A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress.

Mitochondria play essential roles in cancer cell adaptation to hypoxia, but the underlying mechanisms remain elusive. Through mitochondrial proteomic profiling, we here find that the prolyl hydroxylase EglN1 (PHD2) accumulates on mitochondria under hypoxia. EglN1 substrate-binding region in the ß2ß3 loop is responsible for its mitochondrial translocation and contributes to breast tumor growth. Furthermore, we identify AMP-activated protein kinase alpha (AMPKα) as an EglN1 substrate on mitochondria. The EglN1-AMPKα interaction is essential for their mutual mitochondrial translocation. After EglN1 prolyl-hydroxylates AMPKα under normoxia, they rapidly dissociate following prolyl-hydroxylation, leading to their immediate release from mitochondria. In contrast, hypoxia results in constant EglN1-AMPKα interaction and their accumulation on mitochondria, leading to the formation of a Ca2+ /calmodulin-dependent protein kinase 2 (CaMKK2)-EglN1-AMPKα complex to activate AMPKα phosphorylation, ensuring metabolic homeostasis and breast tumor growth. Our findings identify EglN1 as an oxygen-sensitive metabolic checkpoint signaling hypoxic stress to mitochondria through its ß2ß3 loop region, suggesting a potential therapeutic target for breast cancer.

Mechanism of HCG regulating epithelial-mesenchymal transition progression in endometrial cells through the FoxO1/miR223-5p/Wnt5α pathway.

RESEARCH QUESTION: Does human chorionic gonadotrophin (HCG) influence endometrial receptivity and epithelial-mesenchymal transition (EMT) via the FoxO1/miR223-5p/Wnt5α pathway? DESIGN: This study aimed to establish the co-culture system of human embryonic trophoblast cell line (HTR-8-Svneo) cells and human endometrial epithelial cell line (HEEC) cells. The expression of Wnt5α protein and EMT-related proteins in HTR-8-Svneo and HEEC cells treated in a gradient-dependent manner using HCG and exosome inhibitor GW4869 were detected in the co-culture system. RESULTS: In the HTR-8-Svneo/HEEC co-culture system, miR223-5p in HEEC cells increased significantly with induction of HTR-8-Svneo cells by 100 IU/ml HCG for 48 h (P = 0.046), and Wnt5α protein decreased significantly in HEEC cells (P = 0.021). Pretreatment of HTR-8-Svneo cells with GW4869, and knockdown of FoxO1 in HTR-8-Svneo cells, significantly inhibited the above effects of HCG on miR223-5p and Wnt5α expression in HEEC cells in the HTR-8-Svneo/HEEC co-culture system. HTR-8-Svneo cells induced with 100 IU/ml HCG for 48 h significantly enhanced the logarithmic phase proliferation activity of HEEC cells in the co-culture system (P < 0.001), while knockdown of FoxO1 in HTR-8-Svneo cells and inhibition of miR223-5p in HEEC cells suppressed proliferation of HEEC cells in the HTR-8-Svneo/HEEC co-culture system (P < 0.001). CONCLUSIONS: HCG exposure induces HTR-8-Svneo cells to up-regulate miR223-5p expression, which enters HEEC cells in the co-culture system through the exosomal pathway, and inhibits Wnt5α expression and the progress of EMT.

Warming positively promoted community appearance restoration of the degraded alpine meadow although accompanied by topsoil drying.

On-going climate warming is threatening the ecological function of grassland ecosystems. However, whether warming has positive effects on community microhabitats and appearance, especially in degraded grasslands, remains elusive. To address this issue, we conducted a 2-year field experiment on the severely degraded alpine meadow and undegraded alpine meadow with no warming and warming treatments. Community coverage and height in degraded meadow significantly increased under warming, while these changes were not significant in undegraded meadow. Two-year warming increased the community height of degraded meadow and undegraded meadow by 56.55% and 10.99%, respectively. Warming also increased community coverage by 41.88% in degraded meadow and decreased community coverage by 3.01% in undegraded meadow. Moreover, the response of topsoil temperature to warming was stronger in degraded meadow (6.89%) than in undegraded meadow (- 0.26%), while the negative response of topsoil moisture to warming was weaker in degraded meadow (- 13.95%) than in undegraded meadow (- 20.00%). The SEMs further demonstrated that warming had positive effects on topsoil temperature and community height, while had negative effects on topsoil moisture both in degraded and undegraded meadows. Our results confirm that warming-induced soil drying is an important pathway affecting the community appearance in alpine meadows. These findings highlight that warming has positive effects on community height and coverage and is particularly effective in improving community coverage appearance in severely degraded alpine meadow with topsoil drying.

Plant diversity increases spatial stability of aboveground productivity in alpine grasslands.

Plant diversity can significantly affect the grassland productivity and its stability. However, it remains unclear how plant diversity affects the spatial stability of natural grassland productivity, especially in alpine regions that are sensitive to climate change. We analyzed the interaction between plant (species richness and productivity, etc.) and climatic factors (precipitation, temperature, and moisture index, etc.) of alpine natural grassland on the Qinghai-Tibetan Plateau. In addition, we tested the relationship between plant diversity and spatial stability of grassland productivity. Results showed that an increase in plant diversity significantly enhanced community productivity and its standard deviation, while reducing the coefficient of variation in productivity. The influence of plant diversity on productivity and the reciprocal of productivity variability coefficient was not affected by vegetation types. The absolute values of the regression slopes between climate factors and productivity in alpine meadow communities with higher plant diversity were smaller than those in alpine meadow communities with lower plant diversity. In other words, alpine meadow communities with higher plant diversity exhibited a weaker response to climatic factors in terms of productivity, whereas those with lower plant diversity showed a stronger response. Our results indicate that high plant diversity buffers the impact of ambient pressure (e.g., precipitation, temperature) on alpine meadow productivity, and significantly enhanced the spatial stability of grassland productivity. This finding provides a theoretical basis for maintaining the stability of grassland ecosystems and scientifically managing alpine grasslands under the continuous climate change.

Isoproterenol induces MD2 activation by ß-AR-cAMP-PKA-ROS signalling axis in cardiomyocytes and macrophages drives inflammatory heart failure.

Cardiac inflammation contributes to heart failure (HF) induced by isoproterenol (ISO) through activating ß-adrenergic receptors (ß-AR). Recent evidence shows that myeloid differentiation factor 2 (MD2), a key protein in endotoxin-induced inflammation, mediates inflammatory heart diseases. In this study, we investigated the role of MD2 in ISO-ß-AR-induced heart injuries and HF. Mice were infused with ISO (30 mg·kg-1·d-1) via osmotic mini-pumps for 2 weeks. We showed that MD2 in cardiomyocytes and cardiac macrophages was significantly increased and activated in the heart tissues of ISO-challenged mice. Either MD2 knockout or administration of MD2 inhibitor L6H21 (10 mg/kg every 2 days, i.g.) could prevent mouse hearts from ISO-induced inflammation, remodelling and dysfunction. Bone marrow transplantation study revealed that both cardiomyocyte MD2 and bone marrow-derived macrophage MD2 contributed to ISO-induced cardiac inflammation and injuries. In ISO-treated H9c2 cardiomyocyte-like cells, neonatal rat primary cardiomyocytes and primary mouse peritoneal macrophages, MD2 knockout or pre-treatment with L6H21 (10 µM) alleviated ISO-induced inflammatory responses, and the conditioned medium from ISO-challenged macrophages promoted the hypertrophy and fibrosis in cardiomyocytes and fibroblasts. We demonstrated that ISO induced MD2 activation in cardiomyocytes via ß1-AR-cAMP-PKA-ROS signalling axis, and induced inflammatory responses in macrophages via ß2-AR-cAMP-PKA-ROS axis. This study identifies MD2 as a key inflammatory mediator and a promising therapeutic target for ISO-induced heart failure.

Britannin as a novel NLRP3 inhibitor, suppresses inflammasome activation in macrophages and alleviates NLRP3-related diseases in mice.

Overactivation of the NLRP3 inflammasomes induces production of pro-inflammatory cytokines and drives pathological processes. Pharmacological inhibition of NLRP3 is an explicit strategy for the treatment of inflammatory diseases. Thus far no drug specifically targeting NLRP3 has been approved by the FDA for clinical use. This study was aimed to discover novel NLRP3 inhibitors that could suppress NLRP3-mediated pyroptosis. We screened 95 natural products from our in-house library for their inhibitory activity on IL-1ß secretion in LPS + ATP-challenged BMDMs, found that Britannin exerted the most potent inhibitory effect with an IC50 value of 3.630 µM. We showed that Britannin (1, 5, 10 µM) dose-dependently inhibited secretion of the cleaved Caspase-1 (p20) and the mature IL-1ß, and suppressed NLRP3-mediated pyroptosis in both murine and human macrophages. We demonstrated that Britannin specifically inhibited the activation step of NLRP3 inflammasome in BMDMs via interrupting the assembly step, especially the interaction between NLRP3 and NEK7. We revealed that Britannin directly bound to NLRP3 NACHT domain at Arg335 and Gly271. Moreover, Britannin suppressed NLRP3 activation in an ATPase-independent way, suggesting it as a lead compound for design and development of novel NLRP3 inhibitors. In mouse models of MSU-induced gouty arthritis and LPS-induced acute lung injury (ALI), administration of Britannin (20 mg/kg, i.p.) significantly alleviated NLRP3-mediated inflammation; the therapeutic effects of Britannin were dismissed by NLRP3 knockout. In conclusion, Britannin is an effective natural NLRP3 inhibitor and a potential lead compound for the development of drugs targeting NLRP3.

Endothelial deubiquinatase YOD1 mediates Ang II-induced vascular endothelial-mesenchymal transition and remodeling by regulating ß-catenin.

Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 µg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to ß-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain ß-catenin protein stability by removing the K48 ubiquitin chain from ß-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of ß-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-ß-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for ß-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating ß-catenin-mediated vascular diseases.

A robust method for simultaneous determination of eight B vitamins in human serum by liquid chromatography tandem mass spectrometry.

The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra-high-performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin. Limit of quantification, precision, trueness, and matrix effect were validated according to the European Medicines Agency and United States Food and Drug guidelines and Clinical and Laboratory Standards Institute guidelines on bioanalytical method. The limit of quantification for thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin was 0.4, 0.4, 0.8, 2.0, 0.4, 0.1, 0.4, and 0.04 ng/mL separately, respectively. Intra- and interday precisions were 1.1%-12.4% and 2.0%-13.5%, respectively. The relative errors were between 0.3% and 13.3%, and the matrix effects were between 2.6% and 10.4%.

Biosynthesis of silver nanoparticles using Burkholderia contaminans ZCC and mechanistic analysis at the proteome level.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

Alloy Metal Nanocluster: A Robust and Stable Photosensitizer for Steering Solar Water Oxidation.

Metal nanoclusters (NCs) have been unleashed as an emerging category of metal materials by virtue of integrated merits including the unusual atom-stacking mode, quantum confinement effect, and fruitful catalytically active sites. Nonetheless, development of metal NCs as photosensitizers is blocked by light-induced instability and ultrashort carrier lifespan, which remarkably retards the design of metal NC-involved photosystems, hence resulting in the decreased photoactivities. To solve these obstacles, herein, we conceptually probed the charge transfer characteristics of the BiVO4 photoanode photosensitized by atomically precise alloy metal NCs, wherein tailor-made l-glutathione-capped gold-silver bimetallic (AuAg) NCs were controllably self-assembled on the BiVO4 substrate. It was uncovered that alien Ag atom doping is able to effectively stabilize the alloy AuAg NCs and simultaneously photosensitize the BiVO4 photoanode, significantly boosting the photoelectrochemical (PEC) water oxidation performances. The reasons for the robust and stable PEC water oxidation activities of the AuAg NCs/BiVO4 composite photoanode were unambiguously unleashed. We ascertain that Ag atom doping in the staple motif of Aux NCs efficaciously protects the NCs from rapid oxidation, enhancing the photostability, boosting the photosensitization efficiency, and thus leading to the considerably improved PEC water splitting activities compared with the homometallic counterpart. This work could afford a new strategy to judiciously tackle the inherent detrimental instability of metal NCs for solar energy conversion.

Warming-driven indirect effects on alpine grasslands: short-term gravel encroachment rapidly reshapes community structure and reduces community stability.

The community stability is the main ability to resist and be resilient to climate changes. In a world of climate warming and melting glaciers, alpine gravel encroachment was occurring universally and threatening hillside grassland ecosystem. Gravel encroachment caused by climate warming and glacial melting may alter community structure and community stability in alpine meadow. Yet, the effects of climate warming-induced gravel encroachment on grassland communities are unknown. Here, a 1-year short-term field experiment was conducted to explore the early stage drive process of gravel encroachment on community structure and stability at four different gravel encroachment levels 0%, 30%, 60%, and 90% gravel coverage at an alpine meadow on the Qinghai Tibetan Plateau, by analyzing the changes of dominant species stability and species asynchrony to the simulated gravel encroachment processes. Gravel encroachment rapidly changed the species composition and species ranking of alpine meadow plant community in a short period of time. Specifically, community stability of alpine meadow decreased by 61.78-79.48%, which may be due to the reduced dominant species stability and species asynchrony. Species asynchrony and dominant species stability were reduced by 2.65-17.39% and 46.51-67.97%, respectively. The results of this study demonstrate that gravel encroachment presents a severe negative impact on community structure and stability of alpine meadow in the short term, the longer term and comprehensive study should be conducted to accurate prediction of global warming-induced indirect effects on alpine grassland ecosystems.

Nomogram to predict FSH starting dose in poor ovarian response women in progestin primed ovarian stimulation protocol.

Prediction of individual ovarian response to exogenous gonadotropin is a cornerstone for success and safety in all controlled ovarian stimulation (COS) protocols. Providing the best FSH starting dose according to each woman's own characteristics is the key to the success of individualized treatment. The objective of this investigation was to evaluate the potential application of a novel nomogram based on antral follicle counting (AFC), anti-Müllerian hormone (AMH) and body mass index (BMI) as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in women with poor ovarian response in in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycles in progestin-primed ovarian stimulation (PPOS). We performed a retrospective analysis involving 130 poor ovarian responders undergoing IVF/ICSI cycles in a PPOS protocol from June 2017 to February 2019 in our reproductive center. The individual FSH starting dose was selected according to patients' clinical history and characteristics. The influence of variables including age, BMI, AMH and AFC on the FSH starting dose was assessed through multiple regression analysis. We used the variables reaching the statistical significance for calculation for the final predictive model. In the univariate analysis, BMI, AMH and AFC were significant (P < 0.05) predictors of FSH starting dose, age was canceled. In the multivariate analysis, BMI, AMH and AFC remained significant (P < 0.05). According to the nomogram, 118 patients (90.77% of 130) would have received a higher FSH starting dose and 12 patients (9.23% of 130) a lower FSH starting dose than practice dose. The application of the nomogram based on three variables easily determined in clinical practice: BMI, AMH and AFC would lead to a more tailored FSH starting dose in women with poor ovarian response.

Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability.

The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.

Steering Photocatalytic CO2 Conversion over CsPbBr3 Perovskite Nanocrystals by Coupling with Transition-Metal Chalcogenides.

Transition-metal chalcogenides (TMCs) have received enormous attention by virtue of their large light absorption coefficient, abundant catalytically active sites, and markedly reduced spatially vectorial charge-transfer distance originating from generic structural merits. However, the controllable construction of TMC-based heterostructured photosystems for photocatalytic carbon dioxide (CO2) reduction is retarded by the ultrashort charge lifetime, sluggish charge-transfer kinetics, and low target product selectivity. Herein, we present the rational design of two-dimensional (2D)/zero-dimensional (0D) heterostructured CO2 reduction photosystems by an electrostatic self-assembly strategy, which is enabled by precisely anchoring CsPbBr3 quantum dots (QDs) on the 2D TMC (CdIn2S4, ZnIn2S4, In2S3) frameworks. The peculiar 2D/0D integration mode and suitable energy-level alignment between these two assembly units afford maximal interfacial contact and applicable potential for CO2 photoreduction, thus endowing the self-assembled TMCs/CsPbBr3 nanocomposites with considerably improved visible-light-driven photocatalytic performances toward CO2 reduction to carbon monoxide with high selectivity. The enhanced photocatalytic performances of TMCs/CsPbBr3 heterostructures are attributed to the abundant active sites on the TMC frameworks, excellent light absorption of CsPbBr3 QDs, and well-defined 2D/0D heterostructures of TMCs/CsPbBr3 QDs photosystems, which synergistically boosts the directional charge transport from CsPbBr3 QDs to TMCs, enhancing the interfacial charge migration/separation. Our work would inspire the construction of novel TMCs-involved photosystems for solar-to-fuel conversion.

Atomically Precise Metal Nanoclusters versus Metal Nanocrystals: Maneuvering Tunable Charge Transfer in an Integrated Photosystem.

Atomically precise metal nanoclusters (NCs) have recently emerged as a promising sector of metal nanomaterials in terms of peculiar atomic stacking fashion, quantum confinement effect, and enriched catalytically active sites, which are wholly distinct from conventional metal nanocrystals (NYs) in all respects. However, atomically precise metal NCs inevitably suffer from intrinsic poor instability either under light irradiation or thermal treatment owing to the ultrahigh surface energy, thereby resulting in substantial loss of photosensitization efficiency and retarding their emerging utilization in photoredox catalysis. Here, we first conceptually reveal the charge transfer characteristic difference between atomically precise metal NCs and metal NYs attained by self-transformation in boosting interfacial charge migration and separation. The results signify that the interfacial charge transfer impetus of atomically precise metal NCs as a photosensitizer versus metal NYs as a Schottky-type electron-withdrawing mediator is closely associated with the loading amount on the semiconductor substrate. The photosensitization effect of atomically precise metal NCs is superior to the electron trapping capability of metal NYs when the loading amount of the metal ingredient is relatively high and vice versa. Our work would significantly bridge the gap between atomically precise metal NCs and metal NYs in fine tuning of the charge transfer pathway in photocatalysis toward solar energy conversion.

Determining the role of richness and evenness in alpine grassland productivity across climatic and edaphic gradients.

Spatial heterogeneity of climatic and edaphic gradients can substantially affect the grassland productivity function. However, few studies have tested the importance of species richness and evenness on regulating grassland productivity across spatial-scale climatic and edaphic changes. This study examines the complex mechanisms by which species richness and evenness regulate productivity in alpine meadow and steppe. We used field survey data to explore above-ground productivity formation and sensitivity to spatial-scale climatic and edaphic response of alpine grassland based on species richness and evenness. Results showed that the growing season solar radiation was the main driving factor of above-ground biomass and was strongly negatively correlated with above-ground biomass. Furthermore, compared with alpine steppe, above-ground biomass in alpine meadow was more responsive to climatic variables, but less responsive to soil variables. Unexpectedly, we found that the regulation patterns of species richness and evenness on above-ground biomass were different in both habitats by a structural equation model analysis. Our study demonstrated that species evenness and richness were both important in co-regulating above-ground biomass in alpine meadow, whereas species richness mattered more than species evenness in regulating above-ground biomass in alpine steppe. Our results offer further support for species richness and evenness co-regulating grassland productivity across spatial-scale climatic and edaphic gradients, which helps maintain the benefits of plant diversity and alpine grassland ecosystems.

Au(III)-induced extracellular electron transfer by Burkholderia contaminans ZCC for the bio-recovery of gold nanoparticles.

The biorecovery of gold (Au) by microbial reduction has received increasing attention, however, the biomolecules involved and the mechanisms by which they operate to produce Au nanoparticles have been not resolved. Here we report that Burkholderia contaminans ZCC is capable of reduction of Au(III) to Au nanoparticles on the cell surface. Exposure of B. contaminans ZCC to Au(III) led to significant changes in the functional group of cell proteins, with approximately 11.1% of the (C-C/C-H) bonds being converted to CO (8.1%) and C-OH (3.0%) bonds and 29.4% of the CO bonds being converted to (C-OH/C-O-C/P-O-C) bonds, respectively. In response to Au(III), B. contaminans ZCC also displayed the ability of extracellular electron transfer (EET) via membrane proteins and could produce reduced riboflavin as verified by electrochemical and liquid chromatography-mass spectrometric results, but did not do so without Au(III) being present. Addition of exogenous reduced riboflavin to the medium suggested that B. contaminans ZCC could utilize indirect EET via riboflavin to enhance the rate of reduction of Au(III). Transcriptional analysis of the riboflavin genes (ribBDEFH) supported the view of the importance of riboflavin in the reduction of Au(III) and its importance in the biorecovery of gold.

Intervention Effect of Taurine on LPS-Induced Intestinal Mechanical Barrier Injury in Piglets.

Taurine has the advantages of being safe, highly efficient, chemically stabile, and biologically active, together with having versatile functions. Presently, it is employed as a veterinary feed additive in animal research. The tight junctions that constitute the intestinal epithelial cells are the most critical structures for ensuring regular and uninterrupted digestion and absorption of food by the intestinal mucosa, while at the same time resisting invasions by toxins. The purpose of this study was to investigate the protective effect and mechanism of taurine action on intestinal mechanical barrier function of piglets that were infected with LPS. The results showed that 0.3% taurine inhibits LPS-driven increase in intestinal permeability and intestinal mucosal injury, the rise in the ratio of villus length to crypt depth within the duodenum, jejunum, and ileum, and the significant enhancement in the expression of tight junction protein-related genes. In summary, dietary taurine significantly reduces intestinal mucosal structural damage and intestinal mucosal permeability while increasing gene expression of tight junction proteins of the intestinal mucosa of piglets induced by LPS, thereby enhancing the effect of intestinal mucosal mechanical barriers.

Taurine Prevents LPS-Induced Liver Injury in Weaned Piglets.

This study employed taurine as a feed additive to explore the prophylactic effect of taurine on LPS-induced hepatic injury in piglets. The pathological shifts within hepatic tissue were observed by HE staining. Serum levels of ALT and AST together with SOD, CAT, GSH-PX activity, and MDA serum and liver levels were detected. TUNEL was used to detect apoptosis, while qPCR was employed to detect HO-1, Nrf-2, Bcl2, BAX, Caspase-3, and NF- κB p65 transcriptomic expression levels. TRL4, Caspase-3, Nrf-2, and NF- κB p-p65/NF- κB p65 were detected by Western blot. The results revealed that taurine reduces LPS-induced pathological damage of hepatic tissue and reduces the levels of ALT and AST in pig serum. The transcriptomic expression levels of HO-1 and Nrf-2 were upregulated, and proteomic expression of Nrf-2 was increased. SOD, CAT, and GSH-PX activity was elevated, while MDA content was reduced in serum and liver. The levels of mRNA of BAX and Caspase-3 were downregulated, but mRNA content of Bcl2 was increased, and the protein levels of TRL4, NF-κB p-p65/NF-κB p65, and Caspase-3 were diminished. Overall, the degree of hepatocyte apoptosis was also significantly reduced. In conclusion, taurine reduces LPS-induced injury of piglet liver, while reducing hepatocyte apoptotic levels. These data provide a scientific basis for the selection of animal feed additives and lay a foundation for the healthy and sustainable development of the porcine industry.

miR-452-3p Targets HDAC3 to Inhibit p65 Deacetylation and Activate the NF-κB Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a subtype of stroke, and early brain injury (EBI) is a contributor to its unfavorable outcome. microRNA (miRNA) is abundantly expressed in the brain and participates in brain injury. This study investigated the effect of miR-452-3p on EBI after SAH. METHODS: The murine model of SAH was established. miR-452-3p expression was detected 48 h after the model establishment. Neurobehavioral function, blood-brain barrier permeability, brain water content, neuronal apoptosis, and inflammatory factors were evaluated. The cell model of SAH was induced by oxygen hemoglobin. Apoptosis rate, lactate dehydrogenase, and reactive oxygen species were detected. The targeting relationship between miR-452-3p and histone deacetylase 3 (HDAC3) was verified. The acetylation of p65 and the binding of HDAC3 to p65 were detected. The inhibitory protein of the nuclear factor κB pathway (IκBα) was detected. Suberoylanilide hydroxamic acid was injected into the SAH mice treated with miR-452-3p inhibitor. RESULTS: SAH mice showed upregulated miR-452-3p expression; reduced the neurological score; increased blood-brain barrier permeability, brain water content, and neuronal apoptosis; elevated pro-inflammatory factors; and reduced anti-inflammatory factors. SAH increased the apoptosis rate, lactate dehydrogenase release, and reactive oxygen species levels in oxygen-hemoglobin-treated neuron cells. Inhibition of miR-452-3p reversed the above trends. miR-452-3p targeted HDAC3. SAH upregulated p65 acetylation. miR-452-3p inhibitor promoted the binding of HDAC3 to p65, decreased p65 acetylation, and upregulated IκBα. Suberoylanilide hydroxamic acid reversed the protective effect of miR-452-3p inhibitor on SAH mice and aggravated brain injury. CONCLUSIONS: miR-452-3p targeted HDAC3 to inhibit the deacetylation of p65 and activate the nuclear factor κB pathway, thus aggravating EBI after SAH.