The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation.

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology. METHODS: A rat IVDD puncture model was established and treated by gavage with different concentrations of SBD, and clean faeces, serum, liver, kidney, and intervertebral disc (IVD) were collected after 4 weeks. We assessed the safety by liver and kidney weighing, functional tests and tissue staining, the expression of tumor necrosis factor-alpha (TNF-ɑ), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) inflammatory factors in serum was detected by ELISA kits, and X-ray test, magnetic resonance imaging (MRI) examination, immunohistochemistry (IHC), western blotting (WB), hematoxylin-eosin (HE) staining and safranin O-fast green (SO/FG) staining were used to assess the efficacy. Finally, we performed 16S rRNA sequencing analysis on the faeces of different groups and untargeted metabolomics on serum and analyzed the association between them. RESULTS: SBD can effectively reduce the inflammatory response, regulate the metabolic balance of extracellular matrix (ECM), improve symptoms, and restore IVD function. In addition, SBD can significantly improve the diversity of intestinal flora and maintain the balance. At the phylum level, SBD greatly increased the relative abundance of Patescibacteria and Actinobacteriota and decreased the relative abundance of Bacteroidota. At the genus level, SBD significantly increased the relative abundance of Clostridia_UCG-014, Enterorhabdus, and Adlercreutzia, and decreased the relative abundance of Ruminococcaceae_UCG-005 (p < 0.05). Untargeted metabolomics indicated that SBD significantly improved serum metabolites and altered serum expression of 4alpha-phorbol 12,13-didecanoate (4alphaPDD), euscaphic acid (EA), alpha-muricholic acid (α-MCA), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (Kyn) (p < 0.05), and the metabolic pathways were mainly lipid metabolism and amino acid metabolism. CONCLUSIONS: This study demonstrated that SBD can extensively regulate intestinal flora and serum metabolic homeostasis to reduce inflammatory response, inhibit the degradation of ECM, restore IVD height and water content to achieve apparent therapeutic effect for IVDD.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Effects of Gestational Diabetes Mellitus and Selenium Deficiency on the Offspring Growth and Blood Glucose Mechanisms of C57BL/6J Mice.

This study aimed to explore the effects and mechanisms of maternal gestational diabetes mellitus (GDM) and selenium (Se) deficiency on the growth and glucose metabolism of offspring. Female C57BL/6J mice were divided into four groups as follows: a control group, a GDM group, a Se deficiency group, and a GDM with Se deficiency group. GDM animal models were established via S961. Pregnant mice fed their offspring until weaning. Then, offspring continued to be fed with a basic diet until adulthood. Body weight and fasting blood glucose were measured weekly. Se content, oxidative stress indicators, and the protein expression of the PI3K/Akt signaling pathway were detected. GDM increased susceptibility to obesity in lactating offspring, with gender differences observed in adult offspring. The effect of Se deficiency on SOD activity only appeared in female offspring during adulthood but was shown in male offspring during weaning though it disappeared during adulthood. GDM and Se deficiency increased the risk of abnormal glucose metabolism in female offspring from weaning to adulthood but gradually decreased in male offspring. The influence on the expression of PI3K/Akt signaling pathway-related proteins showed the same trend. GDM and Se deficiency affected the growth and glucose metabolism of offspring through oxidative stress and PI3K/Akt signaling pathway-related proteins, and gender differences existed.

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Effects of Mindfulness on Obligatory Exercise During the Return of Injured Athletes to Sports: The Mediating Roles of Self-Criticism and Competitive State Anxiety.

Purpose: Despite the Advances in sports training methods and medicine, they have not reduced the recurrence rate of athletes' injuries significantly, and obligatory exercise may be an important reason for their re-injury. The purpose of this study was to investigate the effects of mindfulness on obligatory exercise behavior, self-criticism, and competitive state anxiety in athletes recovering from injury, and explain their interactions. Patients and Methods: The study adopted the snowball and convenience sampling methods. From November to December 2022, a total of 265 high-level sports players in South China were selected, and ultimately, 208 valid data samples were obtained. Maximum likelihood estimation was used to analyze the data and test the hypotheses proposed using 5000 bootstrap samples to test the mediating effects of the structural equation model. Results: The results demonstrated that there were positive correlations between self-criticism and obligatory exercise (standardized coefficients = 0.38, p < 0.001), as well as competitive state anxiety and self-criticism (standardized coefficients = 0.45, p < 0.001). Mindfulness and obligatory exercise were correlated negatively (standardized coefficients = -0.31, p < 0.001), but there was no significant relation between competitive state anxiety and obligatory exercise (standardized coefficients = 0.05, p > 0.01). Self-criticism and competitive state anxiety mediated mindfulness's positive effects on obligatory exercise in part (standardized indirect effect = -0.16, p < 0.01), and this explanatory power was higher than in any previous study (R2 = 0.37). Conclusion: The irrational beliefs in Activating events-Beliefs-Consequence (ABC) theory play an important role in explaining athletes' obligatory exercise, and mindfulness has a positive effect on reducing obligatory exercise behavior.

Insights into Q-markers and molecular mechanism of Sanguisorba saponins in treating ulcerative colitis based on lipid metabolism regulation.

BACKGROUND: Sanguisorba saponin extract (SSE) is the main active part of Sanguisorba officinalis with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-oxidant. However, its therapeutic role and underlying mechanisms for ulcerative colitis (UC) still need to be elucidated. PURPOSE: This study aims to explore the therapeutic effect, effectiveness-material basis-quality markers (Q-markers) and prospective mechanism of function of SSE on UC. METHODS: Fresh 2.5% dextran sulfate sodium salt (DSS) solution was placed in drinking bottles for 7 days to induce a mouse model of UC. SSE and sulfasalazine (SASP) were supplemented to mice by gavage for consecutive 7 days to investigate the therapeutic role of SSE on UC. Mouse monocyte macrophages (RAW264.7) and human normal colonic epithelial (NCM460) cells were treated with LPS to induce inflammatory responses, followed by pharmacodynamic examination with different concentrations of SSE. Hematoxylin-eosin (HE) and Alcian blue staining were conducted to evaluate the pathological damage of mice colon. Lipidomic technology was conducted to explore the differential lipids closely related to the disease process of UC. Quantitative PCR analysis, immunohistochemistry and ELISA kit were used to measure the expression levels of the corresponding proteins and pro-inflammatory factors. RESULTS: SSE treatment could effectively reduce the elevated expressions of pro-inflammatory factors in RAW264.7 and NCM460 cells due to LPS stimulation. Intragastric administration of SSE was found to significantly alleviate the symptoms of DSS-induced colon injury and low-polar saponins in SSE. Low polarity saponins, especially ZYS-II, were proved to be the main active substances of SSE in treating UC. In addition, SSE could significantly ameliorate the aberrant lipid metabolism in UC mice. The role of phosphatidylcholine (PC)34:1 in the UC pathogenesis has been fully verified in our previous studies. Herein, SSE-dosing effectively reversed the metabolic disorder of PCs in UC mice, and increased the PC34:1 level to normal via up-regulating the expression of phosphocholine cytidylyltransferase (PCYT1α). CONCLUSION: Our data innovatively revealed that SSE could significantly alleviate the symptoms of UC by reversing the disorder of PC metabolism induced by DSS modeling. SSE was proved for the first time to be a promising and effective candidate for UC treatment.

Bufalin Inhibits Tumorigenesis and SREBP-1-Mediated Lipogenesis in Hepatocellular Carcinoma via Modulating the ATP1A1/CA2 Axis.

Altered lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), a common malignancy with a dismal prognosis against which there is a lack of effective therapeutic strategies. Bufalin, a classical Na[Formula: see text]-K[Formula: see text]-ATPase (NKA) inhibitor, shows a potent antitumor effect against HCC. However, the role of bufalin in regulating lipid metabolism-related pathways of HCC remains unclear. In this study, we examined the interaction between bufalin and its target molecule, ATP1A1/CA2, in vitro and in vivo and explored the intersected downstream pathways in silico. A multi-omics analysis of transcriptomics and metabolomics was employed to screen for potential action targets. The results were verified and correlated with the downstream lipid de novo synthesis pathway and the bufalin/ATP1A1/CA2 axis. We found that bufalin suppressed the ATP1A1/CA2 ratio in the treated HCC cells and showed a negative correlation with bufalin drug sensitivity. Functionally, ATP1A1 overexpression and CA2 down-regulation inhibited the bufalin-suppressed HCC proliferation and metastasis. Furthermore, down-regulation of CA2 induced epithelial-mesenchymal transition and bufalin resistance in HCC cells by up-regulating ATP1A1. Mechanistically, lipid metabolism-related signaling pathways were enriched in low ATP1A1 and high CA2 expression subgroups in GSEA. The multi-omics analysis also showed that bufalin was closely related to lipid metabolism. We demonstrated that bufalin inhibits lipogenesis and tumorigenesis by down-regulating SREBP-1/FASN/ACLY via modulating the ATP1A1/CA2 axis in HCC.

Global analysis of qualitative and quantitative metabolism of Notoginsenoside R1 in rat liver-brain-gut axis based on LC-IT-TOF/MS combing mMDF strategy.

BACKGROUND: The metabolism study of active components for traditional Chinese medicine (TCM) in target organs is conducive to clarify the authentic active ingredients. Notoginsenoside R1 (NG-R1), one of the bioactive components of Panax notoginsenoside (PNS), is commonly acknowledged as the characteristic marker of PNS. However, the metabolism of NG-R1 in target organs has not been clarified yet due to the lack of robust technique and approach. PURPOSE: The present study aimed to develop a reliable and efficient strategy and technology for revealing the qualitative and quantitative metabolism of active components of TCMs in target organs, and to clarify the biotransformation of NG-R1 in liver-brain-intestinal axis. METHODS: The metabolic transformation of NG-R1 in the brain gut axis was investigated in the in vitro incubation system of fresh rat brain, liver homogenate, and intestinal flora. To quickly lock the target metabolites, we set the mass defect filter (MDF) in different ranges to screen metabolites with different molecular weight (MW). This strategy was defined as multi-stage MDF (mMDF). In addition, we performed relative quantitative analysis on all metabolites according to the peak area acquired by LC-IT-TOF/MS to overcome the challenge that metabolites are difficult to be quantified due to the lack of standards. RESULTS: When MDF was set at 0.50 to 0.65 to screen metabolites with MW of 900 to 1200 Da, 6 novel metabolites were quickly found, and then identified as glucuronic acid binding, oxidation, dehydrogenation, methylation and hydrogenation products according to their LC and MS characteristics. When setting MDF at 0.42 - 0.52, 6 metabolites with MW of 600 to 900 Da were effectively screened and identified as Rg1, NG-R2, Rh1, Rg1+CH2+2H and Rg1+CH2. To screen the metabolites with MW of 300 to 600 Da, MDF was set at 0.25 - 0.42, and 4 novel metabolites were screened rapidly. The results of quantitative metabolism suggested that intestinal flora was the main metabolic site of NG-R1 in rat, and more than 60% of NG-R1 was converted to Rg1 by deglycosylation in the intestinal flora. CONCLUSION: The mMDF strategy can significantly improve the research efficiency of qualitative metabolism of saponins. Although NG-R1 could be transformed into a variety of metabolites in rat liver and brain homogenate, it still existed mainly in prototype form. In the rat flora, NG-R1 mainly existed in the form of deglycosylated metabolite Rg1.

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy.

Intratumoral immunotherapeutic hydrogel administration is emerging as an effective method for inducing a durable and robust antitumor immune response. However, scaffold hydrogels that can synergize with the loaded drugs, thus potentiating therapeutic efficacy, are limited. Here, we report a ternary hydrogel composed of polyvinyl alcohol (PVA), polyethylenimine (PEI)‒a cationic polymer with potential immunoactivation effects, and magnesium ions‒a stimulator of the adaptive immune response, which exhibits an intrinsic immunomodulation function of reversing the immunologically "cold" phenotype of a murine breast tumor to a "hot" phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel (PEIGel) encapsulating an immune checkpoint blockade (ICB) inhibitor‒anti-PD-L1 antibody (α-PDL1) exhibits synergistic effects resulting in elimination of primary tumors and remote metastases and prevention of tumor relapse after surgical resection. A preliminary mechanistic study revealed a probably hidden role of PEI in modulating the polyamine metabolism/catabolism of tumors to potentiate the immune adjuvant effect. These results deepen our understanding of the innate immune activation function of PEI and pave the way for harnessing PEI as an immune adjuvant for ICB therapy.

Partial Nitrification and Enhanced Biological Phosphorus Removal in a Sequencing Batch Reactor Treating High-Strength Wastewater.

Complex and high levels of various pollutants in high-strength wastewaters hinder efficient and stable biological nutrient removal. In this study, the changes in pollutant removal performance and microbial community structure in a laboratory-scale anaerobic/aerobic sequencing batch reactor (SBR) treating simulated pre-fermented high-strength wastewater were investigated under different influent loading conditions. The results showed that when the influent chemical oxygen demand (COD), total nitrogen (TN), and orthophosphate (PO43--P) concentrations in the SBR increased to 983, 56, and 20 mg/L, respectively, the COD removal efficiency was maintained above 85%, the TN removal efficiency was 64.5%, and the PO43--P removal efficiency increased from 78.3% to 97.5%. Partial nitrification with simultaneous accumulation of ammonia (NH4+-N) and nitrite (NO2--N) was observed, which may be related to the effect of high influent load on ammonia- and nitrite-oxidising bacteria. The biological phosphorus removal activity was higher when propionate was used as the carbon source instead of acetate. The relative abundance of glycogen accumulating organisms (GAOs) increased significantly with the increase in organic load, while Tetrasphaera was the consistently dominant polyphosphate accumulating organism (PAO) in the reactor. Under high organic loading conditions, there was no significant PAO-GAO competition in the reactor, thus the phosphorus removal performance was not affected.

The association between serum selenium level and gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: The relationship between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The purpose is to update and summarize previous studies to understand the relationship in more detail. METHODS: PubMed, The Cochrane Library, EMBASE, Web of science, CNKI, WANFANG DATA and Cqvip were searched for studies published up to 3 September 2021. The random-effects model was used to measure the combined estimation. The overall effect was reported in a standard mean difference (SMD) and 95% confidence interval (95% CI). All data were analysed by Review Manager 5.4. RESULTS: Twenty-seven studies involving 1588 patients with GDM and 2450 healthy pregnant women contributed to this meta-analysis. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.29; 95% CI: -1.60 to -0.97, p < 0.00001). Subgroup analyses showed that such trend was consistent within the non-European population (Asia: SMD = -1.44; 95% CI: -1.79 to -1.08, p < 0.00001; Africa: SMD = -2.62; 95% CI: -4.50 to -0.74, p = 0.006) and in the second and third trimesters (the second trimester: SMD = -1.41; 95% CI: -1.82 to -0.99, p < 0.00001; the third trimester: SMD = -1.54; 95% CI: -2.09 to -0.98, p < 0.00001), but not within the European population (SMD = -0.47; 95% CI: -1.09 to 0.16, p = 0.14) or in the first trimester (SMD = -0.52; 95% CI: -1.13 to 0.10, p = 0.10). CONCLUSIONS: This meta-analysis showed that the serum selenium level of patients with GDM was lower than that in healthy pregnant women, especially within the non-European population and in the second and third trimesters.

[Research advances in prevention and treatment of intervertebral disc degeneration by targeting mitochondrial quality control].

Intervertebral disc degeneration(IDD) is a common clinical degenerative disease of the musculoskeletal system, which increases the risk of lower back pain, severely reduces patients' quality of life and work efficiency, and imposes a large economic burden on society. Mitochondria, as the "power stations" of eukaryotic cells, are involved in many key biological processes, and their abnormal function can induce cellular dysfunction and lead to the development of a series of degenerative diseases. Recent studies have revealed that mitochondrial quality control(MQC) imbalance, characterized by abnormalities in mitochondrial oxidative stress, kinetics, mitophagy and biogenesis, plays an important role in IDD. The research reviewed the progress of the role of MQC in IDD and summarized traditional Chinese medicine monomers and small molecule compounds targeting MQC for the treatment of IDD, with the aim of providing reference and new ideas for studying novel therapeutic strategies for IDD.

Comparison between surgery and thermal ablation for adrenal metastases: a retrospective study.

PURPOSE: To retrospectively compare the efficacy and safety of surgical resection (SR) and thermal ablation for the treatment of adrenal metastases. METHODS: From January 2008 to December 2018, 133 patients with adrenal metastases who underwent SR (n = 76) or thermal ablation (n = 57) were enrolled. The mean tumor size was 58.00 ± 10.65 mm (22-80 mm) in the SR group and 58.03 ± 12.76 mm (34-89 mm) in the thermal ablation group. Local progression-free survival (LPFS) and safety were compared between the two groups using the Kaplan-Meier method and log-rank tests. Cox proportional hazard regression models were used to evaluate the prognostic factors of LPFS. Complications, hospitalization days, and blood loss were also assessed. RESULTS: The median follow-up was 29.0 months (range, 20.4-37.6 months). No treatment-related mortality was observed. The 1-, 3- and 5-year LPFS rates were 74.0%, 62.8%, and 31.4% in the SR group and 72.8%, 68.7%, and 51.5% in the ablation group, with the median LPFS of 41.5 months (95% CI: 9.3-23.4 months) vs. 47.9 months (95% CI 20.6-75.8 months), respectively (p = 0.784). Tumor size ≥3 cm was the only significant risk factor for LPFS (p = 0.031). The ablation group was superior to the SR group with a lower major complication rate (4.1% vs. 14.5%, p = 0.03), less blood loss (1 ml vs. 100 ml, p < 0.001), and a shorter hospital stay (2 d vs. 6 d, p < 0.001). CONCLUSION: Thermal ablation provided a similar LPFS and less comorbidities than SR, indicating that it is an effective and safe treatment for adrenal metastases.

In the presence of TGF-ß1, Asperosaponin VI promotes human mesenchymal stem cell differentiation into nucleus pulposus like- cells.

BACKGROUND: The regeneration of nucleus pulposus (NP) cells is an effective method to prevent intervertebral disc degeneration (IVDD). In this study, we investigated the role of Asperosaponin VI (ASA VI), isolated from a traditional Chinese medicine (TCM), the root of Dipsacus asper Wall, in promoting human mesenchymal stem cell (HMSC) proliferation and differentiation into NP-like cells and explored the possible mechanism of action. METHODS: The effects of ASA VI on HMSC viability and proliferation were determined by the XTT method and EDU staining. Then, Real-time qPCR, immunocytochemistry and immunofluorescence assays were used to measure the effect of ASA VI on the expression of extracellular matrix (ECM) components, such as COL2A1, aggrecan, SOX9, KRT19, PAX1, and glycosaminoglycans (GAGs), in NP cells. In addition, Western blot assay was used to measure the expression of p-ERK1/2 and p-smad2/3. RESULTS: ASA VI was able to promote the proliferation and differentiation of HMSCs into NP-like cells, and the optimum concentration was 1 mg/L. Western blot assay indicated that the possible mechanism might be related to the activation of p-ERK1 / 2 and p-Smad2 / 3. CONCLUSIONS: ASA VI can promote the proliferation and differentiation of HMSCs into NP-like cells, which can potentially be used as a treatment for IVDD.

Transmembrane transport mechanism of n-hexadecane by Candida tropicalis: Kinetic study and proteomic analysis.

Yeasts are the most predominant petroleum hydrocarbon-degrading fungi isolated from petroleum-contaminated soil. However, information of the transmembrane transport of petroleum hydrocarbon into yeast cells is limited. The present study was designed to explore the transmembrane transport mechanisms of the typical petroleum hydrocarbon n-hexadecane in Candida tropicalis cells with petroleum hydrocarbon biodegradation potential. Yeast cells were treated with n-hexadecane in different scenarios, and the percentage of intracellular n-hexadecane and transport dynamics were investigated accordingly. The intracellular concentration of n-hexadecane increased within 15 min, and transportation was inhibited by NaN3, an ATPase inhibitor. The uptake kinetics of n-hexadecane were well fitted by the Michaelis-Menten model, and Kt values ranged from 152.49 to 194.93 mg/L. All these findings indicated that n-hexadecane might cross the yeast cells in an energy-dependent manner and exhibit an affinity with the cell transport system. Moreover, the differentially expressed membrane proteins induced by n-hexadecane were identified and quantified by tandem mass tag labeling coupled with liquid chromatography tandem mass spectrometry analysis. The proteome analysis results demonstrated that energy production and conversion accounted for a large proportion of the functional classifications of the differentially expressed proteins, providing further evidence that sufficient energy supply is essential for transmembrane transport. Protein functional analysis also suggested that differentially expressed proteins associated with transmembrane transport processes are clearly enriched in endocytosis and phagosome pathways (p < 0.05), and the analysis supported the notion that the underlying transmembrane transport mechanism might be associated with endocytosis and phagosome pathways, revealing a new mechanism of n-hexadecane internalization by Candida tropicalis.

Polycyclic aromatic hydrocarbon and n-alkane pollution characteristics and structural and functional perturbations to the microbial community: a case-study of historically petroleum-contaminated soil.

Characterization of the typical petroleum pollutants, polycyclic aromatic hydrocarbons (PAHs) and n-alkanes, and indigenous microbial community structure and function in historically contaminated soil at petrol stations is critical. Five soil samples were collected from a petrol station in Beijing, China. The concentrations of 16 PAHs and 31 n-alkanes were measured by gas chromatography-mass spectrometry. The total concentrations of PAHs and n-alkanes ranged from 973 ± 55 to 2667 ± 183 µg/kg and 6.40 ± 0.38 to 8.65 ± 0.59 mg/kg (dry weight), respectively, which increased with depth. According to the observed molecular indices, PAHs and n-alkanes originated mostly from petroleum-related sources. The levels of ΣPAHs and the total toxic benzo[a]pyrene equivalent (ranging from 6.41 to 72.54 µg/kg) might exert adverse biological effects. Shotgun metagenomic sequencing was employed to investigate the indigenous microbial community structure and function. The results revealed that Proteobacteria and Actinobacteria were the most abundant phyla, and Nocardioides and Microbacterium were the important genera. Based on COG and KEGG annotations, the highly abundant functional classes were identified, and these functions were involved in allowing microorganisms to adapt to the pressure from contaminants. Five petroleum hydrocarbon degradation-related genes were annotated, revealing the distribution of degrading microorganisms. This work facilitates the understanding of the composition, source, and potential ecological impacts of residual PAHs and n-alkanes in historically contaminated soil.

Electroacupuncture Prevents Osteoarthritis of High-Fat Diet-Induced Obese Rats.

The effects of acupuncture on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models. However, the potential for acupuncture to mediate protective effects on obese-induced OA has not been examined. Here, we investigated the effects of different acupuncture patterns on OA pathogenesis in high-fat diet- (HFD-) induced obese rats. After 12-week diet-induced obesity, obese rats were treated with three acupuncture protocols for 2 weeks, including ST36, GB34, and ST36+GB34. The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery.

Multiomics Profiling Reveals Protective Function of Schisandra Lignans against Acetaminophen-Induced Hepatotoxicity.

The action principles of traditional Chinese medicines (TCMs) feature multiactive components, multitarget sites, and weak combination with action targets. In the present study, we performed an integrated analysis of metabonomics, proteomics, and lipidomics to establish a scientific research system on the underlying mechanism of TCMs, and Schisandra lignan extract (SLE) was selected as a model TCM. In metabonomics, several metabolic pathways were found to mediate the liver injury induced by acetaminophen (APAP), and SLE could regulate the disorder of lipid metabolism. The proteomic study further proved that the hepatoprotective effect of SLE was closely related to the regulation of lipid metabolism. Indeed, the results of lipidomics demonstrated that SLE dosing has an obvious callback effect on APAP-induced lipidic profile shift. The contents of 25 diglycerides (DAGs) and 21 triglycerides (TAGs) were enhanced significantly by APAP-induced liver injury, which could further induce liver injury and inflammatory response by upregulating protein kinase C (PKCß, PKCγ, PKCδ, and PKCθ). The upregulated lipids and PKCs could be reversed to the normal level by SLE dosing. More importantly, phosphatidic acid phosphatase, fatty acid transport protein 5, and diacylglycerol acyltransferase 2 were proved to be positively associated with the regulation of DAGs and TAGs. SIGNIFICANCE STATEMENT: Integrated multiomics was first used to reveal the mechanism of APAP-induced acute liver failure (ALF) and the hepatoprotective role of SLE. The results showed that the ALF caused by APAP was closely related to lipid regulation and that SLE dosing could exert a hepatoprotective role by reducing intrahepatic diglyceride and triglyceride levels. Our research can not only promote the application of multicomponent technology in the study of the mechanism of traditional Chinese medicines but also provide an effective approach for the prevention and treatment of ALF.

Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy.

The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu2+-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu2+ into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing 64Cu2+, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an "ideal" PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy.

Comparison of the effects of general and local anesthesia in lumbar interlaminar endoscopic surgery.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) with an interlaminar approach is a technique used to treat lumbar disc hernia. It has not yet been established whether general or local anesthesia (LA) is preferable for lumbar interlaminar endoscopic surgery. METHODS: Between October, 2012 and June, 2016, 60 patients were recruited and randomly divided into 2 groups: the general anesthesia (GA) group and the LA group. The patients' basic clinical data, intraoperative patient experience, Oswestry disability index (ODI), visual analog scale (VAS) score, and the postoperative patient satisfaction rate were assessed. RESULTS: Statistically significant differences were found between the two groups in operative time and length of hospital stay. There were no significant differences in postoperative ODI or VAS scores between the two groups during follow-up at 3, 6, and 12 months. One patient in the GA group sustained a nerve root injury intraoperatively. Two patients in the LA group suffered adverse reactions, as did six patients in the GA group. However, 50% of the patients expressed fear about undergoing the surgery with LA, while all patients felt they could undergo the same surgery with GA. CONCLUSIONS: General and LA are both suitable for use in lumbar interlaminar endoscopic surgery. However, GA makes a positive intraoperative surgical experience more likely for the patient.