R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis.

R-2-hydroxyglutarate (R-2HG), a metabolite produced by mutant isocitrate dehydrogenases (IDHs), was recently reported to exhibit anti-tumor activity. However, its effect on cancer metabolism remains largely elusive. Here we show that R-2HG effectively attenuates aerobic glycolysis, a hallmark of cancer metabolism, in (R-2HG-sensitive) leukemia cells. Mechanistically, R-2HG abrogates fat-mass- and obesity-associated protein (FTO)/N6-methyladenosine (m6A)/YTH N6-methyladenosine RNA binding protein 2 (YTHDF2)-mediated post-transcriptional upregulation of phosphofructokinase platelet (PFKP) and lactate dehydrogenase B (LDHB) (two critical glycolytic genes) expression and thereby suppresses aerobic glycolysis. Knockdown of FTO, PFKP, or LDHB recapitulates R-2HG-induced glycolytic inhibition in (R-2HG-sensitive) leukemia cells, but not in normal CD34+ hematopoietic stem/progenitor cells, and inhibits leukemogenesis in vivo; conversely, their overexpression reverses R-2HG-induced effects. R-2HG also suppresses glycolysis and downregulates FTO/PFKP/LDHB expression in human primary IDH-wild-type acute myeloid leukemia (AML) cells, demonstrating the clinical relevance. Collectively, our study reveals previously unrecognized effects of R-2HG and RNA modification on aerobic glycolysis in leukemia, highlighting the therapeutic potential of targeting cancer epitranscriptomics and metabolism.

Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

PHOSPHATE1-mediated phosphate translocation from roots to shoots regulates floral transition in plants.

Phosphorus nutrition has been known to influence floral transition in plants for a long time, but the underlying mechanism is unclear. Arabidopsis PHOSPHATE1 (PHO1) plays a critical role in phosphate translocation from roots to shoots, but whether and how it regulates floral transition is unknown. Here, we show that knockout mutation of PHO1 delays flowering under both long-day and short-day conditions. The late flowering of pho1 mutants can be partially rescued by Pi supplementation in rosettes or shoot apices. Grafting assay indicates that the late flowering of pho1 mutants is resulted from impaired phosphate translocation from roots to shoots. Knockout mutation of SPX1 and SPX2, two negative regulators of phosphate starvation response, partially rescues the late flowering of pho1 mutants. PHO1 is epistatic to PHO2, a negative regulator of PHO1, in flowering time regulation. Loss of PHO1 represses the expression of some floral activators, including FT encoding florigen, and induces the expression of some floral repressors in shoots. Genetic analyses indicate that at least jasmonic acid signaling is partially responsible for the late flowering of pho1 mutants. In addition, we find rice PHO1;2, the homology of PHO1, plays a similar role in floral transition. These results suggest that PHO1 integrates phosphorus nutrition and flowering time and could be used as a potential target in modulating phosphorus nutrition-mediated flowering time in plants.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials.

BACKGROUND: To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients. METHODS: This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72-96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs. RESULTS: Eighteen RCTs (n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72-96 h (MD, - 0.62; 95% CI, - 1.00 to - 0.25; p = 0.001) and the duration of vasopressor use (MD, - 15.07; 95% CI, - 21.59 to - 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25-100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03). CONCLUSION: In this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.

A Porous π-π Stacking Framework with Dicopper(I) Sites and Adjacent Proton Relays for Electroreduction of CO2 to C2+ Products.

Crystalline porous materials sustained by supramolecular interactions (e.g., π-π stacking interactions) are a type of molecular crystals showing considerable stability, but their applications are rarely reported due to the high difficulty of their construction. Herein, a stable π-π stacking framework formed by a trinuclear copper(I) compound [Cu3(HBtz)3(Btz)Cl2] (CuBtz, HBtz = benzotriazole) with pyrazolate-bridged dicopper(I) sites is reported and employed for electrochemical CO2 reduction, showing an impressive performance of 73.7 ± 2.8% Faradaic efficiency for C2+ products [i.e., ethylene (44%), ethanol (21%), acetate (4.7%), and propanol (4%)] with a current density of 7.9 mA cm-2 at the potential of -1.3 V versus RHE in an H-type cell and a Faradic efficiency (61.6%) of C2+ products with a current density of ≈1 A cm-2 and a reaction rate of 5639 µmol m-2 s-1 at the potential of -1.6 V versus RHE in a flow cell device, representing an impressive performance reported to date. In-situ infrared spectroscopy, density functional theory calculations, and control experiments revealed that the uncoordinated nitrogen atoms of benzotriazolates in the immediate vicinity can act as proton relays and cooperate with the dicopper(I) site to promote the hydrogenation process of the *CO intermediate and the C-C coupling, resulting in the highly selective electroreduction of CO2 to C2+ products.

Interaction between laccase and diethylstilbestrol based on multispectral and chromatography analyses.

Diethylstilbestrol (DES) is a synthetic form of oestrogen that does not easily degrade in the environment and can be harmful to human health. Herein, the mechanism of the interaction between laccase and DES was investigated by various spectroscopic means and high-performance liquid chromatography (HPLC). The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of laccase by DES was due to a static quenching, forming a binding site. According to the Förster non-radiative energy transfer theory (FRET), the action distance R0 between DES and laccase was 4.708 nm, r was 5.81 nm, and the energy transfer efficiency E was 22.08%, respectively. Both UV-Vis absorption spectra and FT-IR spectra indicated changes in the conformation and surroundings of the enzyme and changed in the secondary structure of laccase. Multispectral synthesis showed that the interaction of laccase with DES caused a change in the secondary structure of laccase. The degradation experiments showed that laccase could degrade DES, and the DES content decreased with time. This study provides a new theoretical basis and experimental method for further research on the reaction mechanism of the laccase degradation of DES. It may also provide a reference basis for human biological and environmental safety evaluations.

Primary squamous cell carcinoma of thyroid gland: 11 case reports and a population-based study.

BACKGROUND: Primary squamous cell carcinoma of thyroid gland (PSCCT) is a highly aggressive malignant tumor associated with a poor prognosis. Due to the rare case, there is a knowledge gap on the features of PSCCT. There is limited understanding of the treatment and molecular biology of this tumor. More genomic work and relevant perspective work need to be done. METHODS: We retrospectively reviewed the medical information of patients with PSCCT diagnosed from December 2009 to December 2020 at The First Affiliated Hospital of Guangxi Medical University. In addition, we conducted an electronic search of the paper in CNKI, Wanfang, VIP, PubMed, Embase, Web of Science, and ProQuest databases by recently updated articles. Survival analysis was conducted using the Kaplan-Meier method. RESULTS: There were only 11 patients met the study's inclusion criteria in our institution. The patients ranged in age from 25 to 68 years old and female preponderance (M:F = 1:1.7). The median survival time was 6 months, and 1-year survival rate was 33.3%. Fifty-three patients' individual data from 45 articles were selected for analysis. The median age at diagnosis was 63 years and female preponderance (M:F = 1:2.5). The commonest complaint was the anterior neck mass (77.3%), followed by hoarseness (32.1%). The median survival time was 9 months, and the overall 1-, 2-, and 5-year survival rate was 39.8%, 33.7%, and 26.9%, respectively. The log-rank method shows that age, tumor size, lymph node status, M stage, surgical range, and tracheal status were the relevant factors affecting the prognosis. In contrast, gender, treatment modality, and resection margin were not prognostic factors. On multivariable analysis, age and M stage were associated with overall survival. CONCLUSION: The median overall survival was 6-9 months of PSCCT. Age and M stage are predictors of PSSCT.

Exploration of anti-chromium mechanism of marine Penicillium janthinellum P1 through combinatorial transcriptomic analysis and WGCNA.

Fungi have a promising application prospect in the remediation of heavy-metal wastewater pollution which is a sticky global problem. New marine-derived strain Penicillium janthinellum P1 is of high chromium resistance. However, a comprehensive study of the transcriptomics in Penicillium janthinellum P1 strains is lacking. Firstly, the changing trends of a series of physiological and biochemical indices of P1 strain at 0 M and 1 M Cr concentration were investigated to track the ROS variation. Secondly, transcriptome sequencing of P1 was performed by RNA-Seq sequencing technology. The transcriptome data indicated that 12,352 coding protein regions were predicted, and 6655 differentially expressed genes were identified by DESeq2, of which 4234 genes were up-regulated, and 2421 genes down-regulated. Through further co-expression network of WGCNA analysis, the filtered unigenes were clustered into 19 modules. Combined with the physiological and biochemical findings, the three modules with the highest correlation with the six traits were selected to construct the network, and 52 hub genes were obtained. Furthermore, 10 speculative hub genes related to chromium resistance were selected and verified by real-time PCR. The results were in line with the expected experimental assumption. These results improve our understanding of the transcriptomic dimensions of the high chromium resistance of Penicillium janthinellum P1 strains.

Acylglycerol kinase promotes paclitaxel resistance in nasopharyngeal carcinoma cells by regulating FOXM1 via the JAK2/STAT3 pathway.

OBJECTIVE: Drug resistance is an important factor that impedes the treatment of nasopharyngeal cancer (NPC). Acylglycerol kinase (AGK) has been found to be overexpressed in NPC and correlates with poor prognosis. Our objective was to demonstrate the effect of AGK on paclitaxel resistance in NPC and determine the underlying mechanisms. METHODS: MTT assay was employed to determine the IC50 of paclitaxel in NPC cells after different treatments. Flow cytometry assays were employed to evaluate cell apoptosis. RT-qPCR and Western blot assays were used to detect alterations in mRNA and protein expression, respectively. Luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to determine the relationship between and the regulatory effect of STAT3 on the promoter of FOXM1. RESULTS: AGK was elevated in paclitaxel-resistant NPC cells, and knockdown of AGK suppressed the resistance of CNE1-TR and CNE2-TR cells to paclitaxel. Moreover, upregulation of FOXM1 rescued the effects of AGK knockdown. Furthermore, the JAK2/STAT3 signalling pathway was overactivated in CNE1-TR and CNE2-TR cells, and knockdown of AGK suppressed JAK2/STAT3 signalling. STAT3 was verified to bind to and activate the promoter region of FOXM1. An in vivo tumour xenograft assay also verified that AGK knockdown inhibited tumour growth and mitigated paclitaxel resistance by regulating the JAK2/STAT3/FOXM1 axis. CONCLUSION: AGK levels were increased in paclitaxel-resistant NPC cells. AGK activates JAK2/STAT3 signalling, thus promoting FOXM1 transcription and eventually enhancing the drug resistance of NPC cells.

Evaluating the effects of microparticle addition on mycelial morphology, natural yellow pigments productivity, and key genes regulation in submerged fermentation of Monascus purpureus.

Morphology plays an important role in fungal fermentation and secondary metabolites biosynthesis. One novel technique, microparticle-enhanced cultivation was successfully utilized to control the morphology of Monascus purpureus precisely and enhance the yield of yellow pigments. The production of yellow pigments increased to 554.2 U/ml when 4 g/L 5000 mesh talc added at 24 h. Field emission scanning electron microscope observation indicated that the actual effect depends on the properties of microparticle. Sharp-edged microparticles showed better stimulatory effects than smooth, round-shaped ones. Particle size analysis, scanning electron microscope, and cell integrity evaluation proved obvious morphological changes were induced by talc addition, including smaller mycelial size, rougher hyphae, and decreased cell integrity. Furthermore, the expression levels of MrpigG, MrpigD, MrpigE, and MrpigH were significantly upregulated by the addition of talc. It indicated that the microparticle could not only affect the mycelial morphology, but also influence the expression levels of key genes in biosynthetic pathway of Monascus yellow pigments.

Salicylate Induced GABAAR Internalization by Dopamine D1-Like Receptors Involving Protein Kinase C (PKC) in Spiral Ganglion Neurons.

BACKGROUND Sodium salicylate (SS) induces excitotoxicity of spiral ganglion neurons (SGNs) by inhibiting the response of γ-aminobutyric acid type A receptors (GABAARs). Our previous studies have shown that SS can increase the internalization of GABAARs on SGNs, which involves dopamine D1-like receptors (D1Rs) and related signaling pathways. In this study, we aimed to explore the role of D1Rs and their downstream molecule protein kinase C (PKC) in the process of SS inhibiting GABAARs. MATERIAL AND METHODS The expression of D1Rs and GABARγ2 on rat cochlear SGNs cultured in vitro was tested by immunofluorescence. Then, the SGNs were exposed to SS, D1R agonist (SKF38393), D1R antagonist (SCH23390), clathrin/dynamin-mediated endocytosis inhibitor (dynasore), and PKC inhibitor (Bisindolylmaleimide I). Western blotting and whole-cell patch clamp technique were used to assess the changes of surface and total protein of GABARγ2 and GABA-activated currents. RESULTS Immunofluorescence showed that D1 receptors (DRD1) were expressed on SGNs. Data from western blotting showed that SS promoted the internalization of cell surface GABAARs, and activating D1Rs had the same result. Inhibiting D1Rs and PKC decreased the internalization of GABAARs. Meanwhile, the phosphorylation level of GABAARγ2 S327 affected by PKC was positively correlated with the degree of internalization of GABAARs. Moreover, whole-cell patch clamp recording showed that inhibition of D1Rs or co-inhibition of D1Rs and PKC attenuated the inhibitory effect of SS on GABA-activated currents. CONCLUSIONS D1Rs mediate the GABAAR internalization induced by SS via a PKC-dependent manner and participate in the excitotoxic process of SGNs.

Construction of a eukaryotic expression system with stable and secretory expression of mycobacterium tuberculosis 38 kDa protein.

The 38 kDa protein is a major antigen of mycobacterium tuberculosis and has been widely used in TB serodiagnosis, due to its highly sensitivity and specificity. Here we attempt to establish a production platform of recombinant 38 kDa protein in mammalian cells and to evaluate the potential value of 38 kDa protein in TB serodiagnosis. The 38 kDa gene is synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-38 kDa-eGFP was packaged, titered, and then transduced into HEK 293 T cells. Recombinant cell lines were selected by limiting dilution. Supernatants were collected and purified by HisTrapTM HP column. Western blot showed a molecular weight of approximate 38 kDa in cell supernatants as expected. ELISA assay confirmed the immunological specificity of the obtained protein in the presence of MTB-infected human serum samples. In all, we have obtained a stable cell line with long-term and robust expression of secretory MTB 38 kDa protein, which may provide a promising candidate antigen for the development of TB serological diagnosis.

Interaction kinetics of peptide lipids-mediated gene delivery.

BACKGROUND: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. RESULTS: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (- 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the "proton sponge effect" of the lipid. CONCLUSIONS: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

Soil Properties and Microbial Diversity at the Frontier of Laohugou Glacier Retreat in Qilian Mountains.

Glacier retreat may result in the decomposition of old organic carbon stored at the frontier of glacier retreat and the release of greenhouse gases such as CO2 and methane into the atmosphere. This process may gradually transform the soil in the region from its original status as a carbon sink into a carbon source, thus producing a positive feedback effect on global warming. In this study, Laohugou Glacier No. 12, Qilian Mountains, China, was taken as the research object, and the newly melted soil (Q1) at the frontier of glacier retreat and the sandy soil (Q2) on the bank of the nearby river were collected. The content of accumulation of organic matter (AOM) in Q1 soil was 5.56 ± 0.27 g/kg, and the total nitrogen was 0.60 ± 0.03 g/kg, which was significantly higher than that in Q2. The soil microbial carbon metabolism of Q2 was significantly (P < 0.01) higher than that of Q1 and the ability of organic matter to decompose was greater. The alpha diversity index of bacteria, fungi and archaea of Q2 was significantly higher than that of Q1. It may be that there were dominant species in Q1 causing the lower species evenness. The archaea metabolic function genes in Q1 were higher than those in Q2 because archaea are better adapted to a frozen environment. Bacterial carbohydrate and amino acid metabolism was abundant in Q2 and was related to microbial transformation of the carbon source into CO2.

Effects of salt concentration on microbial diversity and volatile compounds during suancai fermentation.

Suancai is a popular fermented product of Brassica vegetable in China. As important additive, salt concentration has crucial effects on the quality of suancai. To investigate the effects of salt concentration on suancai fermentation, the microbial diversity and volatile compounds (VCs) during fermentation were investigated by using Illumina HiSeq sequencing and GC-MS. Firmicutes, Proteobacteria and Ascomycota were detected as the main phylum during the fermentation with different salt concentrations. Lactobacillus, Lactococcus, Klebsiella, Weissella, Pediococcus, Candida, Cladosporium, Gibberella, Aspergillus, etc., were detected were observed during the fermentation with different concentrations. After fermentation, Lactobacillus predominated the fermentation of suancai and was not affected by salt concentration. Pediococcus, Leuconostoc, Weissella, Sporobolomyces, Azospirillum, Klebsiella, Acinetobacter and Cladosporium were significant affected by salt concentration. Salt addition could affect the VCs profiles and reduce the isothiocyanates after fermentation. Seventy-nine VCs were detected and strongly correlated with the dominant genus Lactobacillus during suancai fermentation. The inoculated fermentation of Lactobacillus could improve the VCs during fermentation. In conclusion, 6% salt addition could acquire a higher Lactobacillus abundance and a better taste quality. These results may facilitate the understanding of the effect of salt concentration on the fermentation ecology to improve suancai characteristics.

Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation.

The purpose of this study was to observe the regulatory effects of GABAA (γ-aminobutyric acid A) receptor on the N-methyl-D-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABAA receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABAA receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABAA receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.

Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore.

Polyamines (putrescine, spermidine, and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells. The study was to investigate their role in cardioprotection against ischemia/reperfusion (I/R) injury and the underlying mechanism. Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac I/R was achieved by 30 min of global ischemia followed by 120 min of reperfusion. Different concentrations of polyamines (0.1, 1, 10, and 15 µmol/L of putrescine, spermidine, and spermine), cyclosporin A (0.2 µmol/L), or atractyloside (20 µmol/L) were given 10 min before the onset of reperfusion. The hemodynamics were monitored; the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically; infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method; and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria. The results showed that compared to I/R alone, 0.1 and 1 µmol/L polyamines treatment improved heart function, reduced LDH release, decreased infarct size, and these effects were inhibited by atractyloside (MPTP activator). In isolated mitochondria from normal rats, 0.1 and 1 µmol/L polyamines treatment inhibited MPTP opening. However, 10 and 15 µmol/L polyamines treatment had the opposite effects, and these effects were inhibited by cyclosporin A (MPTP inhibitor). Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.