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Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet beta (β) cells, characterized by inappropriate production of other islet cell-enriched hormones. Here we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin (Gast)-positive cells generated under conditions of chronic hyperglycemia and obesity. A human β cell line deficient in MAFB, but not one lacking MAFA, also produced a gastrin (GAST)-positive gene expression pattern. In addition, GAST was detected in human T2D β cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repressGASTgene transcription. These results support a novel, species-specific role for MafA and MAFB in maintaining adult mouse and human β cell identity, respectively, by repressing expression of Gast/GAST and other non-β cell hormones.

With their adjustable structures and diverse functions, polyoxometalate (POM)-resorcin[4]arene-based inorganic-organic complexes are a kind of potential multifunctional material. They have potential applications for lithium ion batteries (LIBs). However, the relationship between different coordinated metal ions and electrochemical performance has rarely been investigated. Here, three functionalized POM-resorcin[4]arene-based inorganic-organic materials, [Co2 (TMR4 A)2 (H2 O)10 ][SiW12 O40 ]⋅2 EtOH⋅4.5 H2 O (1), [Ni2 (TMR4 A)2 (H2 O)10 ][SiW12 O40 ]⋅4 EtOH⋅13 H2 O (2), and [Zn2 (TMR4 A)2 (H2 O)10 ][SiW12 O40 ]⋅2 EtOH⋅2 H2 O (3), have been synthesized. Furthermore, to enhance the conductivities of these compounds, 1-3 were doped with reduced graphene oxide (RGO) to give composites 1@RGO-3@RGO, respectively. As anode materials for LIBs, 1@RGO-3@RGO can deliver very high discharge capacities (1445.9, 1285.0 and 1095.3 mAh g-1 , respectively) in the initial run, and show discharge capacities of 898, 665 and 651 mAh g-1 , respectively, at a current density of 0.1 A g-1 over 100 runs. More importantly, the discharge capacities of 319, 283 and 329 mAh g-1 were maintained for 1@RGO-3@RGO even after 400 cycles at large current density (1 A g-1 ).

The North American Midcontinent Sea (NAMS) covered a vast area during Late Pennsylvanian glacio-eustatic highstands, providing a laboratory for analysis of the internal watermass dynamics of large cratonic seas (of which few exist in the Recent). In this study, a novel proxy, copper (Cu) isotopes, was used to gain a better understanding of NAMS watermass dynamics. We analyzed the 63-cm-thick Stark Shale (Dennis Formation, Missourian Stage, Upper Pennsylvanian) in the Iowa Riverton core (IRC) at a centimeter scale in order to reconstruct secular variations in Cu-isotopic compositions (δ65Cu) and other geochemical proxies. The gray shale facies yielded δ65Cu of +0.02 ± 0.06‰ (2σ, n = 14), similar to detrital Cu in modern marine sediments (δ65Cu = +0.08 ± 0.20‰; 2σ, n = 42). In contrast, the black shale facies, in which the proportion of authigenic Cu hosted by the organic fraction is 50–100% of total Cu content, exhibits heavier δ65Cuauth values, mostly between +0.09 and +0.43‰. In modern marine systems, one of the main processes leading to 65Cu-enriched sediment compositions is adsorption of aqueous Cu onto Fe-Mn particulates. The black shale facies of the Stark Shale exhibits four peaks in Mo/U ratios that are indicative of an active particulate shuttle because of the tendency of Mo to adsorb more strongly than U to Fe-Mn particulates. The Sr/Ba ratio, a paleosalinity proxy, shows correlated variations, with high values (indicative of more fully marine conditions) linked to low Mo/U and light δ65Cu, and low values (indicative of brackish conditions) linked to high Mo/U and heavy δ65Cu. These considerations suggest that the flux of isotopically heavy Cu to the sediment–water interface via Fe-Mn cycling was enhanced during brackish intervals, with subsequent reductive dissolution of Fe-Mn particulates allowing transfer of hydrogenous Cu to the organic fraction of the sediment. Control of δ65Cu by Fe-Mn cycling is supported by the results of a sequential extraction experiment showing that organic δ65Cu is positively correlated with Mo/U. These findings provide evidence of large fluctuations in watermass salinity and sea-level elevation within the NAMS at timescales of ∼104 yr during core shale deposition, as previously inferred but not conclusively demonstrated until now. The dynamics of particulate shuttle operation suggest that sea-level fluctuations must have had amplitudes of at least a few tens of meters. These fluctuations ended during the final stages of black shale deposition, probably owing to overall sea-level fall and permanent shallowing of the study site into the oxic, low-salinity surface layer of the NAMS.

3d–4f heterometallic supertetrahedral clusters with the formula of Ln4Zn6(μ6-O)L4(CH3COO)6(NO3)4(CH3OH)4(H2O)2 (1-Ln, Ln = Eu, Gd, Tb, H3L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol) have been successfully introduced as stable secondary building units (SBUs) to construct new cluster-organic frameworks with tunable emission, demonstrating a promising strategy for developing new optical materials.

A series of POM-based all-inorganic open frameworks, H9[Ln9W8(μ4-O)12(μ2-O)24(H2O)24](SiW12O40)3·60H2O (1-Ln, Ln = La, Pr and Nd), have been fabricated and structurally characterized for the first time. The unique architectures are constructed from nanoscale four-shell Ln@W8@Ln8@(SiW12)6 clusters. Additionally, the porous nature of the frameworks has also been investigated.

The failure of a natural dam is an extreme geological event. Palaeo-lake sediments were discovered in the broad Xigaze valley and Dazhuka-Yueju gorge in the middle reach of the Yarlung Tsangpo River in Tibet. However, the sedimentary processes, dam failure, and peak flood of the Xigaze dammed palaeo-lake are poorly understood. Hence, we conducted a field survey of eight lacustrine sedimentary terraces in the area. We divided the sedimentary processes of the palaeo-lake into five stages and deposit types: pre-palaeo-lake sediments (fluvial or aeolian deposits); early stage sediments of the palaeo-lake (coarse sand); main stage palaeo-lake sediments (clayey silt and sand), sediments following the discharge of the palaeo-lake (sand and gravel-cobbles); and cover deposits (aeolian sediments and colluvium). Additionally, the water level along the palaeo-lake was almost constant (3811 m a.s.l.). The dam was likely located at the eastern end of the Dazhuka-Yueju gorge. Based on the water level, dam location and 30-m ASTER GDEM2 data, the capacity of the palaeo-lake was estimated as 22.55 km3. To separate the water volume and sediment volume, the sediment surface elevation along the palaeo-lake was simulated based on the elevations of the six lacustrine sedimentary terraces. The volume of the sediment was ~11.56 km3, which was calculated from the dam location, sediment surface elevation, and the ASTER GDEM2 data. Finally, subtraction of the sediment volume from the capacity of the palaeo-lake gave a backwater volume of 10.99 km3. The peak flood possibly exceeded 3.4 × 105 m3/s as a moraine dam joined the discharge during the dam failure. However, the dammed event probably had a limited effect on the landforms at downstream because of the presence of another dammed palaeo-lake in the broad Zetang valley; moreover, the bedrock upstream of the dam was protected from erosion.

A series of 3D porous lanthanide-substituted polyoxometalate frameworks, Na2[Ln2(H2O)11]2[Ln3(H2O)3(α-SiW11O39)2]2·69H2O (1-Ln, Ln = Sm, Eu, Gd, Tb, and Dy), are built from novel hexadecahedral {Ln6W8O28} heterometallic cage-shaped clusters. Intriguingly, every tetrameric {[Ln3(H2O)3(α-SiW11O39)2]2}14- cage-cluster is linked with another eight tetrameric cage-clusters by Ln3+ cations, leading to a novel 3D inorganic porous framework, which exhibits good thermal and chemical stability, excellent water vapor adsorption capacity, and moderate proton conductive properties. Furthermore, the solid state luminescence spectra demonstrate that 1-Sm, 1-Eu, 1-Tb, and 1-Dy display the lanthanide characteristic emission bands. The temperature-dependent magnetic susceptibility indicates that there are antiferromagnetic interactions in 1-Tb and 1-Dy.

Two unique heterometallic cluster organic frameworks, [Cd4 MnIII 4 MnII 6 (Tri)4 (CH3 COO)14 (μ4 -O)2 (μ3 -O)2 (H2 O)2 ] Cd(H2 O)2 ⋅9 H2 O (1) and Cu[Cd5 Cu6 (Tri)4 (CH3 COO)9 (H2 O)4 ]2 (CH3 COO)3 ⋅24 H2 O (2) (H3 Tri=2-(hydroxymethyl)-2-(pyridine-4-yl)-1,3-propanediol), have been successfully prepared by employing a bifunctional tripodal alcohol ligand as a structure-directing agent. Crystal structure analyses reveal that 1 represents a rare example of frameworks constructed from Cd-Mn heterometallic chains, and 2 is the first heterometallic MOF based on highest-nuclear Cd-Cu heterometallic cluster building blocks. Furthermore, the magnetic properties and gas adsorption abilities of 1 and 2 were systematically studied.

The first two inorganic-organic hybrid three-dimensional (3D) polyoxotantalates (POTas) and the first two inorganic-organic hybrid 2D POTas have been obtained. All of these high-dimensional POTas are built from a new-type POTa dimeric cluster {Cu(en)(Ta6O19)}2/{Cu(enMe)(Ta6O19)}2 (en = ethylenediamine, enMe = 1,2-diaminopropane) bridged by copper complexes. Interestingly, extended POTas 1 and 3 can undergo single-crystal to single-crystal structural transformations triggered by water.

A nested Cu24@Cu72 copper-organic framework, [Cu5(bdc)4(ina)2(H2O)3]·solvent (1, H2bdc = 1,3-benzenedicarboxylic acid and Hina = isonicotinic acid) based on paddlewheel Cu2(COO)4 SBUs, has been synthesized. There are three types of cages with different sizes and shapes: Cu24-cage, Cu60-cage and Cu72-cage. The Cu72-cage, which is the highest-nuclearity Cu-cage reported to date, encapsulates a Cu24-cage to form a double-walled Cu24@Cu72 cage-within-cage structure. Dye adsorption studies reveal that compound 1 can rapidly and selectively adsorb cationic dyes.

Two novel heterometallic organic frameworks built from trinuclear indium and cuprous halide clusters, [(In3O)2(Cu2I2)3(ina)12(H2O)6](NO3)2·7DMA·10H2O (1) and [NH2(CH3)2][In3(OH)2(H2O)2(ina)8(Cu4I4)2]·5DMA·8H2O (2), where Hina = isonicotinic acid, have been successfully constructed with the orientation of the ina ligand. 1 shows a fascinating highly porous honeycomb-like 3D cationic framework with a trigonal-bipyramid-type cage based on a planar [In3O(CO2)6]+ trimer and a rhombohedral Cu2I2 cluster. Comparably, 2 displays a 3D negative network with irregular hexagonal channels constructed from a [In3(OH)2(CO2)8]- trimer and a cubane-like Cu4I4 cluster. Especially, 1 displays a reversible I2 adsorption/release performance with high adsorption capacity, whose mechanism has been disclosed by theoretical simulation. Also, the green/red emission of 2 stems from iodocuprate centers with quenched indium-centered emission.

A quantitative description of surface micromorphology is a topic worthy of attention to establish the relationship between the surface texture and electrochemical behavior of the electrode interfac...

By employing a bowl-like tetra(benzimidazole)resorcin[4]arene (TBR4A) ligand, two new polyoxometalate-templated metal-organic frameworks (POMOFs), [Co8Cl14(TBR4A)6]·3[H3.3SiW12O40]·10DMF·11EtOH·20H2O (1) and [Co3Cl2(TBR4A)2(DMF)4]·[SiW12O40]·2EtOH·3H2O (2), have been prepared under solvothermal conditions (DMF = N,N'-dimethylformamide). 1 shows a 2D cationic layer, whereas 2 exhibits a 3D framework. Remarkably, the Keggin POMs in 1 and 2 were located in the cavities formed by two bowl-like resorcin[4]arenes in sandwich fashions. Their framework structures were highly dependent on the coordination modes of the TBR4A ligands. To increase the conductivity of POMOFs, the samples of 1 and 2 were loaded on the conductive polypyrrole-reduced graphene oxide (PPy-RGO) via ball milling (1@PG and 2@PG). Then, the obtained composites experienced calcination at a proper temperature to produce 1@PG-A and 2@PG-A. The resulting 1@PG-A and 2@PG-A composites, with improved conductivities, uniform sizes and micropores, exhibited promising electrochemical performance for lithium-ion batteries. We herein proposed a size-controlled route for the rational fabrication of functional POMOFs and their usage in energy fields.

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (1O2) probe. Under 660 nm laser irradiation, Ce6 exhibites efficient 1O2 generation, and subsequently the production of 1O2 is assessed by the ratiometric fluorescence of PFO and DPBF under one-photon and two-photon excitation mode. The nanoparticles with excellent biocompatibility can be internalized into Hela cells and applied for tumor treatment. For intracellular PDT, the nanoparticles perform a high phototoxicity, while the PDT proccess can be evaluated in time by monitoring fluorescence signals of DPBF. This theranostic nanosysterm provides a facile strategy to fabricate 1O2-detection PDT, which can realize accurate and efficient photodynamic therapy based on singlet oxygen detection.

A heterozygous missense mutation producing a variant of the islet β-cell- enriched MAFA transcription factor (p.Ser64Phe (S64F)) was identified in patients who developed adult-onset, β-cell dysfunction (diabetes or insulinomatosis), with men more prone to diabetes than women. This mutation engenders increased stability to the normally unstable MAFA protein. To obtain insight into how this variant impacts β cell function, we developed a mouse model expressing S64F MafA and found sex- dependent phenotypes, with heterozygous mutant males (MafAS64F/+) displaying impaired glucose tolerance while females were slightly hypoglycemic with improved blood glucose clearance. Only MafAS64F/+ males showed transiently higher MafA protein levels preceding the onset of glucose intolerance and sex-dependent, differential expression of genes involved in Ca2+ signaling, DNA damage, aging, and senescence. Functional changes in islet Ca2+ handling and signs of islet aging and senescence processes were uniquely observed in male animals. In addition, MAFAS64F expression in male human β cells accelerated cellular senescence and increased production of WT senescence-associated secretory proteins compared to cells expressing MAFA Together, these results implicate a conserved mechanism of accelerated islet aging and senescence in promoting diabetes in MAFAS64F carriers in a sex-dependent manner.

The continental shale oil reservoir has low permeability, high clay content, rich lamellar structure, and strong heterogeneity, which makes the reservoir vulnerable to hydration damage. In order to study characteristics of hydration damage and its influence on permeability of lamellar shale oil reservoirs, a series of experiments such as high-pressure mercury injection, steady gas permeability, rock thin section identification, and scanning electron microscope were carried out with the downhole core in Ordos Basin as the experimental object. The effects of water and water-based drilling fluid on pore size distribution, permeability, and rock microstructure were analyzed. Results show that the pore size of the reservoir is mainly nanoscale, and the pore size of shale changes most dramatically in the stage of hydration for 12-24 hours, while that of tuff changes most dramatically in 24-48 hours. The permeability increases rapidly with hydration time and then tends to be stable, among which the permeability of samples with lamellar structure in the direction parallel to the lamellar structure is most easily affected by hydration and changes fastest. Hydration leads to the formation of new pores, new fractures, and the expansion of existing fractures in rocks, especially in the strata containing large amounts of terrigenous clastic, lamellar structure, and pyrite. The new seepage channel increases the permeability of rock, and the soil powder and plugging particles in drilling fluid are easy to form protective mud cake in these places. These protective mud cakes not only change the microstructure of rock but also inhibit the influence of hydration on the pore space and permeability of rock, which play an effective role in preventing the mineral shedding on the rock surface, reducing the increase of micropores and delaying hydration.

Roasting process impacts the chemical profile and aroma of roasted tea. To compare the impacts of far-infrared irradiation and drum roasting treatments (light, medium and heavy degrees), the corresponding roasted teas were prepared from steamed green tea for chemical analyses and quantitative descriptive analysis on aroma, and correlations between volatiles and aroma attributes were studied. There were 8 catechins, 13 flavonol glycosides and 105 volatiles quantified. Under heavy roasting treatments, most catechins and flavonol glycosides decreased, and aldehydes, ketones, furans, pyrroles/pyrazines, and miscellaneous greatly increased, while far-infrared irradiated teas had distinct nutty aroma compared with the roasty and burnt odor of drum roasted teas. The weighted correlation network analysis result showed that 56 volatiles were closely correlated with the aroma attributes of roasted teas. This study reveals the differential chemical and sensory changes of roasted teas caused by different roasting processes, and provides a novel way for flavor chemistry study.

A series of POM-based all-inorganic open frameworks, H

A missense mutation of the pancreatic islet-enriched transcription factor MAFA (S64F) was identified in patients characterized by familial diabetes or insulinomatosis, with males more prone to diabetes. This variant converts the normally unstable MAFA protein to be unusually stable. A heterozygous germline mouse model expressing this variant (S64F MafA Het) mimics the sex-dependent phenotype in humans: Het males have impaired glucose tolerance while Het females have hypoglycemia. Het males also showed increased MafA protein stability preceding glucose intolerance (Figure 1) and upregulation of genes involved in aging/senescence (Figure 2). These results implicate accelerated aging/senescence in islet β-cell dysfunction in males with the S64F MAFA mutation. Future studies will evaluate the broader significance of these processes in diabetes. Disclosure J. Cha: None. E.M. Walker: None. X. Tong: None. M. Guo: None. J. Liu: None. S. Yu: None. D. Iacovazzo: None. F. Mauvais-Jarvis: None. S.E. Flanagan: None. M. Korbonits: None. J.M. Stafford: None. R. Stein: None. Funding National Institutes of Health (T32DK007061, F32DK109577, R01DK090570); JDRF (3-PDF-2019-738-A-NDK109577)

With the development of petroleum industry, more and more attention has been paid to unconventional energy sources such as shale oil and gas. However, due to the complex geological conditions of shale formation, the strong heterogeneity of rock, and the unclear understanding of the physical and chemical properties of shale formation rock, mechanical properties lead to downhole accidents such as wellbore collapse during drilling. Based on the Chang 7 shale stratum project in southern Ordos Basin, this paper analyses the uniaxial and triaxial compressive strength of rocks from the point of view of the influencing factors of rock mechanical properties. At the same time, it combines XRD clay mineral analysis, shale hydration test, shale expansibility test, thin slice CT scanning and other means to analyze the micro-structure of shale. Using logging and drilling data, rock mechanics profiles are established, three pressure profiles and safety density windows are calculated, and rock strength variation during drilling is predicted. At the same time, the variation law of rock strength during drilling is verified in combination with the engineering practice of YY well in Chang 7 shale in Ordos Basin, which provides a basis for optimizing drilling fluid and safe drilling and completion.

Shale oil is a kind of unconventional oil resource with great potential. China is rich in shale oil resources. There is a good shale oil reservoir in the 3rd sub-member of The Triassic Chang 7 member in Southern Ordos Basin, but at present there is insufficient understanding of the physical and chemical characteristics of the rock. This results in frequent instability of the well wall during the drilling process, which affects the drilling cycle and the length of the horizontal segment. To this end, the research on B1 well, which is a key exploration well in the Southern Ordos Basin, is carried out in the experimental study of the core system observation description, structural analysis, and hydration degree test. The results show that the upper part of the reservoir is mainly black stratiform shale, with a large number of horizontal cracks, large sand sandwich density, low clay mineral content, and basically no hydration capacity The lower part is tuff, which has a certain degree of horizontal cracks and contains some structural seams. The content of clay minerals is high and it has certain hydration ability. The differences in the structural characteristics, hydration and salinity of the two types of reservoirs were clarified, which provided a basis for the design of subsequent anti-collapse drilling fluids, and provided a basis for safe and efficient drilling in the 3rd sub-member of The Triassic Chang 7 member in Southern Ordos Basin.

Herein, we report a two-photon ratiometric fluorescent pH nanosensor based on conjugated polymer poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) nanoparticles loaded with pH-sensitive fluorescein isothiocyanate (FITC) for intracellular pH monitoring. The obtained nanosensor (FITC-PFO NPs) possesses high sensitivity, excellent stability, good reversibility, favorable two-photon excitability and low cytotoxicity. The ratiometric fluorescence of FITC and PFO (F517/F417) in FITC-PFO NPs solution shows an efficient pH-sensitive response over the pH range from 3 to 10 (pKa = 6.43) under two-photon excitation. Additionally, the FITC-PFO NPs is successfully applied for ratiometric imaging of intracellular pH and its fluctuation in both one-photon and two-photon excitation modes. Overall, the two-photon pH nanosensor based on FITC-PFO NPs exhibits great potential in crucial physiological and biological processes related to intracellular pH fluctuations.

As important anodes in lithium-ion batteries, graphene is always faced with the aggregation problem that makes most of the active sites lose their function at high current densities, resulting in low Li-ion intercalation capacity and poor rate performance. To address this issue, a layered g-C3N4@reduced graphene oxide composite (g-C3N4@RGO) was prepared via a scalable and easy strategy. The resultant g-C3N4@RGO composite possesses large interlayer distances, rich N-active sites, and a microporous structure, which largely improves Li storage performance. It shows excellent cycle stability (899.3 mA h g–1 after 350 cycles under 500 mA g–1) and remarkable rate performance (595.1 mA h g–1 after 1000 cycles under 1000 mA g–1). Moreover, the g-C3N4@RGO electrode exhibits desired capacity retention and relatively high initial Coulombic efficiency of 58.8%. Impressively, this result is better than that of RGO (29.1%) and most of RGO-based anode materials reported in the literature. Especially, the g-C3N4@RGO-base...

A rare porous zinc-organic framework with ultrahigh thermal stability over 500 °C was obtained, which exhibits a CaF2-type topology formed by 8-connected tetranuclear Zn4 clusters and 4-connected phosphonocarboxylate ligands. Interestingly, the similar reactions to the zinc-organic framework but in the absence of H2O or by the replacement of Zn2+ with Co2+ can yield three different 3D cluster-based frameworks but with the same CaF2-type topology.

A series of heterometallic cluster organic frameworks based on cuprous-halide Cu4I4 clusters and lanthanide clusters, [Ln2(H2O)8]2(Cu4I4)(pdc)4][NO3]4·solvent (1-Ln, Ln = Y, Tb, Eu, H2pdc = 3,5-pyridinedicarboxylic acid), have been successfully synthesized under solvothermal conditions. Single-crystal X-ray diffraction analysis reveals that 1-Ln show fascinating three-dimensional porous framework structures constructed from two dissimilar types of nanosized coordination cages. Gas sorption measurements indicate that 1-Ln show moderate gas uptake capacities. The UV/vis spectroscopy measurements reveal that 1-Ln are a class of potential materials for the removal of Cr2O72− from aqueous solution. Additionally, the luminescence properties of 1-Tb and 1-Eu have also been investigated.

We herein reported a newly microporous metal–organic framework (MOF), [Mn4(TPTR4A-II)0.5(bpdc)4(H2O)]·2DMF (Mn-MOF) (bpdc = biphenyl-4,4′-dicarboxylate, DMF = N,N′-dimethylformamide), constructed by bpdc anions, Mn(II) cations and a novel functionalized resorcin[4]arene (TPTR4A-II). For the first time, Mn-MOF was immobilized on graphene oxide (GO) to give Mn-MOF@GO composite. During the electrochemical experiments, the reduced graphene oxide (RGO) was obtained because of the electrochemical reduction of GO at a high negative potential. The glassy carbon electrode (GCE) coated with Mn-MOF@RGO (Mn-MOF@RGO/GCE) displayed good electrocatalytic activity for the reduction of nitrophenol isomers. Remarkably, the Mn-MOF@RGO/GCE showed good linear relationships in the ranges of 0.5–150, 0.5–140 and 0.5–180 μM, with the limit of detections (LODs) of 0.066, 0.072 and 0.078 μM for p-nitrophenol (p-NP), m-nitrophenol (m-NP) and o-nitrophenol (o-NP), respectively. More importantly, the Mn-MOF@RGO/GCE was utilized in the simultaneous determination of p-NP and o-NP, delivering the wide linear ranges of 0.75–140 and 0.5–180 μM with the LODs of 0.078 (p-NP) and 0.080 μM (o-NP), respectively

A heterozygous missense mutation producing a variant of the islet β-cell-enriched MAFA transcription factor (Ser(S)64Phe(F) MAFA) was identified in humans who developed adult-onset, β-cell dysfunction (diabetes or insulinomatosis), with men more prone to diabetes. This mutation engenders increased stability to the normally unstable MAFA protein. To obtain insight into how this variant impacts β cell function, we developed a mouse model expressing S64F MafA and found sex-dependent phenotypes, with heterozygous mutant males displaying impaired glucose tolerance while females were slightly hypoglycemic with improved blood glucose clearance. Only heterozygous males showed transiently higher MafA protein levels preceding the onset of glucose intolerance and sex-dependent, differential expression of genes involved in calcium signaling, DNA damage, aging, and senescence. Functional changes in islet calcium handling and signs of islet aging and senescence processes were uniquely observed in male animals. In addition, S64F MAFA expression in human, male EndoC-βH2 β cells accelerated cellular senescence and increased production of senescence-associated secretory proteins compared to cells expressing wild-type MAFA. Together, these results implicate a conserved mechanism of accelerated islet aging and senescence in promoting diabetes in S64F MAFA carriers in a sex-dependent manner.

Radix sp., Gyraulus sp. and Pisidium sp. are aquatic mollusc taxa. Although their fossil shells occur widely in dammed palaeo-lake sediments in the Yarlung Tsangpo valley in Tibet, their hydrochemical and hydrological implications are not fully understood. Moreover, vital effects on the trace element and stable isotope composition of the aragonite shells of these molluscs are unclear. We measured the values of δ13Cshell, δ18Oshell, Sr/Cashell and Mg/Cashell of the fossil shells of Radix sp., Gyraulus sp., and Pisidium sp. collected from the dammed lake sedimentary sequences at Xigaze and Lhainxiang in Tibet, with the aim of reconstructing the palaeo-hydrochemistry and palaeo-hydrology of the dammed palaeo-lake. The results show that the values of δ18Owater, Sr/Cawater and electrical conductivity (EC) of the dammed palaeo-lake water are higher than those of the modern Yarlung Tsangpo River water. Nevertheless, the dammed palaeo-lake still exhibited a through-flow status, together with freshwater characteristics. The values of δ18Oshell and δ13Cshell of Gyraulus sp. and Radix sp. have a positive relationship, but their ratios of Sr/Cashell and Mg/Cashell are not correlated. Moreover, δ18Oshell in the Radix sp. shells is ~2.97 ‰ more enriched and has a stronger relationship with δ18Owater than is the case for shells of Gyraulus sp. The values of δ18Oshell and δ13Cshell of Pisidium sp. are similar to those of the shells of Radix sp., and we conclude that the shells of Radix sp. are the most suitable mollusc shell for recording the δ18Owater of the ambient water of water bodies in the Tibetan Plateau.

Polyoxometalates (POMs) are alternative anode materials of lithium ion batteries (LIBs) for their reversible electrochemical redox behaviors and electron storage functions. To overcome the low conductivity and poor stability of the POMs, embedment of POMs into metal–organic hybrid complexes is a promising synthetic strategy. Here, we designed a family of copper-containing POM-resorcin[4]arene-based complexes supported by a resorcin[4]arene ligand (TPTR4A), copper cations and Keggin-type POMs, namely, [Cu4(TPTR4A)2][PMo12O40](OH)·2DMA·H2O (1a), [Cu4(TPTR4A)2][SiW12O40]·2.5DMA (1b) and [Cu4(TPTR4A)2][PW12O40](OH)·0.5DMA·5H2O (1c) (DMA = N,N’-dimethylacetamide). To improve the conductivity of the complexes, composites 1a@GO-1c@GO were obtained through mechanical grinding of the complexes and graphene oxide (GO). Strikingly, they show high initial specific capacity and stability for LIBs. This work offered a strategy for application of the POM-based complexes as LIBs via combining POM-based complexes and RGO.

The transcription factor encoded by the Pdx1 gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β-cell development, and adult islet β-cell function. Transgenic- and cell line–based experiments have identified 5′-flanking conserved sequences that control pancreatic and β-cell type–specific transcription, which are found within areas I (bp −2694 to −2561), II (bp −2139 to −1958), III (bp −1879 to −1799), and IV (bp −6200 to −5670). Because of the presence in area IV of binding sites for transcription factors associated with pancreas development and islet cell function, we analyzed how an endogenous deletion mutant affected Pdx1 expression embryonically and postnatally. The most striking result was observed in male Pdx1ΔIV mutant mice after 3 weeks of birth (i.e., the onset of weaning), with only a small effect on pancreas organogenesis and no deficiencies in their female counterparts. Compromised Pdx1 mRNA and protein levels in weaned male mutant β-cells were tightly linked with hyperglycemia, decreased β-cell proliferation, reduced β-cell area, and altered expression of Pdx1-bound genes that are important in β-cell replication, endoplasmic reticulum function, and mitochondrial activity. We discuss the impact of these novel findings to Pdx1 gene regulation and islet β-cell maturation postnatally.

Objective: To study the effect of interferon regulatory factors (IRFs) on the plaque nature and T cell subset differentiation in patients with carotid atherosclerosis. Methods: A total of 68 patients who were diagnosed with carotid artery atherosclerosis in Puren Hospital of Wuhan City between June 2014 and December 2016 were selected as AS group and 80 healthy volunteers who received physical examination during the same period were selected as control group. Peripheral blood mononuclear cells were collected to detect the expression of IRFs, and serum was collected to detect the levels of cytokines and plaque stability indicators. Results: IRF1 and IRF8 mRNA expression in peripheral blood mononuclear cells of AS group were significantly higher than those of control group while IRF2 and IRF4 mRNA expression were significantly lower than those of control group; serum IFN-γ, IL-2, IL-17, IL-22, MCP-1, ox- LDL, MMP9 and Caspase-3 levels of AS group were significantly higher than those of control group, positively correlated with IRF1 and IRF8 mRNA expression, and negatively correlated with IRF2 and IRF4 mRNA expression; IL-4, IL-10 and TGF-β levels were significantly lower than those of control group, negatively correlated with IRF1 and IRF8 mRNA expression, and positively correlated with RF2 and IRF4 mRNA expression. Conclusions: The high expression of IRF1 and IRF8 and the low expression of IRF2 and IRF4 in patients with carotid atherosclerosis will reduce the plaque stability and affect the Th1/Th2/Th17/Treg differentiation.

An unusual high-valent Sb(V)-based unit [SbL2]− (L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol) was developed for the first time to combine with various cuprous-halide clusters for the construction of a brand-new class of heterometallic MOFs. This work not only promotes the limited development of Sb-based MOFs, but also provides a practical strategy for developing new types of composite materials.

A series of 3D porous lanthanide-substituted polyoxometalate frameworks, Na

Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β-cell function are controlled by the ATP-dependent Swi/Snf chromatin remodeling coregulatory complex that physically associates with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, was necessary to compromise adult islet β-cell activity, which included whole-animal glucose intolerance, hyperglycemia, and impaired insulin secretion. Notably, lineage-tracing analysis revealed Swi/Snf-deficient β-cells lost the ability to produce the mRNAs for Ins and other key metabolic genes without effecting the expression of many essential islet-enriched transcription factors. Swi/Snf was necessary for Pdx1 to bind to the Ins gene enhancer, demonstrating the importance of this association in mediating chromatin accessibility. These results illustrate how fundamental the Pdx1:Swi/Snf coregulator complex is in the pancreas, and we discuss how disrupting their association could influence type 1 and type 2 diabetes susceptibility.

This work demonstrates a new Lindqvist-like [FeIII6(μ6-O)L4Cl6]2- (Fe6, L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol) cluster for the construction of a novel class of Fe-cluster organic frameworks. The novel Fe6 cluster can be used to build not only a homometallic MOF, but also a heterometallic MOF by introducing copper halide clusters to the reaction system. In particular, the heterometallic MOF achieved a skillful combination of Fe6 SBU and cuprous-halide clusters for the first time. Our synthesis strategy opens up an effective avenue to novel Fe-cluster-based MOF materials.