Fast Nano-IR Hyperspectral Imaging Empowered by Large-Dataset-Free Miniaturized Spatial-Spectral Network.

The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Gentulizumab, a novel anti-CD47 antibody with potent antitumor activity and demonstrates a favorable safety profile.

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. RESULTS: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. CONCLUSION: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

Mycolicibacterium arseniciresistens sp. nov., isolated from lead-zinc mine tailing, and reclassification of two Mycobacterium species as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov.

A Gram-positive, acid-fast, aerobic, rapidly growing and non-motile strain was isolated from lead-zinc mine tailing sampled in Lanping, Yunnan province, Southwest China. 16S rRNA gene sequence analysis showed that the most closely related species of strain KC 300T was Mycolicibacterium litorale CGMCC 4.5724T (98.47 %). Additionally, phylogenomic and specific conserved signature indel analysis revealed that strain KC 300T should be a member of genus Mycolicibacterium, and Mycobacterium palauense CECT 8779T and Mycobacterium grossiae DSM 104744T should also members of genus Mycolicibacterium. The genome size of strain KC 300T was 6.2 Mb with an in silico DNA G+C content of 69.2 mol%. Chemotaxonomic characteristics of strain KC 300T were also consistent with the genus Mycolicibacterium. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values, as well as phenotypic, physiological and biochemical characteristics, support that strain KC 300T represents a new species within the genus Mycolicibacterium, for which the name Mycolicibacterium arseniciresistens sp. nov. is proposed, with the type strain KC 300T (=CGMCC 1.19494T=JCM 35915T). In addition, we reclassified Mycobacterium palauense and Mycobacterium grossiae as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov., respectively.

Efficient Production of Flavonoid Glucuronides in Escherichia coli Using Flavonoid O-Glucuronosyltransferases Characterized from Marchantia polymorpha.

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.

Generating a hollow twisted correlated beam using correlated perturbations.

In this study, a twisted correlated optical beam with a dark hollow center in its average intensity is synthesized by correlated correlation perturbation and incoherent mode superposition. This new hollow beam has a topological charge (TC) mode with a zero value compared with a coherence vortex that has a TC mode with a nonzero value. We transform the twisted correlated beam from solid centered to dark hollow centered by constructing a correlation between the twist factor and the spot structure parameter. Theoretical and experimental results show that twist correlation makes the random optical beam an asymmetric orbital angular momentum spectral distribution and a tunable intensity center. Controlling the correlation parameters can make the focal spot of the twisted beam a dark core when the dominant mode of the TC is still zero. The new nontrivial beams and their proposed generation method provide important technical preparations for the optical particle manipulation with low coherence environment.

ANKRD49 promotes the metastasis of NSCLC via activating JNK-ATF2/c-Jun-MMP-2/9 axis.

BACKGROUND: Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. METHODS: Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method. RESULTS: We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. CONCLUSION: The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49's function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.

Chryseobacterium luquanense sp. nov., a casein-hydrolysing bacterium from the Jiaozi Mountain in Yunnan, PR China.

Strain KC 927T was isolated during an investigation of the soil bacteria diversity on Jiaozi Mountain, central Yunnan, Southwest China. The strain was Gram-stain-negative, rod-shaped, non-motile, oxidase-negative, catalase-positive and aerobic. Results of 16S rRNA gene alignment and phylogenetic analysis indicated that strain KC 927T was a member of the genus Chryseobacterium and closely related to Chryseobacterium caseinilyticum GCR10T (98.4%), Chryseobacterium piscicola DSM 21068T (98.3 %) and 'Chryseobacterium formosus' CCTCC AB 2015118T (97.9 %). With a genome size of 4 348 708 bp, strain KC 927T had 33.5 mol% DNA G+C content and contained 4012 protein-coding genes and 77 RNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain KC 927T and C. caseinilyticum GCR10T, C. piscicola DSM 21068T and 'C. formosus' CCTCC AB 2015118T were 80.1, 79.6 and 90.7 %, and 25.5, 23.6 and 42.0 %, respectively. The main polar lipid of strain KC 927T was phosphatidylethanolamine and the respiratory quinone was MK-6. The major fatty acids (≥10 %) were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 3-OH. Evidence from phenotypic, phylogenetic and chemotaxonomic analyses support that strain KC 927T represents a new species of the genus Chryseobacterium, for which the name Chryseobacterium luquanense sp. nov. is proposed. The type strain is KC 927T (=CGMCC 1.18760T=JCM 35707T).

Revealing the Interaction of Charge Carrier-Phonon Coupling by Quantification of Electronic Properties at the SrTiO3/TiO2 Heterointerface.

Oxide heterointerfaces with high carrier density can interact strongly with the lattice phonons, generating considerable plasmon-phonon coupling and thereby perturbing the fascinating optical and electronic properties, such as two-dimensional electron gas, ferromagnetism, and superconductivity. Here we use infrared-spectroscopic nanoimaging based on scattering-type scanning near-field optical microscopy (s-SNOM) to quantify the interaction of electron-phonon coupling and the spatial distribution of local charge carriers at the SrTiO3/TiO2 interface. We found an increased high-frequency dielectric constant (ε∞ = 7.1-9.0) and charge carrier density (n = 6.5 × 1019 to 1.5 × 1020 cm-3) near the heterointerface. Moreover, quantitative information between the charge carrier density and extension thickness across the heterointerface has been extracted by monochromatic near-field imaging. A direct evaluation of the relationship between the thickness and the interaction of charge carrier-phonon coupling of the heterointerface would provide valuable information for the development of oxide-based electronic devices.

ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway.

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.

Kaempferol ameliorates in-vitro and in-vivo postovulatory oocyte ageing in mice.

RESEARCH QUESTION: Does kaempferol alleviate postovulatory oocyte ageing, thereby maintaining their early embryonic development capacity? DESIGN: The effects of kaempferol on postovulatory ageing were investigated in vitro and in vivo by short-term kaempferol administration (mature oocytes were cultured in a kaempferol-containing medium for 12 h; mice were intragastrically administered with the appropriate amount of kaempferol for 21 days). Spindle morphology and chromosome alignment, levels of oxidative stress and the gap junction were assessed by immunofluorescence. Fertilization ability and early embryonic development ability of each oocyte group was detected by IVF. Fertilization of the ageing oocyte model was used to explore whether kaempferol could improve adverse pregnancy outcome. RNA-sequencing and quantitative polymerase chain reaction were used to identify the cellular pathways through which kaempferol relieves postovulatory oocyte ageing in vivo. RESULTS: Kaempferol administration altered various processes in the ageing oocytes, including oxidative stress, the peroxisome, TNF signalling, cAMP signalling and the gap junction pathway. Expression of several important genes, such as Sirt1, Mapk1, Ampk and Foxo3, was regulated. Moreover, kaempferol ameliorated adverse pregnancy outcomes of fertilized ageing oocytes. IVF results indicate that kaempferol could partially counteract the effects of oocyte ageing on fertilization capacity (pronucleus: kaempferol, 69.08 ± 2.37% versus aged, 38.95 ± 3.58%) and early embryonic development (blastocyst: kaempferol, 50.02 ± 3.34% versus aged, 30.83 ± 5.46%). CONCLUSIONS: Our results indicate that kaempferol may be a potent natural antioxidant, have implications for animal husbandry and may help improve the success rate of IVF and ICSI. Further clinical trials are needed.

Identification of a flavonoid C-glycosyltransferase from fern species Stenoloma chusanum and the application in synthesizing flavonoid C-glycosides in Escherichia coli.

BACKGROUND: Flavonoid C-glycosides have many beneficial effects and are widely used in food and medicine. However, plants contain a limited number of flavonoid C-glycosides, and it is challenging to create these substances chemically. RESULTS: To screen more robust C-glycosyltransferases (CGTs) for the biosynthesis of flavonoid C-glycosides, one CGT enzyme from Stenoloma chusanum (ScCGT1) was characterized. Biochemical analyses revealed that ScCGT1 showed the C-glycosylation activity for phloretin, 2-hydroxynaringenin, and 2-hydroxyeriodictyol. Structure modeling and mutagenesis experiments indicated that the glycosylation of ScCGT1 may be initiated by the synergistic action of conserved residue His26 and Asp14. The P164T mutation increased C-glycosylation activity by forming a hydrogen bond with the sugar donor. Furthermore, when using phloretin as a substrate, the extracellular nothofagin production obtained from the Escherichia coli strain ScCGT1-P164T reached 38 mg/L, which was 2.3-fold higher than that of the wild-type strain. Finally, it is proved that the coupling catalysis of CjFNS I/F2H and ScCGT1-P164T could convert naringenin into vitexin and isovitexin. CONCLUSION: This is the first time that C-glycosyltransferase has been characterized from fern species and provides a candidate gene and strategy for the efficient production of bioactive C-glycosides using enzyme catalysis and metabolic engineering.

Control of orbital angular momentum of optical vortex beams with complex wandering perturbations.

This work investigates how independent perturbations and cross-correlation perturbations affect optical vortex beams. Theoretical and experimental results show that both perturbations cause the intensity, average orbital angular momentum (OAM), and the OAM spectrum of the vortex beam to vary periodically with the perturbation direction, but with different periods. When the beam is subjected to independent perturbations, the average OAM changes periodically with θ in every π/2; when the beam is subjected to cross-correlation perturbations, the average OAM varies with θ in every π. The results of this work provide a method to control the OAM and regulate low-coherence vortex beams in turbulent environments.

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes.

Slow-wave sleep, defined by low frequency (<4 Hz) electrical brain activity, is a basic brain function affecting metabolite clearance and memory consolidation. The origin of low-frequency activity is related to cortical up and down states, but the underlying cellular mechanism of how low-frequency activities affect metabolite clearance and memory consolidation has remained elusive. We applied electrical stimulation with voltages comparable to in vivo sleep recordings over a range of frequencies to cultured glial astrocytes while monitored the trafficking of GFP-tagged intracellular vesicles using total internal reflection fluorescence microscopy (TIRFM). We found that during low frequency (2 Hz) electrical stimulation the mobility of intracellular vesicle increased more than 20%, but remained unchanged under intermediate (20 Hz) or higher (200 Hz) frequency stimulation. We demonstrated a frequency-dependent effect of electrical stimulation on the mobility of astrocytic intracellular vesicles. We suggest a novel mechanism of brain modulation that electrical signals in the lower range frequencies embedded in brainwaves modulate the functionality of astrocytes for brain homeostasis and memory consolidation. The finding suggests a physiological mechanism whereby endogenous low-frequency brain oscillations enhance astrocytic function that may underlie some of the benefits of slow-wave sleep and highlights possible medical device approach for treating neurological diseases.

Perfluorooctane sulfonate affects mouse oocyte maturation in vitro by promoting oxidative stress and apoptosis induced bymitochondrial dysfunction.

Perfluorooctane sulphonate (PFOS), as a surfactant, is widely applied in the agricultural production activities and has become a potential menace to human health. The mechanism of its effect on the maturation of mammalian oocytes is unclear. This study explored the toxic effect of PFOS on mouse oocyte maturation in vitro. The results revealed that PFOS under a concentration of 600 µM could significantly reduce the polar body extrusion rate (PBE) of mouse oocytes and cause symmetrical cell division. Further experiments showed that PFOS resulted in the abnormal cytoskeleton of the oocytes, causing the abnormal spindles and misplaced chromosomes, as well as the impaired dynamics of actin. Moreover, PFOS exposure inhibited the process of oocyte meiosis, which reflected in the slower spindle migration and continuous activation of spindle assembly checkpoint (SAC), then ultimately increased the probability of aneuploidy. Most importantly, PFOS exposure reduced the quality of oocytes, specifically by disrupting the function of mitochondria, inducing cell oxidative stress, and triggering early apoptosis. Furthermore, the level of methylation of histones is additionally influenced. In summary, our findings showed that PFOS exposure interfered with the maturation of mouse oocytes through affecting cytoskeletal dynamics, meiotic progression, oocyte quality, and histone modifications.

Nickel sulfate exposure induces ovarian inflammation and fibrosis and decreases oocyte quality in mice.

Nickel is a heavy metal element extensively distributed in the environment and widely used in modern life. Divalent nickel is one of the most widespread forms of nickel and has been reported as toxic to various tissues. However, whether exposure to divalent nickel negatively affects ovarian homeostasis and oocyte quality remains unclear. In this study, we found that 3 weeks of nickel sulfate exposure affected body growth and decreased the weight and coefficient of the ovary, and increased atretic follicles exhibiting enhanced apoptosis in granulosa cells. Further studies have found that nickel sulfate triggered ovarian fibrosis and inflammation via transforming growth factor-ß1 and nuclear factor-κB pathways, and reduced oocyte development ability. In addition, nickel sulfate increased the level of reactive oxygen species, which induced DNA damage and early apoptosis. Moreover, it was found that nickel sulfate caused damage to the mitochondria showing aberrant morphology, distribution and membrane potential while decreased levels of histone methylation. To summarize, our results indicated that nickel sulfate exposure triggered ovarian fibrosis and inflammation and caused structural and functional disorders of mitochondria in oocytes, which consequently disturbed ovarian homeostasis and follicle development and decreased oocyte quality.

Multinucleated polyploid cardiomyocytes undergo an enhanced adaptability to hypoxia via mitophagy.

AIMS: There is a large subpopulation of multinucleated polyploid cardiomyocytes (M*Pc CMs) in the adult mammalian heart. However, the pathophysiological significance of increased M*Pc CMs in heart disease is poorly understood. We sought to determine the pathophysiological significance of increased M*Pc CMs during hypoxia adaptation. METHODS AND RESULTS: A model of hypoxia-induced cardiomyocyte (CM) multinucleation and polyploidization was established and found to be associated with less apoptosis and less reactive oxygen species (ROS) production. Compared to mononucleated diploid CMs (1*2c CMs), tetraploid CMs (4c CMs) exhibited better mitochondria quality control via increased mitochondrial autophagy (mitophagy). RNA-seq revealed Prkaa2, the gene for AMPKα2, was the most obviously up-regulated autophagy-related gene. Knockdown of AMPKα2 increased apoptosis and ROS production and suppressed mitophagy in 4c CMs compared to 1*2c CMs. Rapamycin, an autophagy activator, alleviated the adverse effect of AMPKα2 knockdown. Furthermore, silencing PINK1 also increased apoptosis and ROS in 4c CMs and weakened the adaptive superiority of 4c CMs. Finally, AMPKα2-/- mutant mice exhibited exacerbation of apoptosis and ROS production via decreases in AMPKα2-mediated mitophagy in 4c CMs compared to 1*2c CMs during hypoxia. CONCLUSIONS: Compared to 1*2c CMs, hypoxia-induced 4c CMs exhibited enhanced mitochondria quality control and less apoptosis via AMPKα2-mediated mitophagy. These results suggest that multinucleation and polyploidization allow CM to better adapt to stress via enhanced mitophagy. In addition, activation of AMPKα2 may be a promising target for myocardial hypoxia-related diseases.

Pachymic acid protects oocyte by improving the ovarian microenvironment in polycystic ovary syndrome mice†.

Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice.

The effects of graphene quantum dots on the maturation of mouse oocytes and development of offspring.

Recently, graphene nanomaterials have attracted tremendous attention and have been utilized in various fields because of their excellent mechanical, thermal, chemical, optical properties, and good biocompatibility, especially in biomedical aspects. However, there is a concern that the unique characteristics of nanomaterials may have undesirable effects. Therefore, in this study, we sought to systematically investigate the effects of graphene quantum dots (GQDs) on the maturation of mouse oocytes and development of the offspring via in vitro and in vivo studies. In vitro, we found that the first polar body extrusion rate in the high dosage exposure groups (1.0-1.5 mg/ml) 2 decreased significantly and the failure of spindle migration and actin cap formation after GQDs exposure was observed. The underlying mechanisms might be associated with reactive oxygen species accumulation and DNA damage. Moreover, transmission electron microscope studies showed that GQDs may have been internalized into oocytes, tending to accumulate in the nucleus and severely affecting mitochondrial morphology, which included swollen and vacuolated mitochondria accompanied by cristae alteration with a lower amount of dense mitochondrial matrix. In vivo, when pregnant mice were exposed to GQDs at 8.5 days of gestation (GD, 8.5), we found that high dosage of GQD exposure (30 mg/kg) significantly affected mean fetal length; however, all the second generation of female mice grew up normal, attained sexual maturity, and gave birth to a healthy offspring after mating with a healthy male mouse. The results presented in this study are important for the future investigation of GQDs for the biomedical applications.