Cold-inducible RNA binding protein alleviates iron overload-induced neural ferroptosis under perinatal hypoxia insult.

Cold-inducible RNA binding protein (CIRBP), a stress response protein, protects cells from mild hypothermia or hypoxia by stabilizing specific mRNAs and promoting their translation. Neurons subjected to hypobaric hypoxia insult trigger various cell death programs. One of these is ferroptosis, a novel non-apoptotic form of programmed cell death, which is characterized by excessive iron ion accumulation and lipid peroxidation. Here, we establish that CIRBP can regulate neuronal ferroptosis both in vivo and in vitro. We observe that hypoxia leads to neuronal death via intracellular ferrous iron overload and impaired antioxidant systems, accompanied by suppressed CIRBP expression. Genetic enrichment of CIRBP in hippocampal neurons CIRBPTg mice bred with Emx1-Cre mice attenuates hypoxia-induced cognitive deficits and neuronal degeneration. Mechanistically, CIRBP alleviates neuronal ferroptosis and intracellular ferrous ion accumulation by binding to the mitochondrial ferritin (FTMT) 3'UTR to stabilize mRNA and promote its translation. Our novel study shows the critical role of CIRBP in the progression of ferroptosis, and provides promising therapeutic target for hypoxia-induced neurological diseases.

Manganese-induced miR-125b-2-3p promotes anxiety-like behavior via TFR1-mediated ferroptosis.

The toxic effects of excessive manganese (Mn) levels in the environment have led to a severe public health concern. Ferroptosis is a newly form of cell death relying on iron, inherent to pathophysiological processes of psychiatric disorders, such as anxiety and depression-like behaviors. Excessive Mn exposure causes various neurological effects, including neuronal death and mood disorders. Whether Mn exposure causes anxiety and depression-like behaviors, and the underlying mechanisms of Mn-induced ferroptosis have yet to be determined. Here, Mn-exposed mice showed anxiety-like behavior. We also confirmed the accumulation of ferrous ion (Fe2+), lipid peroxidation, and depletion of antioxidant defense system both in vitro and in vivo Mn-exposed models, suggesting that Mn exposure can induce ferroptosis. Furthermore, Mn exposure downregulated the expression of miR-125b-2-3p. In turn, overexpression of miR-125b-2-3p alleviated the Mn-induced ferroptosis by targeting Transferrin receptor protein 1 (TFR1). In summary, this novel study established the propensity of Mn to cause anxiety-like behavior, an effect that was regulated by miR-125b-2-3p and ensuing ferroptosis secondary to the targeting of TFR1. These results offer promising targets for the prevention and treatment of Mn-induced neurotoxicity.

Microdiversity sustains the distribution of rhizosphere-associated bacterial species from the root surface to the bulk soil region in maize crop fields.

Over the years, the microbial community of maize (Zea mays) rhizosphere has been extensively studied; however, the role of microdiversity sustain rhizosphere-associated microbial species distribution from root surface to bulk soil in mature maize is still unclear. Although operational taxonomic units (OTUs) have been used to classify species, amplicon sequence variants (ASVs) have been shown to be effective in representing microdiversity within OTUs at a finer genetic scale. Therefore, the aim of this study was to examine the role of microdiversity in influencing the distribution of rhizosphere-associated microbial species across environmental gradients from root surface to bulk soil at the OTU and ASV levels. Here, the microbial community structures of bulk, loosely bound, and tightly bound soil samples from maize rhizosphere were examined at OTU and ASV levels. The results showed that OTU and ASV methods exhibited similar microbial community structures in rhizosphere. Additionally, different ecotypes with varying distributions and habitat preferences were observed within the same bacterial OTU at the ASV level, indicating a rich bacterial microdiversity. In contrast, the fungal community exhibited low microdiversity, with no significant relationship between fungal microdiversity and persistence and variability. Moreover, the ecotypes observed within the bacterial OTUs were found to be positively or negatively associated with environmental factors, such as soil organic carbon (SOC), NO3 --N, NH4 +-N contents, and pH. Overall, the results showed that the rich microdiversity could sustain the distribution of rhizosphere-associated bacterial species across environmental gradients from root surface to bulk soil. Further genetic analyses of rhizosphere-associated bacterial species could have considerable implications for potential mediation of microdiversity for sustainable crop production.

NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction.

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.

Dietary Xylitol Supplement Ameliorated AD-related Neuronal Injury by Regulating Glucose Metabolism Relevant Amino Acids in Mice.

BACKGROUND: Alzheimer's disease (AD) is one of the most common irreversible degenerative diseases of the central nervous system. Recent studies have found that patients with AD generally experience abnormal glucose metabolism. Xylitol is a functional sugar alcohol, which has been reported to regulate glucose metabolism. OBJECTIVE: The present study was designed to determine whether xylitol can alleviate cognitive impairment in AD mice. METHODS: In the current research, 5% xylitol was supplemented in the diet to treat APP/PS1 transgenic AD mice for 2 months. Cognitive ability was measured by the Morris water maze, and anxiety-like behaviors were examined by open-field experiment. Hippocampal cellular apoptosis and mitochondria pathway related apoptotic proteins were tested by TUNEL staining and immunoblotting, respectively. By LC-MS, plasma levels of glucose metabolism intermediates and related amino acids were evaluated. RESULTS: Results showed that xylitol could significantly ameliorate anxiety-like activity in AD mice by partially regulating expression levels of mitochondrial pathway-related apoptotic proteins. Xylitolregulated glucose metabolism may play an important role in the process. CONCLUSION: The current study suggests that xylitol may be a potential candidate for improving neuropsychiatric behavior in AD by regulating the levels of TCA cycle intermediates and related amino acids in glucose metabolism.

Effects of Individualized Nursing Based on Zero-Defect Theory on Perioperative Patients Undergoing Laparoscopic Cholecystectomy.

Objective: This study is aimed at analyzing the effects of individualized nursing based on the zero-defect theory on perioperative patients undergoing laparoscopic cholecystectomy. Methods: 174 patients who underwent laparoscopic cholecystectomy from 1st November 2019 to 30th November 2020 were enrolled as the research subjects and randomly divided into control and observation groups. The patients in the control group received conventional perioperative nursing care, and the patients in the observation group were treated with individualized nursing based on the zero-defect theory. Results: The heart rate, diastolic blood pressure, and systolic blood pressure level of patients in two groups after nursing decreased significantly, and the reduction in the observation group was more significant than that in the control group. The depression and anxiety scores of the two groups after nursing were decreased, and the decrease in the observation group was significantly greater than that in the control group. The time to first postoperative exhaust, return to normal intake, out-of-bed activity, and hospital stay in the observation group was less than that in the control group. The incidence of postoperative complications in the observation group was substantially lower than that in the control group. The satisfaction degree of nursing care in the observation group was significantly higher than that in the control group. Conclusion: Individualized nursing care based on zero-defect theory can effectively reduce the perioperative psychological stress response of patients with laparoscopic cholecystectomy. It helps to improve the negative emotions of depression and anxiety, promotes the recovery of disease, reduces postoperative complications, and improves nursing satisfaction, which is worthy of clinical promotion.

Methylcobalamin Alleviates Neuronal Apoptosis and Cognitive Decline Induced by PM2.5 Exposure in Mice.

BACKGROUND: Fine particulate matter (particulate matter 2.5, PM2.5) is considered one of the harmful factors to neuronal functions. Apoptosis is one of the mechanisms of neuronal injury induced by PM2.5. Methylcobalamine (MeCbl) has been shown to have anti-apoptotic and neuroprotective effects. OBJECTIVE: The current work tried to explore the neuroprotective effects and mechanisms that MeCbl protects mice against cognitive impairment and neuronal apoptosis induced by chronic real-time PM2.5 exposure. METHODS: Twenty-four 6-week-old male C57BL/6 mice were exposed to ambient PM2.5 and fed with MeCbl for 6 months. Morris water maze was used to evaluate the changes of spatial learning and memory ability in mice. PC12 cells and primary hippocampal neurons were applied as the in vitro model. Cell viability, cellular reactive oxygen species (ROS) and the expressions of apoptosis-related proteins were examined. And cells were stained with JC-1 and mitochondrial membrane potential was evaluated. RESULTS: In C57BL/6 mice, MeCbl supplementation alleviated cognitive impairment and apoptosis-related protein expression induced by PM2.5 exposure. In in vitro cell model, MeCbl supplementation could effectively rescue the downregulation of cell viability induced by PM2.5, and inhibited the increased levels of ROS, cellular apoptosis, and the expressions of apoptosis related proteins related to PM2.5 treatment, which may be associated with modulation of mitochondrial function. CONCLUSION: MeCbl treatment alleviated cognitive impairment and neuronal apoptosis induced by PM2.5 both in vivo and in vitro. The mechanism for the neuroprotective effects of MeCbl may at least be partially dependent on the regulation of mitochondrial apoptosis.

S-adenosylmethionine decarboxylase 1 and its related spermidine synthesis mediate PM2.5 exposure-induced neuronal apoptosis.

PM2.5 exposure is considered harmful to central nerve system, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in pathogenesis of neurodegenerative diseases, but evidence supporting neuronal apoptosis as the mechanism for PM2.5 exposure induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to associate with cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. The current study was aimed to better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis. Sixteen C57BL/6 male mice were randomly divided and kept into ambient PM2.5 chamber or filtered air chamber for 6 months to establish the mouse model of whole-body ambient PM2.5 chronic exposure. In parallel, PC12 cells and primary hippocampal neurons were applied for various concentrations of PM2.5 treatment (0, 25, 50, 100, 200, and 400 µg/mL) to explore the possible cellular and molecular mechanism which may be critically involved in the process. Results showed that PM2.5 exposure triggered neuronal apoptosis with increased expression of Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure reduced AMD1 expression and spermidine synthesis. AMD1 inhibition could mimic PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis via impaired depolarization of mitochondrial membrane potential and reduced mitochondrial apoptosis related proteins. In summary, our work demonstrated that exposure to PM2.5 led to neuronal apoptosis, which may be the key event in the process of air pollution induced neurodegenerative diseases. AMD1 and spermidine associated with neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.

Ambient PM2.5 chronic exposure leads to cognitive decline in mice: From pulmonary to neuronal inflammation.

Fine particulate matter 2.5 (PM2.5), one of the main components of air pollutants, seriously threatens human health. Possible neuronal dysfunction induced by PM2.5 has received extensive attention. However, there is little evidence for the specific biochemical mechanism of neuronal injury induced by PM2.5. Moreover, the pathway for PM2.5 transport from peripheral circulation to the central nervous system (CNS) is still unclear. In the current work, C57BL/6 mice were chronically exposed to ambient PM2.5 for 3, 6, 9, and 12 months. Exposure to ambient PM2.5 resulted in a significant reduction of cognitive ability in mice by Morris water maze test. PM2.5 exposure induced a neuroinflammatory reaction after cognitive impairment, while inflammation in the hypothalamus and olfactory bulb tissue occurred earlier. The expression levels of integrity tight junction proteins in the blood-brain barrier (BBB) were reduced by PM2.5 exposure. Pulmonary inflammation occurred much earlier and diminished at later stage of PM2.5 exposure. The results indicated that chronic exposure to ambient PM2.5 led to cognitive decline in mice; CNS dysfunction may be due to neuroinflammatory reactions; the reduced integrity of the BBB allowed the influence of pulmonary inflammation to neuronal alterations. The work may provide promising therapeutic or preventive targets for air pollution-induced neurodegenerative disease.

Recent advances in understanding the mechanisms of PM2.5-mediated neurodegenerative diseases.

PM2.5 particles are widely believed to be associated with respiratory and cardiovascular diseases. However, recent studies have reported that PM2.5 may be associated with neurodegenerative diseases. The exact mechanism by which PM2.5 mediates neurotoxicity and cognitive dysfunction is still unclear. In the current work, we collected evidence supporting the association between PM2.5 exposure and development of neurodegenerative disorders. Evidence from epidemiological investigations, animal experiments, and ex vivo cell experiments showed that PM2.5 exposure may lead to neuroinflammation, oxidative stress, mitochondrial dysfunction, neuronal apoptosis, synaptic damage and ultimately neurodegenerative diseases.

A review of the possible associations between ambient PM2.5 exposures and the development of Alzheimer's disease.

PM2.5 particles in air pollution have been widely considered associated with respiratory and cardiovascular diseases. Recent studies have shown that PM2.5 can also cause central nervous system (CNS) diseases, including a variety of neurodegenerative diseases, such as Alzheimer's disease (AD). Activation of microglia in the central nervous system can lead to inflammatory and neurological damage. PM2.5 will reduce the methylation level of DNA and affect epigenetics. PM2.5 enters the human body through a variety of pathways to have pathological effects on CNS. For example, PM2.5 can destroy the integrity of the blood-brain barrier (BBB), so peripheral systemic inflammation easily crosses BBB and reaches CNS. The olfactory nerve is another way for PM2.5 particles to enter the brain. Surprisingly, PM2.5 can also enter the gastrointestinal tract, causing imbalances in the intestinal microecology to affect central nervous system diseases. The current work collected and discuss the mechanisms of PM2.5-induced CNS damage and PM2.5-induced neurodegenerative diseases.

(+)-JQ1 attenuated LPS-induced microglial inflammation via MAPK/NFκB signaling.

BACKGROUND: Microglia activation is a crucial event in neurodegenerative disease. The depression of microglial inflammatory response is considered a promising therapeutic strategy. NFκB signaling, including IKK/IκB phosphotylation, p65 nucelus relocalization and NFκB-related genes transcription are prevalent accepted to play important role in microglial activation. (+)-JQ1, a BRD4 inhibitor firstly discovered as an anti-tumor agent, was later confirmed to be an anti-inflammatory compound. However, its anti-inflammatory effect in microglia and central neural system remains unclear. RESULTS: In the current work, microglial BV2 cells were applied and treatment with lipopolysaccharide (LPS) to induce inflammation and later administered with (+)-JQ1. In parallel, LPS and (+)-JQ1 was intracerebroventricular injected in IL-1ß-luc transgenic mice, followed by fluorescence evaluation and brain tissue collection. Results showed that (+)-JQ1 treatment could significantly reduce LPS induced transcription of inflammatory cytokines both in vitro and in vivo. (+)-JQ1 could inhibit LPS induced MAPK but not PI3K signaling phosphorylation, NFκB relocalization and transcription activity. In animal experiments, (+)-JQ1 postponed LPS induced microglial and astrocytes activation, which was also dependent on MAPK/NFκB signaling. CONCLUSIONS: Thus, our data demonstrated that (+)-JQ1 could inhibit LPS induced microglia associated neuroinflammation, via the attenuation of MAPK/NFκB signaling.

[Improvement of grating spectrograph and its application to frequency-doubling in PPLN].

Charge-coupled device (CCD) has been widely used in spectral detection and spectral imaging fields, which has a number of benefits: broad spectral range response, low detection limit, wide dynamic range, minimal dark current and readout noise as well as the abilities of signal integration, simultaneous multichannel detection, and real-time detection. The combination of a traditional one meter grating spectrograph and a science charge-coupled device (CCD) led to a real-time grating spectrograph for laser spectrum detection developed in this paper. Based on the new grating spectrograph, the spectral characteristic of frequency-doubling of a broad band double-cladding fiber laser in polarized lithium niobate (PPLN) has been investigated. Dynamic spectrum of the second harmonic with varying temperature of PPLN has been observed and analyzed in detail.