicine for Systemic Lupus Erythematosus. All the studies will be screened according to the inclusion and exclusion criteria and meta-analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. The primary endpoint was the clinical efficacy rate, the secondary outcomes were SLEDAI score, adverse reaction rate, and laboratory test parameters (white blood cells, complement C3). RESULTS: The results of this study will systematically evaluate the effectiveness and safety of the integrated Chinese and western medicine in the treatment of primary dysmenorrhea. CONCLUSION: The efficacy and safety of integrated Chinese and western medicine will be systematically evaluated in this paper, thus providing evidence for the clinical application of this therapy. ETHICS AND DISSEMINATION: This study is a systematic review, which is based on the published studies, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK OSFREGISTRATION NUMBER: https://osf.io/mabxh.

Efficacy and safety of fire acupuncture for psoriasis vulgaris: A protocol of systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Fire acupuncture is commonly used for the treatment of psoriasis vulgaris, but the efficacy and safety of fire acupuncture for psoriasis vulgaris remain unclear. METHODS: This systematic review and meta-analysis will be conducted and reported strictly according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, Chinese biomedical literature, and Pubmed will be retrieved for potentially eligible studies from their inception to Jan. 2021. All randomized clinical trials comparing fire acupuncture versus no fire acupuncture in the treatment of psoriasis vulgaris will be retrieved and assessed for inclusion. RevMan5.3 software provided by Cochrane collaboration will be used for the analysis. Randomized Clinical Trials Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. The primary endpoint is the total effective rate, the secondary outcomes are the Psoriasis Area Severity Index (PASI) score, the recurrence rate and the adverse reactions. RESULTS: This study will systematically evaluate the efficacy and safety of fire acupuncture for psoriasis vulgaris. The results will be published in a peer-reviewed journal. CONCLUSION: This systematic review will evaluate the effects of fire acupuncture in patients with psoriasis vulgaris, thus providing evidence to the clinical application of this therapy.

TOF-SIMS surface analysis of chemical components of size-fractioned urban aerosols in a typical heavy air pollution event in Beijing.

Size-fractioned atmospheric aerosol particles were collected during a typical heavy air pollution event in Beijing. The organic and inorganic components on the surfaces of the samples were analyzed using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The variation characteristics of the surface chemical composition and influencing factors were studied, and the possible sources of these chemical compositions were identified through principal component analysis. The results showed that inorganic components such as crustal elements and sulfate, and organic components such as aliphatic hydrocarbons and oxygen-containing organic groups were present. Some surface components, such as polycyclic aromatic hydrocarbons, heavy metals and fluorides may exert adverse effects on human health. The species and relative percentages of the chemical components varied with particle size, diurnal and pollution progress. During a heavy pollution event, the species and relative percentages of secondary components such as oxygen-containing organic groups and sulfurous compounds increased, indicating that particles aged during this event. The surface chemical composition of the aerosol particles was affected mainly by emissions from coal combustion and motor vehicles. In addition, air pollution, meteorological factors, and air mass transport also exerted a significant effect on the surface chemical composition of aerosol particles.

TD-M06-2X insights into the absorption and emission spectra of dichlorvos and its molecularly imprinted recognition by methacrylic acid.

The absorption and emission spectra of dichlorvos and the dichlorvos-MAA complex in methanol, water, and chloroform in the molecularly imprinted recognition were investigated systematically. The M06-2X results revealed that: 1) the hydroxyl groups in polar solvents such as methanol and water may markedly influence the weak interactions, and then alter the adsorption and emission spectra; 2) the electronic excitation in absorption spectra of dichlorvos is dominated by the configuration HOMO → LUMO, but in the most stable dichlorvos-MAA it becomes the ππ* excitation of HOMO → LUMO + 1; 3) Mulliken charges reveal that dichlorvos almost dissociates to Cl- and a cation in its S1 excitation state; 4) the phosphorescence spectra of dichlorvos-MAA are relatively weak. Graphical Abstract The absorption and emission spectra of dichlorvos and the dichlorvos-MAA complex in the molecularly imprinted recognition of dichlorvos were investigated systematically in methanol, water, and chloroform as solvents.

A preliminary analysis of the surface chemistry of atmospheric aerosol particles in a typical urban area of Beijing.

Atmospheric aerosol particle samples were collected using an Ambient Eight Stage (Non-Viable) Cascade Impactor Sampler in a typical urban area of Beijing from 27th Sep. to 5th Oct., 2009. The surface chemistry of these aerosol particles was analyzed using Static Time of Flight-Secondary Ion Mass Spectrometry (Static TOF-SIMS). The factors influencing surface compositions were evaluated in conjunction with the air pollution levels, meteorological factors, and air mass transport for the sampling period. The results show that a variety of organic ion groups and inorganic ions/ion groups were accumulated on the surfaces of aerosol particles in urban areas of Beijing; and hydrophobic organic compounds with short- or middle-chain alkyl as well as hydrophilic secondary inorganic compounds were observed. All these compounds have the potential to affect the atmospheric behavior of urban aerosol particles. PM1.1-2.1 and PM3.3-4.7 had similar elements on their surfaces, but some molecules and ionic groups demonstrated differences in Time of Flight-Secondary Ion Mass Spectrometry spectra. This suggests that the quantities of elements varied between PM1.1-2.1 and PM3.3-4.7. In particular, more intense research efforts into fluoride pollution are required, because the fluorides on aerosol surfaces have the potential to harm human health. The levels of air pollution had the most significant influence on the surface compositions of aerosol particles in our study. Hence, heavier air pollution was associated with more complex surface compositions on aerosol particles. In addition, wind, rainfall, and air masses from the south also greatly influenced the surface compositions of these urban aerosol particles.

Theoretical study on the oligomerization mechanisms of bihydroxysilicone.

Bihydroxysilicone SiO(OH)2 is the simplest silicone monomer and can be condensed to various silica materials with diverse properties. The oligomerization mechanisms of SiO(OH)2 were investigated systematically at B3LYP/6-311++G(d,p) level. All species including the monomers, dimers, trimers, and tetramers were fully optimized with CPCM solvation model to simulate the solvent environments in methanol. The Si=O bonds of silicones can couple via barrierless processes to form varied ringed structures, and bigger rings can be formed by dehydration and recyclization. The most stable trimer is the one with a hexagonal Si-O ring, and the energetically most favorable tetramer is the one with an octagonal Si-O ring and two hydroxyl groups on each Si atom. Graphical Abstract Selected oligomers in the oligomerization mechanisms of bihydroxysiliconeᅟ.

Mapping of a Novel Race Specific Resistance Gene to Phytophthora Root Rot of Pepper (Capsicum annuum) Using Bulked Segregant Analysis Combined with Specific Length Amplified Fragment Sequencing Strategy.

Phytophthora root rot caused by Phytophthora capsici (P. capsici) is a serious limitation to pepper production in Southern China, with high temperature and humidity. Mapping PRR resistance genes can provide linked DNA markers for breeding PRR resistant varieties by molecular marker-assisted selection (MAS). Two BC1 populations and an F2 population derived from a cross between P. capsici-resistant accession, Criollo de Morelos 334 (CM334) and P. capsici-susceptible accession, New Mexico Capsicum Accession 10399 (NMCA10399) were used to investigate the genetic characteristics of PRR resistance. PRR resistance to isolate Byl4 (race 3) was controlled by a single dominant gene, PhR10, that was mapped to an interval of 16.39Mb at the end of the long arm of chromosome 10. Integration of bulked segregant analysis (BSA) and Specific Length Amplified Fragment sequencing (SLAF-seq) provided an efficient genetic mapping strategy. Ten polymorphic Simple Sequence Repeat (SSR) markers were found within this region and used to screen the genotypes of 636 BC1 plants, delimiting PhR10 to a 2.57 Mb interval between markers P52-11-21 (1.5 cM away) and P52-11-41 (1.1 cM). A total of 163 genes were annotated within this region and 31 were predicted to be associated with disease resistance. PhR10 is a novel race specific gene for PRR, and this paper describes linked SSR markers suitable for marker-assisted selection of PRR resistant varieties, also laying a foundation for cloning the resistance gene.

Ursolic acid-loaded chitosan nanoparticles induce potent anti-angiogenesis in tumor.

Angiogenesis provides necessary nutrients and oxygen for tumor growth and metastasis; thus, every stage of angiogenesis process is the potential target for cancer therapies. Ursolic acid (UA) is reported to decrease tumor burden through anti-angiogenesis pathway, but its poor water solubility greatly limits its efficiency and clinical application. Here, a simple method for preparing UA-loaded chitosan nanoparticles (CH-UA-NPs) with anti-angiogenesis and anti-tumor activity was demonstrated. In vitro, CH-UA-NPs could significantly inhibit the proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs). After uptake by HUVECs, CH-UA-NPs were mainly localized in lysosomes and mitochondria, but not nuclei. CH-UA-NPs induced the destruction of lysosome membrane integrity, collapse of mitochondrial membrane potential, and reorganization of cell cytoskeleton. All these changes led to the apoptosis or necrosis in HUVECs. In vivo, CH-UA-NPs could inhibit the angiogenesis in chicken chorioallantoic membrane (CAM) model and H22 xenograft model. Notably, comparing with free UA, such synthesized CH-UA-NPs could save about tenfold of UA doses, implying that this could significantly decrease the side effects induced by high doses of UA in biological organism. Our data showed that CH-UA-NPs and this nanoparticle-based drug delivery system could be as a potential drug candidate for anti-angiogenesis treatment.

Catalytic mechanisms of Au11 and Au11-nPt n (n=1-2) clusters: a DFT investigation on the oxidation of CO by O2.

The oxidation of CO catalyzed by clusters of Au11, Au10Pt and Au9Pt2 was investigated using the M06 functional suite of the density functional theory. Au and Pt atoms were described with the double-ζ valence basis set Los Alamos National Laboratory 2-double-z (LanL2DZ), whereas the standard 6-311++G(d,p) basis set was employed for the C and O atoms. Our theoretical model showed that (1) after coordination to Au and Au-Pt cluster, O2 and CO are apparently activated, and Mulliken charges show that the gold atoms in the active sites of Au11 are negatively charged; (2) Au-Pt clusters with 11 atoms can effectively catalyze the oxidation of CO by O2; (3) Au11 exhibits good catalytic performance for the oxidation of CO; (4) oxidation of CO occurs preferably on the Au-Pt active sites in Pt-doped clusters, and the single-center mechanisms are more favorable energetically than the two-center mechanisms; (5) after adsorption, an O2 molecule oxidates two CO molecules via stepwise mechanisms; and (6) the catalytic processes are highly exothermic.

[Density functional theory investigations of the spectroscopic characteristics and luminescent mechanisms of dipterex and dichlorvos].

By using G09 program package, the ground-state structures, infrared spectra, NMR spectra, UV-Vis spectra as well as the excited structures and fluorescence/phosphorescence spectra of dipterex and dichlorvos were investigated systematically, and luminescence principles were analyzed with the molecular orbitals to provide the theoretical foundation for the detection of trace dipterex and dichlorvos. Our theoretical model revealed that the IR spectra of dipterex and dichlorvos bear strong absorptions at about 1107 cm(-1), which belong to the P-O stretch modes, but dipterex has strong absorption peaks involving the O-H bond; for UV-Vis spectra, dichlorvos has a strong absorption peak at 182.03 nm, but dipterex has a weak one at 192.42 nm, which are assigned to pipi* and sigmapi* transitions, respectively; the emission spectra of dichlorvos are very weak, and has double fluorescence/phosphorescence characteristics, which may be attributed to the resonance structures of dichlorvos; the fluorescence of dipterex has a unique broad peak at 1849.22 nm, corresponding to the LUMO-->HOMO transition of S1 state.

Theoretical investigations on the synthesis mechanism of cyanuric acid from NH3 and CO2.

In the synthesis of cyanuric acid from NH3 and CO2, urea and isocyanic acid OCNH are two pivotal intermediates. Based on density functional theory (DFT) calculations, the synthesis mechanism of cyanuric acid from NH3 + CO2 was investigated systematically. Urea can be synthesized from NH3 and CO2, and cyanuric acid can be obtained from urea or NH3 + CO2. In the stepwise mechanism of cyanuric acid from urea or NH3 + CO2, the energy barriers are relatively high, and the condition of high pressure and temperature does not decrease the energy barriers. Our theoretical model shows that cyanuric acid is actually acquired from OCNH via a one-step cycloaddition reaction.

Mechanistic investigations of Al(OH)3 oligomerization mechanisms.

Aluminum aerogels have extremely low thermal conductivities, and are ideal candidates for use in thermal superinsulators, adsorbents, sensors, catalyst carriers, and inorganic fillers. In the present work, the oligomerization mechanisms of Al(OH)3 were investigated systematically with the Gaussian 03 package at the B3LYP/6-311++G(d,p) level in combination with CPCM single-point energy calculations. The results of our theoretical model showed that: (1) the Al atoms are tetracoordinate and pentacoordinate; (2) in alkaline solution, Al(OH)3 tends to condense into more soluble polyhydroxy compounds; (3) the neutral dimerization of Al(OH)3 and the transfer of the hydrogen on the bridging hydroxyl are energetically favorable, but the most stable geometry is a four-membered Al-O ring structure linked by two bridging hydroxyls; (4) Al(OH)3 is inclined to form tetracoordinate oligomers, which develop into three-dimensional structures connected by four-membered Al-O rings.