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High efficiency, environmental protection and sustainability have become the main theme of the development of the protection engineering, requiring that the components not only meet the basic functions, but also have chemical properties such as acid and alkali corrosion resistance and aging resistance. Polyisocyanate-oxazodone (POZD) polymer has the above characteristics, it also has the advantages of strong toughness, high strength and high elongation. The concrete slab sprayed with POZD material has excellent anti-blast performance. In order to explore the damage characteristics of POZD sprayed concrete slabs under the action of contact explosion thoroughly, the contact explosion test of POZD concrete slabs with different charges were carried out. On the basis of experimental verification, numerical simulation were used to study the influence of the thickness of the POZD on the blast resistance of the concrete slab. According to the test and numerical simulation results that as the thickness of the coating increases, the anti-blast performance of the concrete slab gradually increases, and the TNT equivalent required for critical failure is larger. Based on the above analysis, empirical expressions on normalized crater diameter, the normalized spall diameter and normalized spall diameter are obtained.

Fungal laccases are industrially important inducible enzymes extensively used in the delignification of lignocellulosics, detoxification of environmental wastes and decolorization of textile dyes. The discovery of new inducers is crucial for laccase productivity by filamentous fungi. In this study, a novel laccase-producing strain S8 from a bambusicolous fungus Shiraia bambusicola was identified by using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) as laccase secretion indicator and native polyacrylamide gel electrophoresis. The corresponding full-length cDNA of laccase was cloned and characterized. The effect of lanthanum (LaCl3) on extracellular laccase activity was tested at the concentration from 0.2 to 2.0 g/L and at different addition time (day 1–4) in the mycelium culture. In the presence of 1.0 g/L La3+ at the beginning of the mycelium cultures, the highest laccase activity (2.7 × 104 U/L) reached after 10 days of cultivation, about tenfold higher compared with non-induced cultures. La3+ was shown to be a very strong inducer for fungal laccase activity with no inhibitory effect on fungal growth at the optimized concentration. In vivo, La3+ added to the mycelium culture not only promoted a continuous and high expression of laccase gene (lcc1), but also induced a rapid generation of signaling molecules including reactive oxygen species (ROS) and nitric oxygen (NO). Both the NO donor sodium nitroprusside (SNP) and exogenous hydrogen peroxide (H2O2) potentiated La3+-induced laccase activity and increased membrane permeability of hyphal cells. Moreover, the scavenger such as 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) for NO and vitamin C for ROS suppressed the induction. These results suggest these signals could mediate La3+-induced laccase biosynthesis and its secretion. Our study provides a basis for understanding the induction mechanism of La3+ on laccase and a practical strategy for enhanced fungal laccase production.

Flexible thermal conducting materials with the combination of excellent thermal conductivity and mechanical strength are highly desired for many practical applications, but meeting this strict requirement remains as a big challenge. Herein, facile preparation of highly aligned carbon nanotube (CNT) films is demonstrated, which involves the continuous production of a hollow cylindrical CNT assembly, followed by in-situ alignment of CNTs through optimizing the winding rate and a further stretching-pressing process. Benefiting from the resultant excellent CNT alignment and high density (1.59 ± 0.05 g cm−3), the CNT film simultaneously has a high thermal conductivity of 558.06–700.15 W m−1 K−1, electrical conductivity of 4870 ± 150 S cm−1, mechanical strength of 2.74–2.95 GPa, and Young's modulus of 55.2–58.9 GPa. The combination of such high thermal and mechanical properties is outstanding for carbon-based thermal conducting materials. Furthermore, the CNT material exhibits negligible structural and mechanical decay even after 500 cycles of bending test. Our study provides an effective strategy toward developing new thermal conducting materials for applications under harsh conditions.

The measurement of ultra-trace level of heavy metals in complex metrics is of great concern and challenge in life and environmental science. Herein, a novel thiol-functionalized covalent organic framework (COF) was prepared and achieved quantitative preconcentration of trace heavy metals in environmental water samples. The material was synthetized by two-step reactions, including a Schiff base reaction between 1,3,5-triformylphloroglucinol (Tp) and 2,5-divinyl-p-phenylenediamine (DvPa) to form preliminary COF (TpDvPa), and a thiol-ene “click” reaction between 1,2-ethanedithiol and the vinyl groups of TpDvPa to produce thiol-functionalized TpDvPa (TpDvPa-S-SH). By packing the material into a home-made SPE micro-column, and hyphenating the micro-column with inductively coupled plasma mass spectrometry (ICP-MS), trace level of Co2+, Ni2+ and Cd2+ in environmental waters could be successfully preconcentrated and measured, with LODs of 1.46, 1.38 and 0.10 ng L-1, respectively. The precisions were all less than 2.7%，with linear ranges extended from 5 to 1000 ng L-1. The proposed method was validated by the analysis of the certificated reference material (GBW08608), and measurement of Co2+, Ni2+ and Cd2+ in tap water, reservoir water, effluent of wastewater treatment plant and sea water, confirming the accuracy and feasibility of the method.

A lysosomal targeted fluorescent probe based on coumarin for monitoring hydrazine (N2H4) in living cells was designed and synthesised. The novel fluorescent probe Cou-Lyso-N2H4, in response to N2H4, exhibited good selectivity, low cytotoxicity, and lysosomal localization, which could be suitable for studying the harmfulness of N2H4 in subcellular organelles during various physiological processes.

Electrocatalytic upgrading of biomass represents a promising way for the green synthesis of value-added fine chemicals. Rational construction of highly active and low-cost electrocatalysts with superior durability is of great importance for promoting this electrochemical process. In this work, we reported a novel 3D hierarchical NixSey–NiFe layered double hydroxide (LDH) core–shell nanostructure in situ grown on Ni foam (NixSey–NiFe@NF) for efficient electrocatalytic oxidation of biomass-derived 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) and furfural (FUR) to furoic acid (FurAc), respectively. By virtue of the excellent electrical conductivity and good mechanical strength of the NixSey nanowire core, abundant exposed active sites of the NiFe LDH nanosheet shell, and the open structure of the hierarchical nanoarrays, the integrated core–shell NixSey–NiFe LDH@NF electrode exhibited outstanding catalytic performance for HMF and FUR oxidation by obtaining considerable yields of FDCA (99.3%) and FurAc (99.7%) with high faradaic efficiency (FE) for FDCA (98.9%) and FurAc (99.5%), as well as superior stability retaining 96.7% FE for FDCA and 97.1% FE for FurAc after six successive electrolysis cycles. This work offers an effective approach to engineer novel electrocatalysts towards efficient upgrading of biomass-derived platform chemicals.

In the past few years, ionic liquids (ILs)-based gels (gels contain ILs) have become a research hotspot. ILs-based gels combine the properties of gels with intrinsic ILs properties. According to the existence form and function of the ILs in the gel, the ILs-based gels are divided into three types. One is ILs hydrogels which the PILs, ILs polymerized into poly-ionic liquids, copolymerized with other polymers served as the continuous phase in the gel system. This type of gel can usually absorb water and is an ILs hydrogel. The other is ionic gels that are usually synthesized by high-molecular organic polymers as spatial network structure and ILs as a dispersed phase, which maintained the good performance of ILs. The third one is that the ILs acts as both the continuous phase and the dispersed phase of the gels. In all research fields, the pursuit of new materials aims at functional materials, which enhances specific and efficiency, and ultimately applications. The application of ILs-based gels ranges from energy storage, sensing, electrochemical devices, to antibacterial and gas capture. Different synthesis methods have different performances and applications of ILs-based gels. The purpose of this review is to provide the latest developments on ILs-based gels, perspectives on several applications, and some challenges that need to be aware of in this field.

Glycosyltransferases have attracted increasing interest for the ability to construct glycosylated molecules in a facile way. However, promiscuous chemoselectivity and poor regioselectivity hinder t...

Point-of-care testing (POCT) with the advantages of simplicity, rapidity, portability, and low-cost is of great importance to improve healthcare, especially in resource-limited settings and home healthcare settings. Moreover, it is a great challenge to quantitative POCT of multiplexed biomarkers within a single accessible assay but provides enhanced diagnostic accuracy and improved diagnostic efficiency. Herein, a smartphone optical device has been designed for POCT of glucose and cholesterol in metabolic syndrome patients using a ratiometric fluorescent sensor. The sensing system of Ag NPs/UiO-66-NH2 and o-phenylenediamine presents a dual-emission response to H2O2 (the main product of glucose and cholesterol catalyzed by glucose oxidase and cholesterol oxidase) on account of the inner filter effect, resulting in an increase in the response of the fluorescence intensity ratio (F555 nm/F425 nm) accompanied by a distinguishable color transition from blue to yellow green. After compositing probes with a flexible substrate, the obtained test strip can be integrated with a smartphone-based portable platform to read RGB values for accurate testing of glucose and cholesterol with both detection limits of 10 μmol L-1, which are hundreds of times lower than their concentrations in human serum. With the advantages of low-cost, ease of operation, and broad adaptability, this smartphone optical device holds great potential for portable detection of numerous targets in personalized healthcare and clinical diagnosis.

Mitochondrial membrane potential (ΔΨm) is a key indicator of cell health or injury due to its vital roles in adenosine 5'-triphosphate synthesis. Thus, monitoring ΔΨm is of great significance for the assessment of cell status, diagnosis of diseases, and medicament screening. Cationic fluorescent probes suffer from severe photobleaching or false positive signals due to the luminescence of the probe on non-mitochondria. Herein, we report a lipophilic cationic fluorescent probe [1-methyl-2-(4-(1,2,2-triphenylvinyl)styryl)-β-naphthothiazol-1-ium trifluoromethanesulfonate (TPE-NT)] with the features of aggregation-induced emission and intramolecular charge transfer for imaging ΔΨm in live cells. TPE-NT is enriched on the surface of the mitochondrial inner membrane due to the negative ΔΨm, and its fluorescence is activated in the high-viscosity microenvironment. The false positive signals of emission from TPE-NT on non-mitochondria are therefore effectively eliminated. Moreover, TPE-NT exhibits a Stokes shift of >200 nm, near-infrared (∼675 nm) emission, excellent photostability, and low cytotoxicity, which facilitate real-time imaging in live cells. Cell imaging confirmed that the probe can rapidly and reliably report mitochondrial depolarization (decrement of ΔΨm) during cell damage caused by CCCP and H2O2 as well as mitochondrial polarization (increment of ΔΨm) by oligomycin. Furthermore, the probe successfully detected the reduction of ΔΨm in these cell models of hypoxia, heat damage, acidification, aging, inflammation, mitophagy, and apoptosis caused by hypoxia, heatstroke, lactate/pyruvate, doxorubicin, lipopolysaccharide, rapamycin, monensin, and nystatin, respectively.

Acetylcholinesterase (AChE) plays crucial roles in the nervous system, and thus the reliable assay of its activity is of great significance for the diagnosis of nervous diseases. In this work, we report a fluorescent sensing platform with silicon quantum dots (Si-QDs) as a fluorescence oscillator and nano iron oxyhydroxide (α-, β-, and γ-FeOOH) as a quencher for the assay of AChE. FeOOH with α-, β-, and γ-crystal forms quenches the fluorescence of Si-QDs at λex/λem = 350/438 nm, which is retrieved in the presence of AChE and its substrate acetylthiocholine (ATCh) to provide an off-on strategy with a high signal/noise ratio. It is interesting that the sensitivity of AChE sensing is closely related to the crystal forms of FeOOH, with the highest sensitivity by adopting α-FeOOH as the quencher. A linear calibration is achieved within 0.02-1.4 U/L along with a limit of detection of 0.016 U/L. The sensing strategy was demonstrated by the AChE assay in human blood, plasma, and hemocytes.

Amyloid-β (Aβ) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer’s disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aβ productions in AD patient’s brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aβ in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aβ production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aβ production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD+/NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aβ1-40/1-42. Taken together, Nmnat2 suppresses Aβ production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.

Residue hepatocellular carcinoma (HCC) cells enduring hypoxic environment triggered by interventional embolization obtain more malignant potential with little clarified mechanism. The N6‐methyladenosine (m6A) biological activity plays essential roles in diverse physiological processes. However, its role under hypoxic condition remains largely unexplored. RT‐qPCR and Western blot were used to evaluate METTL14 expression in hypoxic HCC cells. MDA assay and electronic microscopy photography were used to evaluate ferroptosis. The correlation between SLC7A11 and METTL14 was conducted by bioinformatical analysis. Flow cytometry was used to verify the effect of SLC7A11 on ROS production. Cell counting kit‐8 assay was performed to detect cells proliferation ability. Hypoxia triggered suppression of METTL14 in a HIF‐1α–dependent manner potently abrogated ferroptosis of HCC cells. Mechanistic investigation identified SLC7A11 was a direct target of METTL14. Both in vitro and in vivo assay demonstrated that METTL14 induced m6A modification at 5’UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2‐dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14‐induced tumour‐suppressive effect in hypoxic HCC. Our investigations lay the emphasis on the hypoxia‐regulated ferroptosis in HCC cells and identify the HIF‐1α /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.

Discrimination of glycoproteins and cell types is a significant but difficult issue. Herein, we presented a novel fluorescence sensor array for the detection and identification of glycoproteins and cancer cells based on the specific affinity between boronic acid-containing carbon dots (BA-CDs) and cis-diol residues of polysaccharides. The differential binding affinity of three BA-CDs to various glycoproteins resulted in a different fluorescence turn-on signal pattern caused by aggregation-enhanced emission (AEE), along with negligible response from other proteins. Therefore, BA-CDs encompassing sensing elements and signal indicator into one can enable a fast and accurate discrimination of glycoproteins with simple and easy operation. Seven glycoproteins could be well discriminated at a very low concentration of 10 nmol/L. The discriminating capability of glycoproteins is not sacrificed in both human urine and serum. Notably, different glycoprotein compositions of cancer cells provide more recognizable features for identification of cancer cells, comparing to the total protein. Five cell types could be identified in 15 min at a low concentration of 1000 cells/mL. This method is fast, accurate, and easy operation, and has a potential application in cancer diagnosis.

The medicinal plant Artemisia annua L. is presently the sole plant source of artemisinin, the key ingredient of first-line antimalarial drug. As the content of artemisinin in the native plant is very low, the growth and artemisinin biosynthesis of A. annua attract extensive attentions. Endophytic microbes, which spend their entire life spans within plant tissue are widespread in healthy A. annua plants. Although endophytes have emerged in recent years as the novel resources for secondary metabolites of antioxidant, antimicrobial and anticancer activities, the roles of endophytes in plant growth and metabolism have not been fully understood. This review presents the current development of researches into endophytes in model medicinal herb A. annua and focuses on the regulatory roles of endophytes. We introduced the isolation, cultivation and identification method for endophytes in A. annua. Distribution, biodiversity and novel bioactive metabolites of the endophytes were presented. Endophytes promoted the growth of A. annua through the enhanced photosynthesis, nutrient acquisition and phytohormones. The defense resistance against microbial pathogens of A. annua was partially involved with endophyte metabolites. The development of glandular secretory trichomes and the oxidative stress induced by endophytes could be key factors for enhanced artemisinin production. Understanding the endophyte-host partnerships has the potential to improve agricultural practices for A. annua growth and artemisinin production. The aim of this review is to shed light on the importance of endophytes in plant growth and the production of medicinally important secondary metabolites.

Rationale: The renin-angiotensin system is a complex regulatory network that maintains normal physiological functions. The role of the renin-angiotensin system in sepsis-induced myocardial dysfunction (SIMD) is poorly defined. AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system and gives rise to all angiotensin peptides. The effects and mechanisms of AGT in the development of SIMD have not been defined. Objective: To determine a role of AGT in SIMD and investigate the underlying mechanisms. Methods and Results: Either intraperitoneal injection of lipopolysaccharide or cecal ligation and puncture significantly enhanced AGT abundances in liver, heart, and plasma. Deficiency of hepatocyte-derived AGT, rather than cardiomyocyte-derived AGT, alleviated septic cardiac dysfunction in mice and prolonged survival time. Further investigations revealed that the effects of hepatocyte-derived AGT on SIMD were partially associated with augmented Ang II (angiotensin II) production in circulation. In addition, hepatocyte-derived AGT was internalized by LRP1 (LDL [low-density lipoprotein] receptor-related protein 1) in cardiac fibroblasts and subsequently activated NLRP3 (NLR family pyrin domain-containing 3) inflammasome via an Ang II–independent pathway, ultimately promoting SIMD by suppressing SERCA2a (sarco[endo]plasmic reticulum Ca[2+]-ATPase 2a) abundances in cardiomyocytes. Conclusions: Hepatocyte-derived AGT promoted SIMD via both Ang II–dependent and Ang II–independent pathways. We identified a liver-heart axis by which AGT regulated development of SIMD. Our study may provide a potential novel therapeutic target for SIMD.

Combination therapy has attracted extensive interest in alleviating the shortcomings of monotherapy and enhancing the treatment efficacy. In this work, hollow mesoporous silica nanoparticles (HMSNs) play the role of nanocarriers in the delivery of Cu(II)-doped polydopamine (PDA), termed as HMSNs@PDA-Cu, for synergistic therapy. PDA acts as a traditional photothermal agent to realize photothermal treatment (PTT). Chemodynamic therapy (CDT) is realized by the reaction of Cu(II) with intracellular glutathione (GSH), and subsequently, the generated Cu(I) reacts with H2O2 to produce toxic hydroxyl radical (•OH) through a Fenton-like reaction. The photothermal performance of PDA is improved after its coordination with Cu(II). On the other hand, PDA exhibits superoxide dismutase (SOD)-mimicking activity. PDA converts O2•- to H2O2 and improves the production of H2O2, which promotes the therapeutic effect of CDT. Moreover, the high temperature caused by PTT further enhances the yield of •OH for CDT. This nanotheranostic platform perfectly applied to the tumor depletion of mice, presenting great potential for cancer metastasis therapy in vitro and in vivo.

In recent years, magnetic particle spectroscopy (MPS) has become a highly sensitive and versatile sensing technique for quantitative bioassays. It relies on the dynamic magnetic responses of magnetic nanoparticles (MNPs) for the detection of target analytes in the liquid phase. There are many research studies reporting the application of MPS for detecting a variety of analytes including viruses, toxins, nucleic acids, and so forth. Herein, we report a modified version of the MPS platform with the addition of a one-stage lock-in design to remove the feedthrough signals induced by external driving magnetic fields, thus capturing only MNP responses for improved system sensitivity. This one-stage lock-in MPS system is able to detect as low as 781 ng multi-core Nanomag50 iron oxide MNPs (micromod Partikeltechnologie GmbH) and 78 ng single-core SHB30 iron oxide MNPs (Ocean NanoTech). We first demonstrated the performance of this MPS system for bioassay-related applications. Using the SARS-CoV-2 spike protein as a model, we have achieved a detection limit of 125 nM (equal to 5 pmole) for detecting spike protein molecules in the liquid phase. In addition, using a streptavidin-biotin binding system as a proof-of-concept, we show that these single-core SHB30 MNPs can be used for Brownian relaxation-based bioassays while the multi-core Nanomag50 cannot be used. The effects of MNP amount on the concentration-dependent response profiles for detecting streptavidin were also investigated. Results show that by using a lower concentration/ amount of MNPs, concentration-response curves shift to a lower concentration/amount of target analytes. This lower concentration-response indicates the possibility of improved bioassay sensitivities by using lower amounts of MNPs.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho-alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha-1, 6-11 exhibited more potent herbicidal activity against barnyard grass (Echinochloa crus-galli) and crab grass (Digitaria sanguinalis) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close Ki values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.

Speciation analysis of arsenic in blood is essential for identifying and quantifying the exposure of arsenic and studying the metabolism and toxicity of arsenic. Herein, a novel pretreatment device is rationally designed and used for speciation analysis of arsenic in whole blood by ion chromatography-inductively coupled plasma-mass spectrometry (IC-ICP-MS). The sample centrifuge tubes containing blood, reagents, and a magnetic stir bar are placed on the fidget spinner of the pretreatment device. When flicking the fidget spinner rotation with the finger, the magnetic stir bar in the tube rotates in three dimensions under the magnetic field, thereby assisting dispersive extraction of arsenic species by the mixing of blood with reagents. Afterward, the arsenic extract is separated in situ from the blood matrix using an ultrasonic spray sheet covered with a filter and ultrafiltration membrane, which is directly used for subsequent IC-ICP-MS analysis. For 100 μL of blood, the whole pretreatment operation can be completed within 10 min. With As(III), As(V), MMA, and DMA in blood as analytes, the use of the present pretreatment device will hardly lead to the loss and transformation of arsenic species, and the extraction efficiency of the total arsenic is more than 96%. When the pretreatment device is coupled to IC-ICP-MS, the detection limits of four arsenic species in whole blood are 0.017-0.023 μg L-1, and precisions are within 2.3-4.2%. This pretreatment device provides a simple, fast, efficient, and low-cost tool for extraction and separation of arsenic species in whole blood, opening a new idea for the pretreatment of complex samples.

Background Adenosine 5′-triphosphate (ATP) plays both a central role as an intracellular energy source, and a crucial extracellular signaling role in diverse physiological processes of animals and plants. However, there are less reports concerning the signaling role of microbial extracellular ATP (eATP). Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from bambusicolous Shiraia fungi. The co-culture of Shiraia sp. S9 and a bacterium Pseudomonas fulva SB1 isolated from Shiraia fruiting bodies was established for enhanced hypocrellin A (HA) production. The signaling roles of eATP to mediate hypocrellin biosynthesis were investigated in the co-culture. Results The co-culture induced release of eATP at 378 nM to the medium around 4 h. The eATP release was interdependent on cytosolic Ca2+ concentration and reactive oxygen species (ROS) production, respectively. The eATP production could be suppressed by the Ca2+ chelator EGTA or abolished by the channel blocker La3+, ROS scavenger vitamin C and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). The bacterium-induced H2O2 production was strongly inhibited by reactive blue (RB), a specific inhibitor of membrane purinoceptors, but dependent on the induced Ca2+ influx in the co-culture. On the other hand, the application of exogenous ATP (exATP) at 10–300 µM to Shiraia cultures also promoted fungal conidiation and HA production, both of which were blocked effectively by the purinoceptor inhibitors pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS) and RB, and ATP hydrolase apyrase. Both the induced expression of HA biosynthetic genes and HA accumulation were inhibited significantly under the blocking of the eATP or Ca2+ signaling, and the scavenge of ROS in the co-culture. Conclusions Our results indicate that eATP release is an early event during the intimate bacterial–fungal interaction and eATP plays a signaling role in the bacterial elicitation on fungal metabolites. Ca2+ and ROS are closely linked for activation of the induced ATP release and its signal transduction. This is the first report on eATP production in the fungal–bacterial co-culture and its involvement in the induced biosynthesis of fungal metabolites. Graphic abstract

AIM: To explore whether the retinal neovascularization (NV) in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa (RP) mouse, which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic. METHODS: The Vldlr-/- mice, the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene, with the rd1 mice, the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred. Intercrossing of the above two mice led to the birth of the F1 hybrids, further inbreeding of which gave birth to the F2 offspring. The ocular genotypes and phenotypes of the mice from all generations were examined, with the F2 offspring grouped according to the genotypes. RESULTS: The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function. The Vldlr-/- mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography. The F1 hydrides, with the heterozygote genotype, exhibited no phenotypes of RP or retinal NV. The F2 offspring with homozygous genotypes were grouped into four subgroups. They were the F2-I mice with the wild-type Pde6b and Vldlr genes (Pde6b+/+-Vldlr+/+), which had normal ocular phenotypes; the F2-II mice with homozygous mutant Vldlr gene (Pde6b+/+-Vldlr-/-), which exhibited the retinal NV phenotype; the F2-III mice with homozygous mutant Pde6b gene (Pde6b-/--Vldlr+/+), which exhibited the RP phenotype. Specifically, the F2-IV mice with homozygous mutant Vldlr and Pde6b gene (Pde6b-/--Vldlr-/-) showed only the RP phenotype, without the signs of retinal NV. CONCLUSION: The retinal NV can be inhibited by the RP phenotype, which implies the role of a hyperoxic state in treating retinal NV diseases.

A palladium supported on graphitic carbon nitride (Pd/g-C3 N4 ) catalyzed carbonylative reaction of aryl bromides and arylboronic acids by has been developed for the construction of diaryl ketones. Using benzene-1,3,5-triyl triformate (TFBen) as the CO source, the reaction proceeded well to give various diaryl ketones in moderate to good yields.

Tumor exosomes with molecular marker-proteins inherited from their parent cells have emerged as a promising liquid biopsy biomarker for cancer diagnosis. However, facile, robust, and sensitive detection of exosomal proteins remains challenging. Therefore, a nanozyme sensor array is constructed by using aptamer-modified C3N4 nanosheets (Apt/C3N4 NSs) together with a solvent-mediated signal amplification strategy for ratiometric fluorescence detection of exosomal proteins. Three aptamers specific to exosomal proteins are selected to construct Apt/C3N4 NSs for high specific recognition of exosomal proteins. The adsorption of aptamers enhances the catalytic activity of C3N4 NSs as a nanozyme for oxidation of o-phenylenediamine (oPD) to 2,3-diaminophenazine (DAP). In the presence of target exosomes, the strong affinity between aptamer and exosome leads to the disintegration of Apt/C3N4 NSs, resulting in a decrease of catalytic activity, thereby reducing the production of DAP. The ratiometric fluorescence signal based on a photoinduced electron transfer (PET) effect between DAP and C3N4 NSs is dependent on the concentration of DAP generated, thus achieving highly facile and robust detection of exosomal proteins. Remarkably, the addition of organic solvent-1,4-dioxane can sensitize the luminescence of DAP without affecting the intrinsic fluorescence of C3N4 NSs, achieving the amplification of the aptamer-exosome recognition events. The detection limit for exosome is 2.5 × 103 particles/mL. In addition, the accurate identification of cancer can be achieved by machine learning algorithms to analyze the difference of exosomal proteins from different patients' blood. We hope that this facile, robust, sensitive, and versatile nanozyme sensor array would become a promising tool in the field of cancer diagnosis.

A novel norditerpenoid, sinusiaetone A (1), featuring an uncommon bicyclo[11.3.0]hexadecane carbon skeleton, and four polyoxygenated cembranoids (2-5) were isolated from the Hainan soft coral Sinularia siaesensis. Their structures were established by spectroscopic analysis, X-ray diffraction, quantum chemical computational approaches, and/or a modified Mosher's method. A plausible biosynthetic pathway of 1 and its biogenetic relationship with 2-5 were proposed. New compounds 1-3 displayed an interesting inhibitory activity against lipopolysaccharide-induced inflammation in BV-2 microglial cells.

Dry reforming of methane (DRM) is a feasible solution to cope with the reduction of greenhouse gas under the Paris Convention's obligations, given that it adds value by converting trivial gases of CO2 and CH4 simultaneously into useful syngas. However, conventional Ni catalyst undergoes deactivation due to carbon coking and particle agglomeration. Here we demonstrate for the first time a highly efficient and durable DRM catalyst of exsolved Co-Ni-Fe ternary alloy nanoparticles on the layered perovskite PrBaMn1.7Co0.1Ni0.2O5+d produced by topotactic exsolution. This readily allows the generation of a larger number of exsolved nanoparticles, enhancing catalytic activity above those of Ni monometallic and Co-Ni bimetallic particles. The enhancement is achieved by the optimal up-shift of the d-band center of Co-Ni-Fe than those of Co-Ni and Ni meaning easier charge donation to the adsorbate. Furthermore, the exsolved catalyst shows exceptional stability with the continuous DRM operation for about 350 hours.

Luminescent cuprous complexes are important coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The structures of two CuIP2S-type cuprous complexes, namely, iodido(thiourea-κS)bis(triphenylphosphane-κP)copper(I), [CuI(CH4N2S)(C18H15P)2] or [CuI(TU)(TPP)2] (I), and (2,3-dihydrobenzimidazole-2-thione-κS)iodidobis(triphenylphosphane-κP)copper(I), [CuI(C7H6N2S)(C18H15P)2] or [CuI(DHBIT)(TPP)2] (II), are described. In these two structures, the complex molecules of both are constructed by one copper(I) centre, one iodide ion, two TPP ligands and one thione ligand (TU for I and DHBIT for II). The copper(I) centres of I and II are both located in a distorted CuIP2S tetrahedron and are coordinated by two P atoms from two TPP ligands, one S atom from the thione ligand and the I atom. The UV–Vis absorption and photoluminescence properties of these CuIP2S-type cuprous complexes have been studied using crystalline powder samples. Detailed time-dependent density functional theory (TD-DFT) calculations and wavefunction analysis reveal that the pale-blue–green phosphorescence emission should originate from intra-ligand (TPP for I and DHBIT for II) charge transfer, with a small component of the metal-to-ligand charge transfer 3(IL+ML)CT excited state.

Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders. MicroRNA-195 (miR-195) regulates the stability and translation of target mRNAs and is involved in many aspects of cell processes and pathologies. Here, we reported the posttranscriptional mechanisms by which miR-195 regulates Tuft and Paneth cell function in the small intestinal epithelium. Mucosal tissues from intestinal epithelial tissue-specific miR-195 transgenic (miR195-Tg) mice had reduced numbers of double cortin-like kinase 1 (DCLK1)-positive (Tuft) and lysozyme-positive (Paneth) cells, compared with tissues from control mice, but there were no effects on Goblet cells and enterocytes. Intestinal organoids expressing higher miR-195 levels from miR195-Tg mice also exhibited fewer Tuft and Paneth cells. Transgenic expression of miR-195 in mice failed to alter growth of the small intestinal mucosa but increased vulnerability of the gut barrier in response to lipopolysaccharide (LPS). Studies aimed at investigating the mechanism underlying regulation of Tuft cells revealed that miR-195 directly interacted with the Dclk1 mRNA via its 3′-untranslated region and inhibited DCLK1 translation. Interestingly, the RNA-binding protein HuR competed with miR-195 for binding Dclk1 mRNA and increased DCLK1 expression. These results indicate that miR-195 suppresses the function of Tuft and Paneth cells in the small intestinal epithelium and further demonstrate that increased miR-195 disrupts Tuft cell function by inhibiting DCLK1 translation via interaction with HuR.

Dysregulation of glucose homeostasis contributes to insulin resistance and type 2 diabetes. Whilst exercise stimulated activation of AMP-activated protein kinase (AMPK), an important energy sensor, has been highlighted for its potential to promote insulin-stimulated glucose uptake, the underlying mechanisms for this remain largely unknown. Here we found that AMPK positively regulates the activation of Rab5, a small GTPase which is involved in regulating Glut4 translocation, in both myoblasts and skeletal muscles. We further verified that TBC1D17, identified as a potential interacting partner of Rab5 in our recent study, is a novel GTPase activating protein (GAP) of Rab5. TBC1D17-Rab5 axis regulates transport of Glut1, Glut4, and transferrin receptor. TBC1D17 interacts with Rab5 or AMPK via its TBC domain or N-terminal 1-306 region (N-Ter), respectively. Moreover, AMPK phosphorylates the Ser 168 residue of TBC1D17 which matches the predicted AMPK consensus motif. N-Ter of TBC1D17 acts as an inhibitory region by directly interacting with the TBC domain. Ser168 phosphorylation promotes intra-molecular interaction and therefore enhances the auto-inhibition of TBC1D17. Our findings reveal that TBC1D17 acts as a molecular bridge that links AMPK and Rab5 and delineate a previously unappreciated mechanism by which the activation of TBC/RabGAP is regulated.

Immune checkpoint inhibitors (ICIs) have achieved prominent efficacy in the treatment of numerous cancers, which is the most significant breakthrough in cancer therapy in recent years. However, ICIs are associated with a series of immune‐related adverse events (irAEs). Pneumonitis is an uncommon but potentially fatal irAE. In the case reported here, a patient with advanced small cell lung cancer (SCLC) had rapid progression of disease following chemotherapy and received ICIs. The patient experienced severe immune‐related hyperthermia followed by immune‐related pneumonitis. Fortunately, a good clinical response was achieved after the patient received corticosteroids and tocilizumab., The patient with SCLC reported here experienced severe immune‐related hyperthermia followed by immune‐related pneumonitis. Fortunately, a good clinical response was achieved after the patient received steroids and tocilizumab.

The past decade has seen tremendous progress in the synthesis and surface functionalization of iron oxide nanoparticles (IONPs) for a variety of biomedical applications. However, there is still a g...

Cementum, a specialized bony layer covering an entire molar root surface, anchors teeth into alveolar bone. Gli1, a key transcriptional activator in Hedgehog signaling, has been identified as a mesenchymal progenitor cell marker in various tissues, including the periodontal ligament (PDL). To address the mechanisms by which Gli1+ progenitor cells contribute to cementogenesis, we used the Gli1lacZ/+ knock-in line to mark Gli1+ progenitors and the Gli1CreERT2/+; R26RtdTomato/+ line (named Gli1Lin) to trace Gli1 progeny cells during cementogenesis. Our data unexpectedly displayed a biphasic feature of Gli1+ PDL progenitor cells and cementum growth: a negative relationship between Gli1+ progenitor cell number and cementogenesis but a positive correlation between Gli1-derived acellular and cellular cementoblast cell number and cementum growth. DTA-ablation of Gli1Lin cells led to a cementum hypoplasia, including a significant reduction of both acellular and cellular cementoblast cells. Gain-of-function studies (by constitutive stabilization of β-catenin in Gli1Lin cells) revealed a cementum hyperplasia. A loss of function (by conditional deletion of β-catenin in Gli1+ cells) resulted in a reduction of postnatal cementum growth. Together, our studies support a vital role of Gli1+ progenitor cells in contribution to both types of cementum, in which canonical Wnt/β-catenin signaling positively regulates the differentiation of Gli1+ progenitors to cementoblasts during cementogenesis.

Exosomes are expected to be used as cancer biomarkers because they carry a variety of cancer-related proteins inherited from parental cells. However, it is still challenging to develop a sensitive, robust, and high-throughput technique for simultaneous detection of exosomal proteins. Herein, three aptamers specific to cancer-associated proteins (CD63, EpCAM, and HER2) are selected to connect gold nanoparticles (AuNPs) as core with three different elements (Y, Eu, and Tb) doped up-conversion nanoparticles (UCNPs) as satellites, thereby forming three nanosatellite assemblies. The presence of exosomes causes specific aptamers to recognize surface proteins and release the corresponding UCNPs, which can be simultaneously detected by inductively coupled plasma-mass spectrometry (ICP-MS). It is worth noting that rare earth elements are scarcely present in living systems, which minimize the background for ICP-MS detection and exclude potential interferences from the coexisting species. Using this method, we are able to simultaneously detect three exosomal proteins within 40 min, and the limit of detection for exosome is 4.7 × 103 particles/mL. The exosomes from seven different cell lines (L-02, HepG2, GES-1, MGC803, AGS, HeLa, and MCF-7) can be distinguished with 100% accuracy by linear discriminant analysis. In addition, this analytical strategy is successfully used to detect exosomes in clinical samples to distinguish stomach cancer patients from healthy individuals. These results suggest that this sensitive and high-throughput analytical strategy based on ICP-MS has the potential to play an important role in the detection of multiple exosomal proteins and the identification of early cancer.

The miniaturized optical emission spectrometry (OES) devices based on various microplasma excitation sources provide reliable tools for on-site analysis of heavy metal pollution, while the development of convenient and efficient sample introduction approaches is essential to improve their performances for field analysis. Herein, a small activated carbon electrode tip is employed as solid support to preconcentrate heavy metals in water and subsequently served as an inner electrode of the coaxial dielectric barrier discharge (DBD) to generate microplasma. In this case, heavy metal analytes in water are first adsorbed on the surface of the activated carbon electrode tip via a simple liquid-solid phase transformation during the sample loading process, and then, fast released to produce OES during the DBD microplasma excitation process. The corresponding OES signals are synchronously recorded by a charge-coupled device (CCD) spectrometer for quantitative analysis. This activated carbon electrode tip provides a new tool for sample introduction into the DBD microplasma and facilitates "insert-and-go" in subsequent DBD-OES analysis. With a multiplexed activated carbon electrode tip array, a batch of water samples (50 mL) can be loaded in parallel within 5 min. After drying the activated carbon electrode tips for 5 min, the DBD-OES analysis is maintained at a rate of 6 s per sample. Under the optimized conditions, the detection limits of 0.03 and 0.6 μg L-1 are obtained for Cd and Pb, respectively. The accuracy and practicability of the present DBD-OES system have been verified by measuring several certified reference materials and real water samples. This analytical strategy not only simplifies the sample pretreatment steps but also significantly improves the sensitivity of the DBD-OES system for heavy metal detection. By virtue of the advantages of high sensitivity, fast analysis speed, simple operation, low cost, and favorable portability, the upgraded DBD-OES system provides a more powerful tool for on-site analysis of heavy metal pollution.

Bulk chalcogenide compounds with chemical formula A2X3 (A = As, Sb, Bi, and X = S, Se, Te) are usually semiconductors, topological insulators, and thermoelectric materials. The layers are stacked t...

Objectives Pancreatic carcinoma (PC) has become the fourth leading cause of cancer deaths. Long noncoding RNA DUXAP8 has also been reported to play a regulatory role in PC progression. However, its molecular mechanism in PC is not fully elucidated. Methods Quantitative real-time polymerase chain reaction was used to detect the levels of DUXAP8, microRNA (miR)-448, Wilms tumor 1-associating protein (WTAP), focal adhesion kinase (Fak), and matrix metallopeptidase 2/9. Western blotting was carried out to detect matrix metallopeptidase 2/9, WTAP, Fak, and p-Fak. The interaction between DUXAP8 and miR-448 as well as WTAP and miR-448 was validated by bioinformatics and dual-luciferase reporter assays. Transwell assay was used to analyze cell invasion and migration. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to analyze cell proliferation. Results DUXAP8 was upregulated, whereas miR-448 was downregulated in PC tissue and cells. Meanwhile, DUXAP8 knockdown or miR-448 overexpression inhibited migration, invasion, and proliferation of PC cells. DUXAP8 directly targeted miR-448, and miR-448 directly bound to WTAP. Downregulation of miR-448 reversed the inhibition of migration and invasion of PC cells by DUXAP8 knockdown. Conclusions DUXAP8 sponges miR-448 to modulate migration, invasion, and proliferation of PC cells, indicating a novel mechanistic role of DUXAP8 in the regulation of PC progression.

We developed a salt-template strategy to prepare MoS2 nanoparticles (NPs) embedded, N, S co-doped carbons via the solid-state process. The addition of the inorganic salt played two main roles in the synthetic proceeding. First, the salts could be utilized as the templates to produce the mesopores, which could be removed by simple washing process. Second, the salts could promote the formation of MoS2 NPs. The as-received electrocatalyst, K-G4.0T2.0Mo1.0, possessed high BET surface area of 446 m2 g−1, in addition to high double layer capacitance of 24.5 mF cm−2 in the alkaline media. When evaluated as the electrocatalyst for hydrogen evolution reaction (HER), K-G4.0T2.0Mo1.0 demonstrated excellent performance in the alkaline and neutral medias. In details, K-G4.0T2.0Mo1.0 showed a low overpotential of 173 and 358 mV to afford 10 mA cm−2 under alkaline and neutral conditions, respectively, as well as outstanding durability.

Mercury (Hg), a kind of heavy metal pollutant, has a great impact on the environment and human health. The highly efficient technology for Hg removal has attracted widespread attention from researchers. In this study, the coal gasification slag (CGS) and the slag after sorting were used as sorbents, and the Hg0 removal performance of the sorbents were investigated through the fixed-bed reactor and entrained flow reactor. The characterization methods such as N2 adsorption-desorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) were performed to analyze the physical and chemical characteristics of the sorbents. According to the results of fixed-bed Hg0 removal experiment, the Hg0 removal efficiency of the origin slag (OS) and high carbon slag (HCS) could maintain more than 91% at 60–120°C. The high ash slag (HAS) showed the highest Hg0removal efficiency of 97% at 60°C, which was greatly affected by the Hg0 removal temperature. The Hg-TPD (Hg-temperature program desorption) and XPS results indicated that the chemisorbed oxygen on the sorbent participated in the Hg0 oxidation process with HgO formed on the surface of the sorbent. According to the results of entrained flow Hg0 removal experiments, the Hg0 removal efficiencies of OS and HCS were 56% and 57% at C/Hg ratio of 40000 and the Hg0 removal temperature of 60°C, respectively. When the C/Hg ratio was 80000 and the Hg0 removal temperature was 60°C, the Hg0 removal efficiencies of OS and HCS were 100% and 82%, respectively.

This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR).Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB.This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up.A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups.In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

Lipid droplets (LDs) are intracellular lipid-rich organelles, which not only serve as neutral lipid reservoirs but also involve in many physiological processes and are associated with a variety of metabolic diseases and cancers. Long-term tracking of the state and behavior of LDs is of great significance but challenging. The difficulty is largely due to the lack of low cytotoxicity, high photobleaching resistance, and long intracellular retention probes that are capable of long-term tracking LDs. Herein, we report the discovery of two amphiphilic LD-targeting carbon nanoparticles (CNPs, i.e., CPDs and CDs) prepared by one-step room-temperature and hydrothermal methods. Their high lipid-water partition coefficient (log P > 2.13) and strong positive solvatochromism property ensure the quality of LD imaging. Especially, CDs exhibit favorable biocompatibility (2 mg mL-1, cell viability >90%), excellent photostability (after continuous laser irradiation on a confocal microscope for 2 h, relative FL intensity >85%), and superior intracellular retention ability, thereby enabling long-term tracking of LDs in hepatocytes for up to six passages. Based on the excellent long-term tracking ability, CDs are successfully applied to observe autophagy in a typical catabolic process and to evaluate the effect of a commonly used lipid-lowering drug atorvastatin on hepatocyte lipid uptake.

Intracellular accumulation of tau is a hallmark pathology in Alzheimer disease (AD) and the related tauopathies, thus targeting tau could be promising for drug development. Proteolysis Targeting Chimera (PROTAC) is a novel drug discovery strategy for selective protein degradation from within cells. Methods: A novel small-molecule PROTAC, named as C004019 with a molecular mass of 1,035.29 dalton, was designed to simultaneously recruite tau and E3-ligase (Vhl) and thus to selectively enhance ubiquitination and proteolysis of tau proteins. Western blotting, immunofluoresence and immunohistochemical staining were employed to verify the effects of C004019 in cell models (HEK293 and SH-SY5Y) and mouse models (hTau-transgenic and 3xTg-AD), respectively. The cognitive capacity of the mice was assessed by a suite of behavior experiments. Electrophysiology and Golgi staining were used to evaluate the synaptic plasticity. Results: C004019 induced a robust tau clearance via promoting its ubiquitination-proteasome-dependent proteolysis in HEK293 cells with stable or transient overexpression of human tau (hTau), and in SH-SY5Y that constitutively overexpress hTau. Furthermore, intracerebral ventricular infusion of C004019 induced a robust tau clearance in vivo. Most importantly, both single-dose and multiple-doses (once per 6 days for a total 5 times) subcutaneous administration of C004019 remarkably decreased tau levels in the brains of wild-type, hTau-transgenic and 3xTg-AD mice with improvement of synaptic and cognitive functions. Conclusions: The PROTAC (C004019) created in the current study can selectively and efficiently promote tau clearance both in vitro and in vivo, which provides a promising drug candidate for AD and the related tauopathies.

Microwave ablation is a first-line treatment of small hepatocellular carcinoma (HCC), while incomplete ablation induces recurrence and metastasis. However, its underlying mechanism remains largely unexplored. Here we reported that sublethal heat treatment (46 °C) strongly promoted migration and EMT transition in HCC cells. Mechanistic investigation revealed that compared with 37 °C, HCC cells treated with 46 °C expressed higher level of CD47. Knockdown of CD47 significantly attenuated sublethal heat treatment stimulated migration and EMT transition. In addition, METTL3 which is the key enzyme of m6A modification was also induced by 46 °C treatment and triggered CD47 expression in HCC cells. Moreover, CD47 mRNA degradation was further proved to be stabled in the IGF2BP1-dependent manner. Importantly, sublethal heat treatment stimulated CD47 expression and EMT transition were also confirmed in patient-derived organoid. Taken together, our study suggests that METTL3/IGF2BP1/CD47 mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells. Moreover, these findings identify the METTL3/IGF2BP1/CD47 axis as a potential therapeutic target for the microwave ablation and shed new lights on the crosstalk between incomplete heat ablation and RNA methylation.