Prior to mining, the water in and around the mine is rarely influenced by human activities, and hydrogeochemical processes are the major factors influencing and controlling water chemistry. To ...identify these natural hydrogeochemical processes in Laoheba phosphorite mine (Sichuan Province, China), correlation and multivariate statistical techniques were used. Results show that water quality in the area is generally good before the Laoheba phosphorite mine goes into construction and production. The cluster analysis classified water samples into 4 clusters (C1–C4). Samples from C1 and C2 are of HCO
3
−Ca·Mg and HCO
3
−Ca type, while those from C3 and C4 are of HCO
3
−Ca·Mg type. Most parameters except Cl
−
and pH show an increasing trend in the order of C1 to C4. Three principal components were extracted, and PC1 represents the ion exchange and the weathering of calcite, dolomite, and silicate minerals. PC2 and PC3 indicate the process of water recharge from upstream waters and the process of evaporation, respectively. The hydrochemistry of waters in the area is a result of multiple factors, and natural mineral weathering and ion exchange are the most important ones.
Long noncoding RNAs (lncRNAs), a recently discovered class of cellular RNAs, play important roles in the regulation of many cellular developmental processes. Although lncRNAs have been systematically ...identified in various systems, most of them have not been functionally characterized in vivo in animal models. In this study, we identified 128 testis-specific Drosophila lncRNAs and knocked out 105 of them using an optimized three-component CRISPR/Cas9 system. Among the lncRNA knockouts, 33 (31%) exhibited a partial or complete loss of male fertility, accompanied by visual developmental defects in late spermatogenesis. In addition, six knockouts were fully or partially rescued by transgenes in a trans configuration, indicating that those lncRNAs primarily work in trans Furthermore, gene expression profiles for five lncRNA mutants revealed that testis-specific lncRNAs regulate global gene expression, orchestrating late male germ cell differentiation. Compared with coding genes, the testis-specific lncRNAs evolved much faster. Moreover, lncRNAs of greater functional importance exhibited higher sequence conservation, suggesting that they are under constant evolutionary selection. Collectively, our results reveal critical functions of rapidly evolving testis-specific lncRNAs in late Drosophila spermatogenesis.
The plastic deformation of TWIP steel is greatly inhibited during the expansion process. The stress-strain curves obtained through expansion experiments and observations of fracture morphology ...confirmed the low plastic behavior of TWIP steel during expansion deformation. Through an analysis of the mechanical expansion model, it was found that the expansion process has a lower stress coefficient and a faster strain rate than stretching, which inhibits the plasticity of TWIP steel during expansion deformation. Using metallographic microscopy, transmission electron microscopy, and EBSD to observe the twin morphology during expansion deformation and tensile deformation, it was found that expansion deformation has a higher twin density, which is manifested in a denser twin arrangement and a large number of twin deliveries in the microscopic morphology. During the expansion deformation process, dislocation slips are hindered by twins, the free path of the slips is reduced, and dislocations accumulate significantly. The accumulation area is the initial point of crack expansion. The results show that the significant dislocation accumulation caused by the delivery of a large number of twins under expansion deformation is the main reason for the decrease in the plasticity of TWIP steel.
Dermanyssus gallinae is a major hematophagous ectoparasite in layer hens. Although the acaricide β-cypermethrin has been used to control mites worldwide, D. gallinae has developed resistance to this ...compound. Carboxylesterases (CarEs) are important detoxification enzymes that confer resistance to β-cypermethrin in arthropods. However, CarEs associated with β-cypermethrin resistance in D. gallinae have not yet been functionally characterized. Here, we isolated a CarE gene (Deg-CarE) from D. gallinae and assayed its activity. The results revealed significantly higher expression of Deg-CarE in the β-cypermethrin-resistant strain (RS) than in the susceptible strain (SS) toward α-naphthyl acetate (α-NA) and β-naphthyl acetate (β-NA). These findings suggest that enhanced esterase activities might have contributed to β-cypermethrin resistance in D. gallinae. Quantitative real-time PCR analysis revealed that Deg-CarE expression levels were significantly higher in adults than in other life stages. Although Deg-CarE was upregulated in the RS, significant differences in gene copy numbers were not observed. Additionally, Deg-CarE expression was significantly induced by β-cypermethrin in both the SS and RS. Moreover, silencing Deg-CarE via RNA interference decreased the enzyme activity and increased the susceptibility of the RS to β-cypermethrin, confirming that Deg-CarE is crucial for β-cypermethrin detoxification. Finally, recombinant Deg-CarE (rDeg-CarE) expressed in Escherichia coli displayed high enzymatic activity toward α/β-NA. However, metabolic analysis indicated that rDeg-CarE did not directly metabolize β-cypermethrin. The collective findings indicate that D. gallinae resistance to β-cypermethrin is associated with elevated CarEs protein activity and increased Deg-CarE expression levels. These findings provide insights into the metabolic resistance of D. gallinae and offer scientific guidance for the management and control of D. gallinae.
N6-methyladenosine (m6A) modification accounts for the most prevalent mRNA internal modification and has emerged as a widespread regulatory mechanism in multiple physiological processes. We address a ...role of methyltransferase-like protein 3 (METTL3) in neutrophil activation. METTL3 controls neutrophil release from bone marrow to circulation through surface expression of CXC chemokine receptor 2 (CXCR2) in a Toll-like receptor 4 (TLR4) signaling-dependent manner in lipopolysaccharide (LPS)-induced endotoxemia. We show that the mRNA of TLR4 is modified by m6A, exhibiting increased translation and slowed degradation simultaneously, leading to elevated protein levels of TLR4, which eventually promotes the TLR4 signaling activation of neutrophil. The reduced expression of TLR4 lowers cytokine secretion in METTL3-deleted neutrophils upon LPS stimulation through TLR4/Myd88/nuclear factor κB (NF-κB) signaling. Collectively, these data demonstrate that METTL3 modulation of TLR4 expression is a critical determinant of neutrophil activation in endotoxemia.
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•METTL3 affects BM neutrophil release and retention in endotoxemia•Deletion of METTL3 impairs neutrophil activation by inhibiting TLR4 signaling•METTL3 regulates neutrophil mobility through TLR4 mediated expression of CXCR2•METTL3 initiates m6A modifications on TLR4 mRNA to promote its protein expression
Luo et al. show that METTL3-mediated m6A modification controls neutrophil activation by regulating TLR4/Myd88/NF-κB signaling and modulating the expression of CXCR2 in a TLR4-dependent manner. TLR4 mRNA of neutrophil is marked by m6A, exhibiting increased translation and slowed degradation simultaneously, leading to elevated protein level.
Genetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals, but the underlying mechanisms are unclear. Here, we identify a TSSK homolog ...in Drosophila, CG14305 (termed dTSSK), whose mutation impairs the histone-to-protamine transition during spermiogenesis and causes multiple phenotypic defects in nuclear shaping, DNA condensation, and flagellar organization in spermatids. Genetic analysis demonstrates that kinase catalytic activity of dTSSK, which is functionally conserved with human TSSKs, is essential for male fertility. Phosphoproteomics identify 828 phosphopeptides/449 proteins as potential substrates of dTSSK enriched primarily in microtubule-based processes, flagellar organization and mobility, and spermatid differentiation and development, suggesting that dTSSK phosphorylates various proteins to orchestrate postmeiotic spermiogenesis. Among them, the two substrates, protamine-like protein Mst77F/Ser
and transition protein Mst33A/Ser
, are biochemically validated to be phosphorylated by dTSSK in vitro, and are genetically demonstrated to be involved in spermiogenesis in vivo. Collectively, our findings demonstrate that broad phosphorylation mediated by TSSKs plays an indispensable role in spermiogenesis.
Kinases and phosphatases are crucial for cellular processes and animal development. Various sets of resources in Drosophila have contributed significantly to the identification of kinases, ...phosphatases and their regulators. However, there are still many kinases, phosphatases and associate genes with unknown functions in the Drosophila genome. In this study, we utilized a CRISPR/Cas9 strategy to generate stable mutants for these unknown kinases, phosphatases and associate factors in Drosophila. For all the 156 unknown gene loci, we totally obtained 385 mutant alleles of 105 candidates, with 18 failure due to low efficiency of selected gRNAs and other 33 failure due to few recovered F0, which indicated high probability of lethal genes. From all the 105 mutated genes, we observed 9 whose mutants were lethal and another 4 sterile, most of which with human orthologs referred in OMIM, representing their huge value for human disease research. Here, we deliver these mutants as an open resource for more interesting studies.
Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct ...in-depth propionylomic profiling in Drosophila, and develop a small-sample learning framework to prioritize the propionylation at lysine 17 of H2B (H2BK17pr) to be functionally important. Mutating H2BK17 which eliminates propionylation leads to elevated total protein level in vivo. Further analyses reveal that H2BK17pr modulates the expression of 14.7-16.3% of genes in the proteostasis network, and determines global protein level by regulating the expression of genes involved in the ubiquitin-proteasome system. In addition, H2BK17pr exhibits daily oscillation, mediating the influences of feeding/fasting cycles to drive rhythmic expression of proteasomal genes. Our study not only reveals a role of lysine propionylation in regulating proteostasis, but also implements a generally applicable method which can be extended to other issues with little prior knowledge.
Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, commonly used for critically ill patients (especially septic patients) in intensive care units ...(ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown. Here, we studied the effects of remimazolam on macrophage in response to LPS both
in vivo
and
in vitro
. Interestingly, compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators (such as TNF-α, IL-6, and IL-1β). We further found that remimazolam not only inhibited the activation of MAPK signal pathway at 15 min after LPS treatment but also disturbed Rab5a related TLR4 expression at cell surface in response to LPS at a later time. Such evidence suggests that remimazolam might be beneficial to septic patients who are suffering from uncontrolled inflammatory responses.
This work is aimed at reviewing the chemical characteristics and evaluation of the quality of exploited groundwater in Beijiao water source of Yinchuan. A coupled model based on osculating value ...method (OVM) and entropy is proposed to determine the suitability for drinking. Besides, phreatic water and confined water are evaluated for irrigation purposes and industrial purposes, respectively. Piper diagram shows different hydrochemical characteristics between aquifers, which can be explained by the control mechanisms revealed by Gibbs diagram. Chloroalkaline indices and ions relationship indicate that reverse ion exchanges occur in different aquifers. Based on the osculating values, 96% of the phreatic water samples are fit for human consumption, and the confined water can provide quality drinking water. Most of the phreatic water samples have no sodium hazard but have magnesium hazard. All the confined water samples generate mild foaming reaction, and 93% of them are mildly corrosive for boilers. An assessment by OVM without entropy is calculated. Similar results to the coupled model demonstrate that pure OVM is also objective and valid. The simple algorithm turns multicriteria decision-making problems into an integrated index which is just as useful to water quality assessment.
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