HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.

GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.

Accumulating evidence suggests that prenatal stress (PNS) increases offspring susceptibility to depression, but the underlying mechanisms remain unclear. We constructed a mouse model of prenatal stress by spatially restraining pregnant mice from 09:00-11:00 daily on Days 5-20 of gestation. In this study, western blot analysis, quantitative real-time PCR (qRT‒PCR), immunofluorescence, immunoprecipitation, chromatin immunoprecipitation (ChIP), and mifepristone rescue assays were used to investigate alterations in the GR/P300-MKP1 and downstream ERK/CREB/TRKB pathways in the brains of prenatally stressed offspring to determine the pathogenesis of the reduced neurogenesis and depression-like behaviors in offspring induced by PNS. We found that prenatal stress leads to reduced hippocampal neurogenesis and depression-like behavior in offspring. Prenatal stress causes high levels of glucocorticoids to enter the fetus and activate the hypothalamic‒pituitary‒adrenal (HPA) axis, resulting in decreased hippocampal glucocorticoid receptor (GR) levels in offspring. Furthermore, the nuclear translocation of GR and P300 (an acetylation modifying enzyme) complex in the hippocampus of PNS offspring increased significantly. This GR/P300 complex upregulates MKP1, which is a negative regulator of the ERK/CREB/TRKB signaling pathway associated with depression. Interestingly, treatment with a GR antagonist (mifepristone, RU486) increased hippocampal GR levels and decreased MKP1 expression, thereby ameliorating abnormal neurogenesis and depression-like behavior in PNS offspring. In conclusion, our study suggested that the regulation of the MKP1 signaling pathway by GR/P300 is involved in depression-like behavior in prenatal stress-exposed offspring and provides new insights and ideas for the fetal hypothesis of mental health.

Precise diagnosis and risk stratification of prostate cancer by comprehensive serum metabolic fingerprints: a prediction model study.

OBJECTIVES: Prostate cancer (PCa) is one of the most common malignancies in men worldwide and has caused increasing clinical morbidity and mortality, making timely diagnosis and accurate staging crucial. The authors introduced a novel approach based on mass spectrometry for precise diagnosis and stratification of PCa to facilitate clinical decision-making. METHODS: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of trace blood samples was combined with machine learning algorithms to construct diagnostic and stratification models. A total of 367 subjects, comprising 181 with PCa and 186 with non-PCa were enrolled. Additional 60 subjects, comprising 30 with PCa and 30 with non-PCa were enrolled as an external cohort for validation. Subsequent metabolomic analysis was carried out using Autoflex MALDI-TOF, and the mass spectra were introduced into various algorithms to construct different models. RESULTS: Serum metabolic fingerprints were successfully obtained from 181 patients with PCa and 186 patients with non-PCa. The diagnostic model based on the eight signals demonstrated a remarkable area under curve of 100% and was validated in the external cohort with the area under curve of 87.3%. Fifteen signals were selected for enrichment analysis, revealing the potential metabolic pathways that facilitate tumorigenesis. Furthermore, the stage prediction model with an overall accuracy of 85.9% precisely classified subjects with localized disease and those with metastasis. The risk stratification model, with an overall accuracy of 89.6%, precisely classified the subjects as low-risk and high-risk. CONCLUSIONS: Our study facilitated the timely diagnosis and risk stratification of PCa and provided new insights into the underlying mechanisms of metabolic alterations in PCa.

GR/Ahi1 regulates WDR68-DYRK1A binding and mediates cognitive impairment in prenatally stressed offspring.

Accumulating research shows that prenatal exposure to maternal stress increases the risk of behavioral and mental health problems for offspring later in life. However, how prenatal stress affects offspring behavior remains unknown. Here, we found that prenatal stress (PNS) leads to reduced Ahi1, decreased synaptic plasticity and cognitive impairment in offspring. Mechanistically, Ahi1 and GR stabilize each other, inhibit GR nuclear translocation, promote Ahi1 and WDR68 binding, and inhibit DYRK1A and WDR68 binding. When Ahi1 deletion or prenatal stress leads to hyperactivity of the HPA axis, it promotes the release of GC, leading to GR nuclear translocation and Ahi1 degradation, which further inhibits the binding of Ahi1 and WDR68, and promotes the binding of DYRK1A and WDR68, leading to elevated DYRK1A, reduced synaptic plasticity, and cognitive impairment. Interestingly, we identified RU486, an antagonist of GR, which increased Ahi1/GR levels and improved cognitive impairment and synaptic plasticity in PNS offspring. Our study contributes to understanding the signaling mechanisms of prenatal stress-mediated cognitive impairment in offspring.

The synergistic effect of metal ions and amino acids on the fermentation of ß-CGTase-producing statin DF257.

To meet the growing demand of ß-cyclodextrin (CD), innovative approaches are being developed to improve the production of ß-CD by ß-cyclodextrin glucose-transferase (CGTase). Considering the low production and efficacy of wild-type ß-CGTase-producing strains, to obtain the strains suitable for industrial production of ß-CGTase, the recombinant engineered bacteria strain DF257 is constructed by transfecting with the plasmid expressing His tagged ß-CGTase. The fermentation of ß-CGTase-expressing DF257 was optimized in the presence of different metal ions, amino acids, and incubated at a certain temperature and pH condition. The results showed that when Mg2+ and isoleucine were added into the culture medium at 0.5 mM and 0.5 g/L, respectively, the enzyme activity of ß-CGTase increased significantly after incubation at 37 °C with the initial pH of 7.5. In addition, the optimal temperature for ß-CGTase with the addition of Mg2+ and isoleucine was also determined. The T half of ß-CGTase under 50, 55, 60 and 65 °C was 9.5, 8.8, 6.2 and 1.2 h, respectively. Further investigation showed that ß-CGTase kept stable under the pH 6.0-10.0, and pH 7.5 was identified as the optimal pH condition of ß-CGTase. With the addition of Mg2+ and isoleucine, the kinetic properties of ß-CGTase in the cyclization reaction had a similar form with Michaelis equation under 50 °C and pH 7.5, and Vmax, Km, and Kcat was 3.74 mg/mL/min, 3.28 mg/mL, and 31.17/s, respectively. The possible underlying mechanism by which Mg2+ and isoleucine synergistically improved the thermostability of ß-CGTase was investigated by the surface hydrophobicity index analysis, Fourier transform infrared spectroscopy and differential scanning calorimetry (DSC) analysis. The results indicated that addition of Mg2+ and isoleucine maintained the spatial structure and enhanced the thermostability of ß-CGTase. These findings provided a theoretical basis for realizing the industrialization application of ß-CGTase in promoting the generation of ß-CD.

Efficient Lithium/Sodium-Ion Storage by Core-Shell Carbon Nanospheres@TiO2 Decorate by Epitaxial WSe2 Nanosheets Derived from Bimetallic Polydopamine Composites.

Metal-polydopamine coordination chemistry attracts great attention owing to the synergistic effect of adjustable components and advantageous structures. However, few efforts have been devoted to exploring bimetal-polydopamine composites, especially for multistructural composites with high-capacity components and high stability. In this regard, the TiO2 @C-WSe2 core-shell nanospheres are designed and fabricated based on Ti-W-polydopamine composites after selenization, in which the TiO2 nanoparticles are encapsulated or embedded in the carbon nanospheres and the external WSe2 nanosheets are grown epitaxially on the carbon surfaces, featuring multiple channels for ion diffusion and abundant active edges for electrochemical reactions. The introduction of WSe2 not only greatly improves the capacity but also results in exponential growth of the active edge. As a result, the as-prepared TiO2 @C-WSe2 displayed long-term cycling performance in lithium-ion batteries. Furthermore, the anode is assembled into sodium-ion batteries, manifesting a stable capacity of 352 mA h g-1 at 1.0 A g-1 even after 2000 cycles, one of the best performances for polydopamine-based composites. Enhanced performance can be attributed to the synergies of high-capacity components and different dimensional materials. This work highlights that the rational design of functional structures provides a novel inspiration for electrodes with effective nanoarchitectures.

Synergistic Effects in Ultrafine Molybdenum-Tungsten Bimetallic Carbide Hollow Carbon Architecture Boost Hydrogen Evolution Catalysis and Lithium-Ion Storage.

Constructing hierarchical heterostructures is considered a useful strategy to regulate surface electronic structure and improve the electrochemical kinetics. Herein, the authors develop a hollow architecture composed of MoC1- x and WC1- x carbide nanoparticles and carbon matrix for boosting electrocatalytic hydrogen evolution and lithium ions storage. The hybridization of ultrafine nanoparticles confined in the N-doped carbon nanosheets provides an appropriate hydrogen adsorption free energy and abundant boundary interfaces for lithium intercalation, leading to the synergistically enhanced composite conductivity. As a proof of concept, the as-prepared catalyst exhibits outstanding and durable electrocatalytic performance with a low overpotential of 103 and 163 mV at 10 mA cm-2 , as well as a Tafel slope of 58 and 90 mV dec-1 in alkaline electrolyte and acid electrolyte, respectively. Moreover, evaluated as an anode for a lithium-ion battery, the as-resulted sample delivers a rate capability of 1032.1 mA h g-1 at 0.1 A g-1 . This electrode indicates superior cyclability with a capability of 679.1 mA h g-1 at 5 A g-1 after 4000 cycles. The present work provides a strategy to design effective and stable bimetallic carbide composites as superior electrocatalysts and electrode materials.

In-Situ growing tungsten Sulfide/Carbon nanosheets on sodium titanate nanorods to stabilize Surface-Structure for enhanced Sodium-ion storage.

Sodium-ions hybrid capacitors (SIHCs) have been recognized as one of the most potential energy storage devices, which can deliver high power and energy densities simultaneously. However, the sluggish kinetics of electrode materials severely restricts the performance of SIHCs. Herein, N, P-codoped carbon and WS2 nanosheets coating on sodium titanate nanorods (NTO@WS2/N, PC) were first designed by in-situ growing process and sulfuration treatment for boosting sodium-ion storage. Specifically, NTO@WS2/N, PC electrodes displayed a satisfactory specific capacity of 274.7 mAh g-1 at 3.0 A g-1 after 1200 cycles. Furthermore, as-assembled SIHCs delivered high-energy density of 112.1 Wh kg-1 and high-power density of 4334.4 W kg-1. Besides, long-term cycling test revealed that a remarkable capacity retention rate of 89.7% was obtained at 8.0 A g-1 after 2000 cycles. The excellent cycling stability and rate property could be ascribed to following aspects. On the one hand, N, P-codoped carbon could enhance the electrical conductivity and strengthen the structural integrality of the composites. On the other hand, ultrathin WS2 nanosheets and one-dimensional (1D) NTO nanorods structure were conducive to the rapid diffusion of Na+. This work provides a convenient technique to stabilize the structure of electrode materials, which can promote the practical application of SIHCs.

Boosting lithium-ion storage performance by ultrafine bimetal carbides nanoparticles coupled with Hollow-like carbon composites.

Metallic carbides demonstrated tremendous application potential in energy conversion field deriving from their distinctive electrochemical activity and chemical stability. Herein, a molybdenum-based hybrid self-template strategy was adopted to confine ultrafine molybdenum carbides and tungsten carbides nanoparticles in N, P-codoped carbon nanotubes (MoC/WC@N, P-CNTs) for enhanced lithium-ion storage. Specifically, hierarchical MoW-polydopamine nanotubes were prepared via a self-template strategy, which employed Mo3O10(C6H8N)2·2H2O nanowires as the template. Ultrafine MoC and WC nanoparticles embedded in ultrathin carbon nanosheets could be obtained rationally after carbonization treatment, which could not only prevent carbides nanoparticles from agglomeration and oxidation, but also endow the rapid electron transfer rate. Thus, MoC/WC@N, P-CNTs displayed outstanding lithium storage abilities with great rate property and long-term cycling durability. The stable specific capacity of 475.0 mAh g-1 could be preserved at high current intensity of 5.0 A g-1 after 1000 cycles, which was one of the best performances for metal carbides anodes. Furthermore, the successful fabrication of lithium-ion hybrid capacitors (LIHCs) delivered the maximum energy density of 117 Wh kg-1 and power density of 6571 W kg-1. Moreover, the superior capacity retention of 89.7 % after 2000 cycles also indicated the excellent cycling stability. The present work highlights a self-template strategy for designing nanostructures toward efficient energy storage and conversion fields.

Hierarchical core/shell titanium dioxide/molybdenum disulfide nanosheets coupled with carbon architecture for superior lithium/sodium ion storage.

The peculiar core/shell structure with abundant interfaces is favorable for Li+/Na+ storage, which can elevate the efficiency of energy storage and conversion. Herein, a unique core/shell structure composite with diverse interfaces was successfully designed and fabricated via a facile coordination reaction combined with thermal treatment. Specially, well-crystallized TiO2 nanoparticles were encapsulated and embedded in carbon nanospheres wrapped with MoS2 nanosheets, leading to abundant interfacial structure and boundaries. Benefitting from the synergistic effect between numerous interfaces and distinctive hierarchal core/shell structure, such a hybrid material possesses fascinating features including ultrafast ion diffusion, plentiful storage active sites and prominent electric conductivity. As a proof of concept, as-prepared samples demonstrated superior reversible lithium storage capacity and hybrid lithium-ion capacitor. What is more, when the material was acted as anode material for SIBs, the discharge capacity maintained at a high capacity of 267.2 mA h g-1 after 1000 cycles at 2.0 A g-1. This work highlights a convenient strategy to synthesize other hybrid materials for electrode materials of energy storage and conversion applications.

SiC Nanowire-Si3N4 Nanobelt Interlocking Interfacial Enhancement of Carbon Fiber Composites with Boosting Mechanical and Frictional Properties.

Carbon fiber composites composed of carbon fiber and pyrolytic carbon (PyC) matrix have great potential application in the brakes of aircrafts, where the combination of high mechanical strength and excellent frictional properties are required. In this work, two-component silicon-based interlocking enhancements were designed and constructed into carbon fiber composites for boosting the mechanical and frictional properties. Specially, silicon carbide nanowires (SiCnws) and silicon nitride nanobelts (Si3N4nbs) could form interlocking architectures, where SiCnws are rooted firmly on the carbon fiber surface in the radial direction and Si3N4nbs integrate the PyC matrix with carbon fibers together via a networked shape. SiCnws-Si3N4nbs not only refine the PyC matrix but also promote the bonding of the fiber/matrix interface and the cohesion strength of the PyC matrix, thus enhancing the mechanical and frictional properties. Benefiting from the SiCnws-Si3N4nbs synergistic effect and interlocking enhancement mechanism, the interlaminar shear strength and compressive strength of carbon fiber composites increased by 88.41% and 73.40%, respectively. In addition, the friction coefficient and wear rate of carbon fiber composites decreased by 39.50% and 69.88%, respectively. This work could open up an interlocking enhancement strategy for efficiently fabricating carbon fiber composites and promoting mechanical and frictional properties that could be used in the brakes of aircrafts.

Melamine-assisted synthesis of porous V2O3/N-doped carbon hollow nanospheres for efficient sodium-ion storage.

Vanadium-based oxides with relatively high theoretical capacity have been regarded as promising electrode materials for boosting energy conversion and storage. However, their poor electrical conductivity usually leads to unsatisfied performance and poor cycling stability. Herein, uniform V2O3/N-doped carbon hollow nanospheres (V2O3/NC HSs) with mesoporous structures were successfully synthesized through a melamine-assisted simple hydrothermal reaction and carbonization treatment. We demonstrated that the introduction of melamine played an essential role in the construction of V2O3/NC HSs. Benefitting from the special mesoporous structure and large specific surface area, the as-obtained sample exhibited enhanced conductivity and structural stability. As a proof of concept, well-defined V2O3/NC HSs exhibited excellent cycling stability and rate performance for sodium-ion batteries, and achieved a discharge capacity of 263.8 mA h g-1 at a current density of 1.0 A g-1 after 1000 cycles, one of the best performances of V-based compounds. The enhanced performance could be attributed to the synergistic effect of the hollow structure and surface carbon coating. The present work describes the design of the morphology and structure of vanadium-based oxides for energy storage devices.

Facile Construction of Metal Phosphides (MP, M = Co, Ni, Fe, and Cu) Wrapped in Three-Dimensional N,P-Codoped Carbon Skeleton toward Highly Efficient Hydrogen Evolution Catalysis and Lithium-Ion Storage.

Transition metal phosphides (TMPs) have been demonstrated for prospective applications in electrocatalytic reaction and energy conversion owing to their specialties of catalytic activity and superhigh theoretical capacity. Herein, a facile and robust strategy for confining phosphides in a three-dimensional N,P-codoped carbon skeleton was achieved through a simple evaporation method. After calcination treatment, metal phosphide nanoparticles (MP, M = Co, Ni, Fe, and Cu) were successfully encapsulated in an interconnected N,P-codoped carbon network, which not only endowed high electrical conductivity and electrochemical stability but also provided more active sites and ion diffusion channels. As-prepared CoP@N,P-C exhibited satisfactory hydrogen evolution reaction activity, displaying lower overpotential of 140 and 197 mV at 10.0 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH, respectively. Moreover, CoP@N,P-C also delivered satisfactory lithium-ion storage properties. A higher specific capacity of 604.9 mAh g-1 was retained after 1000 cycles at 0.5 A g-1, one of the best reported performances of CoP-based anode materials. This work highlights a facile pathway to encapsulate metal phosphides in a conductive carbon skeleton, which is suitable for scaled-up production of bifunctional composites for efficient energy storage and conversion.

[Comparative study on anti-inflammatory and immunomodulation of different Isatidis Radix strains growing in Gansu Province].

OBJECTIVE: To investigate anti-inflammatory and immunomodulation effects of different ecotype from Isatidis Radix growing in Gansu province. METHODS: Mice were randomly divided into 6 groups (n=11)and used the auricular swelling and paw edema to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 7 groups (n=11) and through the gasbag synovitis model to observe the anti-inflammatory effects of Isatidis Radix; Mice were randomly divided into 6 groups (n=11), the immunosuppressed model were established by injection of cyclophosphamide (CTX) to study the effects of Isatidis Radix on index of thymus, blood routine and cytokines. RESULTS: Gansu different ecotype from Isatidis Radix could reduce the swelling of the mice auricle, paw edema and total protein, leukotriene B4(LTB4)and malonaldehyde(MDA) in airbag synovitis exudates, and upgrade serum levels of superoxide dismutase (SOD); Degrade the tumor necrosis factor-α (TNF-α) and upgrade the index of thymus, the number of red and white corpuscles, the level of interferon-γ (IFN-γ), interleukin-4 (IL-4) (P<0.05, 0.01) of mice immunosuppressed model; Above the research of anti-inflammatory and immunomodulation, there were no significant differences between Isatidis Radix of Gansu different ecotype and tetraploid. CONCLUSIONS: Different ecotype of Isatidis Radix has obvious functions in anti-inflammatory and immunomodulation, but there are no significant differences between Gansu different ecotype and tetraploid.

[Field evaluation of a novel plant molluscicide "Luo-wei" against Oncomelania hupensis snails II molluscicidal effect in the field of lake areas in Hanchuan City, Hubei Province].

OBJECTIVE: To evaluate the effect of a novel plant molluscicide "Luo-wei" (Tea-seed distilled saponins, TDS) against Oncomelania hupensis in the field of lake areas in Hanchuan City, Hubei Province. METHODS: Immersing experiment and spraying experiment were carried out in 5 ditches and a beach land respectively in Hanchuan City, Hubei Province to compare the molluscicidal effects among 4% TDS, 50% wettable powder of niclosamide ethanolamine salt (WPN), and 26% suspension concentrate of metaldehyde and niclosamide (MNSC) by different dosages and time. The chi2 test or Fish's exact test was used to examine the differences of snail death rates among them. RESULTS: After 72 h of immersing experiment, the snail death rates in the 2.5 g/m3 TDS group, 3.0 g/m3 TDS group, 2.0 g/m3 WPN group and 2.0 g/m3 MNSC group were 99.33%, 100%, 100%, and 100%, respectively, and there was no significant difference among them (P > 0.05). By the end of 15 d after the spraying experiments, the snail death rates were 91.86% in the 2.0 g/m2 MNSC group, 90.26% in the 5.0 g/m2 TDS group, 87.45% in the 2 g/m2 WPN group, and 86.10% in the 3 g/m2 TDS group. The differences between the 5.0 g/m2 TDS group and 2.0 g/m2 MNSC group, as well as the 3.0 g/m2 TDS group and the 2.0 g/m2 WPN group had no statistical significance (both P > 0.05). CONCLUSIONS: The molluscicidal effect of TDS is similar to that of WPN or MNSC. The recommended dosage of TDS is 2.5 g/m3 for immersing or 5 g/ m2 for spraying in the field.