Drp1 Aggravates Copper Nanoparticle-Induced ER-Phagy by Disturbing Mitochondria-Associated Membranes in Chicken Hepatocytes.

As an efficient alternative copper (Cu) source, copper nanoparticles (nano-Cu) have been widely supplemented into animal-producing food. Therefore, it is necessary to assess the effect of nano-Cu exposure on the biological health risk. Recently, the toxic effects of nano-Cu have been confirmed but the underlying mechanism remains unclear. This study reveals the impact of nano-Cu on endoplasmic reticulum autophagy (ER-phagy) in chicken hepatocytes and further identifies Drp1 and its downstream gene FAM134B as crucial regulators of nano-Cu-induced hepatotoxicity. Nano-Cu exposure can induce Cu ion overaccumulation and pathological injury in the liver, trigger excessive mitochondrial fission and mitochondria-associated membrane (MAM) integrity damage, and activate ER-phagy in vivo and in vitro. Interestingly, the knockdown of Drp1 markedly decreases the expression of FAM134B induced by nano-Cu. Furthermore, the expression levels of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I induced by nano-Cu exposure are decreased by inhibiting the expression of Drp1. Simultaneously, the inhibition of FAM134B effectively alleviates nano-Cu-induced ER-phagy by downregulating the expression of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I. Overall, these results suggest that Drp1-mediated impairment of MAM integrity leads to ER-phagy as a novel molecular mechanism involved in the regulation of nano-Cu-induced hepatotoxicity. These findings provide new ideas for future research on the mechanism of nano-Cu-induced hepatotoxicity.

Enhancing Light-Emitting Efficiency of Blue Through-Space Charge Transfer Emitters via Fixing Configuration Induced by Intramolecular Hydrogen Bonding.

Closely aligned configuration of the donor (D) and acceptor (A) is crucial for the light-emitting efficiency of thermally activated delayed fluorescence (TADF) materials with through-space charge transfer (TSCT) characteristics. However, precisely controlling the D-A distance of blue TSCT-TADF emitters is still challenging. Herein, an extra donor (D*) located on the side of the primary donor (D) is introduced to construct the hydrogen bonding with A and thus modulate the distance of D and A units to prepare high-efficiency blue TSCT emitters. The obtained "V"-shaped TSCT emitter presents a minimal D-A distance of 2.890 Å with a highly parallel D-A configuration. As a result, a high rate of radiative decay (>107 s-1) and photoluminescence quantum yield (nearly 90%) are achieved. The corresponding blue organic light-emitting diodes show maximum external quantum efficiencies (EQEmax) of 27.9% with a Commission Internationale de L'Eclairage (CIE) coordinate of (0.16, 0.21), which is the highest device efficiency of fluorene-based blue TSCT-TADF emitters. In addition, the TSCT-TADF emitter-sensitized OLEDs also achieve a high EQEmax of 29.3% with a CIE coordinate of (0.12, 0.16) and a narrow emission.

Identification and extraction of cementation patterns in sand modified by MICP: New insights at the pore scale.

Microbially induced calcium carbonate precipitation (MICP) is an environmentally friendly technology that improves soil permeability resistance through biocementation. In this study, 2D microscopic analysis and 3D volume reconstruction were performed on river sand after 24 cycles of bio-treatment based on stacked images and computed tomography (CT) scanning data, respectively, to extract biocementation patterns between particles. Based on the mutual validation findings of the two techniques, three patterns in the biocemented sand were identified as G-C-G, G-C, and G-G. Specifically, 2D microscopic analysis showed that G-C-G featured multi-particle encapsulation and bridging, with a pore filling ratio of 81.2%; G-C was characterized by locally coated particle layers, with a pore filling ratio of 19.7%; and the G-G was marked by sporadic filling of interparticle pores, with a pore filling ratio of 11.7%. G-C-G had the best cementation effect and permeability resistance (effective sealing rate of 68.5%), whereas G-C (effective sealing rate of 2.4%) had a relatively minor contribution to pore-filling and flow sealing. 3D volume reconstruction showed that G-C-G had the highest pore filling rate, followed by G-G and G-C. The average filling ratios of area and volume for G-C-G were 83.979% and 77.257%, respectively; for G-G 20.360% and 23.600%; and for G-C 11.545% and 11.250%. The analysis of the representative element volume (REV) was conducted, and the feasibility and reliability of the micro-scale pattern extraction results were confirmed to guide the analysis of macro-scale characteristics. The exploration of the effectiveness of cementation patterns in fluid sealing provides valuable insights into effective biocementation at the pore scale of porous media, which may inspire future research.

Mitochondrial derived vesicle-carrying protein MIGA2 promotes copper-induced autophagosomes-lysosomes fusion by regulating ATG14.

As an environmental pollution metal, copper (Cu) exposure-induced toxicity is closely related to mitochondrial damage. Mitochondrial-derived vesicles (MDVs) plays an essential role in mitochondrial quality control and cellular metabolism. However, the mechanism by which MDVs are involved in cellular metabolism under Cu exposure remains unclear. Here, the MDV-carrying protein MIGA2 was identified as a crucial molecule involved in the Cu-induced autophagosomes-lysosomes fusion. Furthermore, Cu exposure significantly promoted MDVs secretion, accompanied by a markedly increased MIGA2 expression in MDVs, as well as accelerated the autophagosomes-lysosomes fusion. However, small RNA interference of SNX9 (the MDVs secretion inductor) and MIGA2 blocked autophagic flux induced by Cu, leading to failure of autophagosomes degradation. Co-immunoprecipitation assay further demonstrated that ATG14 was a regulation target protein of MIGA2. Overexpression and knockdown of ATG14 significantly affected the autophagosomes-lysosomes fusion induced by Cu. Meanwhile, knockdown of ATG14 dramatically reversed the effect of MIGA2-overexpression in promoting autophagosomes-lysosomes fusion, while overexpression of ATG14 shows the opposite effect. These results demonstrated that MDVs-carrying MIGA2 protein promoted autophagosomes-lysosomes fusion induced by Cu. This study demonstrated that MDVs is involved in regulating organelles-to-organelles communication, providing a new insight into the toxicity mechanism of Cu exposure on hepatocytes.

Gut microbiota disorders aggravate terbuthylazine-induced mitochondrial quality control disturbance and PANoptosis in chicken hepatocyte through gut-liver axis.

Terbuthylazine (TBA) is a widely prevalent pesticide pollutant, which is a global concern due to its environmental residual. However, the toxic mechanism of TBA have not been fully solved. Here, we explored that TBA exposure disrupts the intestinal flora and aggravated disturbance of mitochondrial quality control and PANapoptosis in hepatocytes via gut-liver axis. Our findings demonstrated that TBA exposure induced significant damage to the jejunum barrier, evidenced by a marked decrease in the expression of Occludin and ZO-1. Moreover. TBA led to intestinal microflora disorder, manifested as the decreased abundance of Firmicutes, and increased abundance of the Nitrospirota, Chloroflexi, Desulfobacterota, Crenarchaeota, Myxococcota, and Planctomycetota. Meanwhile, intestinal microflora disorder affected the biological processes of lipid metabolism and cell growth and death of hepatocytes by RNA-Seq analysis. Furthermore, TBA could induced mitochondrial quality control imbalance, including mitochondrial redox disorders, lower activity of mitochondrial fusion and biogenesis decrease, and increasing level of mitophagy. Subsequently, TBA significantly increased expression levels of pyroptosis, apoptosis and necroptosis-related proteins. In general, these results demonstrated the underlying mechanisms of TBA-induced hepatotoxicity induced via the gut-liver axis, which provides a theoretical basis for further research of ecotoxicology of TBA.

Gate Controlled Excitonic Emission in Quantum Dot Thin Films.

Formation of charged trions is detrimental to the luminescence quantum efficiency of colloidal quantum dot (QD) thin films as they predominantly undergo nonradiative recombination. In this regard, control of charged trion formation is of interest for both fundamental characterization of the quasi-particles and performance optimization. Using CdSe/CdS QDs as a prototypical material system, here we demonstrate a metal-oxide-semiconductor capacitor based on QD thin films for studying the background charge effect on the luminescence efficiency and lifetime. The concentration ratio of the charged and neutral quasiparticles in the QDs is reversibly controlled by applying a gate voltage, while simultaneous steady-state and time-resolved photoluminescence measurements are performed. Notably, the photoluminescence intensity is modulated by up to 2 orders of magnitude with a corresponding change in the effective lifetime. In addition, chip-scale modulation of brightness is demonstrated, where the photoluminescence is effectively turned on and off by the gate, highlighting potential applications in voltage-controlled electrochromics.

Thermally Activated Delayed Fluorescence Emitters Based on a Special Tetrahedral Silane Core.

Based on the tetraphenylsilane skeleton, a new class of thermally activated delayed fluorescence (TADF) molecules have been designed and synthesized. Benefiting from the unique tetrahedron architecture of tetraphenylsilane, the intermolecular distance between TADF units can be enlarged and thus weakened the aggregation-induced quenching of triplet excitons. By adjusting the numbers of TADF subunits, the spin-orbit coupling processes can be controlled, leading to efficient up-conversion processes. The related OLEDs are fabricated through the solution processing technology, and pure-blue and green electroluminescence were observed with maximum external quantum efficiencies (EQEmax) of 6.6 and 13.8% as well as Commission Internationale de l'Eclairage coordinates of (0.14, 0.15) and (0.25, 0.45), respectively. This study provides a new idea for designing color-tunable TADF emitters through spatial structure regulation.

Design, Synthesis and Second-Order Nonlinear Optical Properties of Azobenzene-Based Polysiloxanes.

To study the effect of polymeric structures on second-order nonlinear optical properties, polysiloxanes materials based on azobenzene as chromophore have been designed and synthesized successfully. Herein, the siloxane monomer is directly bonded to azobenzene units by palladium catalysis, which avoids the influence of flexible chains on the photoelectric properties of azobenzene. According to the different positions of azobenzene units in the polymers, it is divided into side-chain, main-chain, and alternative-type polymers. The chemical structures of obtained polysiloxanes are confirmed by nuclear magnetic resonance spectra and mass spectra. Three polymers present high thermal decomposition temperatures and the medium glass transition temperatures. The effects of polymeric structures on the second-order nonlinear properties are compared. The main-chain polysiloxane possesses the highest thermal stability because of its rigid architecture. The side-chain polysiloxane shows the fastest isomerization transformation rate due to the large free volume. Besides, the alternative polysiloxane displays the best second-order nonlinear performance with second harmonic generation coefficient (d33 ) value of 47.6 pm V-1 , which is 3 times higher than the side-chain one.

Mitochondrial DNA release mediated by TFAM deficiency promotes copper-induced mitochondrial innate immune response via cGAS-STING signalling in chicken hepatocytes.

Copper (Cu) is pollution metal that is a global concern due to its toxic effects. A recent study found that the release of mitochondrial DNA (mtDNA) into the cytoplasm can activate the innate immune response, but the exact mechanisms underlying the effect of Cu exposure remains unknown. In this study, we identified that the reduction in transcription Factor A (TFAM) led to mtDNA leakage into the cytoplasm under Cu exposure in hepatocytes, accompanied by the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway-mediated innate immunity (increased expression of cGAS, STING, TANK-binding kinase-1 (TBK1), and interferon regulatory factor-3 (IRF3)) genes and proteins, and enhanced phosphorylation levels of TBK1 and IRF3). Subsequently, silencing TFAM (siTFAM) significantly aggravated mtDNA release and the innate immune response under Cu treatment. Mitochondrial DNA depletion alleviated Cu-induced innate immunity in hepatocytes, while mtDNA transfection further enhanced the innate immune response. Notably, the inhibition of STING effectively alleviated the phosphorylation levels of the TBK1 and IRF3 proteins induced by Cu, while the upregulation of STING aggravated the Cu-induced innate immunity. Furthermore, EtBr and H-151(a STING inhibitor) treatment dramatically reversed the effect of TFAM depletion on the sharpened innate immune response induced by Cu via the cGAS-STING pathway. In general, these findings demonstrated the TFAM deficiency promotes innate immunity by activating the mtDNA-cGAS-STING signalling pathway under Cu exposure in hepatocytes, providing new insight into Cu toxicology.

Mitochondria-mediated apoptosis and endoplasmic reticulum stress are involved in the toxicity induced by copper in the porcine spleen.

Copper (Cu) is one of the common heavy metal pollutants in the environment, and its toxic mechanisms have been extensively studied. However, the immunotoxicity induced by Cu remains rarely reported, and the effects of Cu on endoplasmic reticulum stress and mitochondria-mediated apoptosis have been little studied in the spleen. In this study, pigs were fed with different contents of Cu (10, 125, and 250 mg/kg Cu) for 80 days to establish a toxicity model. The results showed the Cu exposure triggered endoplasmic reticulum stress in the spleen, as evidenced by increased mRNA and protein levels of GRP94, GRP78, CHOP, XBP1, ATF6, and JNK; the positive rate of GRP78 increased by immunofluorescence analysis. Additionally, mitochondrial fission and fusion homeostasis were disrupted, the expression levels of mitochondrial dynamics-related genes Mfn1, Mfn2, and OPA1 decreased, DRP1 increased, and the positive rate of Mfn1 decreased by immunofluorescence analysis. Furthermore, Cu exposure could induce apoptosis, as demonstrated by the increased expression level of related proteins and genes Bak, Bax, Caspase-3, P53, and Cytc. In conclusion, these results suggest chronic Cu exposure can lead to endoplasmic reticulum stress and imbalance in mitochondrial dynamics and induced apoptosis of pig spleen, and these results provided new insights into the underlying mechanism of Cu exposure caused splenic toxicity, which has public health implications where humans and animals are exposed to copper contamination.

Mitophagy contributes to zinc-induced ferroptosis in porcine testis cells.

Zinc (Zn) is a critical microelement for physiological process, but excess exposure can cause testicular dysfunction. However, the underlying mechanism of Zn-induced ferroptosis via regulating mitophagy is unknown. In this study, a total of 60 male weaned pigs were randomly divided into three groups and the content of Zn were 75 mg/kg (control), 750 mg/kg (Zn-I), 1500 mg/kg (Zn-II). Meanwhile, testicular cells were treated with ZnSO4 (0, 50 and 100 µM), and in combination of ZnSO4 (100 µM) and ferrostation-1, ML-210, or 3-methyladenine for 24 h. Our results verified that Zn could cause ferroptosis and lipid peroxidation, which were characterized by down-regulating level of SLC7A11, GPX4, and ferritin, and up-regulating levels of MDA, CD71, TF, and HMGB1 by Western blot, immunohistochemistry, immunofluorescence, peroxidase assay, et.ac. The opposite effect was shown after treatment with ferrostation-1 or ML-210. Meanwhile, the mitophagy-related proteins (PINK, Parkin, ATG5, LC3-II/LC3-I) were significantly upregulated in vivo and in vitro. Most importantly, 3-methyladenine observably relieved ferroptosis under Zn treatment through inhibiting mitophagy. Collectively, we demonstrated that mitophagy contributes to Zn-induced ferroptosis in porcine testis cells, providing a new insight into Zn toxicology.

Ferromagnetism emerged from non-ferromagnetic atomic crystals.

The recently emerged ferromagnetic two-dimensional (2D) materials provide unique platforms for compact spintronic devices down to the atomic-thin regime; however, the prospect is hindered by the limited number  of ferromagnetic 2D materials discovered with limited choices of magnetic properties. If 2D antiferromagnetism could be converted to 2D ferromagnetism, the range of 2D magnets and their potential applications would be significantly broadened. Here, we discovered emergent ferromagnetism by interfacing non-magnetic WS2 layers with the antiferromagnetic FePS3. The WS2 exhibits an order of magnitude enhanced Zeeman effect with a saturated interfacial exchange field ~38 Tesla. Given the pristine FePS3 is an intralayer antiferromagnet, the prominent interfacial exchange field suggests the formation of ferromagnetic FePS3 at interface. Furthermore, the enhanced Zeeman effect in WS2 is found to exhibit a strong WS2-thickness dependence, highlighting the layer-tailorable interfacial exchange coupling in WS2-FePS3 heterostructures, which is potentially attributed to the thickness-dependent interfacial hybridization.

Single-photon absorption and emission from a natural photosynthetic complex.

Photosynthesis is generally assumed to be initiated by a single photon1-3 from the Sun, which, as a weak light source, delivers at most a few tens of photons per nanometre squared per second within a chlorophyll absorption band1. Yet much experimental and theoretical work over the past 40 years has explored the events during photosynthesis subsequent to absorption of light from intense, ultrashort laser pulses2-15. Here, we use single photons to excite under ambient conditions the light-harvesting 2 (LH2) complex of the purple bacterium Rhodobacter sphaeroides, comprising B800 and B850 rings that contain 9 and 18 bacteriochlorophyll molecules, respectively. Excitation of the B800 ring leads to electronic energy transfer to the B850 ring in approximately 0.7 ps, followed by rapid B850-to-B850 energy transfer on an approximately 100-fs timescale and light emission at 850-875 nm (refs. 16-19). Using a heralded single-photon source20,21 along with coincidence counting, we establish time correlation functions for B800 excitation and B850 fluorescence emission and demonstrate that both events involve single photons. We also find that the probability distribution of the number of heralds per detected fluorescence photon supports the view that a single photon can upon absorption drive the subsequent energy transfer and fluorescence emission and hence, by extension, the primary charge separation of photosynthesis. An analytical stochastic model and a Monte Carlo numerical model capture the data, further confirming that absorption of single photons is correlated with emission of single photons in a natural light-harvesting complex.

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3.

Upatinib, a Janus kinase inhibitor drug, was developed by a biotech company to treat immune diseases. The compound tert-butyl (5-toluenesulfonyl-5h-pyrrole [2,3-b] pyrazine-2-yl) carbamate (ACT051-3) is an important intermediate of Upatinib. To date, the steady industrial production of this intermediate compound (ACT051-3) has not been reported. In this study, we described the specific synthesis method and process of the compound ACT051-3 in terms of laboratory synthesis, pilot scale-up, and industrial production. During the exploration of the process route for ACT051-3, many appropriate adjustments and improvements were made to the reaction conditions, finally leading to the successful development of the optimal industrial production process for ACT051-3. The reaction time was nearly doubled by changing the state of the potassium carbonate involved in the reaction, which greatly improved the reaction efficiency. Additionally, by introducing N,N-diisopropylethylamine (DIPEA) to the reaction, the amount of the expensive catalyst Pd(OAc)2 was reduced 2.5-fold, significantly lowering production costs, confirming the feasibility of this process route and the industrial production of ACT051-3, and satisfying market demand for this important intermediate.

Endoplasmic reticulum stress contributes to pyroptosis through NF-κB/NLRP3 pathway in diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is known as a major microvascular complication in type 1 diabetes. Endoplasmic reticulum (ER) stress and pyroptosis play a critical role in the pathological process of DN, but their mechanism in DN has been litter attention. MAIN METHODS: Here, we firstly used large mammal beagles as DN model for 120 d to explored the mechanism of endoplasmic reticulum stress-mediated pyroptosis in DN. Meanwhile, 4-Phenylbutytic acid (4-PBA) and BYA 11-7082 were added in the MDCK (Madin-Daby canine kidney) cells by high glucose (HG) treatment. ER stress and pyroptosis related factors expression levels were analyzed by immunohistochemistry, immunofluorescence, western blotting, and quantitative real-time PCR assay. KEY FINDINGS: We identified that glomeruli atrophy, renal capsules were increased, and renal tubules thickened in diabetes. Masson and PAS staining resulted showed that the collagen fibers and glycogen were accumulated in kidney. Meanwhile, the ER stress and pyroptosis-related factors were significantly activated in vitro. Importantly, 4-PBA significantly inhibited the ER stress, which also alleviated the HG-induced pyroptosis in MDCK cells. Furthermore, BYA 11-7082 could reduce the expression levels of NLRP3 and GSDMD genes and proteins. SIGNIFICANCE: These data provide evidence for ER stress contributes to pyroptosis through NF-κΒ/ΝLRP3 pathway in canine type 1 diabetic nephropathy.

Self-Induced Valley Bosonic Stimulation of Exciton Polaritons in a Monolayer Semiconductor.

The newly discovered valley degree of freedom in atomically thin two-dimensional transition metal dichalcogenides offers a promising platform to explore rich nonlinear physics, such as spinor Bose-Einstein condensate and novel valleytronics applications. However, the critical nonlinear effect, such as valley polariton bosonic stimulation, has long remained an unresolved challenge due to the generation of limited polariton ground state densities necessary to induce the stimulated scattering of polaritons in specific valleys. Here, we report the self-induced valley bosonic stimulation of exciton polaritons via spin-valley locking in a WS_{2} monolayer microcavity. This is achieved by the resonant injection of valley polaritons at specific energy and wave vector, which allows spin-polarized polaritons to efficiently populate their ground state and induce a valley-dependent bosonic stimulation. As a result, we observe the nonlinear self-amplification of polariton emission from the valley-dependent ground state. Our finding paves the way for the investigation of spin ordering and phase transitions in transition metal dichalcogenides polariton Bose-Einstein condensate, offering a promising route for the realization of polariton spin lattices in moiré polariton systems and spin lasers.

Long-Term Copper Exposure Induced Excessive Autophagy of the Porcine Spleen.

Copper (Cu) is one of the essential trace elements and is widespread in the environment. However, excessive exposure will induce toxicity in animals. To investigate the potential mechanisms of Cu-induced porcine spleen toxicity, sixty 30-day-old pigs were randomly divided into three groups. The control group was fed a basal diet and two treatment groups were separately fed the diet with 125 mg/kg and 250 mg/kg of Cu for 80 days. The result of immunohistochemical staining showed that the autophagy marker p62 was significantly increased under Cu exposure, and the immunofluorescence results showed the same trend as LC33-. Meanwhile, Cu intensified autophagy by increasing the expression levels of autophagy-related genes and proteins (LC3, p62, ATG5, Beclin1, and PINK1). These results suggested that long-term Cu exposure induced excessive autophagy in the porcine spleen, laying the groundwork for future studies on Cu-induced immunotoxicity in the spleen and increasing the public safety awareness of the excessive Cu-induced contamination in the environment.

Effects of Long-Term Exposure to Copper on Mitochondria-Mediated Apoptosis in Pig Liver.

Copper (Cu) is listed as one of the main heavy metal pollutants, which poses potential health risks to humans. Excessive intake of Cu has shown toxic effects on the organs of many animals, and the liver is one of the most important organs to metabolize it. In this study, pigs, the mammal with similar metabolic characteristics to humans, were selected to assess the effects of long-term exposure to Cu on mitochondria-mediated apoptosis, which are of great significance for studying the toxicity of Cu to humans. Pigs were fed a diet with different contents of Cu (10, 125, and 250 mg/kg) for 80 days. Samples of blood and liver tissue were collected on days 40 and 80. Experimental results demonstrated that the accumulation of Cu in the liver was increased in a dose-dependent and time-dependent manner. Meanwhile, the curve of pig's body weight showed that a 125 mg/kg Cu diet promoted the growth of pigs during the first 40 days and then inhibited it from 40 to 80 days, while the 250 mg/kg Cu diet inhibited the growth of pigs during 80 days of feeding. Additionally, the genes and protein expression levels of Caspase-3, p53, Bax, Bak1, Bid, Bad, CytC, and Drp1 in the treatment group were higher than that in the control group, while Bcl-2, Bcl-xL, Opa1, Mfn1, and Mfn2 were decreased. In conclusion, these results indicated that long-term excessive intake of Cu could inhibit the growth of pigs and induced mitochondria-mediated apoptosis by breaking the mitochondrial dynamic balance. Synopsis: Long-term exposure to high doses of Cu could lead to mitochondrial dysfunction by breaking the mitochondrial dynamic balance, which ultimately induced mitochondria-mediated apoptosis in the liver of pigs. This might be closely related to the growth inhibition and liver damage in pigs.

MitomiR-504 alleviates the copper-induced mitochondria-mediated apoptosis by suppressing Bak1 expression in porcine jejunal epithelial cells.

Copper (Cu), an environmental heavy metal pollutant, has been widely researched in its toxicology. Recently, an increasing number of mitochondrial microRNAs (mitomiRs) have been shown to involve in the metabolic regulation. However, the underlying mechanisms of mitomiRs on regulating apoptosis under Cu exposure are still unclear. Here, we proved that Cu induced mitochondria-mediated apoptosis in porcine jejunal epithelial cells, concomitant with distinct reduction of mitomiR-504 in vivo and in vitro. The miR-504 mimic notably enhanced the mRNA and protein expressions of Bak1, Bax, Cleaved-caspase3 and Caspase-9, and significantly decreased the apoptosis rate and Bcl-2 mRNA and protein levels, indicating that overexpression of mitomiR-504 attenuated the Cu-induced mitochondria-mediated apoptosis. Besides, Bak1 was confirmed as a direct target of mitomiR-504 by the bioinformatics analysis and dual-luciferase reporter assay. Subsequently, transfection of siRNA targeting Bak1 significantly enhanced the alleviating effect of miR-504 mimic on the Cu-induced mitochondria-mediated apoptosis. Overall, these suggested that overexpression of mitomiR-504 alleviated the Cu-induced mitochondria-mediated apoptosis in jejunal epithelial cells by suppressing Bak1 expression. These findings are conducive to elucidating the mechanism of Cu-induced jejunal epithelial pathologies, providing a new research idea for the Cu toxicology.

Optimization of a lattice structure inspired by glass sponge.

The biomimetic design of engineering structures is based on biological structures with excellent mechanical properties, which are the result of billions of years of evolution. However, current biomimetic structures, such as ordered lattice materials, are still inferior to many biomaterials in terms of structural complexity and mechanical properties. For example, the structure ofEuplectella aspergillum, a type of deep-sea glass sponge, is an eye-catching source of inspiration for biomimetic design, many researches have introduced similar architecture in cellular solids. However, guided by scientific theory, how to surpass the mechanical properties ofE. aspergillumremains an unsolved problem. We proposed the lattice structure which firstly surpass theE. aspergillummechanically. The lattice structure of the skeleton ofE. aspergillumconsists of vertically, horizontally, and diagonally oriented struts, which provide superior strength and flexural resistance compared with the conventional square lattice structure. Herein, the structure ofE. aspergillumwas investigated in detail, and by using the theory of elasticity, a lattice structure inspired by the biomimetic structure was proposed. The mechanical properties of the sponge-inspired lattice structure surpassed the sponge structure under a variety of loading conditions, and the excellent performance of this configuration was verified experimentally. The proposed lattice structure can greatly improve the mechanical properties of engineering structures, and it improves strength without much redundancy of material. This study achieved the first surpassing of the mechanical properties of an existing sponge-mimicking design. This design can be applied to lattice structures, truss systems, and metamaterial cells.