Role of miRNAs in glucose metabolism of mouse cumulus cells†.

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.

CwJAZ4/9 negatively regulates jasmonate-mediated biosynthesis of terpenoids through interacting with CwMYC2 and confers salt tolerance in Curcuma wenyujin.

Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.

Expression profiling and function analysis identified new genes regulating cumulus expansion and apoptosis.

Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension.

AIMS: Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH. METHODS AND RESULTS: Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs. CONCLUSIONS: Nupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy.

Mixotrophic denitrification of waste activated sludge fermentation liquid as an alternative carbon source for nitrogen removal: Reducing N2O emissions and costs.

Heterotrophic-sulfur autotrophic denitrification (HAD) has been proposed to be a prospective nitrogen removal process. In this work, the potential of fermentation liquid (FL) from waste-activated sludge (WAS) as the electron donor for denitrification in the HAD system was explored and compared with other conventional carbon sources. Results showed that when FL was used as a carbon source, over 99% of NO3--N was removed and its removal rate exceeded 14.00 mg N/g MLSS/h, which was significantly higher than that of methanol and propionic acid. The produced sulfate was below the limit value and the emission of N2O was low (1.38% of the NO3--N). Microbial community analysis showed that autotrophic denitrifiers were predominated in the HAD system, in which Thiobacillus (16.4%) was the dominant genus. The economic analysis showed the cost of the FL was 0.062 €/m3, which was 30% lower than that in the group dosed with methanol. Our results demonstrated the FL was a promising carbon source for the HAD system, which could reduce carbon emission and cost, and offer a creative approach for waste-activated sludge resource reuse.

Evolution of m6A-related genes in insects and the function of METTL3 in silkworm embryonic development.

N6-methyladenosine (m6A) plays a key role in many biological processes. However, the function and evolutionary relationship of m6A-related genes in insects remain largely unknown. Here we analysed the phylogeny of m6A-related genes among 207 insect species and found that m6A-related genes are evolutionarily conserved in insects. Subcellular localization experiments of m6A-related proteins in BmN cells confirmed that BmYTHDF3 was localized in the cytoplasm, BmMETTL3, BmMETTL14, and BmYTHDC were localized in the nucleus, and FL2D was localized to both the nucleus and cytoplasm. We examined the expression patterns of m6A-related genes during the embryonic development of Bombyx mori. To elucidate the function of BmMETTL3 during the embryonic stage, RNA sequencing was performed to measure changes in gene expression in silkworm eggs after BmMETTL3 knockdown, as well as in BmN cells overexpressing BmMETTL3. The global transcriptional pattern showed that knockdown of BmMETTL3 affected multiple cellular processes, including oxidoreductase activity, transcription regulator activity, and the cation binding. In addition, transcriptomic data revealed that many observed DEGs were associated with fundamental metabolic processes, including carbon metabolism, purine metabolism, amino acid biosynthesis, and the citrate cycle. Interestingly, we found that knockdown of BmMETTL3 significantly affected Wnt and Toll/Imd pathways in embryos. Taken together, these results suggest that BmMETTL3 plays an essential role in the embryonic development of B. mori, and deepen our understanding of the function of m6A-related genes in insects.

Imaginal disc growth factor maintains cuticle structure and controls melanization in the spot pattern formation of Bombyx mori.

The complex stripes and patterns of insects play key roles in behavior and ecology. However, the fine-scale regulation mechanisms underlying pigment formation and morphological divergence remain largely unelucidated. Here we demonstrated that imaginal disc growth factor (IDGF) maintains cuticle structure and controls melanization in spot pattern formation of Bombyx mori. Moreover, our knockout experiments showed that IDGF is suggested to impact the expression levels of the ecdysone inducible transcription factor E75A and pleiotropic factors apt-like and Toll8/spz3, to further control the melanin metabolism. Furthermore, the untargeted metabolomics analyses revealed that BmIDGF significantly affected critical metabolites involved in phenylalanine, beta-alanine, purine, and tyrosine metabolism pathways. Our findings highlighted not only the universal function of IDGF to the maintenance of normal cuticle structure but also an underexplored space in the gene function affecting melanin formation. Therefore, this study furthers our understanding of insect pigment metabolism and melanin pattern polymorphisms.

Recovery of phosphorus from wastewater containing humic substances through vivianite crystallization: Interaction and mechanism analysis.

Vivianite crystallization has been regarded as a suitable option for recovering phosphorus (P) from P-containing wastewater. However, the presence of humic substances (HS) would inevitably affect the formation of vivianite crystals. Therefore, the influences of HS on vivianite crystallization and the changes in the harvested vivianite crystals were investigated in this study. The results suggested the inhibition effect of 70 mg/L HS on vivianite crystallization reached 12.24%, while it could be attenuated by increasing the pH and Fe/P ratio of the solution. Meanwhile, the addition of HS altered the size, purity, and morphology of recovered vivianite crystals due to the blockage of the growth sites on the crystal surface. Additionally, the formation of phosphate ester group, hydrogen bonding, and COOH-Fe2+ complexes are the potential mechanisms of HS interaction with vivianite crystals. The results obtained herein will help to elucidate the underlying mechanism of HS on vivianite crystallization from P-containing wastewater.

Revealing the mechanism of quartz sand seeding in accelerating phosphorus recovery from anaerobic fermentation supernatant through vivianite crystallization.

The recovery of phosphorus (P) through vivianite crystallization offers a promising approach for resource utilization in wastewater treatment plants. However, this process encounters challenges in terms of small product size and low purity. The study aimed to assess the feasibility of using quartz sand as a seed material to enhance P recovery and vivianite crystal characteristics from anaerobic fermentation supernatant. Various factors, including seed dosage, seed size, Fe/P ratio, and pH, were systematically tested in batch experiments to assess their influence. Results demonstrated that the effect of seed enhancement on vivianite crystallization was more pronounced under higher seed dosages, smaller seed sizes, and lower pH or Fe/P ratio. The addition of seeds increased P recovery by 4.43% in the actual anaerobic fermentation supernatant and also augmented the average particle size of the recovered product from 19.57 to 39.28 µm. Moreover, introducing quartz sand as a seed material effectively reduced co-precipitation, leading to a notable 12.5% increase in the purity of the recovered vivianite compared to the non-seeded process. The formation of an ion adsorption layer on the surface of quartz sand facilitated crystal attachment and growth, significantly accelerating the vivianite crystallization rate and enhancing P recovery. The economic analysis focused on chemical costs further affirmed the economic viability of using quartz sand as a seed material for P recovery through vivianite crystallization, which provides valuable insights for future research and engineering applications.

Metagenomic insight into the prevalence and driving forces of antibiotic resistance genes in the whole process of three full-scale wastewater treatment plants.

The spread of antibiotic resistance genes (ARGs) is an emerging global health concern, and wastewater treatment plants (WWTPs), as an essential carrier for the occurrence and transmission of ARGs, deserves more attention. Based on the Illumina NovaSeq high-throughput sequencing platform, this study conducted a metagenomic analysis of 18 samples from three full-scale WWTPs to explore the fate of ARGs in the whole process (influent, biochemical treatment, advanced treatment, and effluent) of wastewater treatment. Total 70 ARG subtypes were detected, among which multidrug, aminoglycoside, tetracycline, and macrolide ARGs were most abundant. The different treatment processes used for three WWTPs were capable of reducing ARG diversity, but did not significantly reduce ARG abundance. Compared to that by denitrification filters, the membrane bioreactor (MBR) process was advantageous in controlling the prevalence of multidrug ARGs in WWTPs. Linear discriminant analysis Effect Size (LEfSe) suggested g_Nitrospira, g_Curvibacter, and g_Mycobacterium as the key bacteria responsible for differential ARG prevalence among different WWTPs. Meanwhile, adeF, sul1, and mtrA were the persistent antibiotic resistance genes (PARGs) and played dominant roles in the prevalence of ARGs. Proteobacteria and Actinobacteria were the host bacteria of majority ARGs in WWTPs, while Pseudomonas and Nitrospira were the most crucial host bacteria influencing the dissemination of critical ARGs (e.g., adeF). In addition, microbial richness was determined to be the decisive factor affecting the diversity and abundance of ARGs in wastewater treatment processes. Overall, regulating the abundance of microorganisms and key host bacteria by selecting processes with microbial interception, such as MBR process, may be beneficial to control the prevalence of ARGs in WWTPs.

Analysis of transcriptome differences between subcutaneous and intramuscular adipose tissue of Ningxiang pigs.

To compare and analyze the molecular mechanisms of adipose deposition in subcutaneous fat (SAF)and intramuscular fat (IMF) tissues in Ningxiang pigs, differential gene expression profiles in SAF and IMF tissues of Ningxiang pigs were identified and analysed using RNA-seq technology. Six healthy 250-day-old male Ningxiang pigs with similar body weights (approximately 85 kg) of intraspecific individuals were selected as experimental material and samples of SAF and IMF tissues were collected. Differential genes associated with fat deposition and lipid metabolism were obtained by sequencing two adipose tissue transcriptomes and performing GO (Gene Ontology) functional annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. To verify the reliability of the sequencing results, six differential genes were randomly selected to validate using qRT-PCR. The results showed that we identified 2406 DEGs, with 1422 up-regulated and 984 down-regulated genes in two tissues. GO functional annotation analysis revealed that the differentially expressed genes were mainly involved in lipid metabolism related pathways, such as steroid biosynthesis, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and autophagy pathway. KEGG pathway enrichment showed that the differentially expressed genes were mainly enriched in the biological processes related to lipid binding, fatty acid metabolism, glycol ester metabolism, lipid biosynthesis and other biological processes related to lipid metabolism. Genes related to lipid metabolism, such as TCAP, NR4A1, ACACA, LPL, ELOVL6, DGAT1, PRKAA1, ATG101, TP53INP2, FDFT1, ACOX1 and SCD were identified by bioinformatic analyses and verified by qRT-PCR. Our results indicated that these genes may play important roles in the regulation of fat deposition and metabolism in the SAF and IMF tissue, providing the further mechanistic investigation of fat deposition in Ningxiang pigs.

Qualitative and quantitative analysis of the major components in Qinghao Biejia decoction by UPLC-Orbitrap Fusion-MS/MS and UPLC-QQQ-MS/MS and evaluation of their antibacterial activities.

OBJECTIVE: In the present study, the chemical components of Qinghao Biejia decoction (QBD) were qualitatively and quantitatively analyzed using UPLC-Orbitrap Fusion-MS/MS and UPLC-QQQ-MS/MS techniques, followed by identification of each component's origin and evaluation of the antibacterial activity of QBD and its components. METHODS: High-resolution mass spectrometry was used to obtain information on the precise molecular weight, retention time, and fragmentation ion peaks of the compounds used to identify the components of QBD and establish a method for their quantification. In vitro assays including determination of the minimal inhibitory concentration and growth curves were used to assess the antibacterial activity of QBD and its components. RESULTS: A total of 39 components, including fatty acids, phenolic acids, amino acids, flavonoids, coumarins, terpenoids, and alkaloids, were identified by UPLC-Orbitrap Fusion-MS/MS. A high-performance analytical method was also established to quantify 12 components of QBD. The content of mangiferin was relatively high (estimated to be 814 µg/g). The results of the antibacterial assays indicated that mangiferin exhibits antibacterial effects against two strains causing respiratory tract infections. CONCLUSIONS: The present study suggests that mangiferin may serve as a natural compound which shows high antibacterial activity. The results can aid the discovery and analysis of the active antimicrobial components present in QBD and further provide a reference for quality assessment of multi-component herbal prescriptions.

Sludge reduction and microbial community evolution of activated sludge induced by metabolic uncoupler o-chlorophenol in long-term anaerobic-oxic process.

Excess sludge management is a restrictive factor for the development of municipal wastewater treatment plants. The addition of metabolic uncouplers has been proven to be effective in sludge reduction. However, the long-term effect of metabolic uncoupler o-chlorophenol (oCP) on the biological wastewater treatment system operated in anaerobic-oxic mode is still unclear. To this end, two parallel reactors operated in anaerobic-oxic mode with and without 10 mg/L of oCP addition were investigated for 91 days. The results showed that 56.1 ± 2.3% of sludge reduction was achieved in the oCP-added system, and the nitrogen and phosphorus removal ability were negatively affected. Dosing oCP stimulated the formation of microbial products and increased the DNA concentration, but resulted in a decrease in the electronic transport activity of activated sludge. Microbial community analysis further demonstrated that a significant reduction of bacterial richness and diversity occurred after oCP dosing. However, after stopping oCP addition, the pollutant removal ability of activated sludge was gradually increased, but the sludge yield, as well as species richness and diversity, did not recover to the previous level. This study will provide insightful guidance on the long-term application of metabolic uncouplers in the activated sludge system.

OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway.

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) is a critical regulator of tumor immunology among various cancers. However, the role and underlying molecular mechanism of CMTM6 in oral squamous cell carcinoma (OSCC) progression remains unclear. METHODS: The expression of CMTM6, PD-L1 and CD163 in OSCC tissues were detected by immunohistochemistry on tissue microarray. The effect of CMTM6 knockdown on OSCC cells and macrophage polarization were analyzed by CCK-8 assay, apoptotic assay, would-healing assay, transwell assay and qPCR. OSCC cell derived exosomes were obtained by ultracentrifugation and the mechanistic studies were conducted by qPCR and Western Blot. 4-Nitroquinoline N-oxide (4NQO) induced OSCC mice were used for verifying the effect of CMTM6 downregulation on M2 macrophage infiltration and tumor growth. RESULTS: In OSCC samples, higher CMTM6 expression has been obviously associated with higher pathological stage of OSCC patients, CD163 + macrophages infiltration and PD-L1 expression. CMTM6 knockdown of OSCC cells inhibited proliferative, migrative and invasive abilities of OSCC cells, as well as inhibited M2 macrophage polarization in vitro with downregulating PD-L1 expression. Importantly, exosomes from OSCC cells shuttled CMTM6 to macrophages and promoted M2-like macrophage polarization through activating ERK1/2 signaling. In addition, in 4NQO-induced OSCC mice, CMTM6 level was positively associated with CD163, CD206 and PD-L1 as well as M2-like macrophage infiltration. CONCLUSION: OSCC cell-secreted exosomal CMTM6 induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment.

Metabolomics and integrated network pharmacology analysis reveal Tricin as the active anti-cancer component of Weijing decoction by suppression of PRKCA and sphingolipid signaling.

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.

Tunable fabrication of biomimetic polypropylene nanopillars with robust superhydrophobicity and antireflectivity.

The fine nanopillars on the natural cicada wing, which exhibits outstanding superhydrophobicity and anti-reflectivity, are carefully observed and analyzed. Here, a promising strategy by combining anodic aluminum oxide template and hot embossing is proposed for rapidly and efficiently mimicking the orderly and densely arranged nanopillars on the cicada wing surface to polypropylene (PP) surfaces. By adjusting the compression pressure, the nanostructures on the PP replica surface gradually evolve from nanoprotrusion-like features to nanopillar-like features so that a gradient wetting behavior from hydrophilicity to hydrophobicity and further to superhydrophobicity appears on the PP replica surfaces. Specifically, the biomimetic PP replica surface exhibits a contact angle of 159 ± 3° and a rolling angle of 8 ± 3° at a compression pressure of 15 MPa. Moreover, the biomimetic PP replica surface can stabilize its superhydrophobic state under a 1.96 kPa external pressure during the dynamic droplet impact. Besides robust dynamic superhydrophobicity, the biomimetic PP replica surface also demonstrated excellent anti-reflectivity because of the gradually changed effective refractive index. Therefore, the biomimetic PP replica inherits both the superhydrophobicity and anti-reflectivity of the natural cicada wing, which makes the products can effectively reduce the external damage when applied to agricultural films, dustproof films, and packaging materials.

Acute effects of CH3NH3PbI3 perovskite on Scenedesmus obliquus and Daphnia magana in aquatic environment.

CH3NH3PbI3 is one of the most widely studied and most promising photoelectric conversion materials for large-scale application. However, once it is discharged into the aquatic environment, it will release a variety of lethal substances to the aquatic organisms. Herein, two typical aquatic pollution indicators, Scenedesmus obliquus (a typical phytoplankton) and Daphnia magna (a typical zooplankton), were used to assess the acute effects of CH3NH3PbI3 perovskite on aquatic organisms. The results showed that, when the initial CH3NH3PbI3 perovskite level (CPL) was 40 mg L-1 or higher, the growth of S. obliquus would be remarkably inhibited with significant decreases of chlorophyll content and protein content. And when the CPL was over 5 mg L-1, the survival of D. magna would be notably threatened. Specifically, the 72 h EC-50 of CH3NH3PbI3 perovskite to S. obliquus was calculated as 37.21 mg L-1, and the 24 h LC-50 of this perovskite to D. magna adults and neonates were calculated as 37.53 mg L-1 and 18.55 mg L-1, respectively. Moreover, remarkably solution pH declination and large amounts of lead bio-accumulation was observed in the both acute experiments, which could be the main reasons causing the above acute effects. Considering the strong acute effects of these CH3NH3PbI3 perovskite materials and their attractive application prospect, more attentions should be paid on their harmness to the environment.

What makes leader cells arise: Intrinsic properties and support from neighboring cells.

Cancer cells collectively invading as a cohesive and polarized group is termed collective invasion, which is a fundamental property of many types of cancers. In this multicellular unit, cancer cells are heterogeneous, consisting of two morphologically and functionally distinct subpopulations, leader cells and follower cells. Leader cells at the invasive front are responsible for exploring the microenvironment, paving the way, and transmitting information to follower cells. Here, in this review, we will describe the important role of leader cells in collective invasion and the emerging underlying mechanisms of leader cell formation including intrinsic properties and the support from neighboring cells. It will help us to elucidate the essence of collective invasion and provide new anticancer therapeutic clues.

High-performance mesoporous γ-Fe2O3 sphere/graphene aerogel composites towards enhanced lithium storage.

Transition metal oxides have recently been demonstrated as highly attractive anodes for high-capacity lithium ion batteries, whose electrochemical properties could be further improved through rational architecture design and incorporating reliable conductive network. Herein, mesoporous γ-Fe2O3 spheres/graphene aerogel composites were synthesized via a solvothermal pathway followed by suitable annealing. Experimental results reveal the uniform mesoporous structure and well-dispersed γ-Fe2O3 spheres with the size of 300-400 nm embedded in the mesopores of the graphene aerogel network. Compared with α-Fe2O3/graphene aerogel and pure γ-Fe2O3, the as-synthesized composite delivers, at the first cycle, a high discharging capacity of 1080 mAh g-1 at current density of 200 mA g-1. Even at much higher current density of 8000 mA g-1, satisfactory discharging capacities of 421.5 mAh g-1 can still be achieved. Upon 100 charging-discharging cycles, the specific capacity of as high as 890.5 mAh g-1 at 200 mA g-1 is maintained. The enhanced electrochemical properties could be attributed to their favorable three-dimensional graphene aerogel network, which accounts for the improved structural stability and electronic conductivity of γ-Fe2O3 during the lithiation/delithiation process.

Restraint stress and elevation of corticotrophin-releasing hormone in female mice impair oocyte competence through activation of the tumour necrosis factor α (TNF-α) system.

Studies have observed that restraint stress (RS) and the associated elevation in corticotrophin-releasing hormone (CRH) impair oocyte competence by triggering apoptosis of ovarian cells but the underlying mechanisms are largely unclear. Although one study demonstrated that RS and CRH elevation triggered apoptosis in ovarian cells and oocytes via activating Fas/FasL signalling, other studies suggested that RS might damage cells by activating other pathways as well as Fas signalling. The objective of this study was to test whether RS and CRH elevation impairs oocytes by activating tumour necrosis factor α (TNF-α) signalling. Our invivo experiments showed that RS applied during oocyte prematuration significantly increased expression of TNF-α and its receptor (TNFR1) while inducing apoptosis in both oocytes and mural granulosa cells (MGCs). Invitro treatment of MGCs with CRH significantly increased their apoptotic percentages and levels of TNF-α and TNFR1 expression. Invitro knockdown by interfering RNA, invivo knockout of the TNF-α gene or injection of TNF-α antagonist etanercept significantly relieved the adverse effects of RS and CRH on apoptosis of MGCs and/or the developmental potential and apoptosis of oocytes. The results suggest that RS and CRH elevation in females impair oocyte competence through activating TNF-α signalling and that a TNF-α antagonist might be adopted to ameliorate the adverse effects of psychological stress on oocytes.