Exploring the impact of OSA on short-term survival in patients with AECOPD admitted to the ICU.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms, which significantly contributes to hospitalizations related to COPD symptoms. Previous research has mainly focused on the correlation between obstructive sleep apnea (OSA) and COPD. However, there were few studies that investigated the short-term mortality rate of AECOPD patients with or without OSA. METHODS: Data for our research was taken from the Medical Information Mart for Intensive Care Database IV. A total of 1332 patients were included in the study based on well-defined criteria for selection and exclusion. By analyzing the characteristics of AECOPD patients, we compared those with and without OSA. RESULTS: There were 1122 AECOPD patients without OSA, 210 patients with OSA. In comparison to those without OSA, patients with OSA exhibited lower 30-day and 90-day ICU mortality with unadjusted HR, as well as lower hospital mortality with unadjusted OR. However, after adjustments were made, there were no significant associations observed between OSA and short-term mortality, including 30-day ICU mortality, 90-day ICU mortality, ICU mortality, and hospital mortality in AECOPD patients. Subgroup analysis revealed that OSA may act as a risk factor for AECOPD patients with a BMI lower than 30 kg/m2. CONCLUSIONS: There is no impact on short-term survival in AECOPD patients with OSA under intensive care unit (ICU) management and nursing.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

Image 1.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Authentication of Shenqi Fuzheng Injection via UPLC-Coupled Ion Mobility-Mass Spectrometry and Chemometrics with Kendrick Mass Defect Filter Data Mining.

Nearly 5% of the Shenqi Fuzheng Injection's dry weight comes from the secondary metabolites of Radix codonopsis and Radix astragali. However, the chemical composition of these metabolites is still vague, which hinders the authentication of Shenqi Fuzheng Injection (SFI). Ultra-high performance liquid chromatography with a charged aerosol detector was used to achieve the profiling of these secondary metabolites in SFI in a single chromatogram. The chemical information in the chromatographic profile was characterized by ion mobility and high-resolution mass spectrometry. Polygonal mass defect filtering (PMDF) combined with Kendrick mass defect filtering (KMDF) was performed to screen potential secondary metabolites. A total of 223 secondary metabolites were characterized from the SFI fingerprints, including 58 flavonoids, 71 saponins, 50 alkaloids, 30 polyene and polycynes, and 14 other compounds. Among them, 106 components, mainly flavonoids and saponins, are contributed by Radix astragali, while 54 components, mainly alkaloids and polyene and polycynes, are contributed by Radix codonopsis, with 33 components coming from both herbs. There were 64 components characterized using the KMDF method, which increased the number of characterized components in SFI by 28.70%. This study provides a solid foundation for the authentification of SFIs and the analysis of its chemical composition.

Carbon stock stability in drained peatland after simulated plant carbon addition: Strong dependence on deeper soil.

Peatlands are vital soil carbon sinks, yet this function is jeopardized by plant carbon which could change the decomposition rate of soil organic carbon, knowing as "priming effect". How the priming effect depends on depth is a critical question in drained peatland given the heterogeneity of soil layers defined by the water table, which include the surface acrotelm, inter-mesotelm and deep catotelm. Here, through incubation, we quantified the response of these three soil layers to addition of 13C-labeled oxalate, glucose, cellulose, or cinnamic acid under anoxic or oxic conditions on the Zoige Plateau in Tibet. Soil carbon in the inter-mesotelm showed the greatest decomposition, with the highest humification index and lowest microbial biomass carbon, while the soil carbon at the surface acrotelm was least decomposed. Under anoxic conditions, exogenous carbon addition reduced CO2 emission by 12.2% at the surface acrotelm but increased by 59.8% in the inter-mesotelm and 23.5% in the deep catotelm. In the inter-mesotelm, oxalate addition significantly increased CO2 emission by 63.9%, while cinnamic acid significantly increased it by 92.9%. In the deep catotelm, cinnamic acid significantly increased CO2 emission by 55.3%. These results suggested that deeper soil organic carbon was more sensitive to plant carbon, particularly complex or recalcitrant carbon, than surface acrotelm soil. Under oxic conditions, carbon addition increased surface soil CO2 emission by 18.9%, and triggered even greater increase at inter-mesotelm and deep catotelm soil, with proportions of 48.3% and 32.0%, respectively. Under both conditions, peat profile CO2 release increased by 17.2-31.4% after exogenous carbon addition, and more than 77.8% of the increase came from the deeper two layers. These findings highlighted the need to take full account of priming effect of deeper soil in order to assess and predict the stability of carbon stocks in drained peatland.

Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy.

Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 µM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP+-treated PC12 cells, CB6 inhibited cell apoptosis and increased cell viability by inducing autophagy. In MPTP-induced mouse model of PD, oral administration of CB6 (10, 20 mg· kg-1· d-1, for 21 days) significantly improved motor dysfunction and prevented the loss of dopaminergic neurons in the striatum and substantia nigra pars compacta. Collectively, compound CB6 is a brain-permeable autophagy enhancer via PIK3C3 complex activation, which may help the prevention or treatment of PD.

Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson's Disease.

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson's disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.

Structure and distribution of nitrite-dependent anaerobic methane oxidation bacteria vary with water tables in Zoige peatlands.

The recently discovered nitrite-dependent anaerobic methane oxidation (n-damo) is an important methane sink in natural ecosystems performed by NC10 phylum bacteria. However, the effect of water table (WT) gradient due to global change on n-damo bacterial communities is not well studied in peatlands. Here, we analysed the vertical distribution (0-100 cm) of n-damo bacterial communities at three sites with different WTs of the Zoige peatlands in the Qinghai-Tibetan Plateau. Using an n-damo bacterial specific 16S rRNA gene clone library, we obtained 25 operational taxonomic units (OTUs) that could be divided into Groups A, B, C, D and E (dominated by A and B). The dominant group was Group B at the high (OTU14 and OTU20) and intermediate (OTU7 and OTU8) WT sites and Group A was dominant at the low WT site (OTU6 and OTU5). Using high-throughput sequencing, we observed that n-damo bacteria mainly distributed in subsurface soils (50-60 and 20-30 cm), and their relative abundances were higher at the low WT site than at the other two sites. In addition, we found that pH and nitrate were positively correlated with Group A, while total organic carbon, total nitrogen and ammonia were positively associated with Group B. Our study provides new insights into our understanding of the response of n-damo bacteria to WT gradient in peatlands, with important implications for global change.

Comparison of methane emissions among invasive and native mangrove species in Dongzhaigang, Hainan Island.

The strength of methane (CH4) source of mangroves is not well understood, especially when including all CH4 pathways in consideration. This study measured CH4 fluxes by five pathways (sediments, pneumatophores, water surface, leaves, and stems) from four typical mangrove forests, including Kandelia candel without pneumatophores and three species with pneumatophores: Sonneratia apetala, Laguncularia racemosa and Bruguiera gymnorhiza-Bruguiera sexangula. The CH4 fluxes from sediments were 4.82±1.46mgCH4m-2h-1 for K. candel and 1.36±0.17mgCH4m-2h-1 for the other three with pneumatophores. Among the three communities with pneumatophores, S. apetala community had significantly greater emission rate than the other two (P<0.05). Pneumatophores in S. apetala were found to significantly decrease CH4 emission from sediments (P<0.01), while those in B. gymnorhiza-B. sexangula were significantly increase it (P<0.05). CH4 fluxes from waters were 3.48±1.11mgCH4m-2h-1, with the highest emission rate in the K. candel community for the duck farming. Leaves of mangroves except for those of K. candel were a weak CH4 daytime sink, but stems were a weak source. The total 72ha of mangroves in the Changning river basin emitted about 8.10Gg CH4 per year, with a weighted emission rate of about 1.29mgCH4m-2h-1. Our results suggested that mangroves are only a small methane source to atmosphere with great contribution from sediments and waters, only slight contribution from leaves and stems. Pneumatophores of different mangrove species played different roles in CH4 fluxes from sediments.

Study of BDE-47 induced Parkinson's disease-like metabolic changes in C57BL/6 mice by integrated metabolomic, lipidomic and proteomic analysis.

As the predominant congener of polybrominated diphenyl ethers (PBDEs) detected in human serum, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) has been reported to induce neurotoxicity. However, the possible linkage between BDE-47 and typical neurodegenerative diseases such as Parkinson's disease (PD) is still unclear. Here we carried out omics studies using liquid chromatography-orbitrap mass spectrometry (LC-orbitrap MS) to depict the BDE-47 induced metabolic changes in C57BJ/L mice to explore the possible contribution of BDE-47 exposure to PD pathology. BDE-47 dissolved in corn oil was orally administered to mice for 30 consecutive days. Results of metabolomics and lipidomics studies of PD-related brain regions revealed significant metabolite changes in pathways involved in oxidative stress and neurotransmitter production. Moreover, isobaric tags for relative and absolute quantitation (iTRAQ) proteomics study of the striatum, which is the part of brain that is most intensively studied in PD pathogenesis, revealed that BDE-47 could induce neurotransmitter system disturbance, abnormal phosphorylation, mitochondrial dysfunction and oxidative stress. Overall, this study depicts the possible contribution of BDE-47 exposure to PD pathology and highlights the powerfulness of omics platforms to deepen the mechanistic understanding of environmental pollutant-caused toxicity.

Network pharmacology study reveals energy metabolism and apoptosis pathways-mediated cardioprotective effects of Shenqi Fuzheng.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng (SQ) is a renowned traditional Chinese medicine extracted from Radix Codonopsis and Radix Astragali. Although SQ is widely used to treat myocardial ischemia-reperfusion (I/R) injury, the molecular mechanisms supporting its clinical application remain elusive. AIM OF THE STUDY: The purpose of current study was to understand its cardioprotective effects at the molecular level using network pharmacology approach. MATERIALS AND METHOD: In an I/R injury animal model, the beneficial pharmacological activities of SQ were confirmed by decreased infarct range observed on drug treated rats versus control group. Additionally, several serum biochemical indicators were in concord with this observation. Subsequently, a microarray experiment was performed to reveal the influence on injured heart at the gene expression level by this TCM injection. We then proposed a network analysis algorithm NTRA to discover the key nodes based on both disease network structure and transcriptomics. Using NRIODN, a method developed by our group previously, the holistic changes on the gene network induced by for I/R injury and SQ treatment were evaluated. RESULTS: Pathway enrichment analysis of highly ranked genes by NTRA showed that PPAR and apoptosis pathways were highly related to I/R injury. Finally, western blot results showed increased level of the PPARα and BAX protein in the heart after injection treatment which confirmed the hypothesis. CONCLUSION: In conclusion, our results suggest that SQ injection exerts protective effect against myocardial ischemia-reperfusion injury through multiple pathways, including myocardial energy metabolism improvement, cell adhesion inhibition, inflammatory reaction perturbation, myocardial apoptosis reduction and ventricular remodeling avoidance.

[Research advance in metabolism of effective ingredients from traditional Chinese medicines by probiotics].

The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine.This review summarizes and analyses the research progress on metabolism effects of gut microbiota on Chinese medicines components, the regulating effect of effective ingredients from Chinese medicine on intestinal probiotics, the application status of probiotics in traditional Chinese medicines, and the main problems and prospects in the research and development of Chinese medicines products with probiotic, aiming to provide theoretical guidance and practical value for the fermentation engineering of Chinese herbal medicine.

Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death.

6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson's disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA dramatically enhanced the selectivity and toxicity of 6-OHDA. To understand the mechanisms by which 6-OHDA/AA induces cell death, we established a 6-OHDA/AA cell toxicity model in human dopaminergic neuroblastoma SH-SY5Y cells. We confirmed that the toxicity of 6-OHDA was dramatically increased in the presence of AA, and the toxicity can be prevented by a flavonoid, baicalein. Mechanistically, our research reveals that 6-OHDA/AA induces cell death mainly through the interruption of intracellular calcium homeostasis, which leads to calpain activation and mitochondrial damage. Baicalein prevents 6-OHDA/AA-induced intracellular calcium elevation as well as consequent mitochondria damage. Taken together, our study confirms that 6-OHDA/AA is a more sensitive model for inducing neuronal lesion in vitro and reveals the central role of intracellular calcium in 6-OHDA/AA-induced cell death. Our studies further show that baicalein prevents 6-OHDA/AA-induced cell death by inhibiting intracellular calcium elevation.

A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson's Disease.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I-IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p = 0.019), mood/cognition (p = 0.005), and reduction in hallucinations (p = 0.024). In addition, post hoc analysis showed a significant reduction in constipation (p < 0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p = 0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

Water table drawdown shapes the depth-dependent variations in prokaryotic diversity and structure in Zoige peatlands.

Microbial communities are important to ecosystem function and sensitive to hydrological dynamics. However, we lack predictable knowledge about how soil microorganisms respond to water table drawdown in different depths. This research used a high-throughput sequencing method to determine the responses of prokaryotic communities to the changes of water table and depth on Zoige peatlands. Our results showed that water table drawdown reduced alpha diversity indices (observed species, Shannon diversity and Chao1 richness) of prokaryotic communities. Intriguingly, the reduction of diversity varied in different depths, and was statistically significant in intermediate layers (20-30 cm and 50-60 cm), but not in the surface (0-10 cm) or deep layer (90-100 cm). In deeper layers there was greater relative abundance of most anaerobic microorganisms (e.g. Chloroflexi, Planctomyctes and NC10), but lesser amounts of most aerobes (e.g. Proteobacteria and Acidobacteria). However, the vertical distribution of prokaryotic microbiota along the depth gradient was altered by water table drawdown, mainly by enriching oligotrophs (e.g. Acidobcteria) over copiotrophs (e.g. Bacteriodetes). In addition, we found that the most important soil parameters influencing community structure were soil pH, total organic carbon and total nitrogen. Our study illuminates that the variations of prokaryotic communities caused by water table drawdown are depth-dependent, and that water table drawdown leads to predictive changes of microbiota in peatlands.

Decrease in the Generation of Amyloid-ß Due to Salvianolic Acid B by Modulating BACE1 Activity.

OBJECTIVE: Generation and accumulation of the amyloid-ß (Aß) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by ß-secretase (ß-site APP cleaving enzyme or BACE1) and γ-secretase are the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production of Aß, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China. METHOD: In this study, we discovered that Sal B acted as a BACE1 modulator and reduced the level of secreted Aß in two different Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B significantly and dose-dependently decreased the generation of extracellular Aß, soluble APPß (by-product of APP cleaved by BACE1), and intracellular C-terminal fragment ß from APP without influencing α-secretase and γ-secretase activity and the levels of FL-APP. In addition, using protein-docking, we determined the potential conformation of Sal B on BACE1 docking and revealed the interactions of Sal B with the BACE1 catalytic center. RESULTS: The docking provides a feasible explanation for the experimental results, especially in terms of the molecular basis of Sal B's action. Our results indicate that Sal B is a BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.

Full component analysis of Tianma-Gouteng-Yin.

BACKGROUND: Tianma-Gouteng-Yin (TGY), which is common Chinese medicine formulation consisting of 11 different herbs and being used in China for the treatment of Parkinson's disease, inflammatory conditions and cardiovascular diseases, was selected for full component analysis. The aim of this study was to quantitatively analyze the chemical profiles of ten commercial TGY samples and one sample produced in our laboratory. METHODS: Ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole-tandem time-of-flight mass spectrometry (Q-TOF-MS) was used to analyze the non-saccharide small molecule components of the different TGY samples. The established method was validated in terms of its linearity, sensitivity, precision, accuracy and stability. High performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) was also used to quantify three major saccharides (fructose, glucose and sucrose). RESULTS: The relative standard deviations for the precision, repeatability and stability of these compounds were less than 5 %, while the accuracy of the method was 95-105 %. Twenty-eight of the compounds found in TGY were successfully identified, with 20 being quantified. The macromolecules present in these samples were also identified using an ethanol precipitation method, representing 294.68-696.64 mg/g of the total material depending on the batch. Notably, the components identified using this method represented up to 78 % of the total weight of the TGY samples. CONCLUSIONS: The developed UHPLC/Q-TOF-MS and HPLC-ELSD methods successfully identified 28 of the complex compounds found in TGY.

A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition.

Autophagy dysfunction is a common feature in neurodegenerative disorders characterized by accumulation of toxic protein aggregates. Increasing evidence has demonstrated that activation of TFEB (transcription factor EB), a master regulator of autophagy and lysosomal biogenesis, can ameliorate neurotoxicity and rescue neurodegeneration in animal models. Currently known TFEB activators are mainly inhibitors of MTOR (mechanistic target of rapamycin [serine/threonine kinase]), which, as a master regulator of cell growth and metabolism, is involved in a wide range of biological functions. Thus, the identification of TFEB modulators acting without inhibiting the MTOR pathway would be preferred and probably less deleterious to cells. In this study, a synthesized curcumin derivative termed C1 is identified as a novel MTOR-independent activator of TFEB. Compound C1 specifically binds to TFEB at the N terminus and promotes TFEB nuclear translocation without inhibiting MTOR activity. By activating TFEB, C1 enhances autophagy and lysosome biogenesis in vitro and in vivo. Collectively, compound C1 is an orally effective activator of TFEB and is a potential therapeutic agent for the treatment of neurodegenerative diseases.

Responses of peat carbon at different depths to simulated warming and oxidizing.

Warming and water table drawdown greatly reshape peatland carbon cycle, especially when considering the old carbon stored under the peatland subsurface. However, little is known about the effects of warming, oxidizing by drying or their combination on carbon decomposition at different depths (0-100 cm) of peat. In this research, soil of different depths from Zoige Plateau was incubated in four scenarios (8 °C-anaerobic, 8 °C-aerobic, 18 °C-anaerobic and 18 °C-aerobic) to detect the exported carbon. Our result showed that soil respiration (Rs) increased obviously with enhanced temperature and oxygen. The total CO2 fluxes of 2400.22 ± 57.69 mg m(-2) d(-1) under 8 °C-anaerobic condition increased by 73.6%, 40.7% and 176.5% with warming, oxidizing and their combined effect, respectively. The average dissolved organic carbon (DOC) concentration was 74.90 ± 8.09 mg kg(-1) under 8 °C-anaerobic condition, but increased by 53.5%, 44% and 159.4%, respectively under the condition of warming, oxidizing and their combination. Rs and its variation under warming and oxidization differed significantly among different depths, probably caused by the differences of soil substrate, especially the variation in distribution of soil microbes and enzymes among depths of peatlands. By classifying the source of Rs as young soil (YS: 0-20 cm) and old soil (OS: 21-100 cm), this reseaerch found that OS accounted for a huge part of total Rs under 8 °C-anaerobic condition (CO2: 74.2%; DOC: 60.7%). Such relative contribution of OS to total Rs did not change obviously with warming or oxidizing. Though YS and OS responded equally to warming and oxidizing, OS was responsible for a larger proportion of total increase in Rs. Compared with other studies, we concluded that peatlands soil in our field of mid-latitude and high altitude is less sensitive to warming and oxidizing than peatlands of higher latitude, but that OS of this peatlands is more critical in predicting regional carbon cycle.