Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway.

Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to be extensively investigated. The Morris water maze test was utilized to assess cognitive performance. RNA sequencing was employed to discover the primary regulators and pathological pathways involved in cognitive impairment caused by heat. Before heat exposure in vivo and in vitro, activation of the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) was achieved by CDN1163. Hematoxylin-Eosin, Nissl staining, calcium imaging, transmission electron microscopy, western blot, and immunofluorescence were utilized to visualize histological changes, intracellular calcium levels, endoplasmic reticulum stress (ERS) markers, apoptosis, and synaptic proteins alterations. Heat stress (HS) significantly induced cognitive decline and neuronal damage in mice. By the transcriptome sequencing between control (n = 5) and heat stress (n = 5) mice in hippocampal tissues, we identified a reduction in the expression of the atp2a gene encoding SERCA, accompanied by a corresponding decrease in its protein level. Consequently, this dysregulation resulted in an excessive accumulation of intracellular calcium ions. Furthermore, HS exposure also activated ERS and apoptosis, as evidenced by the upregulation of p-PERK, p-eIF2α, CHOP, and caspase-3. Consistently, a reduction in postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expressions indicated modifications in synaptic function. Notably, the impacts on neurons caused by HS were found to be mitigated by CDN1163 treatment both in vivo and in vitro. Additionally, SERCA-mediated ERS-induced apoptosis was attenuated by GSK2606414 treatment via inhibiting PERK-eIF2α-CHOP axis that not only curtailed the level of caspase-3 but also elevated the levels of PSD95 and SYN. These findings highlight the significant impact of heat stress on cognitive impairment, and further elucidate the underlying mechanism involving SERCA/PERK/eIF2α pathway.

Product maturation and antibiotic resistance genes enrichment in food waste digestate and Chinese medicinal herbal residues co-composting.

The land application of food waste digestate (FWD) requires a composting process to improve its soil amendment performance and alleviate environmental risks. This study proposed co-composting of Chinese medicinal herbal residues (CMHRs) and FWD as a means to improve the maturation performance and investigated the evolution of antibiotic resistance genes (ARGs). Results demonstrated that CMHRs addition effectively accelerated the maturity of FWD composting to less than 35 days, remarkably removed its remaining antibiotics by 83.0% and promoted the formation of humification substances. However, both quantitative PCR and 16S rRNA sequencing analysis indicated that a significant enrichment of ARGs and mobile genetic elements including frA1, tetX, blaTEM, InuB-01, aadA2-02 and IntI-1 was observed via the co-composting of FWD and CMHRs. These results indicated that the land application of products obtained from FWD and CMHRs co-composting is at risk of spreading ARGs, although the composting process could be significantly improved.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace.

OBJECTIVE: This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD). METHODS: The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted. RESULTS: Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression. CONCLUSION: Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Valorization of Biomass-Derived Polymers to Functional Biochar Materials for Supercapacitor Applications via Pyrolysis: Advances and Perspectives.

Polymers from biomass waste including plant/forest waste, biological industrial process waste, municipal solid waste, algae, and livestock are potential sources for renewable and sustainable resources. Converting biomass-derived polymers to functional biochar materials via pyrolysis is a mature and promising approach as these products can be widely utilized in many areas such as carbon sequestration, power production, environmental remediation, and energy storage. With abundant sources, low cost, and special features, the biochar derived from biological polymeric substances exhibits great potential to be an alternative electrode material of high-performance supercapacitors. To extend this scope of application, synthesis of high-quality biochar will be a key issue. This work systematically reviews the char formation mechanisms and technologies from polymeric substances in biomass waste and introduces energy storage mechanisms of supercapacitors to provide overall insight into the biological polymer-based char material for electrochemical energy storage. Aiming to enhance the capacitance of biochar-derived supercapacitor, recent progress in biochar modification approaches including surface activation, doping, and recombination is also summarized. This review can provide guidance for valorizing biomass waste to functional biochar materials for supercapacitor to meet future needs.

Nutritional supplements formulated to prevent cognitive impairment in animals.

Heat stress will cause a series of response in the living system and the most significant impact is on brain functions. The aim of this article is to develop nutritional supplements that can alleviate cognitive decline caused by heat stress. In this article, we screen functional food factors which can prevent or relieve effects on heat stress injury based on bioinformatics. 129 function factors related to the crossover targets were obtained, and a food database related to the prevention of high-temperature impairment was constructed. After a series of scoring standards combined with food classification, two formulas-nutrition fortifier formula (tyrosine and multivitamin B) and plant compound formula (quercetin, proanthocyanidin, and naringin) were investigated using animal experiments to determine their ability to prevent cognitive impairment of heat-stressed animals. Our results demonstrated that certain functional food factors and our two designed formulations significantly prevent cognitive impairment of heat-stressed animals. Further mechanism was carried out by cell viability assay, reactive oxygen species assay, real-time quantitative PCR and Western blot. The results showed that the plant compound formula diluted 4000 times had the best relieving effect on HT22 after heat stress, and this concentration formula can significantly alleviate the elevated levels of reactive oxygen species caused by heat stress. This formula also can significantly down-regulate IL-1ß, IL-6, TNF-α, IL-10, iNOS and COX-2 expression. Likewise, Western blot results showed that the formula could activate the cAMP pathway and increase the expression of phosphorylated PKA and BDNF in hippocampal cells.

The combination of HT-ac and HBET improves the cognitive and learning abilities of heat-stressed mice by maintaining mitochondrial function through the PKA-CREB-BDNF pathway.

The aim was to investigate whether the combination of hydroxytyrosol acetate (HT-ac) and ethyl ß-hydroxybutyrate (HBET) can improve the cognition of heat-stressed mice, meanwhile exploring the mechanism of action. Mice were divided into 5 groups: control, heat-stressed, HT-ac, HBET, and HT-ac + HBET. Mice were gavaged for 21 days and exposed to heat (42.5 ± 0.5 °C, RH 60 ± 10%, 1 h day-1) on days 15-21, except for the control group. Results showed that the combination of HT-ac + HBET improved the cognitive and learning abilities of heat-stressed mice, which were tested by Morris water maze, shuttle box, and jumping stage tests. The combination of HT-ac + HBET maintained the integrity of neurons and mitochondria of heat-stressed mice. Likewise, this combination increased the mitochondrial membrane potential, the ATP content, the expression of phosphorylated PKA, BDNF, phosphorylated CREB and Bcl-2, and decreased the expression of Bax, caspase-3, and intracytoplasmic Cyt C in heat-stressed mice.

Bioelectrochemical assisted landfill technology for the stabilization and valorization of food waste anaerobic digestate.

Anaerobic digestion provides an important approach for food waste treatment and valorization, yet a considerable amount of digestate is produced. The appropriate management and utilization of food waste anaerobic digestate is highly desirable for solving both environmental and economic concerns currently. This work innovatively develops a natural potential difference assisted landfill technology (shown as BESAL) for food waste digestate treatment and energy recovery. The results demonstrate the electrochemical assistant accelerates the stabilization of digestate, provides extra 14.89% of organic matter removal and 20.92 mW/m2 of electrical energy recovery over conventional treatment. BESAL promotes the removal of soluble matters in digestate extraction, prevents 13.07 mg/g ammonium-N and 32.87% of total VFAs from accumulation. BESAL also performs gene level stabilization by inhibiting/eliminating microbial and pathogenic gene to ensure the biosafety in its product. Integrated landfill with bioelectrochemical assistance provides a promising option for organic waste stabilization and valorization.

The EMT-induced lncRNA NR2F1-AS1 positively modulates NR2F1 expression and drives gastric cancer via miR-29a-3p/VAMP7 axis.

Deregulated lncRNAs play critical roles in tumorigenesis and tumor progression. NR2F1-AS1 is an antisense lncRNA of NR2F1. However, the biological function of NR2F1-AS1 in gastric cancer (GC) remains largely unclear. In this study, we revealed that NR2F1-AS1 and NR2F1 were both positively correlated with the degree of malignancy and predicted poor prognosis in two independent GC cohorts. Besides, NR2F1-AS1 and NR2F1 can respond to Epithelial-to-mesenchymal transition (EMT) signaling in GC, since their expression was increased by TGF-beta treatment and decreased after stable overexpression of OVOL2 in GC cell lines. NR2F1-AS1 and NR2F1 were highly co-expressed in pan-tissues and pan-cancers. Depletion of NR2F1-AS1 compromised the expression level of NR2F1 in GC cells. Furthermore, NR2F1-AS1 knockdown inhibited the proliferation, migration, invasion and G1/S transition of GC cells. More importantly, transcriptome sequencing revealed a novel ceRNA network composed of NR2F1-AS1, miR-29a-3p, and VAMP7 in GC. The overexpression of VAMP7 predicted poor prognosis in GC. Rescue assay confirmed that NR2F1-AS1 promotes GC progression through miR-29a-3p/VAMP7 axis. Our finding highlights that the aberrant expression of NR2F1-AS1 is probably due to the abnormal EMT signaling in GC. LncRNA NR2F1-AS1 plays crucial roles in GC progression by modulating miR-29a-3p/VAMP7 axis, suggesting that NR2F1-AS1 may serve as a potential therapeutic target in GC.

miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors.

BACKGROUND: Chronic stress is one of the most important causes of depression, accompanied by neuroinflammation and hippocampal injuries. Long-term elevation of glucocorticoid leads to activation of NF-κB and inhibition of GPR39/CREB/BDNF pathway, which is pivotal for neuroprotection and neurogenesis. The present study thus was designed to determine the relationship between NF-κB and GPR39/CREB/BDNF pathway. METHODS: Depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) in mice. Corticosterone, inflammatory cytokines, and GPR39/CREB/BDNF pathway were determined by ELISA and Western Blot assays. The activation of NF-κB and inhibition of GPR39 were connected by bioinformatic analysis and experimentally validated in hippocampus cells by knock-in and knock-down techniques. RESULTS: CUMS and CRS led to an elevation of serum corticosterone and depressive-like behaviors in mice, with activation of NF-κB subunit p65 in the hippocampus and elevations of TNFα and IL-6. The expression of GPR39/CREB/BDNF pathway in the hippocampus was inhibited. Bioinformatic analysis revealed that four miRNAs, miR-96, miR-143, miR-150, and miR-182, were potentially transcribed by NF-κB and bound with GPR39 mRNA. NF-κB overexpression increased miR-182 expression and decreased GPR39 expression in hippocampus cells. Its inhibitor led to reverse effects. miR-182 mimics or inhibitors also regulated GPR39 expression in hippocampus cells and more importantly, blocked the regulation of NF-κB on GPR39. CONCLUSIONS: The results suggested that activation of NF-κB inhibited GPR39/CREB/BDNF pathway through increasing miR-182 in chronic stress-induced depressive-like behaviors. The negative-regulation features of miRNAs might be important for neuroinflammation-induced inhibition of neurofunction in depression.

GPR39 protects against corticosterone-induced neuronal injury in hippocampal cells through the CREB-BDNF signaling pathway.

BACKGROUND: The release of zinc from glutamatergic terminals in the hippocampal CA3 region can activate postsynaptic GPR39 receptors and regulate cognition and depression. However, the role and mechanism of GPR39 in the stress-induced depression is still poorly understood. METHODS: In this study, hippocampal cells (HT-22) were treated with corticosterone (CORT). Then the effects of stress on the activity, mitochondrial function and apoptosis of HT-22 cells were observed. The effects of GPR39 on CORT-induced stress injury were analyzed by both siRNA and agonist (TC-G-1008). RESULTS: Compared with the 500 nM CORT group, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly increased in the GPR39 siRNA+500 nM CORT group. Compared with the 1 µM CORTgroup, the cell viability, apoptosis, mitochondrial membrane potential, and expression levels of BCL-2, CREB and BDNF were significantly increased in the GPR39 agonist+1 µΜ CORT group, while the expression levels of caspase3, caspase9, AIF and BAX mRNA were significantly decreased in the GPR39 siRNA+500 nM CORT group. Compared with the control group, the mRNA and protein levels of GPR39, CREB and BDNF were significantly increased, and the mRNA and protein levels of CREB and BDNF were significantly decreased after 50 µM zinc sulfate treatment for 6 h. CONCLUSIONS: GPR39 may play a neuroprotective role in CORT-induced cell injury via the improvement of CREB-BDNF expression, by inhibiting pro-apoptotic proteins and by upregulating anti-apoptotic proteins.

Detoxification of aflatoxin B1 by Stenotrophomonas sp. CW117 and characterization the thermophilic degradation process.

Mycotoxins are high toxic, widely distributed contaminants in foodstuff. In this study, a aflatoxin B1 (AFB1) degrading strain S. acidoaminiphila CW117 was screened, and its detoxification characteristics were investigated. Substrate AFB1 at 45 µg/L was degraded by CW117 within 24 h; meanwhile, 4.1 mg/L AFB1 was almost degraded within 48 h. After 24 h degradation, the biotoxicity of the detoxified culture was eliminated. Strain CW117 efficient degradation to AFB1 (especially to low AFB1 concentrations) suggested its potential significance to detoxification development on food and feedstuff. The active degradation components present in the cell-free supernatant. The degradation ratio increased constantly with increasing incubation temperature raised (0-90 °C) and was even stable at 90 °C. Degradation was optimal at pH 6-7, and was only partially inhibited by metal-chelators (EDTA and EGTA), proteinase K, and a protein denaturant (sodium dodecyl sulfate, SDS). The recombinant laccase rLC1 (0.5 mg/mL) from CW117 degraded 29.3% of AFB1 within 24 h; however, the cell-free supernatant degraded 76.7% of the toxin in same time, with much lower protein content. The results indicated the CW117 degrades AFB1 via a combination of enzymes and micro-molecule oxides.

Biological influence of cry1Ab gene insertion on the endophytic bacteria community in transgenic rice.

The commercial release of genetically modified (GMO) rice for insect control in China is a subject of debate. Although a series of studies have focused on the safety evaluation of the agroecosystem, the endophytes of transgenic rice are rarely considered. Here, the influence of endophyte populations and communities was investigated and compared for transgenic and nontransgenic rice. Population-level investigation suggested that cry1Ab gene insertion influenced to a varying degree the rice endophytes at the seedling stage, but a significant difference was only observed in leaves of Bt22 (Zhejiang22 transgenic rice) between the GMO and wild-type rice. Community-level analysis using the 16S rRNA gene showed that strains of the phyla Proteobacteria and Firmicutes were the predominant groups occurring in the three transgenic rice plants and their corresponding parents. By contrast, the endophytic communities of Minghui63 and Xiushui11 showed a weaker response to cry1Ab gene insertion than did Zhejiang22, and the community results were consistent with the population-level investigation. The populations and communities of rice endophytes were affected by the cry1Ab gene to a different extent in different rice varieties and plant tissues. The results of this study broaden our understanding of unexpected transgenic influences on nontarget organisms.