Brittle mineral, especially quartz, exert significant effect on the development of shale gas, however, the formation mechanism of quartz in shale is still unclear. Here, we present X-ray diffraction ...data, scanning electron microscopy (SEM) determination, cathodoluminescence and geochemical data to investigate Longmaxi Formation, which is a key target for shale gas exploration and development in China recently. Siliceous and argillaceous mudstones were recognized from 5 outcrops of Longmaxi Formation, which were examined with respect to the formation mechamism of quartz. Three different types of quartz (silt-size detrital grain with bright luminescence, micro-sized grains and quartz overgrowths with bright luminescence) were identified by SEM/EDS/CL both in the argillaceous and siliceous shale. Siliceous shale deposited by suspension sediment settling with high sea level because of anoxia condition indicated by lower Th/U and higher V/Cr ratios. The quartz in siliceous shale display a positive covariation with Babio, as well as a good correlation between TOC and quartz, suggesting biogenic-quartz is an important constituents. Argillaceous shale was likely dominated by suspension alternate with gravity current in consideration of the mixing of clay- and silt-laminae, there is no correlation between quartz and TOC, and positive correlation between excess silica and Zr, indicating terrestrial quartz in argillaceous is more important relative to siliceous shale. Additionally, reorientation of phyllosilicate particles and positive correlation between KI and quartz contents (R2 = 0.57) suggest the indispensable diagenetic-quartz (illitization of smectite), near or far from the clay minerals, both in siliceous and argillaceous shales. This process also result in high quartz saturation in silt-rich laminae, thus that quartz overgrowths encased in dolomite cements is common in argillaceous shale. Based on the geochemical analysis, the argillaceous shale contains 86% detrital-silica, 14% digenetic-silica. However, the siliceous shale approximately contains 33% detrital-silica, 11% digenetic-silica and 56% biogenic-silica. Occurrence and origin of quartz are of great significance for physical properties of shale and hydraulic fracturing during the development of shale gas.
•Three different types of quartz were identified.•The contents of different types of SiO2 were calculated approximately.•Different formation mechanism of quartz in siliceous and argillaceous shales were proposed.
Copper-based catalysts are widely explored in electrochemical CO2 reduction (CO2RR) because of their ability to convert CO2 into high-value-added multicarbon products. However, the poor stability and ...low selectivity limit the practical applications of these catalysts. Here, we proposed a simple and efficient asymmetric low-frequency pulsed strategy (ALPS) to significantly enhance the stability and the selectivity of the Cu-dimethylpyrazole complex Cu3(DMPz)3 catalyst in CO2RR. Under traditional potentiostatic conditions, Cu3(DMPz)3 exhibited poor CO2RR performance with the Faradaic efficiency (FE) of 34.5% for C2H4 and FE of 5.9% for CH4 as well as the low stability for less than 1 h. We optimized two distinguished ALPS methods toward CH4 and C2H4, correspondingly. The high selectivities of catalytic product CH4 (FECH4 = 80.3% and above 76.6% within 24 h) and C2H4 (FEC2H4 = 70.7% and above 66.8% within 24 h) can be obtained, respectively. The ultralong stability for 300 h (FECH4 > 60%) and 145 h (FEC2H4 > 50%) was also recorded with the ALPS method. Microscopy (HRTEM, SAED, and HAADF) measurements revealed that the ALPS method in situ generated and stabilized extremely dispersive and active Cu-based clusters (∼2.7 nm) from Cu3(DMPz)3. Meanwhile, ex situ spectroscopies (XPS, AES, and XANES) and in situ XANES indicated that this ALPS method modulated the Cu oxidation states, such as Cu(0 and I) with C2H4 selectivity and Cu(I and II) with CH4 selectivity. The mechanism under the ALPS methods was explored by in situ ATR-FTIR, in situ Raman, and DFT computation. The ALPS methods provide a new opportunity to boost the selectivity and stability of CO2RR.
Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been ...reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structureguided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided “proof of concept” for the potential application of metabolic treatment in clinical practice.
Seven pairs of new oxygenated aplysinopsin-type enantiomers, (+)- and (-)-oxoaplysinopsins A‒G (1‒7), two new bromotyrosine-derived alkaloids, subereamollines C and D (18 and 19), together with ten ...known compounds (8‒17) were isolated from the Xisha Islands sponge Fascaplysinopsis reticulata. The planar structures were determined by extensive NMR and MS spectroscopic data. Each of the optically pure enantiomers was achieved by chiral HPLC separation. The absolute configurations were assigned by the quantum chemical calculation methods. Compound 19 showed cytotoxicity against Jurkat cell lines with IC
value of 0.88 μM. Compounds 2, 16 and 17 showed tyrosine phosphatase 1B (PTP1B) inhibition activity with IC
value ranging from 7.67 to 26.5 μM, stronger than the positive control of acarbose and 1-deoxynojirimycin. A structural activity relationship for the aplysinopsin-type enantiomers were observed in PTP1B inhibition activity of 2 and cytotoxicity of 3 that the dextrorotary (+)-2 and (+)-3 showed stronger activity than the levorotary (-)-2 and (-)-3.
The book is the first thorough study of the role of phosphorus chemistry in the origin of life. This book starts with depiction of the phosphorus role in life creation and evolution. Then it outlines ...in vital processes how different phosphorus-containing compounds participate as biomarker in life evolution. Written by renowned scientists, it is suitable for researchers and students in organic phosphorus chemistry and biochemistry.
Terahertz (THz) spectroscopy has drawn great interest for the functional and conformational investigations of nucleic acids, but its intrinsic sensitivity hinders potential bio-sensing applications. ...Here, a novel THz biosensor was developed for detecting microRNA (miRNA) samples based on metamaterials coupled with nanoparticles and strand displacement amplification (SDA). In this method, the SDA reaction amplifies the target miRNA and generates copious yields of secondary DNA molecules (Trigger DNA), which are subsequently conjugated to metallic nanoparticles that form nanoparticle-Trigger DNA complexes. These complexes produce remarkable frequency shifts of metamaterials when linked to a large refractive index metallic nanoparticle like Au. The dependence of the metamaterial resonance on the nanoparticle diameter and metal type was investigated experimentally and theoretically. Under optimal conditions, the THz metamaterial biosensor presents good detection sensitivity with a limit of detection of 14.54 aM and exhibits a linear response for miRNA-21 at a concentration range from 1 fM to 10 pM. By measuring the miRNA-21 in spiked clinical serum samples, the sample recoveries were determined to be in the range between 90.92% and 107.01%. These findings demonstrate that the novel THz biosensor offers the capability for highly sensitive miRNA detection, with noteworthy potential applications in nucleic acid analysis and cancer diagnosis.
•A THz biosensor was developed for detecting miRNA-21 based on THz metamaterials coupled with nanoparticles and SDA.•The dependence of metamaterial sensitivity on different nanoparticles was investigated experimentally and theoretically.•LOD down to 14.54 aM was obtained and differences among three different miRNAs were discriminated.•The application of THz biosensor was practically tested by measuring miRNA-21 in spiked clinical serum samples.
Purpose
Due to a lack of early diagnostic markers, pancreatic cancer (PC) remains a lethal disease. Proteomic approaches are now being applied to identify novel PC biomarkers.
Experimental design
In ...this study, iTRAQ and LC‐MS/MS are used to perform comparative analyses of serum from PC patients and healthy controls (HC), to identify specific serum biomarkers for PC. Serum levels of candidate proteins are determined using ELISA.
Results
Among 869 proteins identified, 55 are potential biomarkers; Vitamin K‐dependent protein Z (PROZ) and tumor necrosis factor receptor superfamily member 6b (TNFRSF6B) are selected for further analysis. Serum levels of PROZ and TNFRSF6B are significantly higher in PC patients than in HC or pancreatic benign controls (BC) (p < 0.01). The AUCs range from 0.816 to 0.971 for PROZ, TNFRSF6B, and carbohydrate antigen 19‐9, either individually or in combination, in PC versus HC+BC, and from 0.711 to 0.932 in PC Stage I versus HC+BC.
Conclusions and clinical relevance
It is demonstrated that PROZ and TNFRSF6B are novel serum biomarkers for detecting early stage PC, and for distinguishing PC from pancreatic benign tumor and healthy individuals. Additional large cohort studies are needed to develop PROZ and TNFRSF6B as clinical PC biomarkers.
Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in ...SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
AT‐rich interaction domain 4A (ARID4A) and AT‐rich interaction domain 4B (ARID4B), which are both the AT‐rich interaction domain (ARID) family, have been reported to be oncogene or tumor suppressor ...gene in various human malignances, but there is no involvement about their functions in prostate cancer (PCa). Our previous study has reported that microRNA‐30d (miR‐30d) expression can predicted poor clinical prognosis in PCa, however, the underlying mechanisms of miR‐30d have not been fully described. The aim of our study is to investigate the expression relevance between miR‐30d and ARID4A or ARID4B, and examine the clinical significance and biological function of ARID4A and AIRD4B in PCa. In this study, both ARID4A and ARID4B were identified as the target genes of miR‐30d. In addition, the mRNA expression of miR‐30d in PCa tissues were significantly negative correlated with ARID4A (Pearson correlation coefficient = −0.313, P = 0.001) and ARID4B (Pearson correlation coefficient = −0.349, P < 0.001), while there was a positive correlation between ARID4A and ARID4B (Pearson correlation coefficient = 0.865, P < 0.001). Moreover, both ARID4A and ARID4B were significantly downregulated in PCa tissues with high Gleason scores (P = 0.005, P = 0.033), PSA failure (P = 0.012, P = 0.05) and short biochemical recurrent‐free survival (P = 0.033, P = 0.031). Furthermore, the knockout expression of ARID4A and ARID4B promoted PCa cell proliferation, migration and invasion in vitro. In conclusion, our results indicated that ARID4A and ARID4B may serve as tumor suppressor in PCa progression, suggesting that they might be the potential therapeutic targets in prostate cancer.
This article is mainly focused on discussed the phenotype of ARID4A and ARID4B in prostate cancer and suggesting it might be a promising therapeutic target for PCa therapy.
Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ...ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB
bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.
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