Recent experiments on FeSe films grown on SrTiO3 (STO) suggest that interface effects can be used as a means to reach superconducting critical temperatures (Tc) of up to 80 K (ref. ). This is nearly ...ten times the Tc of bulk FeSe and higher than the record value of 56 K for known bulk Fe-based superconductors. Together with recent studies of superconductivity at oxide heterostructure interfaces, these results rekindle the long-standing idea that electron pairing at interfaces between two different materials can be tailored to achieve high-temperature superconductivity. Subsequent angle-resolved photoemission spectroscopy measurements of the FeSe/STO system revealed an electronic structure distinct from bulk FeSe (refs , ), with an energy gap vanishing at around 65 K. However, ex situ electrical transport measurements have so far detected zero resistance-the key experimental signature of superconductivity-only below 30 K. Here, we report the observation of superconductivity with Tc above 100 K in the FeSe/STO system by means of in situ four-point probe electrical transport measurements. This finding confirms FeSe/STO as an ideal material for studying high-Tc superconductivity.
Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2‐insensitive fluorophore and an O2‐sensitive phosphor in a polymer matrix, which ...require high cost and multi‐step synthesis of transition metal complexes. The two‐chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA‐UPy), bridged by a bis‐UPy‐functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP=7.7 %, τP=3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv=189.6 kPa−1) in aqueous solution as well as in living HeLa cells.
An organic hypoxia nanoprobe assembled by quadruple hydrogen bonds, shows efficient long‐lived phosphorescence (ΦP=7.7 %, τP=3.2 ms) and fluorescence from a monochromophore at room temperature and can be used for oxygen detection in water and living cells. This is the first example of ratiometric hypoxia sensing by supramolecular assemblies of an organic monochromophore.
Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing ...therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPβ can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPβ may provide more precise therapeutic options in ovarian cancer.
Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth ...type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Here, we present crystal structures of truncated human MFN2 in different nucleotide-loading states. Unlike other dynamin superfamily members including MFN1, MFN2 forms sustained dimers even after GTP hydrolysis via the GTPase domain (G) interface, which accounts for its high membrane-tethering efficiency. The biochemical discrepancy between human MFN2 and MFN1 largely derives from a primate-only single amino acid variance. MFN2 and MFN1 can form heterodimers via the G interface in a nucleotide-dependent manner. CMT2A-related mutations, mapping to different functional zones of MFN2, lead to changes in GTP hydrolysis and homo/hetero-association ability. Our study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways their disruptions cause disease.
Podiform chromitites in the mantle sections of ophiolites belong to either high-Cr (metallurgical) or high-Al (refractory) varieties. Their highly variable compositions are reflected by different ...Cr#s 100Cr/(Cr+Al) and Cr2O3 and Al2O3 contents of the chromite, falling in the boninitic and MORB fields, respectively. Parental magmas of high-Cr chromitites have higher Sc, Mn, Co and Ni, and lower Ti, V, Zn and Ga concentrations than MORB melts; their trace-element patterns are similar to those of boninites, except for Ni and Zn. In contrast, high-Al chromitites have parental magmas characterized by generally flat MORB-normalized patterns, showing slight enrichments in V, Mn and Co, and depletion in Ni and Zn. Regardless of their compositions, both types of chromitites have chondrite-normalized platinum group element (PGE) patterns showing enrichment in IPGE and depletion in PPGE. A variety of platinum group minerals are typically present in both types, occurring either as euhedral inclusions or along fractures in chromite grains. These minerals have a wide span of Re–Os isotopic compositions, reflecting a variety of origins.
There is a diversity of unusual minerals and mineral inclusions associated with podiform chromitites. The presence of these minerals suggest that grains of amphibolite (plagioclase, amphibole and zircon) and eclogite (coesite, kyanite and garnet) were present in the magmas from which chromite crystallized. Multiphase mineral inclusions demonstrate that podiform chromitites form from hydrous mafic magmas in suprasubduction zone environments (SSZ). We propose a new model in which chromitite formation was involved in intra-oceanic subduction zones initiated in closing oceanic basins. Continued subduction carries oceanic and possibly continental crustal materials to deep levels where they are metamorphosed under greenschist, amphibolite and eclogite facies conditions. The tearing and breakoff of the subducted slab, possibly along the transitional contact between amphibolites and eclogites, create a slab window through which the underlying asthenosphere rises and melts to generate Cr-rich mafic magmas. These upward-migrating magmas pass through the subduction zone and assimilate the subducted slab. As a result of slab contamination, these magmas become more siliceous, more oxidized and more hydrous, rapidly triggering chromite crystallization. Minute grains of chromite are suspended in the upward-moving magmas as they migrate through the overlying metasomatized mantle wedge. Such chromite-bearing magmas eventually deposit chromite in magma conduits in the uppermost mantle close to the Moho where the upward flow changes from vertical to subhorizontal and velocity is greatly reduced.
Highly reduced and ultrahigh pressure minerals including diamonds are reported in literature both in podiform chromitites and host peridotites of ophiolites. Some of these minerals in association with host peridotites may have been brought by the uprising asthenosphere at mid-oceanic ridges due to the mantle convection. It is also possible that some diamonds may have formed in the subducted slab below about 150km. Some minerals of subducted slabs are preserved because they are encapsulated in chromite grains where they are protected from the SSZ melts. Some of these SSZ mantle wedges are emplaced on land to become podiform chromitite-bearing ophiolites.
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•Podiform chromitites crystallize from hydrous and high-Mg SSZ melts.•Crustal minerals suggest crystallization of chromite after slab assimination.•Asthenospheric melts pass through slab window.•Chromite deposits in mini-magma conduits near Moho.
The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross-sectional associations ...between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation SD 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio HR, 0.917; P
<0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; P
= 0.010), AST to ALT ratio (HR, 1.195; P
<0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066; P
<0.001), alcoholic liver disease (ALD; HR, 2.872; P
<0.001), and fibrosis and cirrhosis of liver (HR, 2.285; P
= 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (P
<0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (P
<0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (P
<0.05). In sensitivity analysis, metabolic dysfunction-associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence.
Backgrounds
Two technologies, cardiac contractility modulation (CCM) and subcutaneous implantable cardioverter‐defibrillator (S‐ICD), can be successfully combined and applied to patients with ...advanced heart failure (HF) with reduced left ventricular ejection fraction (LVEF).
Case Report
We reported a case of a 51‐year‐old man with reduced ejection fraction (LVEF = 33%) and a narrow QRS complex who first underwent simultaneous implantation of CCM and S‐ICD.
Conclusion
Our case report aimed to reveal that the simultaneous implantation of CCM and S‐ICD could be successfully used in patients with advanced HF, which could significantly improve the clinical symptoms of such patients during one surgery.
Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated ...with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA-mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation "promoter" but not an "inhibitor" in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in facilitating osteoblast differentiation and its systemic regulation of phosphate homeostasis via the mediation of FGF23.
Junctional adhesion molecular 3 (JAM3) is downregulated by hypermethylation in cancers but is unclear in cholangiocarcinoma. The JAM3 expression level was checked in cholangiocarcinoma cell lines and ...tissues. Methylated JAM3 was detected in cell lines, tissues and plasma cell‐free DNAs (cfDNA). The roles of JAM3 in cholangiocarcinoma were studied by transfection of siRNA and pCMV3‐JAM3. The survival analysis was based on the Gene Set Cancer Analysis (GSCA) database. JAM3 was downregulated in HCCC‐9810 and HuCCT1 cell lines and tissues by hypermethylation. Methylated JAM3 was detected in cfDNAs with 53.3% sensitivity and 96.6% specificity. Transfection of pCMV3‐JAM3 into HCCC‐9810 and HuCCT1 induced apoptosis and suppressed cell proliferation, migration and invasion. The depletion of JAM3 in RBE cells using siRNA decreased apoptosis and increased cell proliferation, migration and invasion. Hypermethylation of JAM3 was associated with tumour differentiation, metastasis and TNM stage. Downregulation and hypermethylation of JAM3 were related to poor progression‐free survival. Junctional adhesion molecular 3 may function as a tumour suppressor in cholangiocarcinoma. Methylated JAM3 DNA may represent a non‐invasive molecular marker for the early detection of cholangiocarcinoma and prognosis.
Silicene, a monolayer of silicon atoms arranged in honeycomb lattices, can be synthesized on the Ag(111) surface, where it forms several superstructures with different buckling patterns and ...periodicity. Using scanning tunneling microscopy (STM), we obtained high-resolution images of silicene grown on Ag(111) and revealed its five phases, i.e., 4 × 4 − α, 4 × 4 − β, − α, − β and − γ, some observed for the first time. For each of the phases, we have determined its atomic structure by comparing the atomic-resolution STM images with theoretical simulation results previously reported. We thus eliminate the contradictions of previous studies on the structural models of various silicene phases supported by the Ag(111) surface.
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