FGF21 attenuates neuroinflammation following subarachnoid hemorrhage through promoting mitophagy and inhibiting the cGAS-STING pathway.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic. METHODS: To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed. RESULTS: Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH. CONCLUSION: Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.

Induced transformation of antimony trioxide by Mn(II) oxidation and their co-transformed mechanism.

Antimony (Sb) is a toxic and carcinogenic element that often enters soil in the form of antimony trioxide (Sb2O3) and coexists with manganese (Mn) in weakly alkaline conditions. Mn oxides such as birnessite have been found to promote the oxidative dissolution of Sb2O3, but few researches concerned the co-transformations of Sb2O3 and Mn(II) in environment. This study investigated the mutual effect of abiotic oxidation of Mn(II) and the coupled oxidative dissolution of Sb2O3. The influencing factors, such as Mn(II) concentrations, pH and oxygen were also discussed. Furthermore, their co-transformed mechanism was also explored based on the analysis of Mn(II) oxidation products with or without Sb2O3 using XRD, SEM and XPS. The results showed that the oxidative dissolution of Sb2O3 was enhanced under higher pH and higher Mn(II) loadings. With a lower Mn(II) concentration such as 0.01 mmol/L Mn(II) at pH 9.0, the improved dissolution of Sb2O3 was attributed to the generation of dissolved intermediate Mn(III) species with strong oxidation capacity. However, under higher Mn(II) concentrations, both amorphous Mn(III) oxides and intermediate Mn(III) species were responsible for promoting the oxidative dissolution of Sb2O3. Most released Sb (∼72%) was immobilized by Mn oxides and Sb(V) was dominant in the adsorbed and dissolved total Sb. Meanwhile, the presence of Sb2O3 not only inhibited the removal of Mn(II) by reducing Mn(III) to Mn(II) but also affected the final products of Mn oxides. For example, amorphous Mn oxides were formed instead of crystalline Mn(III) oxides, such as MnOOH. Furthermore, rhodochrosite (MnCO3) was formed with the high Mn(II)/Sb2O3 ratio, but without being observed in the low Mn(II)/Sb2O3 ratio. The results of study could help provide more understanding about the fate of Sb in the environment and the redox transformation of Mn.

The influence of water level fluctuations on the migration and enrichment of phosphorus in an agricultural groundwater system, Jianghan Plain.

The enrichment of phosphorus (P) in groundwater (GW) has been regarded as one of the most important sources of water eutrophication, but its sources and mechanisms have remained unclear. This study focused on hydraulic change show that drove the migration of P in an agricultural groundwater system, Jianghan Plain, Central China. Based on four rounds of field investigation over different seasons and across two consecutive years. Seasonable water table fluctuations (WLFs) reached 1.6 m and 3.8 m in GW and surface water (SW), respectively. Moreover, the concentrations of P in GW were obviously higher than those in SW where 54.1% of all GW samples presented higher content of P than the World Health Organization (WHO) limit of 0.4 mg/L with the highest one arriving to 1.97 mg/L. Although the trends and amplitudes varied at different points and depths, the spatial and temporal distribution of P corresponded with the local WLFs that were responsible for the enrichment of GW P. On the one hand, WLFs changed hydraulic conditions to enhance the migration of soluble P in the unsaturated zone into the aquifer. On the other hand, WLFs resulted in changes to the redox conditions or to the GW hydrochemical compositions, which promoted the dissolution of Fe or Mn containing P. These caused the release and enrichment of P in GW. Therefore, this study helps understand the geochemical cycling of P and improves GW management in the local GW system, Jianghan Plain.

Amorphous InGaZnO Thin-Film Transistors with Double-Stacked Channel Layers for Ultraviolet Light Detection.

Amorphous InGaZnO thin film transistors (a-IGZO TFTs) with double-stacked channel layers (DSCL) were quite fit for ultraviolet (UV) light detection, where the best DSCL was prepared by the depositions of oxygen-rich (OR) IGZO followed by the oxygen-deficient (OD) IGZO films. We investigated the influences of oxygen partial pressure (PO) for DSCL-TFTs on their sensing abilities by experiments as well as Technology Computer Aided Design (TCAD) simulations. With the increase in PO values for the DSCL depositions, the sensing parameters, including photogenerated current (Iphoto), sensitivity (S), responsivity (R), and detectivity (D*) of the corresponding TFTs, apparently degraded. Compared with PO variations for the OR-IGZO films, those for the OD-IGZO depositions more strongly influenced the sensing performances of the DSCL-TFT UV light detectors. The TCAD simulations showed that the variations of the electron concentrations (or oxygen vacancy (VO) density) with PO values under UV light illuminations might account for these experimental results. Finally, some design guidelines for DSCL-TFT UV light detectors were proposed, which might benefit the potential applications of these novel semiconductor devices.

Atmosphere Effect in Post-Annealing Treatments for Amorphous InGaZnO Thin-Film Transistors with SiOx Passivation Layers.

We investigated the electrical performance and positive bias stress (PBS) stability of the amorphous InGaZnO thin-film transistors (a-IGZO TFTs) with SiOx passivation layers after the post-annealing treatments in different atmospheres (air, N2, O2 and vacuum). Both the chamber atmospheres and the device passivation layers proved important for the post-annealing effects on a-IGZO TFTs. For the heat treatments in O2 or air, the larger threshold voltage (VTH) and off current (IOFF), smaller field-effect mobility (µFE), and slightly better PBS stability of a-IGZO TFTs were obtained. The X-ray photoemission spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) measurement results indicated that the oxygen atoms from the ambience led to less oxygen vacancies (VO) and more oxygen-related defects in a-IGZO after the heat treatments in O2 or air. For the annealing processes in vacuum or N2, the electrical performance of the a-IGZO TFTs showed nearly no change, but their PBS stability evidently improved. After 4500 seconds' stressing at 40 V, the VTH shift decreased to nearly 1 V. In this situation, the SiOx passivation layers were assumed to effectively prevent the oxygen diffusion, keep the VO concentration unchanged and refuse the oxygen-related defects into the a-IGZO films.

Phenol driven changes onto MnO2 surface for efficient removal of methyl parathion: The role of adsorption.

Manganese oxides (MnO2), important environmental oxides, have drawn significant attention in areas such as detoxification of micro-hazardous organic contaminants with electron-donating functional groups such as -OH. However, studies on whether these oxidized processes might further impact the fate of some esters like organophosphorus pesticide (OPPs) remain poorly understood. Herein, we propose a new mechanism involved in the enhanced removal of methyl parathion in mixtures of MnO2 and phenol. Specifically, the removal of methyl parathion (up to 73.7%) was significantly higher for a binary system than for MnO2 alone (approximately 9.3%) and was primarily due to adsorption rather than degradation. The extent of methyl parathion adsorption was dependent significantly on pH, reactant loading and metal ion co-solutes (such as Ca2+, Mg2+, Fe3+ and Mn2+). Both spectroscopic (FT-IR, SEM-EDX and XPS) and chromatographic (LC/HRMS) analyses showed that the remarkable increase in the number of organics (e.g., polymers) onto the MnO2 surface dominated methyl parathion adsorption via hydrogen bonding, n-π and π-π interactions, van der Waals forces and pore-diffusion. The results from this study provided evidence for the role of manganese oxides in adsorption of methyl parathion in soil-aquatic environments involving phenolic compounds.

Mechanisms of radical-initiated methylmercury degradation in soil with coexisting Fe and Cu.

Methylmercury (MeHg) is a toxic compound. It forms mainly in reducing environments, and then degrades through biogeochemical processes. Photodegradation and microorganism degradation of MeHg are among the processes that have been reported. However, little attention has been focused on the abiotic degradation of MeHg in soil/sediment without light. In our study, the percent MeHg of total Hg in Guangzhou soil in southern China was found to be variable and exhibited a significant negative correlation with the content of Fe or Cu where annite (KFe2+3(AlSi3O10)(OH)2), a Fe-bearing mineral, was identified. To understand the mechanisms of radical-initiated MeHg degradation by Fe/Cu-containing components, batch experiments were done. Results showed that annite in the soils could activate O2 to generate OH and O2- and facilitate MeHg degradation under oxic conditions. Meanwhile, Cu components in the soil further enhanced the production of O2-, and was oxidized to Cu(III) promoting degradation of MeHg directly. These findings help us understand that the distribution of MeHg in soil depends on not only external pollution sources, but also on biogeochemical processes in subsurface environments.

Single-nucleotide polymorphisms of LIG1 associated with risk of lung cancer.

To investigate the association of LIG1 with the risk of lung cancer, all subjects of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital-based case-control study. The case group consisted of 370 histologically diagnosed lung cancer patients; 314 controls were selected from cancer-free patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan real-time PCR method. All statistical analyses were performed with Statistical Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency of LIG1 rs1050298 SNP displayed significant difference between the case and the control group. Individuals carrying the LIG1 rs1050298 T genotype had higher risks of lung cancer, especially those with squamous cell carcinoma.