Molecular interaction mechanism for humic acids fouling resistance on charged, zwitterion-like and zwitterionic surfaces.

Humic acids (HA) are ubiquitous in surface waters, leading to significant fouling challenges. While zwitterion-like and zwitterionic surfaces have emerged as promising candidates for antifouling, a quantitative understanding of molecular interaction mechanism, particularly at the nanoscale, still remains elusive. In this work, the intermolecular forces between HA and charged, zwitterion-like or zwitterionic monolayers in aqueous environments were quantified using atomic force microscope. Compared to cationic MTAC ([2-(methacryloyloxy)ethyl]trimethylammonium chloride), which exhibited an adhesion energy of âˆ¼1.342 mJ/m2 with HA due to the synergistic effect of electrostatic attraction and possible cation-π interaction, anionic SPMA (3-sulfopropyl methacrylate) showed a weaker adhesion energy (∼0.258 mJ/m2) attributed to the electrostatic repulsion. Zwitterion-like MTAC/SPMA mixture, driven by electrostatic attraction between opposite charges, formed a hydration layer that prevented the interaction with HA, thereby considerably reducing adhesion energy to âˆ¼0.123 mJ/m2. In contrast, zwitterionic MPC (2-methacryloyloxyethyl phosphorylcholine) and DMAPS ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide) displayed ultralow adhesion energy (0.06-0.07 mJ/m2) with HA, arising from their strong dipole moments which could induce a tight hydration layer that effectively inhibited HA fouling. The pH-mediated electrostatic interaction resulted in the increased adhesion energy for MTAC but decreased adhesion energy for SPMA with elevated pH, while the adhesion energy for zwitterion-like and zwitterionic surfaces was independent of environmental pH. Density functional theory (DFT) simulation confirmed the strong binding capability of MPC and DMAPS with water molecules (∼-12 kcal mol-1). This work provides valuable insights into the molecular interaction mechanisms underlying humic-substance-fouling resistance of charged, zwitterion-like and zwitterionic materials at the nanoscale, shedding light on developing more effective strategy for HA antifouling in water treatment.

Efficacy of PE-PLIF with a novel ULBD approach for lumbar degeneration diseases: a large-channel endoscopic retrospective study.

PURPOSE: This study aims to assess the effectiveness of Percutaneous Endoscopic Posterior Lumbar Interbody Fusion (PE-PLIF) combined with a novel Unilateral Laminotomy for Bilateral Decompression (ULBD) approach using a large-channel endoscope in treating Lumbar Degenerative Diseases (LDD). METHODS: This retrospective analysis evaluates 41 LDD patients treated with PE-PLIF and ULBD from January 2021 to June 2023. A novel ULBD approach, called 'Non-touch Over-Top' technique, was utilized in this study. We compared preoperative and postoperative metrics such as demographic data, Visual Analogue Scale (VAS) for pain, Oswestry Disability Index (ODI), Japanese Orthopedic Association (JOA) score, surgical details, and radiographic changes. RESULTS: The average follow-up duration was 14.41 ± 2.86 months. Notable improvements were observed postoperatively in VAS scores for back and leg pain (from 5.56 ± 0.20 and 6.95 ± 0.24 to 0.20 ± 0.06 and 0.12 ± 0.05), ODI (from 58.68 ± 0.80% to 8.10 ± 0.49%), and JOA scores (from 9.37 ± 0.37 to 25.07 ± 0.38). Radiographic measurements showed significant improvements in lumbar and segmental lordosis angles, disc height, and spinal canal area. A high fusion rate (97.56% at 6 months, 100% at 12 months) and a low cage subsidence rate (2.44%) were noted. CONCLUSIONS: PE-PLIF combined with the novel ULBD technique via a large-channel endoscope offers significant short-term benefits for LDD management. The procedure effectively expands spinal canal volume, decompresses nerve structures, improves lumbar alignment, and stabilizes the spine. Notably, it improves patients' quality of life and minimizes complications, highlighting its potential as a promising LDD treatment option.

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury.

JOURNAL/nrgr/04.03/01300535-202409000-00033/figure1/v/2024-01-16T170235Z/r/image-tiff We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury. However, its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear. In this study, we first used an HT22 scratch injury model to mimic traumatic brain injury, then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p. We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress. Furthermore, luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α, while an IRE1α functional salvage experiment confirmed that miR-124-3p targeted IRE1α and reduced its expression, thereby inhibiting endoplasmic reticulum stress in injured neurons. Finally, we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced. These findings suggest that, after repetitive mild traumatic brain injury, miR-124-3 can be transferred from microglia-derived exosomes to injured neurons, where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress. Therefore, microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

The efficacy and safety of ultrasonic bone scalpel for removing retrovertebral osteophytes in anterior cervical discectomy and fusion: A retrospective study.

In this study, we present a novel surgical method that utilizes the ultrasonic bone scalpel (UBS) for the removal of large retrovertebral osteophytes in anterior cervical discectomy and fusion (ACDF) and evaluate its safety and efficacy in comparison to the traditional approach of using high-speed drill (HSD). A total of 56 patients who underwent ACDF for retrovertebral osteophytes were selected. We recorded patients' baseline information, operation time, intraoperative blood loss, complications, JOA and VAS scores, and other relevant data. The mean operation time and the mean intraoperative blood loss in the UBS group were less than those in the HSD group (P < 0.05). Although both groups exhibited considerable improvements in JOA and VAS scores following surgery, there was no statistically significant difference between the two groups (P > 0.05). Additionally, no significant disparities were found in bone graft fusion between the two groups at 6- and 12-months postsurgery. Notably, neither group exhibited complications such as dura tear or spinal cord injury. Our study found that the use of UBS reduced operative time, minimized surgical bleeding, and led to clinical outcomes comparable to HSD in ACDF. This technique offers an effective and safe method of removing large retrovertebral osteophytes.

Understanding the role of infusing lubricant composition in the interfacial interactions and properties of slippery surface.

Liquid-infused surfaces (LISs) have attracted tremendous attention in recent years owing to their excellent surface properties, such as self-cleaning and anti-fouling. Understanding the effect of lubricant composition on LIS performance is of vital importance, which will help establish the criteria to choose suitable infusing lubricants for specific applications. In this work, the role of chemical composition of lubricant in the properties of LISs was investigated. The apparent water contact angle θapp was dependent on the temperature and beeswax/silicone oil ratio. Nevertheless, the trend of moving velocity of water drop on the tilted LISs did not follow that of θapp at 20 °C and 37 °C, which was attributed to the increased lubricant viscosity with beeswax/silicone oil ratio. At 60 °C, the drop velocity and θapp shared the similar variation trend with beeswax/silicone oil ratio, highlighting the significant role of chemistry of the components in beeswax. The alkanes and fatty acids promoted the drop movement, while the fatty acid esters impeded the movement. The interaction forces between water drop and lubricant surfaces were measured using atomic force microscopy. It was demonstrated that the interaction between water drop and lubricant was not the only factor to control the drop movement, while the interaction between lubricant and substrate as well as of lubricant itself also determined the movement. When the adhesions of water-lubricant and lubricant-substrate were similar for different lubricants, the influence of cohesion of lubricant became significant. This work provides useful insights into the fundamental understanding of the interfacial interactions of test drop, infusing lubricant and solid substrate of LISs, and the effect of infusing lubricant composition on the LIS performance.

Breeding of high-tolerance yeast by adaptive evolution and high-gravity brewing of mutant.

BACKGROUND: Ethanol and osmotic stresses are the major limiting factors for brewing strong beer with high-gravity wort. Breeding of yeast strains with high osmotic and ethanol tolerance and studying very-high-gravity (VHG) brewing technology is of great significance for brewing strong beer. RESULTS: This study used an optimized microbial microdroplet culture (MMC) system for adaptive laboratory evolution (ALE) of Saccharomyces cerevisiae YN81 to improve its tolerance to osmotic and ethanol stress. Meanwhile, we investigated the VHG and VHG with added ethanol (VHGAE) brewing processes for the evolved mutants in brewing strong beer. The results showed that three evolved mutants were obtained; among them, the growth performance of YN81mc-8.3 under 300, 340, 380, 420 and 460 g L-1 sucrose stresses was greater than that of the other strains. The ethanol tolerance of YN81mc-8.3 was 12%, which was 20% higher than that of YN81. During strong-beer brewing in a 100 L cylindrical cone-bottom tank, the sugar utilization and ethanol yield of YN81mc-8.3 outperformed those of YN81 in both the VHG and VHGAE brewing processes. Measurement of the diacetyl concentration showed that YN81mc-8.3 had a stronger diacetyl reduction ability; in particular, the real degree of fermentation of beers brewed by YN81mc-8.3 in VHG and VHGAE brewing processes was 75.35% and 66.71%, respectively - higher than those of the two samples brewed by YN81. Meanwhile, the visual, olfactive and gustative properties of the strong beer produced by YN81mc-8.3 were better than those of the other beers. CONCLUSION: In this study, the mutant YN81mc-8.3 and the VHGAE brewing process were optimal and represented a better alternative strong-beer brewing process. © 2023 Society of Chemical Industry.

Quorum sensing: cell-to-cell communication in Saccharomyces cerevisiae.

Quorum sensing (QS) is one of the most well-studied cell-to-cell communication mechanisms in microorganisms. This intercellular communication process in Saccharomyces cerevisiae began to attract more and more attention for researchers since 2006, and phenylethanol, tryptophol, and tyrosol have been proven to be the main quorum sensing molecules (QSMs) of S. cerevisiae. In this paper, the research history and hotspots of QS in S. cerevisiae are reviewed, in particular, the QS system of S. cerevisiae is introduced from the aspects of regulation mechanism of QSMs synthesis, influencing factors of QSMs production, and response mechanism of QSMs. Finally, the employment of QS in adaptation to stress, fermentation products increasing, and food preservation in S. cerevisiae was reviewed. This review will be useful for investigating the microbial interactions of S. cerevisiae, will be helpful for the fermentation process in which yeast participates, and will provide an important reference for future research on S. cerevisiae QS.

Growth of alfalfa in the presence of metabolites from a dark septate endophyte strain Alternaria sp. 17463 cultured with a nonionic surfactant and emulsifier.

AIM: Dark septate endophytes (DSE) were widely used in the agriculture and ecological restoration. The objective of this work was to assess the effect of culture media nonionic surfactant and emulsifier on the biomass and metabolites of DSE strain Alternaria sp. 17463. METHODS AND RESULTS: Changes in the composition of DSE metabolites following the addition of Tween 80 during liquid culture of a DSE fungus were analyzed and used in growth tests of alfalfa.Shaking flask fermentation was carried out and the surfactant was fed to the fungus during the fermentation. The residual sugar content and pH declined significantly in the medium and the biomass of DSE increased by 7.27% over controls with no surfactant. Metabolomic analysis showed that adding the surfactant significantly increased the content of 63 metabolites (P < 0.05). These include lipids and lipid-like molecules, organooxygen compounds, amino acids and organic acids, and flavonoids. Enrichment analysis of metabolic pathways indicates that surfactant addition promoted carbohydrate metabolism and amino acid synthesis. A plant hydroponic experiment indicated that these changes in metabolites altered the root structure of alfalfa seedlings. They also promoted significant increases in root length and root surface area, and increased alfalfa total biomass by 50.2%. CONCLUSIONS: The addition of the surfactant promoted sugar utilization by the DSE fungus and increased the synthesis of lipids and amino acids, resulting in the ability of the fungal metabolites to change root structure and promote plant growth.

Potential blood biomarkers for chronic traumatic encephalopathy: The multi-omics landscape of an observational cohort.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, which is susceptible in elderly people with declined mobility, athletes of full contact sports, military personnel and victims of domestic violence. It has been pathologically diagnosed in brain donors with a history of repetitive mild traumatic brain injury (rmTBI), but cannot be clinically diagnosed for a long time. By the continuous efforts by neuropathologists, neurologists and neuroscientists in recent 10 years, an expert consensus for the diagnostic framework of CTE was proposed in 2021 funded by the National Institute of Neurological Disorders and Stroke. The new consensus contributes to facilitating research in the field. However, it still needs to incorporate in vivo biomarkers to further refine and validate the clinical diagnostic criteria. From this, a single-center, observational cohort study has been being conducted by Tianjin Medical University General Hospital since 2021. As a pilot study of this clinical trial, the present research recruited 12 pairs of gender- and age-matched rmTBI patients with healthy subjects. Their blood samples were collected for exosome isolation, and multi-omics screening to explore potential diagnostic biomarkers in blood and its exosomes. The expression level of CHL1 protein, KIF2A mRNA, LIN7C mRNA, miR-297, and miR-1183 in serum and exosomes were found to be differentially expressed between groups. Besides, serum and exosomal CHL1, KIF2A, and miR-1183, as well as exosomal miR-297 were further verified as potential biomarkers for CTE by low-throughput assays. They are expected to contribute to establishing a novel set of CTE diagnostic signatures with classic neurodegenerative indicators in our future study, thereby updating the consensus diagnostic criteria for CTE by incorporating new evidence of the in vivo biomarkers.

Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy.

Hippocampal neurons are sensitive to changes in the internal environment and play a significant role in controlling learning, memory, and emotions. A remarkable characteristic of the aging brain is its ability to shift from a state of normal inflammation to excessive inflammation. Various cognitive abilities of the elderly may suffer from serious harm due to the change in the neural environment. Hippocampal neurons may have various subsets involved in controlling their internal environment at different stages of development. Developmental differences may eventually result from complex changes in the dynamic neuronal system brought on by metabolic changes. In this study, we used an in vitro hippocampal neuron model cultured in C57BL/6J mice in conjugation with Raman spectroscopy to examine the relative alterations in potential biomarkers, such as levels of metabolites in the internal environment of hippocampal neurons at various developmental stages. The various differentially expressed genes (DEGs) of hippocampal neurons at various developmental stages were simultaneously screened using bioinformatics, and the biological functions as well as the various regulatory pathways of DEGs were preliminarily analyzed, providing an essential reference for investigating novel therapeutic approaches for diseases that cause cognitive impairment, such as Alzheimer's disease. A stable hippocampal neuron model was established using the GIBCO C57BL/6J hippocampal neuron cell line as a donor and in vitro hippocampal neuron culture technology. The Raman peak intensities of culture supernatants from the experimental groups incubated for 0, 7, and 14 days in vitro(DIV) were examined. The GEO database was used to screen for different DEGs associated with various developmental stages. The data was then analyzed using a statistical method called orthogonal partial least squares discriminant analysis (OPLS-DA). The levels of ketogenic and glycogenic amino acids (such as tryptophan, phenylalanine, and tyrosine), lipid intake rate, glucose utilization rate, and nucleic acid expression in the internal environment of hippocampal neurons were significantly different in the 14 DIV group compared to the 0 DIV and 7 DIV groups (P < 0.01). The top 10 DEGs with neuronal maturation were screened, and the results were compared to the OPLS-DA model's analysis of the differential peaks. It was found that different genes involved in maturation can directly relate to changes in the body's levels of ketogenic and glycogenic amino acids (P < 0.01). The altered expression of the maturation-related genes epidermal growth factor receptor, protein tyrosine kinase 2-beta, discs large MAGUK scaffold protein 2, and Ras protein-specific guanine nucleotide releasing factor 1 may be connected to the altered uptake of ketogenic and glycogenic amino acids and nucleic acids in the internal environment of neurons at different developmental stages. The levels of ketogenic, glycogenic amino acids, and lipid intake increased while glucose utilization decreased, which may be related to mature neurons' metabolism and energy use. The decline in nucleic acid consumption could be connected to synaptic failure. The Raman spectroscopy fingerprint results of relevant biomarkers in conjugation with multivariable analysis and biological action targets suggested by differential genes interpret the heterogeneity of the internal environment of mature hippocampal neurons in the process of maturation, open a new idea for exploring the dynamic mechanism of the exchange energy metabolism of information molecules in the internal environment of hippocampal neurons, and provide a new method for studying this process.

Screening and transcriptomic analysis of the ethanol-tolerant mutant Saccharomyces cerevisiae YN81 for high-gravity brewing.

Ethanol stress is one of the major limiting factors for high-gravity brewing. Breeding of yeast strain with high ethanol tolerance, and revealing the ethanol tolerance mechanism of Saccharomyces cerevisiae is of great significance to the production of high-gravity beer. In this study, the mutant YN81 was obtained by ultraviolet-diethyl sulfate (UV-DES) cooperative mutagenesis from parental strain CS31 used in high-gravity craft beer brewing. The ethanol tolerance experiment results showed that cell growth and viability of YN81 were significantly greater than that of CS31 under ethanol stress. The ethanol tolerance mechanisms of YN81 were studied through observation of cell morphology, intracellular trehalose content, and transcriptomic analysis. Results from scanning electron microscope (SEM) showed alcohol toxicity caused significant changes in the cell morphology of CS31, while the cell morphology of YN81 changed slightly, indicating the cell morphology of CS31 got worse (the formation of hole and cell wrinkle). In addition, compared with ethanol-free stress, the trehalose content of YN81 and CS31 increased dramatically under ethanol stress, but there was no significant difference between YN81 and CS31, whether with or without ethanol stress. GO functional annotation analysis showed that under alcohol stress, the number of membrane-associated genes in YN81 was higher than that without alcohol stress, as well as CS31, while membrane-associated genes in YN81 were expressed more than CS31 under alcohol stress. KEGG functional enrichment analysis showed unsaturated fatty acid synthesis pathways and amino acid metabolic pathways were involved in ethanol tolerance of YN81. The mutant YN81 and its ethanol tolerance mechanism provide an optimal strain and theoretical basis for high-gravity craft beer brewing.

Mesenchymal stromal cell treatment attenuates repetitive mild traumatic brain injury-induced persistent cognitive deficits via suppressing ferroptosis.

The incidence of repetitive mild traumatic brain injury (rmTBI), one of the main risk factors for predicting neurodegenerative disorders, is increasing; however, its underlying mechanism remains unclear. As suggested by several studies, ferroptosis is possibly related to TBI pathophysiology, but its effect on rmTBI is rarely studied. Mesenchymal stromal cells (MSCs), the most studied experimental cells in stem cell therapy, exert many beneficial effects on diseases of the central nervous system, yet evidence regarding the role of MSCs in ferroptosis and post-rmTBI neurodegeneration is unavailable. Our study showed that rmTBI resulted in time-dependent alterations in ferroptosis-related biomarker levels, such as abnormal iron metabolism, glutathione peroxidase (GPx) inactivation, decrease in GPx4 levels, and increase in lipid peroxidation. Furthermore, MSC treatment markedly decreased the aforementioned rmTBI-mediated alterations, neuronal damage, pathological protein deposition, and improved cognitive function compared with vehicle control. Similarly, liproxstatin-1, a ferroptosis inhibitor, showed similar effects. Collectively, based on the above observations, MSCs ameliorate cognitive impairment following rmTBI, partially via suppressing ferroptosis, which could be a therapeutic target for rmTBI.

Isolation, Mutagenesis, and Organic Acid Secretion of a Highly Efficient Phosphate-Solubilizing Fungus.

The highly effective phosphate-solubilizing microorganisms are significant for making full use of the potential phosphorus resources in the soil and alleviating the shortage of phosphorus resources. In this study, a phosphate-solubilizing fungus was isolated from wheat and cotton rhizosphere soils in the lower reaches of the Yellow River in China and was identified as Penicillium oxalicum by morphological and ITS sequencing analysis. In order to obtain a fungus with more efficient phosphorus solubilization ability, we tested three positive mutant strains (P1, P2, and P3) and three negative mutant strains (N1, N2, and N3) through low-energy nitrogen ion implantation mutagenesis. Compared with the parental strain, the phosphate-solubilizing capacity of P1, P2, and P3 was enhanced by 56.88%, 42.26%, and 32.15%, respectively, and that of N1, N2, and N3 was weakened by 47.53%, 35.27%, and 30.86%, respectively. Compared with the parental strain, the total amount of organic acids secreted significantly increased in the three positive mutant strains and decreased in the negative mutant strains; the pH of culture medium was significantly lower in the positive mutant strains and higher in the negative mutant strains. The capacity of phosphate-solubilizing fungus to secrete organic acids and reduce the growth-medium pH was closely related to its phosphate-solubilizing ability. The changes in the amount of organic acids secreted by mutants can alter their acidification and phosphate-solubilizing capacity. In conclusion, this study offers a theoretical basis and strain materials for the exploration and application of phosphate-solubilizing fungi.

Inhibition of Exosome Release Alleviates Cognitive Impairment After Repetitive Mild Traumatic Brain Injury.

BACKGROUND: Repetitive mild traumatic brain injury (rmTBI) is closely associated with chronic traumatic encephalopathy (CTE). Neuroinflammation and neuropathological protein accumulation are key links to CTE progression. Exosomes play important roles in neuroinflammation and neuropathological protein accumulation and spread. Here, we explored the role of brain-derived exosomes (BDEs) in mice with rmTBI and how the inhibition of BDE release contributes to neuroprotection. METHODS: GW4869 was used to inhibit exosome release, and behavioural tests, PET/CT and western blotting were conducted to explore the impact of this inhibition from different perspectives. We further evaluated cytokine expression by Luminex and microglial activation by immunofluorescence in mice with rmTBI after exosome release inhibition. RESULTS: Inhibition of BDE release reversed cognitive impairment in mice with rmTBI, enhanced glucose uptake and decreased neuropathological protein expression. Inhibition of BDE release also changed cytokine production trends and enhanced microglial proliferation. CONCLUSION: In this study, we found that BDEs are key factor in cognitive impairment in mice with rmTBI and that microglia are the main target of BDEs. Thus, inhibition of exosome release may be a new strategy for improving CTE prognoses.

MiR-124-3p attenuates brain microvascular endothelial cell injury in vitro by promoting autophagy.

Traumatic brain injury (TBI) can cause the pathological disruption of the blood-brain barrier (BBB) and associated neurological injury. Reducing the severity of such barrier disruption following TBI can decrease the degree of brain edema, suppress intracranial inflammation, and thereby protect against neurological damage. The BBB is made up of brain microvascular endothelial cells (BMVECs), neurons, pericytes, astrocytes, and extracellular matrix components. In prior analyses, we have demonstrated that miR-124-3p expression is enhanced in microglia-derived exosomes following TBI, with this miRNA being capable of promoting neural repair after such injury. Based upon these results, the present study was formulated to examine the impact of miR-124-3p on BMVEC function and to evaluatethe mechanistic basis for its activity by overexpressing miR-124-3p in these endothelial cells. We utilized a bEnd.3 cell scratch wound in vitro model to simulate TBI-associated brain microvascular endothelial cell injury. Lipofectamine3000 was used to transfect endothelial cells such that they overexpressed miR-124-3p. Fluorescence microscopy was used to observe the effects of miR-124-3p expression on these endothelial cells. TUNEL+CD31 immunofluorescence stainingwas employed to observe endothelial cell apoptosis. Tight junctions were observed via ionconductivity microscopy. Western blotting was used to detect the expression of tight junction proteins (occludin, ZO-1), autophagy-associated proteins (Beclin-1, p62, LC3-II/LC3-I), and mTOR-associated proteins (p-mTOR, PDE4B). Chloroquine was used to treat these injured endothelial cells overexpressing miR-124-3p, and endothelial cell apoptosis was assessed via TUNEL+CD31 immunofluorescence staining. We found that the upregulation of miR-124-3p was sufficient to suppress bEnd.3 cell apoptotic death following in vitro scratch injury while promoting the upregulation of the tight junction proteins ZO-1 and occludin in these cells, thereby reducing the degree of leakage across the cerebral microvascular endothelial barrier. These protective effects may be related to the ability of miR-124-3p to suppress mTOR signaling and to induce autophagic activity within BMVECs. These data support a model wherein miR-124-3p can inhibit mTOR signaling and promote autophagic induction in BMVECs, thereby protecting these cells against TBI-induced damage.

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The high-efficiency phosphate solubilizing mutants of Penicillium oxalicum YTY were screened by mutagenesis of ion beam combined with UV. We analyzed the changes and correlation of phosphate solubilizing ability, pH, and organic acid for YTY and its mutants, and examined the phosphate solubilizing mechanism of P. oxalicum YTY. The results showed that five high-efficiency mutants, P9-8, P9-9, P15-4, P15-6, and P15-7 were screened, and that the phosphate solubili-zing ability of mutants was increased by more than 60% compared with YTY. In the process of pho-sphorus solubilization, both phosphorus solubilizing ability and rate of mutants were higher than that of YTY, and the mutants pH was significantly lower than YTY. The type and content of organic acids secreted by the mutants showed some variations. All mutants and YTY could secrete lactic acid, acetic acid and oxalic acid, while P9-8 also produced citric acid. The pH and the phosphate solubilizing ability of YTY and its mutants had a significant negative correlation. Phosphate solubilizing ability with organic acid and pH were all significantly correlated for YTY and the mutants, except P15-4. Organic acids and low environmental pH reduced by organic acids were the probable mechanism for P. oxalicum to dissolve phosphorus. Radiation of ion beam combined with UV could change the type and content of organic acids of P. oxalicum YTY, and initiate other H+ releasing pathways to lower pH, and participate phosphorus dissolution. The study provided biological mate-rials and theoretical basis for the research and development of high-efficiency phosphate solubilizing P. oxalicum and understanding the phosphate solubilizing mechanism of P. oxalicum.

Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice.

BACKGROUND: Some evidence suggests that depression is more common in obese patients. This fact gives us a hint that obesity might be a promoter of depression, though a conclusion can not be drawn. The aim of the study was: (1) to confirm whether obesity induced by high-fat diet (HFD) promotes depression-like behaviors in mice, (2) to explore the protective role of insulin-like growth factor-1 (IGF-1) in such behavioral disorder of the animals and (3) to reveal whether mitochondrial mechanism was involved in such protective effect of the reagent. METHODS: C57BL/6 J mice were fed with HFD to establish a model of obesity. Then, the animals were separately or simultaneously treated with PEG-IGF-1, 666-15 (CREB blocker) and SR-18292 (PGC-1α blocker). After that, depression-like behaviors were assessed using sucrose preference test and tail suspension test. In hippocampus, respiratory control ratio, ATP generation and red/green fluorescence ratio were adopted to reveal mitochondrial function. Also in hippocampus, expressions of p-CREB and PGC-1α were measured using western blotting. RESULTS: HFD mice showed depression-like behaviors compared with control mice. Such diet also caused mitochondrial dysfunction and inhibition of CREB/PGC-1α signal pathway in hippocampus of these animals. After PEG-IGF-1 intervention, all the abnormalities mentioned above can be partly reversed. After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus. CONCLUSION: IGF-1 alleviated depression-like behaviors and mitochondrial dysfunction through the activation of CREB/PGC-1α signal pathway in HFD mice.

Relationship between normal weight obesity and mild cognitive impairment is reflected in cognitive-related genes in human peripheral blood mononuclear cells.

AIM: Obesity contributes to the development of mild cognitive impairment, but the potential role of normal weight obesity in this disease has not been explored in humans. The aim of the study was to reveal the relationship between normal weight obesity and mild cognitive impairment in elderly individuals. METHODS: This study consisted of 360 patients with amnestic mild cognitive impairment and 360 cognitively normal controls. Normal weight obesity was defined as having metabolic syndrome but a normal weight. Metabolic health meant having no metabolic syndrome. Reverse transcription quantitative real-time polymerase chain reaction was adopted to measure the messenger RNA expression of four cognitive-related genes (amyloid precursor protein, cyclic adenosine monophosphate-responsive element-binding protein 1, sortilin-related receptor 1, and synapsin I) in peripheral blood mononuclear cells. RESULTS: Normal weight obesity was related to a higher risk of amnestic mild cognitive impairment (odds ratio = 3.14, 95% confidence interval: 2.13-4.60). In the patients, the expression of each gene in the peripheral blood mononuclear cells was linearly related to Mini-Mental State Examination and Montreal Cognitive Assessment scores (P < 0.05). The expression of these genes in the patients with metabolic health deviated from the normal levels found in the controls (P < 0.05), and the deviations were more significant in the patients with normal weight obesity (P < 0.05). CONCLUSION: Normal weight obesity may be a potential risk factor for amnestic mild cognitive impairment in elderly. This relationship was reflected in the abnormal expression of several cognitive-related genes in peripheral blood mononuclear cells.

Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture.

BACKGROUND: Neuroinflammation is a characteristic pathological change of acute neurological deficit and chronic traumatic encephalopathy (CTE) after traumatic brain injury (TBI). Microglia are the key cell involved in neuroinflammation and neuronal injury. The type of microglia polarization determines the direction of neuroinflammation. MiR-21-5p elevated in neurons and microglia after TBI in our previous research. In this study, we explore the influence of miR-21-5p for neuroinflammation by regulating microglia polarization. METHODS: In this study, PC12 and BV2 used to instead of neuron and microglia respectively. The co-cultured transwell system used to simulate interaction of PC12 and BV2 cells in vivo environment. RESULTS: We found that PC12-derived exosomes with containing miR-21-5p were phagocytosed by microglia and induced microglia polarization, meanwhile, the expression of miR-21-5p was increased in M1 microglia cells. Polarization of M1 microglia aggravated the release of neuroinflammation factors, inhibited the neurite outgrowth, increased accumulation of P-tau and promoted the apoptosis of PC12 cells, which formed a model of cyclic cumulative damage. Simultaneously, we also got similar results in vivo experiments. CONCLUSIONS: PC12-derived exosomes with containing miR-21-5p is the essential of this cyclic cumulative damage model. Therefore, regulating the expression of miR-21-5p or the secretion of exosomes may be an important novel strategy for the treatment of neuroinflammation after TBI.