Source to risk receptor transport and spatial hotspots of heavy metals pollution in peri-urban agricultural soils of the largest megacity in China.

The traditional concentration-based health risk assessment of heavy metal (HMs) pollution in soil has often overlooked the initial loading and toxicity differences of HMs from various sources. This oversight hinders effective identification of the risky source, complicating precise risk management of soil HMs pollution. This study applied a source-oriented health risk assessment framework that integrates source profiling, exposure risk assessment, and spatial cluster analysis. Taking the Shanghai City, the largest megacity in China as a case, the findings revealed that overall environmental quality of peri-urban agricultural soil in Shanghai remains good, though 3.03 % of Cd concentrations exceeded the national reference standards. Industrial & traffic activities, primarily contributing Hg, Cd, and Pb, accounted for the highest proportion (44.3 %) of total metal concentrations and posed the greatest non-cancer risk (54.6 % for children and 53.1 % for adults). Notably, natural activities, mainly contributing Cr, ranked only third in concentration contribution (26.55 %) but induced the highest cancer risk (58.55 % for children and 57.08 % for adults). These findings suggest that sources with lower concentration contributions may still pose significant health risk. Integrating source apportionment with health risk assessment can more precisely identify the risky source and target areas for mitigating the human health hazards.

Appropriate sulfur fertilization in contaminated soil enhanced the cadmium uptake by hyperaccumulator Sedum alfredii Hance.

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

Transcription factor OsSHR2 regulates rice architecture and yield per plant in response to nitrogen.

MAIN CONCLUSION: Mutation of OsSHR2 adversely impacted root and shoot growth and impaired plant response to N conditions, further reducing the yield per plant. Nitrogen (N) is a crucial factor that regulates the plant architecture. There is still a lack of research on it. In our study, it was observed that the knockout of the SHORTROOT 2 (OsSHR2) which was induced by N deficiency, can significantly affect the regulation of plant architecture response to N in rice. Under N deficiency, the mutation of OsSHR2 significantly reduced root growth, and impaired the sensitivity of the root meristem length to N deficiency. The mutants were found to have approximately a 15% reduction in plant height compared to wild type. But mutants showed a significant increase in tillering at post-heading stage, approximately 26% more than the wild type, particularly in high N conditions. In addition, due to reduced seed setting rate and 1000-grain weight, mutant yield was significantly decreased by approximately 33% under low N fertilizer supply. The mutation also changed the distribution of N between the vegetative and reproductive organs. Our findings suggest that the transcription factor OsSHR2 plays a regulatory role in the response of plant architecture and yield per plant to N in rice.

Evaluating the protective capacity of soil heavy metals regulation limits on human health: A critical analysis concerning risk assessment - Importance of localization.

Heavy metal pollution of agricultural soil is a major global concern, prompting the establishment of maximum allowable limits (MALs) to ensure food safety and protect human health. This study collected and compared MALs for six heavy metals (As, Cd, Hg, Pb, Zn, and Cu) in agricultural soils from representative countries and organizations (EU and WHO/FAO). The research evaluated the critical health risks and efficacy of these MALs under the hypothetical scenario of metals concentrations reaching the maximum allowable level. Safe thresholds for heavy metals were then derived based on maximum acceptable health risk levels. The comparative analysis revealed significant variations in the specific limit values and terms of MALs across countries and organizations, even for the same metal. This suggests that there is no consensus among countries and organizations regarding the level of metal-related health risks. Furthermore, the risk analysis of metal concentrations reaching the maximum level accentuated heightened risks associated with As, suggesting that the current risk of soil As exposure was underestimated, particularly for children. However, soil Cu, Cd, and Zn limits generally resulted in low health risks, implying that the current limits may overestimate their hazard. Overall, the results highlight that the current MALs for soil heavy metals may not fully safeguard human health. There is a critical need to optimize current soil MALs based on localized risks and the actual impact of these metals on human health. It is suggested to appropriately lower the limits of metals (such as As) whose impact on health risks is underestimated, and cautiously increase the limits of metals (such as Cu, Cd, and Zn) that currently pose minor health risks. This approach aims to reduce both over and insufficient protection problems of soil heavy metal MALs, emphasizing the importance of considering the locality in setting these limits.

Deoxynivalenol Induces Intestinal Epithelial Barrier Damage through RhoA/ROCK Pathway-Mediated Apoptosis and F-Actin-Associated Tight Junction Disruption.

Deoxynivalenol (DON) poses a serious global food safety risk due to its high toxicity and contamination rate. It disrupts the intestinal epithelial barrier, allowing exogenous toxins to enter the circulation and resulting in sepsis and systemic toxicity. In this research, 32 male Kunming mice and Porcine Small Intestinal Epithelial (IPEC-J2) cells were treated with DON at 0-4.8 mg/kg (7 d) and 0-12 µM (24 h), respectively. Histopathological results revealed that DON disrupted the intestinal epithelial barrier, causing apoptosis and tight junction (TJ) injury. Immunofluorescence and protein expression results showed that DON-induced p53-dependent mitochondrial pathway apoptosis and fibrillar actin (F-actin)-associated TJ injury and that the RhoA/ROCK pathway were activated in mice jejunal tissue and IPEC-J2 cells. Pretreatment with RhoA or ROCK inhibitors (Rosin or Y-27632) maintained DON-induced apoptosis and F-actin-associated TJ injury in IPEC-J2 cells. Thus, DON induces damage to the intestinal epithelial barrier through the RhoA/ROCK pathway-mediated apoptosis and F-actin-associated TJ disruption.

Long-Term Stable Superlubricity Coatings Enabled by the Interaction between the Polydimethylsiloxane Brush and Silicone Oil.

Recently, materials with superlubricity captured widespread attention on account of their great potential in energy savings and environmental protection. However, certain issues still remain to be solved for the traditional materials, such as the dependence on strict conditions and an unstable superlubricity state. Herein, a long-term stable superlubricity coating was prepared using a low-cost and simple method via an epoxy-based coating with polydimethylsiloxane (PDMS) brushes under silicone oil (SO) lubrication conditions. Compared with the pure epoxy resin matrix, the friction coefficient and wear track width of the superlubricity coating with the optimal amount of 6 wt % PDMS are reduced to 0.006 and 50.9 µm (reduced by 10-fold and 5.6-fold decrease, respectively). In addition, the coating can maintain a stable superlubricity state during a 5 h tribological test. The superlubricity of the coating results from the synergistic lubrication effect of the PDMS brush and SO. First, PDMS brushes with high-stretched conformation due to the swelling effect of the SO can significantly reduce friction. Second, a stable oil film is generated between the contact surfaces, which significantly improves the frictional performance. Moreover, the PDMS incorporated into the coating matrix, along with oil-swelling PDMS brushes on the surface, is highly beneficial for enhancing corrosion resistance of the epoxy resin matrix. Such an epoxy-based coating with long-term stable superlubricity is considered as a potential lubricating and protective surface for tribological components for long-term service.

Deciphering prognostic indicators in AQP4-IgG-seropositive neuromyelitis optica spectrum disorder: An integrative review of demographic and laboratory factors.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory diseases affecting the central nervous system, characterized by optic neuritis and myelitis. The complex nature of NMOSD and varied patient response necessitates personalized treatment and efficient patient stratification strategies. OBJECTIVE: To provide a comprehensive review of recent advances in clinical and biomarker research related to aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive NMOSD prognosis and identify key areas for future research. METHODS: A comprehensive review and synthesis of recent literature were conducted, focusing on demographic factors and laboratory investigations. RESULTS: Demographic factors, such as age, ethnicity, and sex, influence NMOSD prognosis. Key biomarkers for NMOSD prognosis include homocysteine, antinuclear antibodies, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, thyroid hormone levels, neurofilament light chain levels, and serum glial fibrillary acidic protein might also predict NMOSD attack prognosis. CONCLUSION: Further investigation is required to understand sex-related disparities and biomarker inconsistencies. Identification and understanding of these factors can aid in the development of personalized therapeutic strategies, thereby improving outcomes for NMOSD patients. Future studies should focus on unifying research design for consistent results.

Phosphate Transporter OsPT4, Ubiquitinated by E3 Ligase OsAIRP2, Plays a Crucial Role in Phosphorus and Nitrogen Translocation and Consumption in Germinating Seed.

Phosphorus (P) and nitrogen (N) are essential macronutrients necessary for plant growth and development. OsPT4 is a high-affinity phosphate (Pi) transporter that has a positive impact on nutrient uptake and seed development. In this study, the expression patterns of different Pi transporter genes in germinating seeds were determined, and the relative expression of OsPT4 was induced in Pi-deficient seeds and gradually increased with the passage of germination time. The analysis of P, N, Pi, and amino acid concentrations in germinating seeds of OsPT4 mutants showed that the OsPT4 mutation caused P and N retention and a continuous reduction in multiple amino acid concentrations in germinating seeds. Transcriptome analysis and qRT-PCR results also indicated that the OsPT4 mutation inhibits the expression of genes related to P and N transportation and amino acid synthesis in germinating seeds. In addition, the paraffin section and TUNEL assay of OsPT4 mutant germinating seeds suggests that OsPT4 mutation causes programmed cell death (PCD) delayed in the aleurone layer and inhibition of leaf outgrowth. Moreover, we also found that OsPT4 was ubiquitinated by OsAIRP2, which is a C3HC4-type RING E3 Ub ligase. Our studies illustrate that OsPT4 plays a crucial role in P and N collaborative translocation and consumption in germinating seeds. It also provides a theoretical basis for the molecules and physiological mechanisms of P and N cross-talk under suppressed Pi uptake conditions.

Counting d-Orbital Vacancies of Transition-Metal Catalysts for the Sulfur Reduction Reaction.

The electrocatalytic sulfur reduction reaction (SRR) would allow the production of renewable high-capacity rechargeable lithium-sulfur (Li-S) batteries using sustainable and nontoxic elemental sulfur as a cathode material, but its slow reaction rate causes a serious shuttle effect and dramatically reduces the capacity. We found that a catalyst composed of Pd nanoparticles supported by ordered mesoporous carbon (Pd/OMC) had a high reaction rate in the SRR, and a Li-S battery assembled with this catalyst had a low shuttle constant of 0.031 h-1 and a high-rate performance with a specific capacity of 1527 mAh g-1 at 0.1 C which is close to the theoretical value. The high activity of Pd/OMC with a d-orbital vacancy of 0.87 e was predicted from a volcano relationship between the d charge for the metal and the adsorption activation entropy and reaction rate for the SRR by examining Pd, Au, Pt, Rh, and Ru transition-metal nanocatalysts. The strategy of using a single electronic structure descriptor to design high-efficiency SRR catalysts has suggested a way to produce practical Li-S batteries.

A prospective health risks analysis of regulatory limits for heavy metals in rice from representative organizations and countries worldwide: Are they protective?

Heavy metals contamination in rice has been one of the most public concerns globally; thus, many countries and organizations issued the maximum acceptable limits (MALs) of their concentrations in rice to regulate food safety and health risks. However, the applicability of these MALs has rarely been thoroughly evaluated. This study collected the MALs of heavy metals for rice from representative countries and organizations around the world. We assessed the critical health risks in the case of metal concentrations that reached the MALs for the first time. Results showed great variability of rice regulation limits owing to different processing methods (paddy, polished, and brown rice) and metal types (mainly focusing on inorganic As, Cd, and Pb). Risk analysis revealed that the inorganic As limits and part of Cd limits for polished rice generated relatively high health risks, indicating that their risks may be underestimated. Monte Carlo simulation further showed that the daily intake rate of rice (IRrice) is the largest contributor to total variances for the derivation of MALs, and regulation limits decreased with the augment of IRrice. Overall, we suggest a cautious reduction in the allowable limits of certain metals (such as inorganic As and part of Cd) in rice as their health risks and toxicity may be underestimated.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

Secreted aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) is a promising predictor for the severity of acute AQP4-IgG positive neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Aminoacyl-tRNA synthetase complex interacting with multifunctional protein-1 (AIMP1) has been reported to carry pro-inflammatory properties and anti-angiogenesis effects. However, the exact role of AIMP1 in patients with NMOSD is not yet clear. Our objective was to investigate the relationship between plasma AIMP1 levels and disease severity in patients with AQP4-IgG+ NMOSD from North China based on the Expanded Disability Status Scale (EDSS) score. METHODS: Plasma AIMP1 levels were measured using ELISA kits in 94 patients with AQP4-IgG+NMOSD (48 in the acute phase before high-dose intravenous methylprednisolone (IVMP) therapy, 21 in the acute phase after IVMP therapy, 25 in the clinical remission-phase)as well as 33 healthy controls (HCs). The disability function of NMOSD patients was evaluated using the EDSS score. Furthermore, the clinical characteristics of the patients were also evaluated, and laboratory tests were performed on blood samples. RESULTS: The plasma AIMP1 levels in AQP4-IgG+NMOSD patients with acute phase before IVMP therapy were significantly higher as compared to those in patients after the IVMP therapy (p < 0.001) as well as those in the clinical remission phase (p = 0.021) or HCs (p < 0.001). Plasma AIMP1 levels were positively correlated with EDSS scores (r = 0.485, p < 0.001) and negatively correlated with serum complement 3 concentrations (r =-0.452, p = 0.001). AIMP1 exhibited the potential to distinguish NMOSD from HCs (AUROC 0.820, p < 0.0001) and could differentiate mild and moderate-severe NMOSD (AUROC 0.790, p = 0.0006). Furthermore, plasma AIMP1 levels of ≥49.55pg/mL were found to be an independent predictor of the risk for moderate-severe NMOSD (with OR 0.03, 95%CI 0.001-0.654, p = 0.026). CONCLUSION: AIMP1 may be involved in the pathogenesis of AQP4-IgG+NMOSD disease and predict the disease activity, severity, or effect of treatment in patients with NMOSD. Further studies should be performed to reveal the precise mechanisms of AQP4-IgG+NMOSD.

Towards an integrated health risk assessment framework of soil heavy metals pollution: Theoretical basis, conceptual model, and perspectives.

The health risk of soil heavy metals pollution has been gaining increasing public concern. However, many countries have not set their own health risk assessment (HRA) framework and most of the existing studies directly referred to the USEPA risk assessment model and parameters. For those countries that do not propose an original HRA framework, the experience of developed countries is crucial for advancing their own HRA system. This study systematically reviewed the development of HRA framework in some representative developed countries. The theoretical basis, conceptual model, progress, and challenges of HRA researches concerning soil heavy metals pollution were summarized. By recalling and comparing the health risk-related laws and guidance in the USA, UK, and Japan, results showed that the construction of HRA framework varied between these countries, but HRA has become the main method for deriving their soil environmental criteria. We further summarized the evaluation scales, land use types, exposure pathways, and sensitive receptors of HRA studies, and highlighted the key parameters affecting health risk outputs. There has been a shift toward the incorporation of probabilistic modeling, metals bioavailability, and sources emission characteristics into recent HRA studies. Nonetheless, challenges remained on how to minimize the uncertainty of generating probability distribution and detecting metal bioavailability. To facilitate the development of HRA framework, it was advised that developing countries should strengthen the theoretical researches of health risk and localization researches of exposure factors. Future directions are suggested to tend to: 1) promote sensitive analysis to quantify the impact of distribution assumptions on health risk outputs, 2) derive reasonable risk threshold and consistent evaluation protocol for bioavailability-based health risk assessment method, and 3) strive to explore the combined health effect of exposure to heavy metals in soil through source-media-receptor integrated studies.

Hemolymph Node - An Immunomorphlogical Organ: Modeling the Hemolymph Node by Allografting Renal Tissue in the Rat.

There is no authoritative characterization of the attributes of the hemolymph node (HLN) since Gibbes' first description in 1884. Early reports showed that HLN are found near the kidney in human and animals with the feature of numerous erythrocytes in sinuses. Subsequent studies mainly focused on anatomy and histology, such as the source, distribution, and quantity of erythrocytes in sinuses. Recent articles mentioned that the emergence of HLN was related to immunity, but there was no strong evidence to support this hypothesis. Therefore, it is still uncertain whether the HLN is an organ of anatomy, histology, or immunology. It has been found that the development of HLN could be elicited in the parathymic area by stimuli such as Escherichia coli, allogeneic breast cancer cells, and renal tissue that were injected/transplanted into the tail of rats in our pilot studies. In this study, the model of the HLN was established by transferring allogeneic renal tissue in the rat. Intrasinusoidal erythrocytes of the node were the component for producing a red macroscopic appearance, while macrophage-erythrocyte-lymphocyte rosettes were the major immunomorphological changes, reflecting the immune activity against the invasion of the allogeneic tissue within the node. Therefore, the HLN is an immunomorphological organ.

Recent advances and perspectives of CeO2-based catalysts: Electronic properties and applications for energy storage and conversion.

Cerium dioxide (CeO2, ceria) has long been regarded as one of the key materials in modern catalysis, both as a support and as a catalyst itself. Apart from its well-established use (three-way catalysts and diesel engines), CeO2 has been widely used as a cocatalyst/catalyst in energy conversion and storage applications. The importance stems from the oxygen storage capacity of ceria, which allows it to release oxygen under reducing conditions and to store oxygen by filling oxygen vacancies under oxidizing conditions. However, the nature of the Ce active site remains not well understood because the degree of participation of f electrons in catalytic reactions is not clear in the case of the heavy dependence of catalysis theory on localized d orbitals at the Fermi energy E F . This review focuses on the catalytic applications in energy conversion and storage of CeO2-based nanostructures and discusses the mechanisms for several typical catalytic reactions from the perspectives of electronic properties of CeO2-based nanostructures. Defect engineering is also summarized to better understand the relationship between catalytic performance and electronic properties. Finally, the challenges and prospects of designing high efficiency CeO2-based catalysts in energy storage and conversion have been emphasized.

Analysis of co-expression gene network associated with intracranial aneurysm and type 2 diabetes mellitus.

To screen for common target genes in intracranial aneurysms (IA) and type 2 diabetes mellitus (T2DM), construct a common transcriptional regulatory network to predict clusters of candidate genes involved in the pathogenesis of T2DM and IA, and identify the common neurovascular markers and pathways in T2DM causing IA. Microarray datasets (GSE55650, GSE25462, GSE26969, GSE75436, and GSE13353) from the GEO database were analyzed in this research. Screening of the IA and the T2DM datasets yielded a total of 126 DEGs, among which 78 were upregulated and 138 were downregulated. Functional enrichment analysis revealed that these DEGs were enriched for a total of 68 GO pathways, including extracellular matrix composition, coagulation regulation, hemostasis regulation, and collagen fiber composition pathways. We also constructed transcriptional regulatory networks, and identified key transcription factors involved in both the conditions. Univariate logistic regression analysis showed that ARNTL2 and STAT1 were significantly associated with the development of T2DM and IA, acting as the common neurovascular markers for both the diseases. In cellular experiments, hyperglycemic microenvironments exhibited upregulated STAT1 expression. STAT1 may be involved in the pathogenesis of IA in T2DM patients. Being the common neurovascular markers, STAT1 may acts as novel therapeutic targets for the treatment of IA and T2DM.

Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy.

Objective: Macrovascular invasion (MVI) is an important factor leading to poor prognosis in hepatocellular carcinoma (HCC). Liver resection may offer favorable prognosis for selected patients with HCC. This study aimed to analyze the prognostic factors of HCC with MVI after liver resection as well as demonstrate a case of conversion therapy in an HCC patient with portal vein tumor thrombus (PVTT). Methods: A total of 168 HCC patients with MVI who underwent primary liver resection at the Affiliated Hospital of Qingdao University between January 2013 and October 2021 were enrolled in the study. Clinicopathological data were collected retrospectively. Univariate and multivariate regression analyses were used to investigate the risk factors influencing recurrence and overall survival. Additionally, conversion therapy with drug-eluting bead transarterial chemoembolization (D-TACE), and sorafenib plus sintilimab treatment was performed in an HCC patient with PVTT. Results: Among the 168 patients with HCC, 11 were diagnosed with hepatic vein tumor thrombosis, and the rest were diagnosed with PVTT. The 1-year disease-free survival rate was 37.5%, and the 3-year overall survival rate was 52.7%. Univariate and multivariate regression analyses revealed that HBsAg positivity, alpha-fetoprotein (AFP) level ≥400 ng/ml, liver capsule invasion, and tumor number ≥2 were independent prognostic factors for tumor recurrence, whereas HBsAg positivity was an independent risk factor for overall survival. Postoperative prophylactic medication did not significantly prolong the recurrence time. The median survival time (MST) after tumor recurrence was 13.4 months. In the patient treated with conversion therapy, the tumor gradually shrank and was eventually surgically resected. Conclusions: This study identified the independent prognostic and risk factors associated with recurrence and overall survival in HCC patients with MVI. Additionally, we successfully performed conversion therapy in an HCC patient with PVTT. The findings would help identify patients at high risk of recurrence and indicate that combined therapy may prolong the survival of HCC patients with PVTT.

Resetting Proteostasis of CIRBP with ISRIB Suppresses Neural Stem Cell Apoptosis under Hypoxic Exposure.

Neurological disorders are often progressive and lead to disabilities with limited available therapies. Epidemiological evidence implicated that prolonged exposure to hypoxia leads to neurological damage and a plethora of complications. Neural stem cells (NSCs) are a promising tool for neurological damage therapy in terms of their unique properties. However, the literature on the outcome of NSCs exposed to severe hypoxia is scarce. In this study, we identified a responsive gene that reacts to multiple cellular stresses, marked cold-inducible RNA-binding protein (CIRBP), which could attenuate NSC apoptosis under hypoxic pressure. Interestingly, ISRIB, a small-molecule modulator of the PERK-ATF4 signaling pathway, could prevent the reduction and apoptosis of NSCs in two steps: enhancing the expression of CIRBP through the protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) axis. Taken together, CIRBP was found to be a critical factor that could protect NSCs against apoptosis induced by hypoxia, and ISRIB could be acted upstream of the axis and may be recruited as an open potential therapeutic strategy to prevent or treat hypoxia-induced brain hazards.

Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory.

The earth land area is heterogeneous in terms of elevation; about 45% of its land area belongs to higher elevation with altitude above 500 meters compared to sea level. In most cases, oxygen concentration decreases as altitude increases. Thus, high-altitude hypoxic stress is commonly faced by residents in areas with an average elevation exceeding 2500 meters and those who have just entered the plateau. High-altitude hypoxia significantly affects advanced neurobehaviors including learning and memory (L&M). Hippocampus, the integration center of L&M, could be the most crucial target affected by high-altitude hypoxia exposure. Based on these points, this review thoroughly discussed the relationship between high-altitude hypoxia and L&M impairment, in terms of hippocampal neuron apoptosis and dysfunction, neuronal oxidative stress disorder, neurotransmitters and related receptors, and nerve cell energy metabolism disorder, which is of great significance to find potential targets for medical intervention. Studies illustrate that the mechanism of L&M damaged by high-altitude hypoxia should be further investigated based on the entire review of issues related to this topic.