Manganese overexposure results in ferroptosis through the HIF-1α/p53/SLC7A11 pathway in ICR mouse brain and PC12 cells.

Manganese (Mn) overexposure has been associated with the development of neurological damage reminiscent of Parkinson's disease, while the underlying mechanisms have yet to be fully characterized. This study aimed to investigate the mechanisms leading to injury in dopaminergic neurons induced by Mn and identify novel treatment approaches. In the in vivo and in vitro models, ICR mice and dopaminergic neuron-like PC12 cells were exposed to Mn, respectively. We treated them with anti-ferroptotic agents ferrostatin-1 (Fer-1), deferoxamine (DFO), HIF-1α activator dimethyloxalylglycine (DMOG) and inhibitor LW6. We also used p53-siRNA to verify the mechanism underlying Mn-induced neurotoxicity. Fe and Mn concentrations increased in ICR mice brains overexposed to Mn. Additionally, Mn-exposed mice exhibited movement impairment and encephalic pathological changes, with decreased HIF-1α, SLC7A11, and GPX4 proteins and increased p53 protein levels. Fer-1 exhibited protective effects against Mn-induced both behavioral and biochemical changes. Consistently, in vitro, Mn exposure caused ferroptosis-related changes and decreased HIF-1α levels, all ameliorated by Fer-1. Upregulation of HIF-1α by DMOG alleviated the Mn-associated ferroptosis, while LW6 exacerbated Mn-induced neurotoxicity through downregulating HIF-1α. p53 knock-down also rescued Mn-induced ferroptosis without altering HIF-1α protein expression. Mn overexposure resulted in ferroptosis in dopaminergic neurons, mediated through the HIF-1α/p53/SLC7A11 pathway.

Study on Thermomechanical Properties and Morphology of an Epoxy Resin Thermally Conductive Adhesive under Different Curing Conditions.

An epoxy resin thermally conductive adhesive is a type of thermosetting polymer encapsulation material that exhibits comprehensive performance, and the thermomechanical properties of this adhesive vary significantly under different curing conditions. In this paper, spherical alumina was used as a filler for thermal conductivity to prepare an epoxy resin thermal conductivity adhesive using a multistage freezing mixing method. The effects of various curing conditions on the thermal-mechanical properties and fracture morphology of the epoxy resin thermal conductivity adhesive were studied. The results showed that the curing condition of 150 °C/2.5 h significantly improved the performance of the epoxy resin thermally conductive adhesive. Through the shear test of the composite material, the influence of the curing agent on the adhesion of the thermally conductive adhesive under fixed conditions was explored. It was found that the curing agent with a superbranched structure exhibited latent properties and greatly enhanced the toughness of the cured epoxy resin product. Altering the curing conditions increases the shear strength by up to 307%. With the increase in curing temperature and the extension of curing temperature, the glass transition temperature gradually increased from 103.9 to 159.8 °C. The initial decomposition temperature TIDT gradually increased from 295.4 to 310.1 °C, and the temperature at which the fastest decomposition rate occurs (Tmax) gradually increased from 312.48 to 330.33 °C. The thermal stability of the substance increased with both temperature and time. The curing time and curing temperature were increased, and the morphology of the fracture of the epoxy resin thermally conductive adhesive cured sample gradually showed a ductile fracture from a typical brittle fracture. The research results reveal the influence of curing conditions on the thermal conductivity and thermal stability of the epoxy resin thermally conductive adhesive, which has a specific reference value for improving the performance of the epoxy resin thermally conductive adhesive, optimizing its usage conditions, and improving production efficiency.

Persistent Charging of CsPbBr3 Perovskite Nanocrystals Confined in Glass Matrix.

Manipulation of persistent charges in semiconductor nanostructure is the key point to obtain quantum bits towards the application of quantum memory and information devices. However, realizing persistent charge storage in semiconductor nano-systems is still very challenge due to the disturbance from crystal defects and environment conditions. Herein, the two-photon persistent charging induced long-lasting afterglow and charged exciton formation are observed in CsPbBr3 perovskite nanocrystals (NCs) confined in glass host with effective lifetime surpassing one second, where the glass inclosure provides effective protection. A method combining the femtosecond and second time-resolved transient absorption spectroscopy is explored to determine the persistent charging possibility of perovskite NCs unambiguously. Meanwhile, with temperature-dependent spectroscopy, the underlying mechanism of this persistent charging is elucidated. A two-channel carrier transfer model is proposed involving athermal quantum tunneling and slower thermal-assisted channel. On this basis, two different information storage devices are demonstrated with the memory time exceeding two hours under low-temperature condition. These results provide a new strategy to realize persistent charging in perovskite NCs and deepen the understanding of the underlying carrier kinetics, which may pave an alternative way towards novel information memory and optical data storage applications.

Solution-grown millimeter-scale Mn-doped CsPbBr3/Cs4PbBr6 crystals with enhanced photoluminescence and stability for light-emitting applications.

Metal halide perovskites are particularly emerging for optoelectronic applications in light-emitting diodes, photodetectors, and solar cells due to their flourishing photophysical properties. However, the poor stability of three-dimensional (3D) lead halide perovskite nanocrystals (NCs) significantly hampers their optoelectronics and photovoltaics applications. Embedding 3D perovskites into zero-dimensional (0D) perovskite crystals and doping ions of appropriate elements into host lattices provide effective approaches to improve the stability and optical-electronic performance. In this study, millimeter-scale Mn-doped and undoped CsPbBr3/Cs4PbBr6 perovskite crystals were successfully fabricated by a one-step slow cooling method. We systematically investigated the effects of Mn2+ ion doping on the PL performance and stability of CsPbBr3/Cs4PbBr6 crystals. Compared with undoped crystals, the existence of Mn2+ ions not only blue-shifted the PL peak but also improved the luminescence performance and stability of the prepared millimeter-sized crystals. Moreover, doping Mn2+ ions can increase the proportion of radiative recombination at low temperature, which may be because Mn2+ ions can effectively accelerate the decay of a dark exciton by the magnetic mixing of bright and dark excitons. In addition, green LED devices with high efficiency packaged as-grown crystals are explored, which promises further application in display backlights.

Effects of different light intensity on the growth of tomato seedlings in a plant factory.

Light-emitting diodes (LEDs) were the best artificial light source for plant factories. Red light-emitting diodes (LEDs, R) and blue light-emitting diodes (LEDs, B) were used to obtain different light intensities of uniform spectra, and the greenhouse environment was considered as a comparison. The results showed that root dry weight, shoot dry weight and stem diameter were superior in plant growth under 240 µmolm-2s-1, additionally, the Dixon Quality Index (DQI) was also best. Under 240 µmolm-2s-1, the net photosynthesis rate (Pn) was consistent with the greenhouse's treatment, superior to other experimental groups. The results implied that the PPFD was more suitable for the cultivation of tomato seedlings under the condition of 240 µmolm-2s-1, and can replace the greenhouse conditions so as to save energy and reduce emissions.

Effect of the alumina micro-particle sizes on the thermal conductivity and dynamic mechanical property of epoxy resin.

Epoxy thermal conductive adhesives with high thermal conductivity and dynamic mechanical properties are important thermally conductive materials for fabricating highly integrated electronic devices. In this paper, micro-Al2O3 is used as a thermally conductive filler for the epoxy resin composite and investigated the effect of micron-sized alumina particle size on the thermal conductivity and dynamic mechanical property of epoxy resin by the transient planar hot plate method and DMA (Dynamic mechanical analysis). The experimental results show that with the same amount of alumina filling, the thermal conductivity and Tg (glass transition temperature) of epoxy/Al2O3 composite material decrease with the increase of alumina particle size. The maximum thermal conductivity of the composite material is 0.679 (W/mK), while the energy storage modulus of epoxy/Al2O3 composite material increases with the increase of alumina particle size, and the maximum energy storage modulus of the composite material is 160MPa. Compared with pure epoxy resin, the thermal conductivity and energy storage modulus have increased by 2.7 and 3.2 times, respectively. The epoxy/Al2O3 composite was applied to the COB (Chips On Board) type LED package, and the substrate temperature of the LED dropped to the lowest after 1.5 hours of operation using EP-A5 composite, and the temperature was stabilized at 38.2°C, indicating that the addition of 5-micron alumina composite has the best heat dissipation in the COB type LED package. These results are critical for the implementation of particulate-filled polymer composites in practical applications because relaxed material specifications and handling procedures can be incorporated in production environments to improve efficiency.

MACC1 and Gasdermin-E (GSDME) regulate the resistance of colorectal cancer cells to irinotecan.

Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and metastasis of many solid cancer entities. High expression of MACC1 is found in colorectal cancer (CRC) tissues. So far, the role of MACC1 in CRC cell pyroptosis and resistance to irinotecan is unclear. The cleavage of Gasdermin-E (GSDME) is the main executors of activated pyroptosis. We found that GSDME enhanced CRC cell pyroptosis and reduced their resistance to irinotecan, while MACC1 inhibited the cleavage of GSDME and CRC cell pyroptosis, promoted CRC cell proliferation, and enhanced the resistance of CRC cells to irinotecan. Therefore, CRC cells with high MACC1 expression and low GSDME expression had higher resistance to irinotecan, while CRC cells with low MACC1 expression and high GSDME expression had lower resistance to irinotecan. Consistently, by analyzing CRC patients who received FOLFIRI (Fluorouracil + Irinotecan + Leucovorin) in combination with chemotherapy in the GEO database, we found that CRC patients with low MACC1 expression and high GSDME expression had higher survival rate. Our study suggests that the expression of MACC1 and GSDME can be used as detection markers to divide CRC patients into irinotecan resistant and sensitive groups, helping to determine the treatment strategy of patients.

A novel material Cs2RbxAg1-xIn0.875Bi0.125Cl6 with a special blue shift and application for white light LED devices.

Perovskite microcrystals have attracted wide attention and have been applied in extensive optical applications. The CsPbX3 perovskite poses a great threat to the environment due to the presence of lead (Pb), and there is an urgent need to improve the photoluminescence quantum yield. Therefore, a lead-free perovskite microcrystal material Cs2RbxAg1-xIn0.875Bi0.125Cl6 with a high photoluminescence quantum yield (PLQY) was synthesized by a convenient hydrothermal method, with comprehensive characterization of both the structure and optical performance at varying Rb ratios. Optimal properties were observed at x = 0.15 with bright white emission and a PLQY of 32.15%. Superior stability of the novel material in ethanol was observed under the radiation of an excitation light of 365 nm. Interestingly, a blue shift of the emission peak occurred after exposure to humid air, possibly due to the reconstruction of the crystal structure. Moreover, a LED device packaged with this novel material was developed with a desirable color temperature of 3190 K, promising for further lighting applications.

Fasting Enhances the Acute Toxicity of Acrylonitrile in Mice via Induction of CYP2E1.

Cytochrome P450 2E1 (CYP2E1) plays an essential role in the susceptibility to acute acrylonitrile (AN)-induced toxicity. Here, we investigated the toxicity and mechanism of AN in fasting mice and potential underlying mechanisms. Convulsions, loss of righting reflex, and death 4 h after AN treatment were observed and recorded for each group of mice. Relative to ad lib-fed mice, 48 h fasting significantly increased the acute toxicity of AN, as noted by a more rapid onset of convulsions and death. In addition, fasting significantly enhanced CYP2E1-mediated oxidative metabolism of AN, resulting in increased formation of CN- (one of the end-metabolites of AN). Moreover, fasting decreased hepatic GSH content, abrogating the detoxification of GSH. However, trans-1,2-dichloroethylene (DCE), a CYP2E1 inhibitor, altered the level of hepatic CYP2E1 activity in response to fasting, reduced the acute toxic symptoms of AN and the content of CN- in AN-treated mice. These data establish that fasting predisposes to AN toxicity, attributable to induced CYP2E1 and reduced hepatic GSH.

Differential effects of subchronic acrylonitrile exposure on hydrogen sulfide levels in rat blood, brain, and liver.

Background: Hydrogen sulfide (H2S), as the third gasotransmitter participates in both cellular physiological and pathological processes, including chemical-induced injuries. We recently reported acute acrylonitrile (AN) treatment inhibited endogenous H2S biosynthesis pathway in rat and astrocyte models. However, there is still no evidence to address the correlation between endogenous H2S and sub-chronic AN exposure. Objectives: This study aims to explore the modulatory effects of prolonged AN exposure on endogenous H2S levels and its biosynthetic enzymes in rat blood, brain and liver. Methods: A total of 50 male Sprague-Dawley rats were randomly divided into 5 groups, including the control group and AN-treated groups at dosages of 6.25, 12.5, 25 or 50 mg/kg. Rats received one exposure/day, 5 days/week, for 4 consecutive weeks. The rat bodyweight and brain/liver organ coefficient were detected, along with liver cytochrome P450 2E1(CYP2E1) expression. In addition, the H2S contents in rat serum and plasma, and in cerebral cortex and liver tissues were measured by methylene blue method. The expression of H2S-generating enzymes, including cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MPST) was also measured with Western blot both in rat cerebral cortex and liver. Results: Subchronic exposure to AN significantly inhibited bodyweight-gain and increased the liver CYP2E1 expression compared with the control. In addition, AN significantly increased H2S levels in rat plasma and serum, but not in liver. The endogenous H2S level in rat cerebral cortex was also significantly increased upon AN treatment, when expression of the major H2S-generating enzymes, CBS and 3-MPST were significantly enhanced. However, hepatic protein levels of CBS and CSE were significantly increased, whereas hepatic levels of 3-MPST were significantly decreased. Conclusion: This study showed that sub-chronic AN exposure increased endogenous H2S contents in rat blood and brain tissues, but not liver, which may be resulted from the distinct expression profile of H2S-producing enzymes in response to AN. The blood H2S contents may be applied as a potential novel biomarker for surveillance of chronically AN-exposed populations. Highlights: Subchronic intraperitoneal exposure to acrylonitrile increased H2S content in rat blood and cerebral cortex, but not in liver.Distinct tissue expression profiles of H2S-producing enzymes contribute to the acrylonitrile-induced differential effects on the H2S level.Blood H2S level may be a biomarker for subchronic exposure to acrylonitrile.

Ferroptosis contributes to methylmercury-induced cytotoxicity in rat primary astrocytes and Buffalo rat liver cells.

OBJECTIVE: Ferroptosis is an iron-dependent nonapoptotic form of cell death, characterized by iron accumulation and lipid peroxidation. However, the role of ferroptosis in methylmercury (MeHg)-induced cytotoxicity has yet to be fully characterized. The purpose of this study was to investigate the role of ferroptosis in MeHg-induced cytotoxicity in both brain and liver cells. METHODS: The effects of MeHg on cell viability, cytotoxicity, intracellular iron content, reduced glutathione (GSH) content, ferroptosis-related proteins, cytosolic and lipid reactive oxygen species (ROS) generation were determined in rat primary astrocytes (AST) and Buffalo Rat Liver (BRL) cells in the absence or presence of the ferroptosis inhibitors deferoxamine (DFO) or ferrostatin-1 (Fer-1). RESULTS: MeHg treatment decreased cell viability and increased cytotoxicity in AST and BRL cells. MeHg induced ferroptosis in AST and BRL cells was reflected by increased cytosolic ROS, lipid ROS and intracellular iron content, all of which were inhibited by the ferroptosis inhibitors DFO and/or Fer-1. MeHg inhibited the expression of ferritin heavy chain 1 (FTH1). Furthermore, MeHg treatment decreased the expression of glutathione peroxidase 4 (GPx4) without altering solute carrier family 7 member 11 (SLC7A11). DFO and Fer-1 significantly increased the expression of GPx4, yet had no effect on SLC7A11 upon MeHg treatment. CONCLUSIONS: Our novel results are consistent with ferroptosis as a key event mediating MeHg-induced toxicity, inhibiting GPx4 in AST and BRL cells. Ferroptosis may offer a new target for attenuating MeHg-induced toxic injury.

Synergistic Effect of Halogen Ions and Shelling Temperature on Anion Exchange Induced Interfacial Restructuring for Highly Efficient Blue Emissive InP/ZnS Quantum Dots.

InP quantum dots (QDs) have attracted much attention owing to their nontoxic properties and shown great potential in optoelectronic applications. Due to the surface defects and lattice mismatch, the interfacial structure of InP/ZnS QDs plays a significant role in their performance. Herein, the formation of In-S and Sx -In-P1-x interlayers through anion exchange at the shell-growth stage is revealed. More importantly, it is proposed that the composition of interface is dependent on the synergistic effect of halogen ions and shelling temperature. High shelling temperature contributes to the optical performance improvement resulting from the formation of interlayers, besides the thicker ZnS shell. Moreover, the effect relates to the halogen ions where I- presents more obvious enhancement than Br- and Cl- , owing to their different ability to coordinate with In dangling bonds, which are inclined to form In-S and Sx -In-P1-x bonds. Further, the anion exchange under I- -rich environment causes a blue-shift of emission wavelength with shelling temperature increasing, unobserved in a Cl- - or Br- -rich environment. It contributes to the preparation of highly efficient blue emissive InP/ZnS QDs with emission wavelength of 473 nm, photoluminescence quantum yield of ≈50% and full width at half maximum of 47 nm.

BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.

Manganese (Mn) is an essential mineral, but excess exposure can cause dopaminergic neurotoxicity. Restless legs syndrome (RLS) is a common neurological disorder, but the etiology and pathology remain largely unknown. The purpose of this study was to identify the role of Mn in the regulation of an RLS genetic risk factor BTBD9, characterize the function of BTBD9 in Mn-induced oxidative stress and dopaminergic neuronal dysfunction. We found that human subjects with high blood Mn levels were associated with decreased BTBD9 mRNA levels, when compared with subjects with low blood Mn levels. In A549 cells, Mn exposure decreased BTBD9 protein levels. In Caenorhabditis elegans, loss of hpo-9 (BTBD9 homolog) resulted in more susceptibility to Mn-induced oxidative stress and mitochondrial dysfunction, as well as decreased dopamine levels and alternations of dopaminergic neuronal morphology and behavior. Overexpression of hpo-9 in mutant animals restored these defects and the protection was eliminated by mutation of the forkhead box O (FOXO). In addition, expression of hpo-9 upregulated FOXO protein levels and decreased protein kinase B levels. These results suggest that elevated Mn exposure might be an environmental risk factor for RLS. Furthermore, BTBD9 functions to alleviate Mn-induced oxidative stress and neurotoxicity via regulation of insulin/insulin-like growth factor signaling pathway.

Recent Advances in Blue Perovskite Quantum Dots for Light-Emitting Diodes.

Metal halide perovskite nanostructures have sparked intense research interest due to their excellent optical properties. In recent years, although the green and red perovskite light-emitting diodes (PeLEDs) have achieved a significant breakthrough with the external quantum efficiency exceeding 20%, the blue PeLEDs still suffer from inferior performance. Previous reviews about blue PeLEDs focus more on 2D/quasi-2D or 3D perovskite materials. To develop more stable and efficient blue PeLEDs, a systematic review of blue perovskite quantum dots (PQDs) is urgently demanded to clarify how PQDs evolve. In this review, the recent advances in blue PQDs involving mixed-halide, quantum-confined all-bromide, metal-doped and lead-free PQDs as well as their applications in PeLEDs are highlighted. Although several excellent PeLEDs based on these PQDs have been demonstrated, there are still many problems to be solved. A deep insight into the advantages and disadvantages of these four types of blue-emitting PQDs is provided. Then, their respective potential and issues for blue PeLEDs have been discussed. Finally, the challenges and outlook for efficient and stable blue PeLEDs based on PQDs are addressed.

Type 2 diabetes mellitus potentiates acute acrylonitrile toxicity: Potentiation reduction by phenethyl isothiocyanate.

Acrylonitrile (AN) is a known animal carcinogen and suspected human carcinogen. Recently, occupational exposure to AN has considerably increased. Previously, we demonstrated that streptozotocin-induced diabetes potentiates AN-induced acute toxicity in rats and that the induced cytochrome P450 2E1 (CYP2E1) is responsible for this effect. In the present study, we examined whether induction of CYP2E1 is also the underlying mechanism for the potentiation of AN-induced acute toxicity in type 2 diabetes in db/db mice. The effect of phenethyl isothiocyanate (PEITC) in reducing potentiation was also investigated. The mice were randomly divided into the normal control, diabetic control, AN, diabetes + AN, PEITC + AN, and diabetes + PEITC + AN groups. PEITC (40 mg/kg) was orally administered to rats for 3 days, and 1 h after the last PEITC gavage, 45 mg/kg AN was intraperitoneally injected. Time to death was observed. The CYP2E1 level and enzymatic activity, cytochrome c oxidase (CCO) activity, and reactive oxygen species (ROS) levels were measured. The survival rate was decreased in AN-treated db/db mice compared with that in AN-treated wild-type mice. The hepatic CYP2E1 level and enzymatic activity remained unaltered in db/db mice. Phenethyl isothiocyanate alleviated AN-induced acute toxicity in db/db mice as evident in the increased survival rate, restored CCO activity, and decreased ROS level in both the liver and brain. The study results suggested that CYP2E1 may not be responsible for the sensitivity to AN-induced acute toxicity in db/db mice and that PEITC reduced the potentiation of AN-induced acute toxicity in db/db mice.

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders.

Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system.

Acute acrylonitrile exposure inhibits endogenous H2S biosynthesis in rat brain and liver: The role of CBS/3-MPST-H2S pathway in its astrocytic toxicity.

Hydrogen sulfide (H2S) as the third gasotransmitter molecule serves various biological regulatory roles in health and disease. Acrylonitrile (AN) is a common occupational toxicant and environmental pollutant, causing brain and liver damage in mammals. The biotransformation of AN is dependent-upon reduced glutathione (GSH), cysteine and other sulfur-containing compounds. However, the effects of AN on the endogenous H2S biosynthesis pathway have yet to be determined. Herein, we demonstrated that a single exposure to AN (at 25, 50, or 75 mg/kg for 1, 6 or 24 h) decreased the endogenous H2S content and H2S-producing capacity in a dose-dependent manner, both in the cerebral cortex and liver of rats in vivo. In addition, the inhibitory effects of AN (1, 2.5, 5, 10 mM for 12 h) on the H2S content and/or the expression of H2S-producing enzymes were also found both in primary rat astrocytes and rat liver cell line (BRL cells). Impairment in the H2S biosynthesis pathway was also assessed in primary rat astrocytes treated with AN. It was found that inhibition of the cystathionine-ß-synthase (CBS)/3-mercaptopyruvate sulfurtransferase (3-MPST)-H2S pathway with the CBS inhibitor or 3-MPST-targeted siRNA significantly increased the AN-induced (5 mM for 12 h) cytotoxicity in astrocytes. In turn, CBS activation or 3-MPST overexpression as well as exogenous NaHS supplementation significantly attenuated AN-induced cytotoxicity. Taken together, endogenous H2S biosynthesis pathway was disrupted in rats acutely exposed to AN, which contributes to acute AN neurotoxicity in primary rat astrocytes.

Susceptibility to the acute toxicity of acrylonitrile in streptozotocin-induced diabetic rats: protective effect of phenethyl isothiocyanate, a phytochemical CYP2E1 inhibitor.

Diabetes mellitus is a significant global public health issue. The diabetic state not only precipitates chronic disease but also has the potential to change the toxicity of drugs and chemicals. Acrylonitrile (AN) is a potent neurotoxin widely used in industrial products. This study used a streptozotocin (STZ)-induced diabetic rat model to examine the role of cytochrome P450 2E1 (CYP2E1) in acute AN toxicity. The protective effect of phenethyl isothiocyanate (PEITC), a phytochemical inhibitor of CYP2E1, was also investigated. A higher incidence of convulsions and loss of the righting reflex, and decreased rates of survival, as well as elevated CYP2E1 activity, were observed in diabetic rats treated with AN when compared to those in non-diabetic rats, suggesting that diabetes confers susceptibility to the acute toxicity of AN. Pretreatment with PEITC (20-80 mg/kg) followed by AN injection alleviated the acute toxicity of AN in diabetic rats as evidenced by the decreased incidence of convulsions and loss of righting reflex, and increased rates of survival. PEITC pretreatment at 40 and 80 mg/kg decreased hepatic CYP2E1 activity in AN-exposed diabetic rats. PEITC pretreatment (20 mg/kg) increased the glutathione (GSH) content and glutathione S-transferase (GST) activity and further decreased ROS levels in AN-exposed diabetic rats. Collectively, STZ-induced diabetic rats were more sensitive to AN-induced acute toxicity mainly due to CYP2E1 induction, and PEITC pretreatment significantly alleviated the acute toxicity of AN in STZ-induced diabetic rats. PEITC might be considered as a potential effective chemo-preventive agent against AN-induced acute toxicity in individuals with an underlying diabetic condition.

Dual-emission of silicon nanoparticles encapsulated lanthanide-based metal-organic frameworks for ratiometric fluorescence detection of bacterial spores.

Dipicolinic acid (DPA) is employed as a significant biomarker to detect Bacillus anthracis, which can do serious damages to the health of human beings. Hence, it is crucial to develop a fast and highly efficient strategy for DPA monitoring. In this work, based on silicon nanoparticles (Si NPs) and terbium metal-organic frameworks (Tb-MOFs), a hybrid structure (Si NPs/Tb-MOFs) as a novel dual-emitting fluorescence probe was fabricated for ratiometric detection of DPA, where blue light-emitting Si NPs (Ex: 280 nm; Em: 422 nm) are encapsulated into green light-emitting Tb-MOFs (Ex: 280 nm; Em: 547 nm). The optical properties and chemical composition of the as-obtained Si NPs/Tb-MOFs were characterized in detail. The Si NPs/Tb-MOFs probe not merely possesses the merits of a facile synthesis method but also is an excellent fluorescence probe. The response time towards DPA is less than 30 s, revealing that the process of detecting DPA can be completed in such a short time. The limit of detection for DPA is 5.3 nM, which is four orders of magnitude lower than an infectious dosage of anthrax spores for human beings (60 µM). This dual-emitting Si NPs/Tb-MOFs probe with interference-free and self-calibrating properties may be a potential candidate for further development in medical diagnosis. Graphical abstract.

MicroRNA-200b/c-3p regulate epithelial plasticity and inhibit cutaneous wound healing by modulating TGF-ß-mediated RAC1 signaling.

Cutaneous wound healing is pivotal for human skin to regain barrier function against pathogens. MicroRNAs (miRNAs) have been found to play regulatory roles in wound healing. However, the mechanism of miRNA regulation remains largely unknown. In this study, we focused on microRNA-200b/c-3p (miR-200b/c-3p) whose expression was abundant in intact epidermis, but dramatically decreased in skin wounds. In silico prediction identified RAC1 as a potential miR-200b/c-3p target. Luciferase reporter assay confirmed that miR-200b/c-p repressed RAC1 by direct targeting to its mRNA 3'UTR. Consistently, miR-200b/c-3p expression was discordantly related to RAC1 protein level during wound healing. Forced miR-200b/c-3p expression repressed RAC1 and inhibited keratinocyte migration as well as re-epithelialization in a mouse back skin full-thickness wound healing model. Mechanistically, miR-200b/c-3p modulated RAC1 to inhibit cell migration by repressing lamellipodia formation and intercellular adhesion dissolution in keratinocytes. Furthermore, we found that TGF-ß1, which was highly expressed in skin wounds, contributed to the downregulation of miR-200b/c-3p in wound edge keratinocytes. Taken together, miR-200b/c-3p-mediated RAC1 repression inhibited keratinocyte migration to delay re-epithelialization. TGF-ß1 induction attenuated miR-200b/c-3p regulation of RAC1 signaling in cutaneous wounds and the repression of miR-200b/c-3p accelerated keratinocyte migration to promote wound healing. Our data provide new insight into how miR-200b/c-3p affects keratinocyte migration and highlight the potential of miR-200b/c-3p targeting for accelerating wound healing.