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.

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.

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.

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.

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.

Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury.

In our recent study, we observed consistent increases in miR-124-3p levels in exosomes derived from cultured BV2 microglia which was treated with repetitive traumatic brain injury (rTBI) mouse model brain extracts. To clarify the mechanisms underlying increases in microglia-derived exosomal miR-124-3p and their role in regulating neuronal autophagy after TBI, we investigated the impact of exosomal miR-124-3p on neuronal autophagy in scratch-injured HT22 neurons and rTBI mice. We harvested injured brain extracts from rTBI mice at 3 to 21 days post injury (DPI) for the treatment of cultured BV2 microglia in vitro. We observed significant induction of autophagy following TBI in vitro, and that inhibition of activated neuronal autophagy could protect against trauma-induced injury. Our results indicated that co-culture of injured HT22 neurons with miR-124-3p overexpressing BV2 microglia exerted a protective effect by inhibiting neuronal autophagy in scratch-injured neurons. Further research revealed that these effects were achieved mainly via upregulation of exosomal miR-124-3p, and that Focal adhesion kinase family-interacting protein of 200 kDa (FIP200) plays a key role in trauma-induced autophagy. Injection of exosomes into the vena caudalis in in vivo experiments revealed that exosomal miR-124-3p was associated with decreases in the modified neurological severity score (mNSS) and improvements in Morris water maze (MWM) test results in rTBI mice. Altogether, our results indicate that increased miR-124-3p in microglial exosomes following TBI may inhibit neuronal autophagy and protect against nerve injury via their transfer into neurons. Thus, treatment with microglial exosomes enriched with miR-124-3p may represent a novel therapeutic strategy for the treatment of nerve injury after TBI.

Exosomes from MiR-21-5p-Increased Neurons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury.

BACKGROUND Traumatic brain injury (TBI) produces a series of pathological processes. Recent studies have indicated that autophagy pathway is persistently activated after TBI, which may lead to deterioration of nerve injury. Our preliminary work found miR-21-5p was upregulated in both in vivo and in vitro TBI models. MicroRNAs (miRNAs) could be loaded into exosomes to perform cell-to-cell interactions. This research aimed to evaluate the therapeutic effect of neuron-derived exosomes enriched with miR-21-5p on the TBI in vitro and to further explore the possible mechanisms. MATERIAL AND METHODS Brain extracts harvested from an rTBI mouse model were added to cultured HT-22 neurons to imitate the microenvironment of injured brain on in vitro cultured cells. Ultracentrifugation was performed to isolate exosomes. Transmission electron microscopy and Nano sight technology were used to examine exosomes. An in vitro model of TBI was established to study the effect of exosomal miR-21-5p on nerve injury and on neuronal autophagy regulation. RESULTS The expression of miR-21-5p was increased in exosomes derived from HT-22 neurons after treatment with rTBI mouse brain extracts. Autophagy was activated in HT-22 neurons after scratch injury. Exosomal miR-21-5p produced a protective effect by suppressing autophagy in a TBI model in vitro. MiR-21-5p could directly target the Rab11a 3'UTR region to reduce its translation and further suppressed Rab11a-mediated neuronal autophagy. CONCLUSIONS The levels of miR-21-5p in neuronal exosomes increased from the acute to the chronic phase of TBI. Neuronal exosomes enriched with miR-21-5p can inhibit the activity of neuronal autophagy by targeting Rab11a, thus attenuating trauma-induced, autophagy-mediated nerve injury in vitro.

Association of body mass index with amnestic and non-amnestic mild cognitive impairment risk in elderly.

BACKGROUND: Previous studies focused on the relationship between body mass index and cognitive disorder and obtained many conflicting results. This study explored the potential effects of body mass index on the risk of mild cognitive impairment (amnestic and non-amnestic) in the elderly. METHODS: The study enrolled 240 amnestic mild cognitive impairment patients, 240 non-amnestic mild cognitive impairment patients and 480 normal cognitive function controls. Data on admission and retrospective data at baseline (6 years ago) were collected from their medical records. Cognitive function was evaluated using Mini-Mental State Examination and Montreal Cognitive Assessment. RESULTS: Being underweight, overweight or obese at baseline was associated with an increased risk of amnestic mild cognitive impairment (OR: 2.30, 95%CI: 1.50 ~ 3.52; OR: 1.74, 95%CI: 1.36 ~ 2.20; OR: 1.71, 95%CI: 1.32 ~ 2.22, respectively). Being overweight or obese at baseline was also associated with an increased risk of non-amnestic mild cognitive impairment (OR: 1.51, 95%CI: 1.20 ~ 1.92; OR: 1.52, 95%CI: 1.21 ~ 1.97, respectively). In subjects with normal weights at baseline, an increased or decreased body mass index at follow-up was associated with an elevated risk of amnestic mild cognitive impairment (OR: 1.80, 95%CI: 1.10 ~ 3.05; OR: 3.96, 95%CI: 2.88 ~ 5.49, respectively), but only an increased body mass index was associated with an elevated risk of non-amnestic mild cognitive impairment (OR: 1.71, 95%CI: 1.16 ~ 2.59). CONCLUSIONS: Unhealthy body mass index levels at baseline and follow-up might impact the risk of both types of mild cognitive impairment (amnestic and non-amnestic).

Long-Term Subclinical Hyperglycemia and Hypoglycemia as Independent Risk Factors for Mild Cognitive Impairment in Elderly People.

Dementia is one of the most common geriatric diseases, and mild cognitive impairment (MCI) is considered to be incipient dementia. MCI patients have elevated risk of progressing to dementia. Multiple metabolic abnormalities have an unconfirmed effect on MCI risk, and taking adequate measures against metabolic abnormalities might prevent the developing of MCI. Thus, the present study explored the association of MCI risk with common metabolic abnormalities, such as hyperglycemia, hypoglycemia, hyperlipidemia and hypouricemia, and to provide the basis for MCI prevention. A total of 1,262 elderly outpatients with normal cognitive function and without confirmed diabetes mellitus, hyperlipoidemia and gout were enrolled. During the five-year follow-up period, 142 subjects were diagnosed with MCI according to Mini Mental State Examination and Montreal Cognitive Assessment. Furthermore, annual blood glucose, glycated hemoglobin, lipids and uric acid values were obtained, and mean of each indicator was calculated. Only mean values were included in the study to reflect long-term effect of metabolic abnormalities on MCI risk. Thus, the increased risk of MCI was associated with the mean values of blood glucose < 4.7 mmol/L (RR: 1.57, 95% CI: 1.14-2.32), blood glucose ≥ 6.3 mmol/L (RR: 1.49, 95% CI: 1.03-2.39), glycated hemoglobin ≥ 5.9% (RR: 2.28, 95% CI: 1.59-3.91), triglycerides ≥ 2.0 mmol/L (RR: 2.79, 95% CI: 2.14-3.79), total cholesterol ≥ 5.5 mmol/L (RR: 2.37, 95% CI: 1.69-3.39) and uric acid ≤ 380 µmol/L (RR: 1.62, 95% CI: 1.08-2.51). In conclusion, long-term subclinical hyperglycemia, hypoglycemia, hyperlipidemia, and hypouricemia are independent risk factors for MCI in elderly people.

Hyperuricemia as a Protective Factor for Mild Cognitive Impairment in Non-Obese Elderly.

Mild cognitive impairment (MCI) is regarded as incipient dementia. Patients with MCI have increased risk of later progressing to dementia. Blood uric acid (UA) is an important non-enzymatic antioxidant in peripheral circulation, and plays an unconfirmed protective role in MCI. Furthermore, obesity-induced inflammation, which affects UA metabolism and MCI onset, might regulate such protective role. Thus, the aim of the study was to determine the relationship of UA to MCI and the potential effect from inflammation. The study consisted of 933 MCI patients diagnosed by neuropsychological scales and 933 controls with normal cognitive function. All subjects were ≥ 60 years old. There were 378 obese subjects in MCI group and 410 obese subjects in control group. A relationship between lower serum UA levels and higher risk of MCI was found in all MCI patients and non-obese MCI patients (OR: 0.78, 95% CI: 0.72 ~ 0.86; OR: 0.66, 95% CI: 0.55 ~ 0.78), but not in obese MCI patients (OR: 0.94, 95% CI: 0.81 ~ 1.12). Serum UA and hypersensitive C reactive protein (hs-CRP) levels were higher in obese MCI patients than in non-obese MCI patients (P < 0.001 and P < 0.001). Serum UA levels showed a positive linear correlation with serum hs-CRP levels in obese MCI patients (r = 0.284, P < 0.001), but not in non-obese MCI patients (r = 0.030, P = 0.481). In conclusion, we show the significant association between lower serum UA levels and higher risk of MCI in non-obese subjects. Obesity-induced inflammation may weaken such relationship.

Response Mechanism of Extracellular Polymeric Substances Synthesized by Alternaria sp. on Drought Stress in Alfalfa (Medicago sativa L.).

This study investigates how extracellular polymeric substances (EPS) synthesized by dark septate endophytic (DSE) improve alfalfa's drought resistance. Drought stress was simulated in hydroponic culture, and roots were treated with different EPS concentrations to determine their effects on drought tolerance and applicable concentrations. Hydroponic solutions with 0.25 and 0.50% EPS concentrations alleviated leaf wilting and increased total plant fresh weight by 35.8 and 57.7%, respectively. SEM shows that EPS attached to the roots and may have served to protect the root system. EPS treatment significantly depressed the MDA contents of the roots, stems, and leaves. Roots responded to drought stress by increasing soluble sugar contents and antioxidant enzyme activities, while mitigating stem and leaf stress by synthesizing lipid compounds, amino acids, and organic acid metabolites. Five metabolites in the stem have been reported to be associated with plant stress tolerance and growth, namely 3-O-methyl 5-O-(2-methyl propyl) (4S)-2,6-dimethyl-4-(2-nitrophenyl)-3,4-dihydropyridine-3,5-dicarboxylate, malic acid, PA (20:1(11Z)/15:0), N-methyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, and 2-(S-glutathionyl) acetyl glutathione. In summary, EPS treatment induced oxidative stress and altered plant metabolism, and this in turn increased plant antioxidant capacity. The results provide a theoretical basis for the application of EPS in commercial products that increase plant resistance and ecological restoration.

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.

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.

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.

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.

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.

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.

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.