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Abstract Alzheimer’s disease (AD) is the leading form of dementia, characterized by the accumulation and aggregation of amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) is an ion channel involved in diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), an activator of TRPV2, improves microglial amyloid-β (Aβ) phagocytosis by TRPV2 modulation. However, the molecular mechanism of TRPV2 in microglial Aβ phagocytosis remains unknown. In this study, we aimed to investigate the involvement of TRPV2 channel in microglial Aβ phagocytosis and the underlying mechanisms. Utilizing human datasets, mouse primary neuron and microglia cultures, and AD model mice, to evaluate TRPV2 expression and microglial Aβ phagocytosis in both in vivo and in vitro. TRPV2 was expressed in cortex, hippocampus, and microglia.Cannabidiol (CBD) could activate and sensitize TRPV2 channel. Short-term CBD (1 week) injection intraperitoneally (i.p.) reduced the expression of neuroinflammation and microglial phagocytic receptors, but long-term CBD (3 week) administration (i.p.) induced neuroinflammation and suppressed the expression of microglial phagocytic receptors in APP/PS1 mice. Furthermore, the hyper-sensitivity of TRPV2 channel was mediated by tyrosine phosphorylation at the molecular sites Tyr(338), Tyr(466), and Tyr(520) by protein tyrosine kinase JAK1, and these sites mutation reduced the microglial Aβ phagocytosis partially dependence on its localization. While TRPV2 was palmitoylated at Cys 277 site and blocking TRPV2 palmitoylation improved microglial Aβ phagocytosis. Moreover, it was demonstrated that TRPV2 palmitoylation was dynamically regulated by ZDHHC21. Overall, our findings elucidated the intricate interplay between TRPV2 channel regulated by tyrosine phosphorylation/dephosphorylation and cysteine palmitoylation/depalmitoylation, which had divergent effects on microglial Aβ phagocytosis. These findings provide valuable insights into the underlying mechanisms linking microglial phagocytosis and TRPV2 sensitivity, and offer potential therapeutic strategies for managing AD.

ABSTRACT Background After acute myocardial infarction (AMI), it is common to observe new‐onset atrial fibrillation (NOAF), which is often related to a negative prognosis. Some P‐wave variables (P‐wave duration [PWD], P‐wave amplitude, and interatrial block [IAB]), reflecting the process of electrical and structural remodeling, could predict the risk of atrial fibrillation (AF). This study aimed to assess the predictive value of P‐wave variables for post‐AMI NOAF. Methods We retrospectively analyzed 1581 AMI patients with no prior AF, using follow‐up data from January 2023 to January 2024. P‐wave variables were measured, and patients were grouped based on in‐hospital NOAF occurrence. Results Overall, 164 (10.3%) of the 1581 patients had NOAF. The age (61.08 ± 12.02 vs. 67.91 ± 11.60, p 1 (25.3% vs. 55.5%, p

BackgroundThe yearly escalation in hypertension prevalence signifies a noteworthy public health challenge. Adhering to a nutritious diet is crucial for enhancing the quality of life among individuals managing hypertension. However, the relationship between vitamin C and hypertension, as well as homocysteine, remains unclear.ObjectiveThe primary aim of this investigation was to scrutinize the potential mediating role of Vitamin C in the association between homocysteine levels and blood pressure, utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES) database.MethodsA total of 7,327 participants from the NHANES 2003–2006 were enrolled in this cross-sectional survey. The main information was obtained using homocysteine, Vitamin C, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Correlation analysis was used to assess the correlation between homocysteine, SBP, DBP and vitamin C. Linear regression analysis was utilized to determine the β value (β) along with its 95% confidence intervals (CIs). Mediation analysis was performed to investigate whether the relationship between homocysteine and blood pressure was mediated by Vitamin C, and to quantify the extent to which Vitamin C contributed to this association.ResultsThe results manifested that the homocysteine was positively associated with SBP (r = 0.24, p

Abstract Objective To evaluate the incidence, clinical laboratory characteristics, and gene mutation spectrum of Ph‐negative MPN patients with atypical variants of JAK2, MPL, or CALR. Methods We collected a total of 359 Ph‐negative MPN patients with classical mutations in driver genes JAK2, MPL, or CALR, and divided them into two groups based on whether they had additional atypical variants of driver genes JAK2, MPL, or CALR: 304 patients without atypical variants of driver genes and 55 patients with atypical variants of driver genes. We analyzed the relevant characteristics of these patients. Results This study included 359 patients with Ph‐negative MPNs with JAK2, MPL, or CALR classical mutations and found that 55 (15%) patients had atypical variants of JAK2, MPL, or CALR. Among them, 28 cases (51%) were male, and 27 (49%) were female, with a median age of 64 years (range, 21–83). The age of ET patients with atypical variants was higher than that of ET patients without atypical variants [70 (28–80) vs. 61 (19–82), p = 0.03]. The incidence of classical MPL mutations in ET patients with atypical variants was higher than in ET patients without atypical variants [13.3% (2/15) vs. 0% (0/95), p = 0.02]. The number of gene mutations in patients with atypical variants of driver genes PV, ET, and Overt‐PMF is more than in patients without atypical variants of PV, ET, and Overt‐PMF [PV: 3 (2–6) vs. 2 (1–7), p

The utilization of lithium–sulfur battery is hindered by various challenges, including the “shuttle effect”, limited sulfur utilization, and the sluggish conversion kinetics of lithium polysulfides (LiPSs). In the present work, a theoretical design for the viability of graphitic carbon nitride (g-C3N4) and phosphorus-doping graphitic carbon nitride substrates (P-g-C3N4) as promising host materials in a Li-S battery was conducted utilizing first-principles calculations. The PDOS shows that when the P atom is introduced, the 2p of the N atom is affected by the 2p orbital of the P atom, which increases the energy band of phosphorus-doping substrates. The energy bands of PC and Pi are 0.12 eV and 0.20 eV, respectively. When the lithium polysulfides are adsorbed on four substrates, the overall adsorption energy of PC is 48–77% higher than that of graphitic carbon nitride, in which the charge transfer of long-chain lithium polysulfides increase by more than 1.5-fold. It is found that there are powerful Li-N bonds between lithium polysulfides and P-g-C3N4 substrates. Compared with the graphitic carbon nitride monolayer, the anchoring effect of the LiPSs@P-g-C3N4 substrate is enhanced, which is beneficial for inhibiting the shuttle of high-order lithium polysulfides. Furthermore, the catalytic performance of the P-g-C3N4 substrate is assessed in terms of the S8 reduction pathway and the decomposition of Li2S; the decomposition energy barrier of the P-g-C3N4 substrate decrease by 10% to 18%. The calculated results show that P-g-C3N4 can promote the reduction of S8 molecules and Li-S bond cleavage within Li2S, thus improving the utilization of sulfur-active substances and the ability of rapid reaction kinetics. Therefore, the P-g-C3N4 substrates are a promising high-performance lithium-sulfur battery anchoring material.

Several cases such as myeloproliferative neoplasms (MPN) with the coexistence of JAK2 and BCR-ABL have been reported. However, cases of transformation of essential thrombocythemia (ET) into chronic myeloid leukemia (CML) during the disease progression were rarely reported. Here, we report the case of a patient with JAK2 V617F- positive ET who subsequently acquired BCR–ABL1, which transformed the disease into CML after 10 years from the initial diagnosis. In this study, we dynamically monitored JAK2 V617F and BCR-ABL and observed multiple gene mutations, including IDH2, IDH1, ASXL1, KRAS, and RUNX1. It is important to be aware of this potentially clone evolution in disease progression.

Nanostructure silicon is one of the most promising anode materials for the next-generation lithium-ion battery, but the complicated synthesis process and high cost limit its large-scale commercial application. Herein, a simple and low-cost method was proposed to prepare silicon nanofibers (SNF) using natural sepiolite as a template via a low-temperature aluminum reduction process. The low temperature of 260°C during the reduction process not only reduced the production cost but also avoided the destruction of the natural sepiolite structure caused by the high temperature above 600°C in the traditional magnesium thermal reduction process, leading to a more complete nanofiber structure in the final product. For the first time, the important role of Mg-O octahedral structure in the maintenance of nanofiber structure during the process of low-temperature aluminothermic reduction was verified by experiments. When used as an anode for lithium-ion batteries, SNF yield a high reversible capacity of 2005.4 mAh g−1 at 0.5 A g−1 after 50 cycles and 1017.6 mAh g−1 at 2 A g−1 after 200 cycles, remarkably outperforming commercial Si material. With a low-cost precursor and facile approach, this work provides a new strategy for the synthesis of a commercial high-capacity Si anode.

The low cycle performance and low Coulomb efficiency of tin-based materials confine their large–scale commercial application for lithium–ion batteries. To overcome the shortage of volume expansion of pristine tin, Sn–Co alloy/rGO composites have been successfully synthesized by chemical reduction and sintering methods. The effects of sintering temperature on the composition, structure and electrochemical properties of Sn–Co alloy/rGO composites were investigated by experimental study and first-principles calculation. The results show that Sn–Co alloys are composed of a large number of CoSn and trace CoSn2 intermetallics, which are uniformly anchored on graphene nanosheets. The sintering treatment effectively improves the electrochemical performance, especially for the first Coulomb efficiency. The first charge capacity of Sn–Co alloy/rGO composites sintered at 450 °C is 675 mAh·g−1, and the corresponding Coulomb efficiency reaches 80.4%. This strategy provides a convenient approach to synthesizing tin-based materials for high-performance lithium–ion batteries.

Alzheimer’s disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-β (Aβ) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon–dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking. The current review aimed to explain the mechanisms of the PDK1/Akt/TACE signaling axis that exerts its modulatory effect on AD physiopathology. We provide an overview of the neuropathological features, genetics, Aβ aggregation, Tau protein hyperphosphorylation, neuroinflammation, and aging in the AD brain. Additionally, we summarized the phosphoinositide 3-kinase (PI3K)/PDK1/Akt pathway-related features and its molecular mechanism that is dependent on TACE in the pathogenesis of AD. This study reviewed the relationship between the PDK1/Akt signaling pathway and AD, and discussed the role of PDK1/Akt in resisting neuronal toxicity by suppressing TACE expression in the cell membrane. This work also provides a perspective for developing new therapeutics targeting PDK1/Akt and TACE for the treatment of AD.

Urban green space soil heavy metal pollution seriously affected the lives of residents, and soil environmental quality data is important for urban planning and functional construction. In this study, the concentrations of arsenic (As), cadmium (Cd), chromium (Cr),copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn) in 148 soil samples collected from green spaces in Beijing City, China were measured. The mean concentrations were 7.60, 0.29, 50.32, 31.61, 1.53, 23.89, 29.68, and 76.53 mg/kg, respectively. With the exception of Ni, the concentrations of the seven other heavy metals were greater than their background values. Additionally, the concentration of Hg was 3.06 times greater than the Grade 2 value (0.5 mg/kg) of Environmental quality standard for soils in China (GB 15618-1995), also exceeded the limit value (1–1.5 mg/kg) for Hg in soil of European Union (86/278/EEC). Soil pollution assessment was carried out using the geoaccumulation index (Igeo), the $I_{{\rm geo}}$ value of Cd and Hg were 0.70 and 4.11, respectively. It suggested that, the green space soil of Beijing was slightly polluted by Cd and seriously polluted by Hg, which posed great harm to public health. A positive correlation exists between Cu and Hg, Pb, and Zn, as well as between Hg and Pb, suggesting the metals in the green space soils originated from similar sources. Multivariate statistical analysis, such as principal component analysis (PCA) and cluster analysis (CA), were adopted to identify heavy metal sources. The results suggest that the sources of heavy metals in Beijing green space soils differ. Cd, Cu, Hg, and Zn derived from vehicular transport; Cd and Cr originated from industrial activities and phosphate fertilisers; As and Ni mainly contributed by parent materials. The spatial distribution characteristics of the eight heavy metals varied greatly, and the presence of these metals was strongly associated with anthropogenic activities.

Extended line defect (ELD) graphene is a two-dimensional (2D) topologically defective graphene with alternate octagonal and quadrilateral carbon rings as basic defective units. This paper reports on the CH4 adsorption properties of ELD graphene according to the first principles of density functional theory (DFT). The effects on the CH4 adsorption of ELD graphene when modified by a single Mn atom or two Mn atoms were investigated, respectively. An ELD-42C graphene configuration consisting of 42 C atoms was first constructed. Then, the ELD-42C graphene configuration was used as a substrate, and a Mn-ELD-42C graphene configuration was obtained by modifying it with a single Mn atom. The results showed that the most stable adsorption site for Mn atoms was above the quadrilateral carbon ring. This Mn-ELD-42C graphene configuration could only stably adsorb up to 30 CH4 molecules on each side, with an average adsorption energy of −0.867 eV/CH4 and an adsorption capacity of 46.25 wt%. Three 2Mn-ELD-42C graphene configurations were then obtained by modifying the ELD-42C graphene substrate with two Mn atoms. When the two Mn atoms were located on either side of a 2Mn-ELD-42C graphene configuration and above the two octagonal carbon rings adjacent to the same quadrilateral carbon ring, it was able to adsorb up to 40 CH4 molecules on each side, with an average adsorption energy of −0.862 eV/CH4 and a CH4 adsorption capacity of 51.09 wt%.

A special gas-phase diffusion precipitation method with ammonia as the gas-phase diffusion precipitant was adopted. After fully reacting with different cobalt sources in a sealed space, the liquid funnel was separated and dried, and calcined at different temperatures for 2 h. The prepared Co3O4 powder was used as a supercapacitor (SCs) electrode to measure the electrochemical properties of the prepared material. The influences of different cobalt sources and sodium phosphate monobasic dehydrate on the preparation of Co3O4 SCs electrodes were investigated. The optimal performance of Co3O4 was 640 F·g−1 before modification, and this reached 1140 F·g−1 after modification, which was an improvement of 78.1%.

Lithium-sulfur batteries are very promising next-generation energy storage batteries due to their high theoretical specific capacity. However, the shuttle effect of lithium-sulfur batteries is one of the important bottlenecks that limits its rapid development. Herein, physical and chemical dual adsorption of lithium polysulfides are achieved by designing a novel framework structure consisting of MnO2, reduced graphene oxide (rGO), and carbon nanotubes (CNTs). The framework-structure composite of MnO2/rGO/CNTs is prepared by a simple hydrothermal method. The framework exhibits a uniform and abundant mesoporous structure (concentrating in ~12 nm). MnO2 is an α phase structure and the α-MnO2 also has a significant effect on the adsorption of lithium polysulfides. The rGO and CNTs provide a good physical adsorption interaction and good electronic conductivity for the dissolved polysulfides. As a result, the MnO2/rGO/CNTs/S cathode delivered a high initial capacity of 1201 mAh g−1 at 0.2 C. The average capacities were 916 mAh g−1, 736 mAh g−1, and 547 mAh g−1 at the current densities of 0.5 C, 1 C, and 2 C, respectively. In addition, when tested at 0.5 C, the MnO2/rGO/CNTs/S exhibited a high initial capacity of 1010 mAh g−1 and achieved 780 mAh g−1 after 200 cycles, with a low capacity decay rate of 0.11% per cycle. This framework-structure composite provides a simple way to improve the electrochemical performance of Li-S batteries.

The Akt kinase has been widely assumed for years as a key downstream effector of the PI3K signaling pathway in promoting neuronal survival. This notion was however challenged by the finding that neuronal survival responses were still preserved in mice with reduced Akt activity. Moreover, here we show that the Akt signaling is elevated in the aged brain of two different mice models of Alzheimer Disease. We manipulate the rate of Akt stimulation by employing knock-in mice expressing a mutant form of PDK1 (phosphoinositide-dependent protein kinase 1) with reduced, but not abolished, ability to activate Akt. We found increased membrane localization and activity of the TACE/ADAM17 α-secretase in the brain of the PDK1 mutant mice with concomitant TNFR1 processing, which provided neurons with resistance against TNFα-induced neurotoxicity. Opposite to the Alzheimer Disease transgenic mice, the PDK1 knock-in mice exhibited an age-dependent attenuation of the unfolding protein response, which protected the mutant neurons against endoplasmic reticulum stressors. Moreover, these two mechanisms cooperatively provide the mutant neurons with resistance against amyloid-beta oligomers, and might singularly also contribute to protect these mice against amyloid-beta pathology.

Among the popular electrochemical energy storage devices, supercapacitors (SCs) have attracted much attention due to their long cycle life, fast charge and discharge, safety, and reliability. Transition metal oxides are one of the most widely used electrode materials in SCs because of the high specific capacitance. Among various transition metal oxides, Co3O4 and related composites are widely reported in SCs electrodes. In this review, we introduce the synthetic methods of Co3O4, including the hydrothermal/solvothermal method, sol−gel method, thermal decomposition, chemical precipitation, electrodeposition, chemical bath deposition, and the template method. The recent progress of Co3O4-containing electrode materials is summarized in detail, involving Co3O4/carbon, Co3O4/conducting polymer, and Co3O4/metal compound composites. Finally, the current challenges and outlook of Co3O4 and Co3O4-containing composites are put forward.

Perylene diimide (PBI) had high thermal stability and solubility, so it could be used as a practical new type material of energy saving and environmental protection. The solubilization and photoelectrical properties of the bays can be effectively improved by introducing substituents in the bays. On the other hand, the imide group has a strong ability to absorb electrons, and the alkoxy group after the bay site substitution makes it easy to form micro-nano fiber in good and bad solvents. In other words, most of the properties of PBI derivatives are related to their ability to form micro-nano fiber. A systematic study of N, N' -isoctyl-1, 7-bis (octanoxy) perylene diimide (DFPBI) was carried out by UV-VIS spectrophotometry, thermogravimetry and fluorescence spectrophotometry. A number of test results show that DFPBI has better solubility and thermal stability than PBI, and can grow micro-nano fiber in both good and bad solvent systems. Therefore, DFPBI has broad application prospects in sensors. [ABSTRACT FROM AUTHOR]