Cuproptosis is involved in decabromodiphenyl ether-induced ovarian dysfunction and the protective effect of melatonin.

Decabromodiphenyl ether (BDE-209) has been universally detected in environmental media and animals, but its damage to ovarian function and mechanism is still unclear, and melatonin has been shown to improve mammalian ovarian function. This study aimed to investigate the toxic effects of BDE-209 on the ovary and tried to improve ovarian function with melatonin. Herein, BDE-209 was administered orally to female SD rats for 60 days. Enzyme-linked immunosorbent assay, HE staining, transcriptome analysis, qPCR and immunohistochemical staining were used to explore and verify the potential mechanism. We found that BDE-209 exposure had effects on the ovary, as shown by abnormal changes in the estrous cycle, hormone levels and ovarian reserve function in rats, while increasing the proportion of collagen fibres in ovarian tissue. In terms of mechanism, cuproptosis, a form of cell death, was identified to play a crucial role in BDE-209-induced ovarian dysfunction, with the phenotype manifested as copper salt accumulation in ovary, downregulation of glutathione pathway metabolism and copper transfer molecule (ATP7A/B), and upregulation of FDX1, lipoic acid pathway (LIAS, LIPT1), pyruvate dehydrogenase complex components (DLAT, PDHB, PDHA1), and copper transfer molecule (SLC31A1). Furthermore, possible interventions were explored. Notably, a supplement with melatonin has a repair effect on the damage to ovarian function by reversing the gene expression of cuproptosis-involved molecules. Overall, this study revealed that cuproptosis is involved in BDE-209-induced ovarian damage and the beneficial effect of melatonin on ovarian copper damage, providing evidence for the prevention and control of female reproductive damage induced by BDE-209.

Characterization of a secondary hydroxy-acyltransferase for lipid A in Vibrio parahaemolyticus.

Lipid A plays a crucial role in Vibrio parahaemolyticus. Previously we have reported the diversity of secondary acylation of lipid A in V. parahaemolyticus and four V. parahaemolyticus genes VP_RS08405, VP_RS01045, VP_RS12170, and VP_RS00880 exhibiting homology to the secondary acyltransferases in Escherichia coli. In this study, the gene VP_RS12170 was identified as a specific lipid A secondary hydroxy-acyltransferase responsible for transferring a 3-hydroxymyristate to the 2'-position of lipid A. Four E. coli mutant strains WHL00, WHM00, WH300, and WH001 were constructed, and they would synthesize lipid A with different structures due to the absence of genes encoding lipid A secondary acyltransferases or Kdo transferase. Then V. parahaemolyticus VP_RS12170 was overexpressed in W3110, WHL00, WHM00, WH300, and WH001, and lipid A was isolated from these strains and analyzed by using thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry. The detailed structural changes of lipid A in these mutant strains with and without VP_RS12170 overexpression were compared and conclude that VP_RS12170 can specifically transfer a 3-hydroxymyristate to the 2'-position of lipid A. This study also demonstrated that the function of VP_RS12170 is Kdo-dependent and its favorite substrate is Kdo-lipid IVA. These findings give us better understanding the biosynthetic pathway and the structural diversity of V. parahaemolyticus lipid A.

The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways.

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 µg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

On the contact electrification mechanism in semiconductor-semiconductor case by vertical contact-separation triboelectric nanogenerator.

With the speed of industrialization accelerating, the traditional energy is in the predicament of being exhausted. Humans urgently need a clean energy to maintain the peace and development. Triboelectric nanogenerator (TENG) is a tiny device that collects and converts the renewable energy, such as wind, vibration and tidal/blue energy, into electrical energy. As the most significant working principle of TENG, contact electrification (CE) has been broadly studied since it was documented thousands of years ago. A large number of related researches are reported. However, most of them are focused on the polymer materials, device structures and potential applications. There are few literatures about the mechanism of CE, especially in the semiconductor-semiconductor case. Semiconductor-semiconductor CE is a promising method to generate electricity, which has been used in many fields, such as the photodetector and displacement sensor. Therefore, it is necessary to establish a serious and detailed theory in order to deeply explain the underlying mechanisms of semiconductor-semiconductor CE. In this work, a novel Fermi level model based on energy band theory is proposed to illustrate the semiconductor-semiconductor CE mechanism. By assembling a ZnO/Si vertical contact-separation (CS) mode TENG, the charge transfer introduced by CE is systematically measured. According to the energy band theory and TENG governing equation, the experimental data is qualitatively and quantitatively analyzed. Moreover, the effects of different concentrations of growth solutions on the morphology of ZnO nanowires and the Fermi level difference between ZnO and Si are explored as well. Results show that it is the Fermi level difference that dominates the short circuit transfer charge amount and direction of semiconductor-semiconductor CE mechanism. Our work can be applied to understand the CE mechanism in semiconductor-semiconductor case and broaden the application prospects of semiconductor-based TENG.

Improve L-isoleucine production in Corynebacterium glutamicum WM001 by destructing the biosynthesis of trehalose dicorynomycolate.

Trehalose dicorynomycolates are structurally important constituents of the cell envelope in Corynebacterium glutamicum. The genes treS, treY, otsA, mytA and mytB are necessary for the biosynthesis of trehalose dicorynomycolates. In this study, the effect of biosynthesis of trehalose dicorynomycolates on L-isoleucine production in C. glutamicum has been investigated by deleting the genes treS, treY, otsA, mytA, and mytB in the L-isoleucine producing C. glutamicum WM001. L-isoleucine production was slightly improved in the mutants ΔtreY, ΔotsA, and ΔtreYA, and not improved in the single deletion mutant ΔtreS , but significantly improved in the triple deletion mutant ΔtreSYA. Deletion of mytA or mytB in ΔtreSYA could further improve L-isoleucine production. However, deletion of both mytA and mytB in ΔtreSYA significantly decreased L-isoleucine production. The final L-isoleucine producing C. glutamicum WL001 was constructed by deletion of treS, treY, otsA, and mytB, insertion of lrp, and replacement of the native promoter of ilvA with the L-isoleucine sensitive promoter PbrnFE7. WL001 grew worse than the control WM001, but produced 36.1% more L-isoleucine after 72 h shake flask cultivation than WM001.

Collagen hydrogel viscoelasticity regulates MSC chondrogenesis in a ROCK-dependent manner.

Mesenchymal stem cell (MSC) chondrogenesis in three-dimensional (3D) culture involves dynamic changes in cytoskeleton architecture during mesenchymal condensation before morphogenesis. However, the mechanism linking dynamic mechanical properties of matrix to cytoskeletal changes during chondrogenesis remains unclear. Here, we investigated how viscoelasticity, a time-dependent mechanical property of collagen hydrogel, coordinates MSC cytoskeleton changes at different stages of chondrogenesis. The viscoelasticity of collagen hydrogel was modulated by controlling the gelling process without chemical cross-linking. In slower-relaxing hydrogels, although a disordered cortical actin promoted early chondrogenic differentiation, persistent myosin hyperactivation resulted in Rho-associated kinase (ROCK)-dependent apoptosis. Meanwhile, faster-relaxing hydrogels promoted cell-matrix interactions and eventually facilitated long-term chondrogenesis with mitigated myosin hyperactivation and cell apoptosis, similar to the effect of ROCK inhibitors. The current work not only reveals how matrix viscoelasticity coordinates MSC chondrogenesis and survival in a ROCK-dependent manner but also highlights viscoelasticity as a design parameter for biomaterials for chondrogenic 3D culture.

A Gradient Doping Strategy toward Superior Electrochemical Performance for Li-Rich Mn-Based Cathode Materials.

Lithium-rich layered oxides (LLOs) are concerned as promising cathode materials for next-generation lithium-ion batteries due to their high reversible capacities (larger than 250 mA h g-1 ). However, LLOs suffer from critical drawbacks, such as irreversible oxygen release, structural degradation, and poor reaction kinetics, which hinder their commercialization. Herein, the local electronic structure is tuned to improve the capacity energy density retention and rate performance of LLOs via gradient Ta5+ doping. As a result, the capacity retention elevates from 73% to above 93%, and the energy density rises from 65% to above 87% for LLO with modification at 1 C after 200 cycles. Besides, the discharge capacity for the Ta5+ doped LLO at 5 C is 155 mA h g-1 , while it is only 122 mA h g-1 for bare LLO. Theoretical calculations reveal that Ta5+ doping can effectively increase oxygen vacancy formation energy, thus guaranteeing the structure stability during the electrochemical process, and the density of states results indicate that the electronic conductivity of the LLOs can be boosted significantly at the same time. This strategy of gradient doping provides a new avenue to improve the electrochemical performance of the LLOs by modulating the local structure at the surface.

The Influence of Outer Membrane Protein on Ampicillin Resistance of Vibrio parahaemolyticus.

The antibiotic resistance of the food-borne pathogen Vibrio parahaemolyticus has attracted researchers' attention in recent years, but its molecular mechanism remains poorly understood. In this study, 7 genes encoding outer membrane proteins (OMPs) were individually deleted in V. parahaemolyticus ATCC33846, and the resistance of these 7 mutants to 14 antibiotics was investigated. The results revealed that the resistance of the 7 mutants to ampicillin was significantly increased. Further exploration of 20-gene transcription changes by real time-qPCR (RT-qPCR) demonstrated that the higher ampicillin resistance might be attributed to the expression of ß-lactamase and reduced peptidoglycan (PG) synthesis activity through reduced transcription of penicillin-binding proteins (PBPs), increased transcription of l,d-transpeptidases, downregulated d,d-carboxypeptidase, and alanine deficiency. This study provides a new perspective on ampicillin resistance in OMP mutants with respect to PG synthesis.

Metabolic engineering of Escherichia coli to efficiently produce monophosphoryl lipid A.

Monophosphoryl lipid A (MPL), mainly isolated from Salmonella minnesota R595, has been used as adjuvant in several vaccines. In this study, an Escherichia coli strain that can efficiently produce the MPL has been constructed. The gene clusters related to the biosynthesis of O-antigen, core oligosaccharide, enterobacterial common antigen, and colanic acid were sequentially removed to save the carbon source and to increase the activity of PagP in E. coli MG1655. Then, the genes pldA, mlaA, and mlaC related to the phospholipid transport system were further deleted, resulting in the strain MW012. Finally, the genes lpxE from Francisella novicida and pagP and pagL from Salmonella were overexpressed in MW012 to modify the structure of lipid A, resulting in the strain MW012/pWEPL. Lipid A species were isolated from MW012/pWEPL and analyzed by thin-layer chromatography and liquid chromatography-mass spectrometry. The results showed that mainly two MPL species were produced in E. coli MW012/pWEPL, one is hexa-acylated, and the other is penta-acylated. More importantly, the proportion of the hexa-acylated MPL, which is the most effective component of lipid A vaccine adjuvant, reached 75%. E. coli MW012/pWEPL constructed in this study provided a good alternative for the production of lipid A vaccine adjuvant MPL.

Free lipid A and full-length lipopolysaccharide coexist in Vibrio parahaemolyticus ATCC33846.

Lipid A plays an important role in the pathogenicity and antimicrobial resistance of Vibrio parahaemolyticus, but little is known about the structure and biosynthesis of lipid A in V. parahaemolyticus. In this study, lipid A species were either directly extracted or obtained by the acid hydrolysis of lipopolysaccharide from V. parahaemolyticus ATCC33846 cells and analyzed by thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry. Several lipid A species in V. parahaemolyticus cells were characterized, and two of these species were not connected to polysaccharides. One free lipid A species has the similar structure as the hexa-acylated lipid A in Escherichia coli, and the other is a hepta-acylated lipid A with an additional secondary C16:0 acyl chain. Three lipid A species were isolated by the acid hydrolysis of lipopolysaccharide: the 1st one has the similar structure as the hexa-acylated lipid A in E. coli, the 2nd one is a hepta-acylated lipid A with an additional secondary C16:0 acyl chain and a secondary 2-OH C12:0 acyl chain, and the 3rd one is equal to the 2nd species with a phosphoethanolamine modification. These results are important for understanding the biosynthesis of lipid A in V. parahaemolyticus.

The role of trehalose biosynthesis on mycolate composition and L-glutamate production in Corynebacterium glutamicum.

Corynebacterium glutamicum has been widely utilized for the industrial production of various amino acids. Trehalose is a prerequisite for the biosynthesis of mycolates which are structurally important constituents of the cell envelope in C. glutamicum. In this study, C. glutamicum mutant ΔSYA, which is unable to synthesize trehalose was constructed by deleting genes treS, treY and otsA in the three pathways of trehalose biosynthesis. In the fermentation medium, ΔSYA grew as well as the control C. glutamicum ATCC13869, synthesized similar levels of glucose monocorynomycolate, trehalose dicorynomycolate, and phospholipids to ATCC13869, but produced 12.5 times more L-glutamate than ATCC13869. Transcriptional levels of the genes relevant to L-arginine biosynthesis, encoding ODHC and relevant to the biosynthesis of sulfur-containing amino acids were down-regulated in ΔSYA. In minimal medium with different concentrations of glucose, ΔSYA grew worse than ATCC13869 but excreted more L-glutamate. When grown in minimal medium, phospholipids are the major lipid in ΔSYA, while glucose monocorynomycolate, trehalose dicorynomycolate, and phospholipids are the major lipid in ATCC13869. The transcriptional levels of mscCG in ΔSYA was significantly up-regulated when grown in minimal medium.

Structure analysis of lipid A species in Vibrio parahaemolyticus by constructing mutants lacking multiple secondary acyltransferases of lipid A.

Four secondary acyltransferases of Vibrio parahaemolyticus lipid A encoded by VP_RS00880, VP_RS08405, VP_RS12170, and VP_RS01045 have been identified. In this study, mutants of V. parahaemolyticus were constructed by deleting two, three, or four of these genes. The double mutants showed similar growth pattern with the wild-type, but the quadruple mutant VPW011 showed significant growth defect at both 37°C and 21°C. Lipid A samples were extracted from these mutants and analyzed by electrospray ionization-mass spectrometry. The double and triple mutants could synthesize hepta- and octa-acylated lipid A species, while the quadruple mutant VPW011 could synthesize hexa- and hepta-acylated lipid A. The results suggest that the four secondary acyltransferases could complement each other in V. parahaemolyticus. More importantly, additional secondary acyltransferases of lipid A might exist in V. parahaemolyticus and their activities might be as strong as the four known secondary acyltransferases. The unusual multiple secondary acyltransferases of lipid A might play roles in pathogenicity and antimicrobic resistance of V. parahaemolyticus.

Au-Stabilized Nanoporous PdCuAu Alloys Exhibiting Outstanding Catalytic Activity and Durability for the Formic Acid Oxidation Reaction.

Metallic Pd is widely recognized as an efficient electrocatalyst for the formic acid oxidation reaction (FAOR), which unfortunately suffers from poor durability owing to Pd dissolution and CO poisoning. The present work describes an effective method to enhance Pd durability by alloying with Cu and Au. Cu could provide surface OH at low potentials to remove poisonous CO for improved CO resistance. Au, the most inert metal, was added to reduce Pd and Cu dissolution. Moreover, alloying with Cu and Au could also modulate the electronic structure of Pd which is just profitable for the FAOR. The constructed PdCuAu with a nanoporous structure exhibits a specific activity of 14.9 mA cm-2 and a Pd mass activity of 6012 A g-1, which is ∼15 times and ∼14 times higher than those of commercial Pd/C. While these two electrocatalysts were used as fuel cell anodes, the maximum power density of the PdCuAu anode (Pd loading 10 µg cm-2) is 93.2 mW cm-2 and the value of the Pd/C anode (Pd loading 1.2 mg cm-2) is 60.3 mW cm-2. The power efficiency of Pd has been notably increased by 185 times in this home-made nanoporous PdCuAu ternary alloy electrocatalyst.

A sonication-induced silk-collagen hydrogel for functional cartilage regeneration.

Cartilage tissue has limited self-regeneration capacity and current treatment methods often result in fibrocartilage formation. Although collagen has shown the ability to induce chondrogenesis of mesenchymal stem cells (MSCs) and regenerate hyaline cartilage, the application of a pure collagen hydrogel is inherently limited by its fast degradation, poor mechanical properties and excessive cell-mediated shrinkage. To overcome this challenge, we developed a sonication-induced silk-collagen composite hydrogel (COL + SF(S)) and investigated its physicochemical and biological properties compared with a collagen hydrogel (COL) and a non-sonicated silk-collagen composite hydrogel (COL + SF(NS)). The results showed that the sonication treatment of silk fibroin induced antiparallel ß-sheet formation and a stronger negative charge on the silk fibroin molecule, which resulted in improved mechanical properties of the COL + SF(S) hydrogel. The COL + SF(S) hydrogel exhibited superior stability during cell culture and promoted the gene expression of SOX9 at the early stage and sulfated glycosaminoglycan (sGAG) deposition without any exogenous growth factor. Moreover, the cartilage regeneration capacity of the COL + SF(S) group was evaluated in rabbit knee defects. The COL + SF(S) group exhibited well-integrated articular hyaline cartilage closely resembling native articular cartilage after 6 months. Overall, the COL + SF(S) hydrogel holds great potential as a scaffold material to regenerate functional hyaline cartilage.

Cancellation method to improve signal to noise ratio of an electrodeless microwave-biased ZnO single crystal x-ray detector.

Semiconductor x-ray detectors are usually fabricated with proper ohmic or Schottky contact electrodes, which make the fabrication process complex and even unable to realize, especially for new materials. In this paper, we demonstrated an electrodeless ZnO single crystal x-ray detector using microwave (MW) bias with a high signal-to-noise ratio obtained by a cancellation method. The MW-biased x-ray detector is fabricated using the split-ring-resonator with the ZnO crystal mounted on the split-ring gap. The analytical response model was built for the detector. The MW cancellation process was realized by a phase and amplitude matching network. By using the cancellation method, the signal-to-noise ratio of the detector is about 59.4 dB, which is 58 dB higher than that of the DC-biased ZnO photodetector. The sensitivity of the detector is 139 µC Gy-1 cm-2 for the x-ray dose rate of 3.54 Gy/s, which is 86 times higher than that of the DC-biased ZnO photodetector. The high sensitivity of the detector is due to the high equivalent stimulated voltage caused by the split-ring resonator. The MW-biased detector can be used for x-ray dose monitoring.

Constructing epitaxially grown heterointerface of metal nanoparticles and manganese dioxide anode for high-capacity and high-rate lithium-ion batteries.

Low ion migration rate and irreversible change in the valence state in transition-metal oxides limit their application as anode materials in Li-ion batteries (LIBs). Interfacial optimization by loading metal particles on semiconductor can change the band structure and thus tune the inherent electrical nature of transition-metal oxide anode materials for energy applications. In this work, Au nanoparticles are epitaxially grown on MnO2 nanoroads (MnO2-Au). Interestingly, the MnO2-Au anode shows excellent electrochemical activity. It delivers high reversible capacity (about 2-3 fold compared to MnO2) and high rate capability (740 mA h g-1 at 1 A g-1). The electron holography and density functional theory (DFT) results demonstrate that the Au particles on the surface of MnO2 can form a negative charge accumulation area, which not only improves the Li ion migration rate but also catalyzes the transition of MnOx to Mn0. This study provides a direction to heterointerface fabrication for transition-metal oxide anode materials with desired properties for high-performance LIBs and future energy applications.

Global metabolic regulation in Vibrio parahaemolyticus under polymyxin B stimulation.

Vibrio parahaemolyticus is responsible for infection diseases of people who consume the contaminated seafood, but its metabolic regulation profile in response to colistin, the last treatment option for multidrug-resistant Gram-negative bacteria, remains unclear. In this study, the metabolic regulation profile of V. parahaemolyticus ATCC33846 under polymyxin B stimulation has been investigated. V. parahaemolyticus exposed to polymyxin B resulted in 4597 differentially transcribed genes, including 673 significantly up-regulated genes and 569 significantly down-regulated genes. In V. parahaemolyticus under polymyxin B stimulation, the cellular antioxidant systems to prevent bacteria from oxidant stress was activated, the synthesis of some nonessential macromolecules was reduced, and the assembly and modification of lipopolysaccharide and peptidoglycan to resist the attack from other antibiotics were promoted. These findings provide new insights into polymyxin B-related stress response in V. parahaemolyticus which should be useful for developing novel drugs for infection.

Feature Screening for Network Autoregression Model.

Network analysis has drawn great attention in recent years. It is applied to a wide range disciplines. These include but are not limited to social science, finance and genetics. It is typical that one collects abundant covariates along the response variable in practice. Since the network structure makes the responses at different nodes no longer independent, existing screening methods may not perform well for network data. We propose a network-based sure independence screening (NW-SIS) method. This approach explicitly takes the network structure into consideration. The strong screening consistency property of the NW-SIS is rigorously established. We further investigated the estimation of the network effect and establish the n -consistency of the estimator. The finite sample performance of the proposed method is assessed by simulation study and illustrated by an empirical analysis of a dataset from Chinese stock market.

Automatic, dynamic, and nearly optimal learning rate specification via local quadratic approximation.

In deep learning tasks, the update step size determined by the learning rate at each iteration plays a critical role in gradient-based optimization. However, determining the appropriate learning rate in practice typically relies on subjective judgment. In this work, we propose a novel optimization method based on local quadratic approximation (LQA). In each update step, we locally approximate the loss function along the gradient direction by using a standard quadratic function of the learning rate. Subsequently, we propose an approximation step to obtain a nearly optimal learning rate in a computationally efficient manner. The proposed LQA method has three important features. First, the learning rate is automatically determined in each update step. Second, it is dynamically adjusted according to the current loss function value and parameter estimates. Third, with the gradient direction fixed, the proposed method attains a nearly maximum reduction in the loss function. Extensive experiments were conducted to prove the effectiveness of the proposed LQA method.

Construction and Application of an Escherichia coli Strain Lacking 62 Genes Responsible for the Biosynthesis of Enterobacterial Common Antigen and Flagella.

The biosynthesis of the enterobacterial common antigen and flagella in Escherichia coli consumes lots of substrates and energy. In this study, 12 genes responsible for the biosynthesis of the enterobacterial common antigen were deleted in E. coli MG1655, resulting in WQM021. WQM021 grew better than MG1655 in both rich LB medium and minimum M9 medium. Compared with MG1655, WQM021 showed higher membrane permeability and higher production efficiency for recombinant proteins, polyhydroxyalkanoate, and l-threonine. Transcriptome analysis revealed that genes relevant to glucose consumption, glycolysis, and flagellar synthesis were significantly upregulated in WQM021. Therefore, 50 genes responsible for flagellar biosynthesis were further deleted in WQM021, resulting in WQM022. WQM022 grew better and could synthesize more polyhydroxyalkanoate and l-threonine than WQM021. The results demonstrate that the productivity of E. coli can be efficiently improved when the enterobacterial common antigen and flagella are eliminated. This strategy has guiding significance in the optimization of other industrial products and microorganisms.