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Sclerotinia sclerotiorum is a devastating plant pathogen that causes substantial losses in various agricultural crops. Although plants have developed some well-known defense mechanisms against invasive fungi, much remains to be learned about plant responses to fungal pathogens. In this study, we investigated how S. sclerotiorum infection affects plant primary and secondary metabolism in the model plant Arabidopsis thaliana. Our results showed that soluble sugar and amino acid content changed significantly in A. thaliana leaves upon fungal colonization, with a decrease in sucrose and an increase in mannitol, attributed to fungal biosynthesis. Furthermore, the jasmonate signaling pathway was rapidly activated by S. sclerotiorum infection, and there was a striking accumulation of antifungal metabolites such as camalexin, p-coumaroyl agmatine, feruloyl agmatine, and Nδ-acetylornithine. On the other hand, the characteristic defense compounds of the Brassicaceae, the glucosinolates, were not induced in A. thaliana infected by S. sclerotiorum. Our study provides a better understanding of how A. thaliana primary and secondary metabolism is modified during infection by a fungal pathogen like S. sclerotiorum that has both hemibiotrophic and necrotrophic stages.

Ultradeep carbonate gas reservoirs are a major resource of interest in clean energy development, and complex pore structures and reservoir conditions with high-temperatures and pressures are great ...

Micro-hole voltammetry exhibiting rectified current-voltage curves was performed in hydrochloric acid by varying the lengths and the diameters of the micro-holes on one end of which a Nafion film was mounted. Some voltammetric properties were compared with those in NaCl solution. The voltammograms were composed of two line-segments, the slope of one segment being larger than the other. They were controlled by electric migration partly because of the linearity of the voltammograms and partly the independence of the scan rates. Since the low conductance which appeared in the current from the hole to the Nafion film was proportional to the cross section area of the hole and the inverse of the length of the hole, it should be controlled by the geometry of the hole. The conductance of the hydrogen ion in the Nafion film was observed to be smaller than that in the bulk, because the transport rate of hydrogen ion by the Grotthuss mechanism was hindered by the destruction of hydrogen bonds in the film. In contrast, the conductance for the current from the Nafion to the hole, enhancing by up to 30 times in magnitude from the opposite current, was controlled by the cell geometry rather than the hole geometry except for very small holes. A reason for the enhancement is a supply of hydrogen ions from the Nafion to increase the concentration in the hole. The concentration of the hydrogen ion was five times smaller than that of sodium ion because of the blocking of transport of the hydrogen ion in the Nafion film. However, the rectification ratio of H+ was twice as large as that of Na+.

Brassicales plants produce glucosinolates and myrosinases that generate toxic isothiocyanates conferring broad resistance against pathogens and herbivorous insects. Nevertheless, some cosmopolitan fungal pathogens, such as the necrotrophic white mold Sclerotinia sclerotiorum, are able to infect many plant hosts including glucosinolate producers. Here, we show that S. sclerotiorum infection activates the glucosinolate-myrosinase system, and isothiocyanates contribute to resistance against this fungus. S. sclerotiorum metabolizes isothiocyanates via two independent pathways: conjugation to glutathione and, more effectively, hydrolysis to amines. The latter pathway features an isothiocyanate hydrolase that is homologous to a previously characterized bacterial enzyme, and converts isothiocyanate into products that are not toxic to the fungus. The isothiocyanate hydrolase promotes fungal growth in the presence of the toxins, and contributes to the virulence of S. sclerotiorum on glucosinolate-producing plants., Some plants produce toxic isothiocyanates that protect them against pathogens. Here, Chen et al. show that the plant pathogenic fungus Sclerotinia sclerotiorum converts isothiocyanates into non-toxic compounds via glutathione conjugation and, more effectively, via hydrolysis to amines using an isothiocyanate hydrolase.

The design of powerful, more biocompatible microrobots calls for faster catalytic reactions. Here we demonstrate a two-fold increase in the speed of photocatalytic TiO2-metal Janus micromotors via a Au/Ag bi-layered coating. Electrochemical measurements show that such a bimetallic coating is a better photocatalyst than either metal alone. Similarly, an additional sputtered Ag layer could also significantly increase the speed of Pt-PS or TiO2-Pt micromotors, suggesting that applying bimetallic coatings is a generalizable strategy in the design of faster catalytic micromotors.

A facile and efficient synthesis of hemin containing metal–organic framework (MOF) nanocomposite was reported. Two dimensional (2D) Ni–MOF nanosheets have been used as a new type of matrix material to immobilize hemin. Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS)–mapping, thermal gravity analysis (TGA) suggest the hemin is uniformly distributed in the Ni–MOF nanosheets. Ultraviolet–visible spectroscopy (UV–vis) analysis shows that hemin molecules are combined with MOFs nanosheets through π–π interaction. Electrochemical study indicates the Ni–MOFs/Hemin nanocomposite exhibits high electro–catalytic activities for H2O2 reduction and the biosensor offers high performance with a low detection limit of 0.2 μM and a wide linear range of 1 μM–0.4 mM. Furthermore, the Ni–MOFs/Hemin nanocomposite based biosensor displays high selectivity and stability owing to the protective effect of the 2D MOF nanosheets. More importantly, the biosensor was used to determine the H2O2 levels in human serum and disinfectant samples with satisfactory results.

Cation transport through nanochannels in graphene oxide can be rectified to give ionic diode devices for future applications, for example, in desalination. A film of graphene oxide is applied to a 6 μm thick poly(ethylene terephthalate) substrate with a 20 μm diameter microhole and immersed in aqueous HCl solution. Strong diode effects are observed even at high ionic strength (0.5 M). Switching between open and closed states, microhole size effects, and time-dependent phenomena are explained on the basis of a simplified theoretical model focusing on the field-driven transport within the microhole region. In aqueous NaCl, competition between Na + transport and field-driven heterolytic water splitting is observed but shown to be significant only at low ionic strength. Therefore, nanostructured graphene oxide is demonstrated to exhibit close to ideal behavior for future application in ionic diode desalination of seawater.

A silver electrode was anodized in lowly concentrated potassium chloride solution almost under the steady state to generate a deposit of silver chloride on the electrode, and the deposit was cathodically stripped by linear potential scan to evaluate the reduction charge. Then the oxidation charge was larger than the reduction one. Since the equality was valid for long term chronocoulometry at the double potential step, the inequality is not due to any irreversibility of electrode reactions, but can be attributed to the process of the cathodic potential scan. A reason for the inequality is the negative charge of the capacitance involved in the electrode reaction, which has been observed in simple, dissolved redox species like a ferrocenyl derivative. The negative capacitive currents are conspicuous for high concentrations of redox species on the electrode because they result from the orientation of the dipoles of the redox species coupled with counterion, of which direction is opposite to that of the solvent dipoles. If a silver chloride film was thin enough to be regarded as a monolayer, we found that half of the cathodic stripping charge should be lost by the negative capacitance.

Background. There is significant controversy relating to whether chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with pulmonary arterial hypertension- (PAH-) targeted therapies and which therapy is the optimal choice for patients. A large number of randomized controlled trials (RCTs) have compared PAH-targeted therapies with placebo or conventional therapies. In this study, we aimed to compare all of the PAH-targeted medications that are used to treat CTEPH and rank their efficacy by the application of network meta-analysis (NMA). Methods. We searched PubMed, EMBASE, Web of Science, the Cochrane Central Register, https://clinicaltrials.gov, and who.int/trialsearch/, for relevant RCTs published up to January 2020. In addition to traditional meta-analysis, we also performed NMA in our systematic review, as deployed in a previous protocol (PROSPERO: CRD42020173765). Results. Our study identified eight eligible RCTs that evaluated seven PAH-targeted therapies in 703 patients with CTEPH. NMA revealed that riociguat was ranked first as the most optimized therapy for ameliorating the 6-minute walk distance with a probability of 80.4%. Bosentan was significantly better than others with regard to reducing brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide with a probability of 84.3%. Sildenafil was identified as the best drug in terms of improving the New York Heart Association/World Health Organization functional class with a probability of 87.3%. Treprostinil and macitentan were more beneficial than other drugs in reducing pulmonary vascular resistance and lowering the incidence of clinical worsening with probabilities of 86.2% and 79.2%, respectively. Conclusion. Analysis revealed positive advantages for the use of PAH-targeted drugs in patients with CTEPH. Overall, treprostinil and riociguat were superior to all other PAH-targeted medications in most of the outcomes investigated.

Background The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future. Methods In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs. Results The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration. Conclusion In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.

While transient fibroblast activation is a normal and adaptive aspect of injury-repair in many contexts, persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF) and other chronic fibrotic lung diseases. The mechanisms regulating persistent fibroblast activation in IPF have not been fully elucidated. In the lungs of IPF patients and in mice with experimental lung fibrosis, we observed that expression of the thromboxane-prostanoid receptor (TBXA2R) was increased in fibroblasts. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, suggesting an alternative ligand activates profibrotic TBXA2R signaling. We found that F2-isoprostanes (F2-IsoPs), nonezymatic products of arachidonic acid metabolism generated in the setting of reactive oxygen species (ROS), are persistently elevated in experimental lung fibrosis and act as an alternative TBXA2R ligand. Further studies demonstrated that F2-isoprostanes signal through TBXA2R to activate Smad signaling, revealing TBXA2R as a previously unrecognized regulator of the transforming growth factor beta (TGF-β) pathway. Further, treatment with the small-molecule TBXA2R antagonist ifetroban protected mice from lung fibrosis in three pre-clinical models: bleomycin treatment, Hermansky-Pudlak Syndrome, and radiation-induced fibrosis. Importantly, treatment with ifetroban during the fibrotic phase of bleomycin injury markedly enhanced fibrotic resolution. Together, these studies implicate TBXA2R signaling as a crucial mediator linking oxidative stress to fibroblast activation and indicate that TBXA2R antagonists could be efficacious for treatment of IPF and other chronic fibrotic disorders.

Background Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. Methods In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. Results Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. Conclusion In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.

Assembly of microdevices from constituent parts currently relies on slow serial steps via direct assembly processes such as pick-and-place operations. Template Electrokinetic Assembly (TEA), a guided, noncontact assembly process, is presented in this work as a promising alternative to serial assembly processes. To characterize the process and its implementation of electrokinetic, dielectrophoretic, and electro-osmotic phenomena, we conducted studies to examine the assembly of polymer microparticles at specific locations on glassy carbon interdigitated electrode arrays (IDEAs). The IDEAs are coated with a layer of lithographically patterned resist, so that when an AC electric field is applied to the IDEA, microparticles suspended in the aqueous solution are attracted to the open regions of the electrodes not covered by photoresist. Interplay between AC electro-osmosis and dielectrophoretic forces guides 1 and 5 μm diameter polystyrene beads to assemble in regions, or "wells", uncovered by photoresist atop the electrodes. It was discovered that AC electro-osmosis under an applied frequency of 1 kHz is sufficient to effectively agglomerate 1 μm beads in the wells, whereas a stepwise process involving the application of a 1 MHz signal, followed by a 1 kHz signal, is required for the positioning of 5 μm beads, which are mainly affected by dielectrophoretic forces. Permanent entrapment of the microparticles is then demonstrated via the electropolymerization process of the conducting polymer polypyrrole.

The pore structures of shallow and mid-deep carbonate gas reservoirs have been well explored. Totally different from these reservoirs, however, the pore structure of a target ultra-deep carbonate gas reservoir, the Qixia Reservoir in the Shuangyushi play is still unknown. Affected by tectonic movement and deep hydrothermal transformation, the lithology of this target reservoir has significantly changed and it has developed different scales of pores and fractures. Thus, a multiscale micro-CT (computed tomography) method is needed to combine different scales of its pore space to evaluate carbonate samples more realistically. In this study, the multiscale micro-CT method and other traditional methods including X-ray diffraction (XRD), casting thin section, scanning electron microscope (SEM), routine petrophysical measurements (RPM), and high-pressure mercury intrusion (HPMI) are first combined to quantitatively describe a distribution of multi-scale pores, throats, and fractures in the target ultra-deep carbonate gas reservoir. The results showed that micro pores (70%–90%), micro throats (>90%), and micro fractures (>90%) dominated in this reservoir. Dolomite accounted for more than 90% of the rock mineral composition in the Qixia reservoir with few clay minerals. Intercrystalline pores and micro fractures were the main pore types and the mean reservoir porosity was less than 2%. Micro fractures play a great role in improving reservoir permeability. The HPMI method presented with errors in the classification of ultra-deep carbonate reservoir types owing to the development of vugs, large pores, and fractures. In this study, a new classification method was proposed to classify this type of reservoirs based on porosity, permeability, and the studied parameters from the multiscale micro-CT method such as throat number and connected porosity proportion. The target reservoir was divided into the following four categories according to the new classification method: fracture macropore type (FMA), macropore type (MA), fracture micropore type (FMI), and micropore type (MI). According to the results of multiscale CT scanning, a strong linear relationship was observed between the number of throats, the connected porosity, and the permeability of the ultra-deep carbonate rock samples studied. Fractures improved the permeability of rock samples by aiding the connection of isolated pores and the expansion of the number of throats. Therefore, the MA and MI types of reservoirs should be properly fractured to increase their productivity.

A two-dimensional (2D) Ni based metal-organic framework (MOF) nanosheets were synthesized using a one-step solvent-thermal method. The as-prepared nanosheets were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and energy disperse spectroscopy (EDS) mapping. Ni-MOF nanosheet was first time found to used as a peroxidase mimetic with catalytic activities and could catalyze the oxidation of the substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). Catalytic mechanism analysis suggested the enzymatic kinetics of Ni-MOF nanosheets followed typical Michaelis-Menten theory and Ni-MOF nanosheets possess a higher affinity for two substrates (TMB and H2O2) than horseradish peroxidase (HRP). Furthermore, Ni-MOF nanosheet was applied to establish an H2O2 colorimetric sensor which deserves a wide linear range of 0.04 ~ 160 μM and a low detection limit of 8 nM. Also the application of this sensor for H2O2 detection in human serum and disinfectant was demonstrated and satisfactory results were obtained. Thus, the simple and sensitive Ni-MOF/TMB/H2O2 colorimetric system has great promising applications in clinical medicine and food environment analysis.

The Hippo‑yes‑associated protein (YAP) signaling pathway was previously identified to serve an important role in controlling chondrocyte differentiation and post‑natal growth. Growth plate cartilage tissue is avascular, and hypoxia‑inducible factor (HIF)‑1α is essential for chondrocytes to maintain their chondrogenic phenotype in a hypoxic environment. In the present study, the role of hypoxia and HIF‑1α in the regulation of YAP in chondrocytes was investigated. The data demonstrated that hypoxia promoted the maintenance of the chondrogenic phenotype, HIF‑1α expression and YAP activation in chondrocytes in a time‑dependent manner. Hypoxia promoted YAP activation in a Hippo‑independent manner. Inhibiting the expression of HIF‑1α decreased the activation of YAP and downregulated the expression of sex‑determining region‑box 9 protein (SOX9) under hypoxic conditions, while the upregulation of HIF‑1α by cobalt chloride promoted the expression and nuclear translocation of YAP and upregulated the expression of SOX9 and collagen II chain under normoxic conditions. In addition, inhibition of YAP expression under hypoxia did not affect the expression of the HIF‑1α signaling pathway, but inhibited the up‑regulation of SOX9 expression caused by hypoxia. In addition, reoxygenation following hypoxia inhibited the activation of YAP caused by hypoxia in chondrocytes, whereas the upregulation of SOX9 and collagen II chain also appeared to be inhibited. In conclusion, the results of the present study demonstrated that hypoxia promoted YAP activation via HIF‑1α. Therefore, the HIF‑1α/YAP signaling axis may serve an important role in controlling growth plate chondrocyte differentiation and the maintenance of the chondrogenic phenotype in growth plate chondrocytes.

Background Restoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated. Methods In the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation. Results It was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups. Conclusion The combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.

Exercise training (ET) is a safe and efficacious therapeutic approach for myocardial infarction (MI). Given the numerous benefits of exercise, exercise‐induced mediators may be promising treatment targets for MI. C57BL/6 mice were fed 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidine‐4‐yl) urea (TPPU), a novel soluble epoxide hydrolase inhibitor (sEHI), to increase epoxyeicosatrienoic acid (EET) levels, for 1 week before undergoing MI surgery. After 1‐week recovery, the mice followed a prescribed exercise programme. Bone marrow‐derived endothelial progenitor cells (EPCs) were isolated from the mice after 4 weeks of exercise and cultured for 7 days. Angiogenesis around the ischaemic area, EPC functions, and the expression of microRNA‐126 (miR‐126) and its target gene Spred1 were measured. The results were confirmed in vitro by adding TPPU to EPC culture medium. ET significantly increased serum EET levels and promoted angiogenesis after MI. TPPU enhanced the effects of ET to reduce the infarct area and improve cardiac function after MI. ET increased EPC function and miR‐126 expression, which were further enhanced by TPPU, while Spred1 expression was significantly down‐regulated. Additionally, the protein kinase B/glycogen synthase kinase 3β (AKT/GSK3β) signalling pathway was activated after the administration of TPPU. EETs are a potential mediator of exercise‐induced cardioprotection in mice after MI. TPPU enhances exercise‐induced cardiac recovery in mice after MI by increasing EET levels and promoting angiogenesis around the ischaemic area.

Background Neuroinflammation induced by lead exposure (Pb) is a major cause of neurotoxicity of Pb in the central nervous system (CNS). The NLR family, domain of pyrin containing 3 (NLRP3) involves in various neurological diseases, while the question of whether NLRP3 plays a role in lead-induced neuroinflammation has not yet been reported. Methods Developmental and knockout (KO) NLRP3 mice were used to establish two in vivo models, and BV2 cells were used to establish an in vitro model. Behavioral and electrophysiologic tests were used to assess the neurotoxicity of Pb, and immunofluorescence staining was used to assess neuroinflammation. Real-time PCR and western blot were performed to examine the mRNA and protein levels of inflammatory cytokines and NLRP3 inflammasomes. siRNA technology was used to block NLRP3 expression. Results Pb exposure led to neural injure and microglial activation in the hippocampus region, while minocycline intervention attenuated Pb-induced neurotoxicity by inhibiting neuroinflammation. Pb increased the expression of NLRP3 and promoted cleavage of caspase-1 in mRNA and protein levels, and minocycline partially reversed the effects of Pb on NLRP3 inflammasomes. Blocking of NLRP3 by KO mice or siRNA attenuated neural alterations induced by Pb, weakened microglial activation in vivo and in vitro as well, without affecting the accumulation of Pb. Pb increased autophagic protein levels and phosphorylation of NF-κB, while suppressing autophagy or NF-κB inhibited Pb's effects on NLRP3. Conclusions NLRP3 is involved in the regulation of Pb-induced neurotoxicity. These findings expand mechanism research of Pb neurotoxicity and may help establish new prevention strategies for Pb neurotoxicity.

Using a facile and efficient method, two-dimensional (2D) ultra-thin MnO 2 nanosheets were successfully prepared. Due to the large specific surface area and mesoporous structure, MnO 2 nanosheet is a good candidate for use as an enhanced electrochemical sensing material. MnO 2 nanosheets were immobilized onto glassy carbon electrodes with Nafion film to construct a H 2 O 2 electrochemical nonenzymatic sensor. Amperometric study showed MnO 2 nanosheets exhibited very high electrocatalytic activity towards H 2 O 2 reduction. A very low detection limit (5 nM) was reached with a wide linear range (25 nM–2 μM and 10–454 μM) and a high sensitivity of 3261 mA M −1 cm −2 . The fabricated H 2 O 2 sensor also exhibited excellent selectivity, good reproducibility and long-time stability. Furthermore, the constructed high sensitive sensor was successfully applied to perform real-time monitoring trace concentration of H 2 O 2 released by SP2/0 cells, indicating that MnO 2 nanosheets provide a new platform for developing high performance electrochemical sensors in biological applications.

Sepsis initiates a neuroinflammatory cascade that contributes to spinal cord inflammation and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In this study, we tested the hypothesis that ulinastatin (ULI) inhibits sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction through the TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB signaling pathway. Muscular function, spinal cord water content, and cytokine levels of spinal cord were tested in TLR4-inhibited rats subjected to cecal ligation and puncture (CLP). The normal rats were intrathecally injected with different concentrations of ULI or normal saline 60 min before CLP. At 24 h after CLP, the activation of microglia/macrophage was detected by immunofluorescence staining; and the cytokines were assayed by ELISA. The protein expression level of the TLR4 and its downstream effectors (MyD88 and NF-κB), the neuregulin-1, and the γ- and α7-nicotinic acetylcholine receptor was measured using western blotting. The protein expression of TLR4 in the spinal cord reached a maximum at 24 h post-CLP. Compared to the sham rats, the TLR4-inhibited rats showed attenuated functional impairment and cytokine release. ULI (5000 U/kg ) treatment pre-CLP significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release in septic rats. Furthermore, the levels of TLR4, MyD88, and NF-κB and the expression level of γ-/α7-nicotinic acetylcholine receptors also decreased after ULI treatment. ULI administration may improve patient outcome by reducing the spinal inflammation through a mechanism involving the TLR4/MyD88/NF-κB signaling in sepsis.

This study describes the reverse of the well-known double layer effects on charge transfer kinetics in the relationship between a cause and an effect. The reversible redox reaction of a ferrocenyl derivative decreased the capacitive values of the double layer impedance up to negative values, corresponding to an inductive component. This observation was disclosed by the subtraction of the real admittance from the imaginary admittance, which can extract the net double layer capacitance from the Warburg impedance. The inductance-like behavior is caused due to two reasons: (i) the double layer capacitance in the polarized potential domain is determined by the low concentrations of the field-oriented solvent dipoles that are considered as the conventionally employed redox concentrations and (ii) the double layer capacitance is caused by the orientation of the dipoles in the same direction as that of the electric field, whereas the redox reaction generates charge in the direction opposite to the field. The faradaic effect was demonstrated via the ac-impedance data obtained for the ferrocenyl compound in a KCl solution in the unpolarized potential domain between 1 Hz and 3 kHz frequency. The negative admittance was proportional to the frequency. The theory of negative capacitance was presented by combining the mirror-image surface charge with the Nernst equation.

Sialic acid (Sia), the acylated derivative of the nine-carbon sugar neuraminic acid, is a terminal component of the oligosaccharide chains of many glycoproteins and glycolipids. In light of its important biological and pathological functions, the relationship between Sia and coronary artery disease (CAD) has been drawing great attentions recently. Large-scale epidemiological surveys have uncovered a positive correlation between plasma total Sia and CAD risk. Further research demonstrated that N-Acetyl-Neuraminic Acid, acting as a signaling molecule, triggered myocardial injury via activation of Rho/ROCK-JNK/ERK signaling pathway both in vitro and in vivo. Moreover, there were some evidences showing that the aberrant sialylation of low-density lipoprotein, low-density lipoprotein receptor and blood cells was involved in the pathological process of atherosclerosis. Significantly, the Sia regulates immune response by binding to sialic acid-binding immunoglobulin-like lectin (Siglecs). The Sia-Siglecs axis is involved in the immune inflammation of atherosclerosis. The generation of Sia and sialylation of glycoconjugate both depend on many enzymes, such as sialidase, sialyltransferase and trans-sialidase. Abnormal activation or level of these enzymes associated with atherosclerosis, and inhibitors of them might be new CAD treatments. In this review, we focus on summarizing current understanding of Sia metabolism and of its relevance to atherosclerosis.

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease‐associated PAH (CHD‐PAH) and 20 healthy controls were collected and analysed by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐HRMS). Orthogonal partial least square‐discriminate analysis (OPLS‐DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)‐induced PAH rat model. The OPLS‐DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD‐PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS‐DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N‐acetylcholine‐d‐sphingomyelin, oleic acid, palmitic acid and 2‐Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real‐time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT‐1 in right heart/lung were significantly up‐regulated in MCT group than the control group.

Flavonols are widely distributed plant metabolites that inhibit microbial growth. Yet many pathogens cause disease in flavonol-containing plant tissues. We investigated how Sclerotinia sclerotiorum, a necrotrophic fungal pathogen that causes disease in a range of economically important crop species, is able to successfully infect flavonol-rich tissues of Arabidopsis (Arabidopsis thaliana). Infection of rosette stage Arabidopsis with a virulent S. sclerotiorum strain led to the selective hydrolysis of flavonol glycosidic linkages and the inducible degradation of flavonol aglycones to phloroglucinol carboxylic and phenolic acids. By chemical analysis of fungal biotransformation products and a search of the S. sclerotiorum genome sequence, we identified a quercetin dioxygenase gene (QDO) and characterized the encoded protein, which catalyzed cleavage of the flavonol carbon skeleton. QDO deletion lines degraded flavonols with much lower efficiency and were less pathogenic on Arabidopsis leaves than wild-type S. sclerotiorum, indicating the importance of flavonol degradation in fungal virulence. In the absence of QDO, flavonols exhibited toxicity toward S. sclerotiorum, demonstrating the potential roles of these phenolic compounds in protecting plants against pathogens.

Background: Sepsis is a serious and elusive syndrome caused by infection, which is accompanied by a high rate of mortality worldwide. Studies have speculated the role of long non-coding RNAs (lncRNAs) in sepsis. However, the potential role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in sepsis is largely unknown. Thus, the present study intended to investigate the possible role of MALAT1 in relation to the development of sepsis and to explore the underlying mechanism. Methods: In vivo mouse model and in vitro cell model of sepsis induced by lipopolysaccharide (LPS) were constructed. Then in order to evaluate the effect of MALAT1 on the progression of sepsis, the expression of MALAT1 was silenced in sepsis mice, followed by the measurement of number of neutrophils in peripheral blood, serum levels of inflammatory factors, as well as skeletal muscle cell apoptosis. Furthermore, interactions among MALAT1, EZH2 and BRCA1 and the regulatory role of MALAT1/EZH2 on sepsis were determined in skeletal muscles cells of sepsis. Results: High expression of MALAT1 along with low expression of BRCA1 was detected in sepsis. MALAT1 was observed to regulate the expression and nucleation of BRCA1. Silencing MALAT1 resulted in reduced serum levels of IL-6, IL-8 and TNF-α, neutrophil migration, skeletal muscle cell apoptosis, number of EZH2 positive cells, extent of AKT-1 phosphorylation along with stimulated BRCA1 expression. Furthermore, MALAT1 regulated the expression and localization of BRCA1 by recruiting EZH2. Conclusion: Taken together, the key observations of the study provide evidence that MALAT1 interacting with EZH2 stimulated AKT-1 phosphorylation and decreased BRCA1 expression, consequently aggravating the progression of sepsis, highlighting a promising therapeutic option for sepsis. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81772128). Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: All animal experiment protocols were approved by the Animal Care Committee of The First Affiliated Hospital of Southwest Medical University and were in compliance with the guidelines established by the Guide for the Care and Use of Laboratory Animals.

Background: Cadmium exposure is increasingly prevalent, especially in many developing countries, such as China. Studies have demonstrated that cadmium exposure poses a large public health threat. However, evidence for early health damage in response to cadmium exposure is still scant. Methods: We first conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3,390 participants above 18 years of age were selected with cluster sampling from three districts in the Hunan region. After demographic information and blood test data were collected, a total of 3,283 subjects who met the inclusion criteria were eligible for inclusion. To screen for early health damage associated with cadmium before clinical diagnosed disease, we further excluded the individuals with hypertension, hyperlipidemia and diabetes as well as smokers and alcohol users and a total of 1,393 individuals remained. To determine which subsets of monocyte exhibit the most dramatic changes in response to cadmium exposure, 1,393 individuals were divided by plasma cadmium levels into quarters and 15 subjects were selected from the lowest and highest quartiles for single-cell RNA sequencing (scRNA-seq). Furthermore, we randomly enrolled 260 individuals from 780 subjects without chronic diseaes in Shimen district from January to March 2019 in the prospective validation study. Immunofluorescence staining for detecting CD14+ cells was performed in peripheral blood mononuclear cells (PBMCs) among the recruited individuals. Findings: From August 2016 to July 2017, 3,283 individuals were enrolled in the cross-sectional study. The median plasma and urine cadmium levels were 0·11 μg/L and 3·94 μg/L, respectively· Among all the blood cell types examined, only the monocyte percentage was negatively associated with plasma cadmium levels (coefficient =-0·11, P=0·048) in the multivariable linear regression analysis. ScRNA-seq analysis revealed that the CD14+ monocyte subset had the most predominant reduction in the highest quartile of cadmium exposure. Both the PBMC smear analysis and flow cytometry showed that the number of CD14+ monocytes decreased significantly in subjects in the highest cadmium quartile. In the validation study, the proportion of circulating CD14+ monocytes was also negatively associated with plasma cadmium levels (coefficient =-0·09, P=0·047) by the multivariable linear regression model. Interpretation: Cadmium exposure-associated alterations in the peripheral blood cell profile imply its effect on systemic immune surveillance and inflammatory function. This study demonstrates that the number of CD14+ monocytes is negatively associated with cadmium exposure levels and that these monocytes constitute a potential early marker for monitoring cadmium-induced health damage. Funding Statement: National Science and Technology Project (No 2015FY111100) and the National Natural Science Foundation of China (No 81470535, 81570451, 81770403, 81870171, and 81800393). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study complied with the Declaration of Helsinki, and the ethical committee of the Xiangya Hospital of Central South University and School of Public Health of Tongji Medical College of Huazhong University of Science and Technology approved the research protocol. Informed consent was obtained from the subjects or their legally authorized representatives.

Near−infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent fluorescent nanoprobes for bioassays with low toxicity. A novel fluorescent sensing platform which employing NIR fluorescent Ag2S QDs and MnO2 2D nanosheets as NIR emitters and quenchers is designed for rapid and selective determination of glutathione (GSH). A facile and efficient approach was demonstrated for the synthesis of NIR fluorescent Ag2S QDs with the emission of 845 nm. Then the NIR fluorescent nanoprobe of Ag2S QDs−MnO2 nanosheets is obtained by adsorbing Ag2S QDs onto the surface of MnO2 nanosheets which have atomically thick two−dimensional structure and high specific surface area. And the NIR fluorescence of Ag2S QDs is quenched by the MnO2 nanosheets. The presence of GSH could reduce MnO2 to Mn2+ that results in the restoration of NIR fluorescence for Ag2S QDs. The NIR fluorescent nanoprobe could be used for highly selective detection of GSH. Also a low detection limit of 60 μmol/L was obtained. Because NIR fluorescence of the Ag2S QDs can efficiently reduce the interferences from background scattering and autofluorescence. The NIR fluorescent nanoprobe was directly applied to monitor the GSH level in human serum sample with high accuracy and precision.

Rectified current-voltage curves were observed by micro-hole voltammetry in various concentrations of sodium ion electrolyte for transport through a micro-hole and a cationic exchange membrane (Nafion). Data suggest a linear current-concentration relation, implying electric migration-control. The rectification is observed as difference in current-potential slopes at positive and at negative applied voltages. The voltammograms are analyzed quantitatively in the context of Ohm's law as a function of both the geometry of the micro-hole and of the entire cell. The conductivity in the direction of the ion transport from the micro-hole to Nafion, corresponding to the lower conductance (closed diode), is proportional both to the cross-section area of the micro-hole and to the inverse micro-hole length. This is consistent with control by electro-migration within the micro-hole. In contrast, the conductivity in the opposite cation transport direction (open diode) is almost independent of the micro-hole geometry but varies with the length of the glass tube of the cell. The current-potential slope is consistent with the value calculated for the NaCl concentration and the geometry of the measurement cell. Under these conditions, the micro-hole is filled with a high concentration of NaCl as the flux of Na+ from the Nafion to the hole, and the high concentration causes the migration current larger that the current in the opposite direction. Consequently, the rectification ratio can be enhanced by careful design of both (i) the cell geometry including ion-exchange membranes and (ii) the micro-hole geometry rather than nano-scaled chemistry in holes.

A novel structure of polarization beam splitter (PBS) using hybrid slot structure (HSS) consisting of horizontal/vertical slot waveguide (H/VSW) is proposed and characterized. A silicon nitride augmented low index guiding (ALIG) is employed to improve the performances of PBS device. TE mode is well confined in VSW formed by bottom silicon layers, and is transmitted through bar port, while TM mode is strongly cross-coupled to the adjacent waveguide and is directed to cross port by an asymmetric directional coupler (ADC). The results demonstrate a compact device with 4.05 μm coupling length, low insertion loss (IL) of 0.92 dB(0.55 dB), low crosstalk (XT) of −47.9 dB(−43.6 dB) for TM(TE) mode at 1.55 μm. To keep XT

An ultra-compact silicon triplexer based on waveguide Bragg grating assisted non-reciprocal optical ring add-drop filter has been proposed. This novel scheme consists of two straight strip waveguides laterally coupled to a microring resonator. A magneto-optically active material deposited inside the microcavity is etched to induce strong non-reciprocity, which can cause resonance wavelength splitting ΔλMO of two counter propagating modes. Uniform Bragg grating reflector is fabricated in proximity to one of the input/output (I/O) ports. As a result, two downstream WDM channels (1490 nm/1550 nm) can be separated into the output ports of strip waveguide below the ring resonator, while the third channel considered as upstream signal is transmitted through the waveguide above the microring without any interaction with either the microring resonator or the waveguide Bragg grating reflector. Results show that a total length of 13.5 μm with the highest isolation ratio (IR) of 35 dB is obtained at the adjacent ports of the same strip waveguide; the lowest crosstalk (XT) of −38 dB for 1310 nm channel has also been obtained.

Carbon Nanotube (CNT) agglomerates can be aligned along field lines between adjacent electrodes to form conductive bridges. This study discusses the step-wise process of dielectrophoretic deposition of CNTs to form conducting bridges between adjacent electrodes. For the first time, the creation of conductive CNT bridges spanning lengths over 50 microns is demonstrated. The CNT bridges are permanently secured using electrodeposition of the conducting polymer polypyrrole. Morphologies of the CNT bridges formed within a frequency range of 1 kHz and 10 MHz are explored and explained as a consequence of interplay between dielectrophoretic and electroosmotic forces. Postdeposition heat treatment increases the conductivity of CNT bridges, likely due to solvent evaporation and resulting surface tension inducing better contact between CNTs.

Cyclic voltammograms of a ferrocenyl derivative in aqueous solution showed diffusion-controlled peak, of which currents deviated downward from the proportionality of the square-root of potential scan rates, v, and of which potentials were shifted with an increase in v. The dependence of the peak on v can be attributed conventionally to sluggish charge transfer rates and the solution resistance. This redox species has been proved to exhibit extremely fast transfer rates by microelectrode voltammetry. The solution resistance was suppressed by using small currents less than 3 μA at a thin cylindrical electrode even at scan rates of 8 V s−1. The dependence was inconsistent with the theory for the heterogeneous kinetics. It can be explained in terms of the negative capacitance associated with the redox reaction. Electrochemical reactions occur in the direction of relaxing the applied electric field, as for the double layer charging currents. However, the electrochemically generated charge enhances the electric field, so that the negatively charging current should flow. The negative capacitance was close to ca. −64 μF cm−2 for 1 mM redox concentration. The values varied linearly with the concentration.

Trans-ferulic acid-4-&beta, glucoside (C16H20O9, TFA-4&beta, G) is a monomer extracted from the Chinese medicine called radix aconiti carmichaeli (Fuzi). To date, research on this substance is lacking. Here, we found that trans-ferulic acid-4-&beta, glucoside effectively promoted cold acclimatization in mice via increased heat production and alleviation of oxidative stress in a cold environment. Thus, our work indicates that ferulic acid-4-&beta, glucoside is a potential therapeutic candidate for prevention and treatment of cold stress injury.

The postmenopausal state is associated with an increased risk of metabolic disorder including reduced energy expenditure and weight gain, leading to higher cardiovascular and cancer risks among other diseases. Mitochondrial-derived peptide (MOTS-c) is a 16-amino acid peptide encoded by mitochondrial DNA. Here, we showed that MOTS-c treatment in mice prevented ovariectomy-induced obesity and insulin resistance. After ovariectomy, low levels of estrogens increased fat mass overload and disturbed normal adipose function, forcing the development of insulin resistance. MOTS-c treatment increased brown fat activation and reduced OVX-induced fat accumulation and inflammatory invasion in white adipose tissue, which contributes to the lower level of fatty acid in serum and liver. Moreover, MOTS-c activated AMPK pathway to improve energy dissipation and insulin sensitivity. And a blocker of AMPK pathway was found to attenuate the role of MOTS-c in the regulation of adipocyte lipid metabolism. In conclusion, MOTS-c is a high potential candidate for chronic treatment of menopausal induced metabolic dysfunction. KEY MESSAGES: • MOTS-c prevents ovariectomy (OVX)-induced body weight gain and insulin resistance. • MOTS-c reduces fat mass and suppresses inflammatory response under OVX condition. • MOTS-c sustains the activity of the brown adipose under OVX condition. • MOTS-c mediates AMPK pathway activation to control adipose metabolic homeostasis.

Lead (Pb) is known to impair children’s cognitive function. It has been previously shown that developmental Pb exposure alters dendritic spine formation in hippocampal pyramidal neurons. However, the underlying mechanism has not yet been defined. In this study, a low-level gestational Pb exposure (GLE) rat model was employed to investigate the impact of Pb on the spine density of the hippocampal pyramidal neurons and its regulatory mechanism. Pb exposure resulted in impaired performance of the rats in the Morris water maze tasks, and in decreased EPSC amplitudes in hippocampal CA3-CA1 regions. With a 3D reconstruction by the Imaris software, the results from Golgi staining showed that the spine density in the CA1 region was reduced in the Pb-exposed rats in a dose-dependent manner. Decreased spine density was also observed in cultured hippocampal neurons following the Pb treatment. Furthermore, the expression level of NLGN1, a postsynaptic protein that mediates synaptogenesis, was significantly decreased following the Pb exposure both in vivo and in vitro. Up-regulation of NLGN1 in cultured primary neurons partially attenuated the impact of Pb on the spine density. Taken together, our resultssuggest that Pb exposure alters spine plasticity in the developing hippocampus by down-regulating NLGN1 protein levels.

Overexposure to manganese (Mn) leads to manganism and neurotoxicity induced by Mn is the focus of recent research. Microglia play a vital role in Mn-induced neurotoxicity, and our previous studies firstly showed that Mn could stimulate activation of microglia, leading to the neuroinflammation, and inhibition of microglial inflammation effectively attenuated Mn-induced death of dopamine neurons. However, the detailed mechanism of manganese-induced neuroinflammation is still unclear. Leucine rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of many neurodegenerative disorders. Recent studies have indicated that LRRK2, which is highly expressed in microglia, plays a specific role in microglia and autophagy process. In this paper, we try to find the effect of LRRK2 on Mn-triggered neuroinflammation and its possible mechanism in vivo and in vitro. By establishing a Mn exposure animal model, our studies found that Mn exposure could induce dopaminergic neurons damage and activate microglia. Activated microglia triggered neuroinflammation by releasing multiple inflammatory cytokines, and the expression of LRRK2 was upregulated in vivo and in vitro. We also found that Mn exposure induced autophagy dysfunction in vivo and in vitro. Next, we used LRRK2 siRNA and LRRK2-IN-1 to inhibit the expression of LRRK2, and found that inhibition of LRRK2 could not only decrease the expression of inflammatory cytokines, but also recover autophagic function of microglia. Our investigation not only reveals the role of LRRK2 in Mn-induced neuroinflammation but also sheds light on the prevention and protection of manganism.

Two-dimensional (2D) ultrathin nickel-cobalt phosphate nanosheets were synthesized using a simple one-step hydrothermal method. The morphology and structure of nanomaterials synthesized under different Ni/Co ratios were investigated by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Moreover, the influence of nanomaterials' structure on the electrochemical performance for glucose oxidation was investigated. It is found that the thinnest nickel-cobalt phosphate nanosheets synthesized with a Ni/Co ratio of 2:5 showed the best electrocatalytic activity for glucose oxidation. Also, the ultrathin nickel-cobalt phosphate nanosheet was used as an electrode material to construct a nonenzymatic electrochemical glucose sensor. The sensor showed a wide linear range (2-4470 μM) and a low detection limit (0.4 μM) with a high sensitivity of 302.99 μA·mM-1·cm-2. Furthermore, the application of the as-prepared sensor in detection of glucose in human serum was successfully demonstrated. These superior performances prove that ultrathin 2D nickel-cobalt phosphate nanosheets are promising materials in the field of electrochemical sensing.

Hemin, an iron porphyrin, functions as a carriage of dioxygen in mammalian respiration in the ferrous form. It works also as an electrochemical catalyst of the reduction of dioxygen by reproducing the ferrous form from the ferric one. Since the carriage requires stabilization of the dioxygen adduct, the catalytic reduction of dioxygen with the ferric form might hinder the stabilization. This work aims at finding the discrimination between the functions of the carriage and of the catalysis. A hint of the finding lies in the difference between the remarkable catalytic currents in high concentrations of hemin and negligibly small ones in very low concentrations. The catalytic current at the hemin-coated electrode is confirmed to occur at the stoichiometry of two hemin molecules and one dioxygen molecule. When this stoichiometry is applied to the dioxygen adduct of hemin as an intermediate species of the catalysis, high concentrations of dissolved hemin should provide the catalytic current. Spectro-electrochemistry demonstrates that ferrous hemin is not oxidized simply to the ferric form but is converted to other species, e.g. the dioxygen adduct.

The double layer capacitance per weight of graphene (GN) flakes in aqueous solution at the polarized potential increases with a decrease in the ac-frequency, obeying the inverse of the power law of the frequency. The power law is demonstrated to be equivalent to the constant phase element. The frequency-dependence increases with the thickness of the GN films. Thus, the lower the frequency and the thinner the film is, the larger is the capacitance density per weight. This is confirmed by cyclic voltammetry for several thickness of GN films and several scan rates. Resistance-like voltammograms at thick films are caused by frequency-dispersion. The overall capacitive properties of the GN films are as follows: the thickness of one GN flake is estimated to be 2 nm in average from the comparison of the thickness with the capacitances at the HOPG, which is consistent with values by the STM and AFM images.

With the aim to develop pH-paper-like lead ion (Pb2+) sensing materials, we demonstrate a colorimetric strip, which relies on a SiO2 nanoparticle (NP) decorated polydiacetylene embedded polyacrylonitrile nanofibrous membrane (PAN NFM), that undergoes a brilliant blue-to-red color transition as well as ‘Turn-On’ fluorescence upon incubation with Pb2+. The introduction of an amino acid (glycine) headgroup into a supramolecularly assembled 10,12-pentacosadiynoic acid results in a Pb2+-induced chromic conjugated polymer that is quickly photopolymerizable, rapidly responsive to Pb2+ and specifically identifiable. Moreover, the SiO2 NPs are certified as an efficient sensitivity promoter when their content reaches 0.5 wt% in the strip. With this understanding, the color change that is caused by 0.24 μM Pb2+ at ambient temperature can be easily perceived by the naked eye, which indicates the superiority of our strip compared with previous approaches, and it is also noteworthy that a fluorescent signal could also be produced in 2 min. Furthermore, RGB (red-green-blue) digital parameters obtained from images of the strips and automatic read outs via a smartphone were processed statistically through principal component analysis and then used to elaborate the standard curve and quantify Pb2+ concentration. This methodology for assaying and quantifying Pb2+ avoids time-consuming sample preparation, expensive laboratory techniques, and specialized personnel required to carry out conventional analytical methods.

Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure.

A nonenzymatic glucose electrochemical sensor was constructed based on Au nanoparticles (AuNPs) decorated Ni metal-organic-framework (MOF)/Ni/NiO nanocomposite. Ni-MOF/Ni/NiO nanocomposite was synthesized by one-step calcination of Ni-MOF. Then AuNPs were loaded onto the Ni-based nanocomposites’ surface through electrostatic adsorption. Through characterization by transmission electron microscopy (TEM), high resolution TEM (HRTEM) and energy disperse spectroscopy (EDS) mapping, it is found that the AuNPs were well distributed on the surface of Ni-based nanocomposite. Cyclic voltammetric (CV) study showed the electrocatalytic activity of Au-Ni nanocomposite was highly improved after loading AuNPs onto it. Amperometric study demonstrated that the Au-Ni nanocomposites modified glassy carbon electrode (GCE) exhibited a high sensitivity of 2133.5 mA M−1 cm−2 and a wide linear range (0.4–900 μM) toward the oxidation of glucose with a detection limit as low as 0.1 μM. Moreover, the reproducibility, selectivity and stability of the sensor all exhibited outstanding performance. We applied the as-fabricated high performance sensor to measure the glucose levels in human serum and obtained satisfactory results. It is believed that AuNPs decorated Ni MOF/Ni/NiO nanocomposite provides a new platform for developing highly performance electrochemical sensors in practical applications.

Osteoarthritis (OA) is a common degenerative joint disease in older adults. A number of previous studies have demonstrated that natural flavonoids can serve as promising therapeutic drugs for OA. Kaempferol, a phytochemical ingredient mainly present in various fruits, has exhibited its prominent anti-inflammatory and antioxidant effects in numerous diseases. However, whether Kaempferol ameliorates the deterioration of arthritis remains to be elucidated. The aim of the present study was to investigate the therapeutic role of Kaempferol on OA in rat chondrocytes. The results revealed that Kaempferol significantly inhibited the interleukin (IL)-1β-induced protein expression of inflammatory mediators such as inducible nitric oxide synthase and cyclo-oxygenase-2. In addition, the common matrix degrading enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motif-5] induced by IL-1β were also suppressed by Kaempferol, and consequently abolished the degradation of collagen II. Furthermore, the anti-inflammatory effect of Kaempferol was mediated by the inhibition of the mitogen activated protein kinase-associated extracellular signal-regulated kinase and P38 signaling pathways. These results collectively indicated that Kaempferol can potentially prevent OA development and serve as a novel pharmacological target in the treatment of OA.