ß-1,4-Galactosyltransferase 1 protects against cerebral ischemia injury in mice by suppressing ferroptosis via the TAZ/Nrf2/HO-1 signaling pathway.

BACKGROUND: Ischemic stroke leads a primary cause of mortality in human diseases, with a high disability rate worldwide. This study aims to investigate the function of ß-1,4-galactosyltransferase 1 (B4galt1) in mouse brain ischemia/reperfusion (I/R) injury. METHODS: Recombinant human B4galt1 (rh-B4galt1) was intranasally administered to the mice model of middle cerebral artery occlusion (MCAO)/reperfusion. In this study, the impact of rh-B4galt1 on cerebral injury assessed using multiple methods, including the neurological disability status scale, 2,3,5-triphenyltetrazolium chloride (TTC), Nissl and TUNEL staining. This study utilized laser speckle Doppler flowmeter to monitor the cerebral blood flow. Western blotting was performed to assess the protein expression levels, and fluorescence-labeled dihydroethidium method was performed to determine the superoxide anion generation. Assay kits were used for the measurement of iron, malondialdehyde (MDA) and glutathione (GSH) levels. RESULTS: We demonstrated that rh-B4galt1 markedly improved neurological function, reduced cerebral infarct volume and preserved the completeness of blood-brain barrier (BBB) for preventing damage. These findings further illustrated that rh-B4galt1 alleviated oxidative stress, lipid peroxidation, as well as iron deposition induced by I/R. The vital role of ferroptosis was proved in brain injury. Furthermore, the rh-B4galt1 could increase the levels of TAZ, Nrf2 and HO-1 after I/R. And TAZ-siRNA and ML385 reversed the neuroprotective effects of rh-B4galt1. CONCLUSIONS: The results indicated that rh-B4galt1 implements neuroprotective effects by modulating ferroptosis, primarily via upregulating TAZ/Nrf2/HO-1 pathway. Thus, B4galt1 could be seen as a promising novel objective for ischemic stroke therapy.

Mechanistic insights into Fe3O4-mediated inhibition of H2S gas production in sludge anaerobic digestion.

The addition of iron-based conductive materials has been extensively validated as a highly effective approach to augment methane generation from anaerobic digestion (AD) process. In this work, it was additionally discovered that Fe3O4 notably suppressed the production of hazardous H2S gas during sludge AD. As the addition of Fe3O4 increased from 0 to 20 g/L, the accumulative H2S yields decreased by 89.2 % while the content of element sulfur and acid volatile sulfide (AVS) respectively increased by 55.0 % and 30.4 %. Mechanism analyses showed that the added Fe3O4 facilitated sludge conductive capacity, and boosted the efficiency of extracellular electron transfer, which accelerated the bioprocess of sulfide oxidation. Although Fe3O4 can chemically oxidize sulfide to elemental sulfur, microbial oxidation plays a major role in reducing H2S accumulation. Moreover, the released iron ions reacted with soluble sulfide, which promoted the chemical equilibrium of sulfide species from H2S to metal sulfide. Microbial analysis showed that some SRBs (i.e., Desulfomicrobium and Defluviicoccus) and SOB (i.e., Sulfuritalea) changed into keystone taxa (i.e., connectors and module hubs) in the reactor with Fe3O4 addition, showing that the functions of sulfate reduction and sulfur oxidation may play important roles in Fe3O4-present system. Fe3O4 presence also increased the content of functional genes encoding sulfide quinone reductase and flavocytochrome c sulfidedehydrogenase (e.g., Sqr and Fcc) that could oxidize sulfide to sulfur. The impact of other iron-based conductive material (i.e., zero-valent iron) was also verified, and the results showed that it could also significantly reduce H2S production. These findings provide new insights into the effect of iron-based conductive materials on anaerobic process, especially sulfur conversion.

Targeting IGF1/IGF1r signaling relieve pain and autophagic dysfunction in NTG-induced chronic migraine model of mice.

BACKGROUND: Chronic migraine is a severe and common neurological disorder, yet its precise physiological mechanisms remain unclear. The IGF1/IGF1r signaling pathway plays a crucial role in pain modulation. Studies have shown that IGF1, by binding to its receptor IGF1r, activates a series of downstream signaling cascades involved in neuronal survival, proliferation, autophagy and functional regulation. The activation of these pathways can influence nociceptive transmission. Furthermore, alterations in IGF1/IGF1r signaling are closely associated with the development of various chronic pain conditions. Therefore, understanding the specific mechanisms by which this pathway contributes to pain is of significant importance for the development of novel pain treatment strategies. In this study, we investigated the role of IGF1/IGF1r and its potential mechanisms in a mouse model of chronic migraine. METHODS: Chronic migraine was induced in mice by repeated intraperitoneal injections of nitroglycerin. Mechanical and thermal hypersensitivity responses were assessed using Von Frey filaments and radiant heat, respectively. To determine the role of IGF1/IGF1r in chronic migraine (CM), we examined the effects of the IGF1 receptor antagonist ppp (Picropodophyllin) on pain behaviors and the expression of calcitonin gene-related peptide (CGRP) and c-Fos. RESULT: In the nitroglycerin-induced chronic migraine model in mice, neuronal secretion of IGF1 is elevated within the trigeminal nucleus caudalis (TNC). Increased phosphorylation of the IGF1 receptor occurs, predominantly co-localizing with neurons. Treatment with ppp alleviated basal mechanical hypersensitivity and acute mechanical allodynia. Furthermore, ppp ameliorated autophagic dysfunction and reduced the expression of CGRP and c-Fos. CONCLUSION: Our findings demonstrate that in the chronic migraine (CM) model in mice, there is a significant increase in IGF1 expression in the TNC region. This upregulation of IGF1 leads to enhanced phosphorylation of IGF1 receptors on neurons. Targeting and inhibiting this signaling pathway may offer potential preventive strategies for mitigating the progression of chronic migraine.

Molecular Mechanism Underlying ROS-Mediated AKH Resistance to Imidacloprid in Whitefly.

Synthetic insecticides used to control Bemisia tabaci include organophosphorus, pyrethroids, insect growth regulators, nicotinoids, and neonicotinoids. Among these, neonicotinoids have been used continuously, which has led to the emergence of high-level resistance to this class of chemical insecticides in the whitefly, making whitefly management difficult. The adipokinetic hormone gene (AKH) and reactive oxygen species (ROS) play roles in the development of insect resistance. Therefore, the roles of AKH and ROS in imidacloprid resistance in Bemisia tabaci Mediterranean (MED; formerly biotype Q) were evaluated in this study. The expression level of AKH in resistant B. tabaci MED was significantly lower than that in sensitive B. tabaci (MED) (p < 0.05). AKH expression showed a decreasing trend. After AKH silencing by RNAi, we found that ROS levels as well as the expression levels of the resistance gene CYP6CM1 and its upstream regulatory factors CREB, ERK, and P38 increased significantly (p < 0.05); additionally, whitefly resistance to imidacloprid increased and mortality decreased (p < 0.001). These results suggest that AKH regulates the expression of resistance genes via ROS in Bemisia tabaci.

Exposure of polyethylene microplastics affects sulfur migration and transformation in anaerobic system.

Polyethylene (PE) microplastic, which is detected in various environmental media worldwide, also inevitably enters wastewater treatment plants, which may have an impact on anaerobic processes in wastewater treatment. In this work, the effect of PE microplastics on anaerobic sulfur transformation was explored. Experimental results showed that PE microplastics addition at 0.1%- 0.5% w/w promoted H2S production by 14.8%-27.4%. PE microplastics enhanced the release of soluble organic sulfur and inorganic sulfate, and promoted the bioprocesses of organosulfur compounds hydrolysis and sulfate reduction. Mechanism analysis showed that PE microplastics increased the content of electroactive components (e.g., protein and humic acids) contained in extracellular polymeric substances (EPS). In particular, PE microplastics increased the proportion and the dipole moment of α-helix, an important component involved in electron transfer contained in extracelluar protein, which provided more electron transfer sites and promoted the α-helix mediated electron transfer. These enhanced the direct electron transfer ability of EPSs, which might explain why PE microplastics facilitated the bioprocesses of organosulfur compounds hydrolysis and sulfate reduction. Correspondingly, metagenomic analysis revealed that PE microplastics increased the relative abundance of S2- producers (e.g., Desulfobacula and Desulfonema) and the relative abundance of functional genes involved in anaerobic sulfur transformation (e.g., PepD and cysD), which were beneficial to H2S production in anaerobic system.

The Impact of Bisphenol A on the Anaerobic Sulfur Transformation: Promoting Sulfur Flow and Toxic H2S Production.

Bisphenol A (BPA), as a typical leachable additive from microplastics and one of the most productive bulk chemicals, is widely distributed in sediments, sewers, and wastewater treatment plants, where active sulfur cycling takes place. However, the effect of BPA on sulfur transformation, particularly toxic H2S production, has been previously overlooked. This work found that BPA at environmentally relevant levels (i.e., 50-200 mg/kg total suspended solids, TSS) promoted the release of soluble sulfur compounds and increased H2S gas production by 14.3-31.9%. The tryptophan-like proteins of microbe extracellular polymeric substances (EPSs) can spontaneously adsorb BPA, which is an enthalpy-driven reaction (ΔH = -513.5 kJ mol-1, ΔS = -1.60 kJ mol-1K -1, and ΔG = -19.52 kJ mol-1 at 35 °C). This binding changed the composition and structure of EPSs, which improved the direct electron transfer capacity of EPSs, thereby promoting the bioprocesses of organic sulfur hydrolysis and sulfate reduction. In addition, BPA presence enriched the functional microbes (e.g., Desulfovibrio and Desulfuromonas) responsible for organic sulfur mineralization and inorganic sulfate reduction and increased the abundance of related genes involved in ATP-binding cassette transporters and sulfur metabolism (e.g., Sat and AspB), which promoted anaerobic sulfur transformation. This work deepens our understanding of the interaction between BPA and sulfur transformation occurring in anaerobic environments.

Shared metabolic shifts in endothelial cells in stroke and Alzheimer's disease revealed by integrated analysis.

Since metabolic dysregulation is a hallmark of both stroke and Alzheimer's disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabolic networks of the these diseases is still lacking. In this study, we integrated single-cell RNA sequencing datasets of ischemic stroke (IS), hemorrhagic stroke (HS) and AD models to construct metabolic flux profiles at the single-cell level. We discovered that the three disorders cause shared metabolic shifts in endothelial cells. These altered metabolic modules were mainly enriched in the transporter-related pathways and were predicted to potentially lead to a decrease in metabolites such as pyruvate and fumarate. We further found that Lef1, Elk3 and Fosl1 may be upstream transcriptional regulators causing metabolic shifts and may be possible targets for interventions that halt the course of neurodegeneration.

Revealing an unrecognized role of free ammonia in sulfur transformation during sludge anaerobic treatment.

Free ammonia (FA), the unionized form of ammonium, is presented in anaerobic fermentation of waste activated sludge (WAS) at high levels. However, its potential role in sulfur transformation, especially H2S production, during WAS anaerobic fermentation process was unrecognized previously. This work aims to unveil how FA affects anaerobic sulfur transformation in WAS anaerobic fermentation. It was found that FA significantly inhibited H2S production. With an increase of FA from 0.04 to 159 mg/L, H2S production reduced by 69.9%. FA firstly attacked tyrosine-like proteins and aromatic-like proteins in sludge EPSs, with CO groups being responded first, which decreased the percentage of α-helix/(ß-sheet + random coil) and destroyed hydrogen bonding networks. Cell membrane potential and physiological status analysis showed that FA destroyed membrane integrity and increased the ratio of apoptotic and necrotic cells. These destroyed sludge EPSs structure and caused cell lysis, thus strongly inhibited the activities of hydrolytic microorganisms and sulfate reducing bacteria. Microbial analysis showed that FA reduced the abundance of functional microbes (e.g., Desulfobulbus and Desulfovibrio) and genes (e.g., MPST, CysP, and CysN) involved in organic sulfur hydrolysis and inorganic sulfate reduction. These findings unveil an actually existed but previously overlooked contributor to H2S inhibition in WAS anaerobic fermentation.

An LC-APCI+-MS/MS-based method for determining the concentration of neurosteroids in the brain of male mice with different gut microbiota.

BACKGROUND: Although the interaction between the gut microbiota and central nervous system (CNS) is well-known, the effects of gut microbiota on different brain regions remain obscure. NEW METHOD: In present study, we developed a simple and sensitive high-performance liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode (LC-APCI+-MS/MS) for simultaneous detection of 12 analytes in the rodent' brain with different housing conditions RESULTS: The results showed that male mice in XZ group had significantly higher brain levels of dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), progesterone (P), corticosterone (CORT), aldosterone (ALD) and 11-dehydrocorticosterone (11-DHC) than those in SPF group. CORT level was higher in the left prefrontal cortex, whereas ALD and 11-DHC levels were higher in the left hypothalamus than in the right symmetrical areas in both groups. DHEA and CORT levels were highest in the striatum than in the prefrontal cortex, hippocampus, hypothalamus, regardless of the region and group (XZ and SPF). COMPARISON WITH EXISTING METHODS: These results demonstrated that the method developed in this study provides, for the first time, direct quantitation of neurosteroids in male mice brain. CONCLUSIONS: DHEA levels showed a left-lateralized pattern in the hippocampus and hypothalamus. Mice in the XZ group showed significantly elevated levels of CORT and/or its metabolites, ALD and 11-DHC in brain than mice in the SPF group. Insanitation living conditions increased more diverse gut microbiota.

Distribution of Asbestos Enterprises and Asbestosis Cases - China, 1997-2019.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Asbestos is classified as a Class I Carcinogen by the International Agency for Research on Cancer (IARC) because exposure causes mesothelioma and lung cancer in addition to asbestosis and plaques. So far, asbestos has been banned in 67 countries, but chrysotile, a commonly encountered form of asbestos, is still widely used in China and most developing countries. Most asbestos-caused cancers are not reported, recorded, and compensated in many countries. WHAT IS ADDED BY THIS REPORT?: Enterprises manufacturing asbestos products have been migrating from economically developed Eastern China to relatively underdeveloped central and western regions between 2010 and 2019. Asbestosis cases reported in Tianjin, Beijing, Shandong, Xinjiang, Gansu, Qinghai, and Sichuan accounted for a large proportion of the total cases in China, which was inconsistent with the distribution of asbestos-related enterprises (AREs). The reported asbestosis cases versus total pneumoconiosis cases declined from 2.81% to 0.39% from 2006-2017, and this proportion reached 0.69% in 2018. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Robust occupational and environmental health assessments and reporting are needed to define the epidemiology of asbestos-related lung diseases, and management of using asbestos and existing products containing asbestos need strengthening and follow-up. Enterprises should be encouraged to use safer substitutes and gradually ban asbestos materials in China.

A core-shell nanomaterial with endogenous therapeutic and diagnostic functions.

In the present communication we report the fabrication a unique core-shell inorganic nanomaterial with potential therapeutic and diagnostic functions. It contains an iron-cobalt (FeCo) core that demonstrates MRI contrast property and a thin nanoshell of gold that inhibits the function of a pro-angiogenic growth factor, VEGF165. Au(FeCo) core-shell nanomaterials are fabricated in the gas phase and characterized using transmission electron microscopy (TEM), energy dispersive spectrum (EDS), inductively coupled plasma analysis (ICP) and magnetic resonance imaging (MRI). Inhibition of VEGF165 function by Au(FeCo) is demonstrated against VEGF165/VPF induced signaling cascades and proliferation of HUVECs. Self-contrast property of Au(FeCo) is determined in vitro by MRI after incubating HUVECs with Au(FeCo), demonstrating intrinsic contrast property of this potentially therapeutic nanomaterial. In brief, we report here the successful fabrication of an inorganic core-shell nanomaterials with potential therapeutic and diagnostic functions. It inhibits the function of VEGF165 and function as a MRI contrast agent.

Biomarkers identification and detection based on GMR sensor and sub 13 nm magnetic nanoparticles.

In this paper, we present a ultra high sensitive (Zeptomole, 10(-21)) technique to enable the detection of any potential low abundance biomarkers. We demonstrated for the first time the detection of sub 13nm high-moment magnetic nanoparticle and the implementation of a novel magnetoresistive (GMR) biosensor concept with higher sensitivity and 10 times lower external field in real biomarker sensing schemes. A potential lung cancer biomarker, interleukin-6 (IL-6), was successfully detected with extremely low concentration (as few as only 200 pieces of IL-6). Together with other features of GMR sensor systems like low-cost, portability, easy-to-use, our demonstrated device may lead to future family-based personalized medicine for cancer prevention.

High-magnetic-moment nanoparticles for biomedicine.

Magnetic nanoparticles play an important role in biomedical applications, such as MR imaging, drug delivery and hyperthermia. Nanoparticles made of high-moment materials like Fe-Co and Fe have become active in the field due to superior performance. Protected by a biocompatible shell (Au/Ag/Si/C), high-moment nanoparticles can retain their magnetic property over a long time and disperse well. By using a physical gas condensation technique, such high-moment nanoparticles and core-shell structured nanoparticles can be made and used for biomedicine.

A detection system based on giant magnetoresistive sensors and high-moment magnetic nanoparticles demonstrates zeptomole sensitivity: potential for personalized medicine.

Zeptomole detector: A highly sensitive giant-magnetoresistive chip and FeCo nanoparticles can be used to linearly detect 600-4500 copies of streptavidin. Under unoptimized conditions, this system also detects human IL-6 with a sensitivity 13-times higher than that of standard ELISA techniques.