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Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σâπ* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.
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BACKGROUND: The genus Hydrocotyle Tourn. ex L. is a key group for further study on the evolution of Apiales, comprising around 170 species globally. Previous studies mainly focused on separate sections and provided much information about this genus, but its infrageneric relationships are still confusing. In addition, the genetic basis of its adaptive evolution remains poorly understood. To investigate the phylogeny and evolution of the genus, we selected ten representative species covering two of three diversity distribution centers and exhibiting rich morphology diversity. Comparative plastome analysis was conducted to clarify the structural character of Hydrocotyle plastomes. Positive selection analyses were implemented to assess the evolution of the genus. Phylogenetic inferences with protein-coding sequences (CDS) of Hydrocotyle and 17 related species were also performed. RESULTS: Plastomes within Hydrocotyle were generally conservative in structure, gene order, and size. A total of 14 regions (rps16-trnK, trnQ-rps16, atpI-atpH, trnC-petN-psbM, ycf3-trnS, accD-psaI-ycf4, petA-psbJ, rps12-rpl20, rpl16 intron, rps3-rpl16 intron, rps9-rpl22, ndhF-rpl32, ndhA intron, and ycf1a) were recognized as hotspot regions within the genus, which suggested to be promising DNA barcodes for global phylogenetic analysis of Hydrocotyle. The ycf15 gene was suggested to be a protein-coding gene for Hydrocotyle species, and it could be used as a DNA barcode to identify Hydrocotyle. In phylogenetic analysis, three monophyletic clades (Clade I, II, III) were identified with evidence of rapid radiation speciation within Clade I. The selective pressure analysis detected that six CDS genes (ycf1b, matK, atpF, accD, rps14, and psbB) of Hydrocotyle species were under positive selection. Within the genus, the last four genes were conservative, suggesting a relation to the unique evolution of the genus in Apiales. Seven genes (atpE, matK, psbH, ycf1a, ycf1b, rpoA, and ycf2) were detected to be under some degree of positive selection in different taxa within the genus Hydrocotyle, indicating their role in the adaptive evolution of species. CONCLUSIONS: Our study offers new insights into the phylogeny and adaptive evolution of Hydrocotyle. The plastome sequences could significantly enhance phylogenetic resolution and provide genomic resources and potential DNA markers useful for future studies of the genus.
Subject(s)
Phylogeny , Evolution, Molecular , Genome, Plastid , Apiaceae/geneticsABSTRACT
BACKGROUND: Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. AIM: To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). METHODS: The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1ß, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. CONCLUSION: LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.
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BACKGROUND: Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. METHODS: The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. RESULTS: Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01-1.05, P < 0.0005). After the NHR was divided into tertiles, those in the top tertile had an 18% higher chance of developing depression than those in the bottom tertile (OR = 1.18; 95% CI: 1.05-1.32; P for trend = 0.0041). Subgroup analyses revealed variations in this association based on race and marital status. Additionally, the relationship between NHR and depression demonstrated a U-shaped pattern, with a significant breakpoint identified at an NHR of 6.97. CONCLUSION: These results imply that the NHR may be a potential biomarker for depression risk, with implications for early detection and personalized treatment. Further research is needed to elucidate the mechanisms underlying the NHR-depression link and establish causality.
Subject(s)
Cholesterol, HDL , Depression , Neutrophils , Humans , Male , Depression/blood , Depression/epidemiology , Female , Cholesterol, HDL/blood , Adult , Cross-Sectional Studies , Middle Aged , United States/epidemiology , Neutrophils/metabolism , Nutrition Surveys , Biomarkers/blood , Risk Factors , Aged , Logistic ModelsABSTRACT
NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.
Subject(s)
Gastrointestinal Microbiome , Gynostemma , Non-alcoholic Fatty Liver Disease , Plant Extracts , Animals , Gastrointestinal Microbiome/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Mice , Gynostemma/chemistry , Plant Extracts/pharmacology , Male , Inflammation/drug therapy , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacologyABSTRACT
Anaerobic ammonium oxidation (anammox), an energy-efficient deamination biotechnology, faces operational challenges in low-temperature environments. Enhancing the metabolic activity of anammox bacteria (AnAOB) is pivotal for advancing its application in mainstream municipal wastewater treatment. Inspired by the metabolic adaptability of AnAOB and based on our previous findings, this work investigated the enhancement of intracellular ATP and NADH synthesis through the exogenous supply of reduced humic acid (HAred) and H2O2 redox couple, aiming to augment AnAOB activity under low-temperature conditions. Our experimental setup involved continuous dosing of 0.0067 µmol g-1 volatile suspended solid of H2O2 and 10 mg g-1 volatile suspended solid of HAred into a mainstream anammox reactor operated at 15 °C with an influent TN content of 60 mg/L. The results showed that HAred / H2O2 couple succeeded in maintaining the effluent TN at 10.72 ± 0.91 mg l-1. The specific anammox activity, ATP and NADH synthesis levels of sludge increased by 1.34, 2.33 and 6.50 folds, respectively, over the control setup devoid of the redox couple. High-throughput sequencing analysis revealed that the relative abundance of Candidatus Kuenenia after adding HAred / H2O2 couple reached 3.65 % at the end of operation, which was 5.14 folds higher than that of the control group. Further metabolomics analysis underscored an activation in the metabolism of amino acids, nucleotides, and phospholipids, which collectively enhanced the availability of ATP and NADH for the respiratory processes. These findings may provide guidance on strategy development for improving the electron transfer efficiency of AnAOB and underscore the potential of using redox couples to promote the mainstream application of anammox technology.
Subject(s)
Oxidation-Reduction , Sewage , Sewage/microbiology , Bioreactors , Ammonium Compounds/metabolism , Anaerobiosis , Hydrogen Peroxide/metabolism , Waste Disposal, Fluid/methods , Bacteria/metabolism , NAD/metabolismABSTRACT
We described an 82-year-old man who was taken to our emergency department after being found unconscious. His electrocardiogram (ECG) showed ST-segment elevation in leads V4-V6 and cardiac troponin I (cTnI) was abnormally elevated. In addition to ECG and cTnI changes, this patient was combined with unconsciousness, high fever, abnormal liver function, acute renal failure, and rhabdomyolysis. The initial diagnosis was heat stroke, so cooling measures were initiated immediately, but a concurrent myocardial infarction was suspected. Meanwhile, emergency coronary angiography was performed, but no severe coronary stenosis or thrombosis was found. We first evaluated quantitative flow ratio (QFR) and coronary angiography-derived index of microvascular resistance (ca-IMR) in patients with heat stroke. Ca-IMR was 260 mmHg*s/m in the left circumflex artery, indicating the presence of coronary microvascular dysfunction (CMD). After several days of treatment, the patient recovered from multiple organ damage. Therefore, ECG and troponin results should be interpreted carefully in patients with high fever and coma during high temperature seasons.
Subject(s)
Electrocardiography , Heat Stroke , Myocardial Infarction , Troponin I , Humans , Male , Heat Stroke/blood , Heat Stroke/diagnosis , Heat Stroke/physiopathology , Heat Stroke/complications , Aged, 80 and over , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Myocardial Infarction/physiopathology , Troponin I/blood , Diagnosis, DifferentialABSTRACT
Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.
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Background: Tuberculosis (TB) remains a significant public health challenge in China. Early detection and diagnosis of TB cases are crucial to interrupt disease transmission and prevent its progression. This study aims to describe the delay in seeking care and diagnosis among patients with pulmonary tuberculosis (PTB) and identify the influencing factors in two counties in Beijing. Methods: A retrospective analysis was carried out to investigate care-seeking and diagnosis delay in two counties in Beijing. Basic information of PTB patients from January 1 to December 31, 2021, was extracted from the Tuberculosis Information Management System of China (TBIMS), and all enrolled patients were interviewed via telephone using a standard questionnaire. Statistical description was performed using the median and interquartile range (IQR). Chi-square test and multivariate logistic regression model were used to analyze the influencing factors. Results: 537 patients were enrolled. The median duration of care-seeking and diagnosis delay was 11 (IQR: 5-26) days and 8 (IQR: 0-18) days, with 41.71 and 35.20% of patients experiencing delays (>14 days). The study found that being asymptomatic (OR = 2.791, 95%CI: 1.710-4.555) before seeking medical care and not attending work during treatment (OR = 2.990, 95%CI: 1.419-6.298) were identified as risk factors for care-seeking delay. Patients who were tracked (OR = 2.632, 95%CI: 1.062-6.521) and diagnosed at tuberculosis control and prevention institutions (OR = 1.843, 95%CI: 1.061-3.202) had higher odds of diagnostic delays. 44.69% of patients presented a total delay (>28 days), with a median duration of 25 (IQR: 13-39) days. A multivariate logistic regression analysis showed that healthy examination (OR = 0.136, 95%CI: 0.043-0.425) was a protective factor for total delay. Conclusion: Public interventions are necessary to improve the efficiency of PTB patients detection and treatment in Beijing. Medical services should focus on the target population and improve access to medical care to further reduce delays for PTB patients.
Subject(s)
Delayed Diagnosis , Patient Acceptance of Health Care , Tuberculosis, Pulmonary , Humans , Female , Tuberculosis, Pulmonary/diagnosis , Male , Delayed Diagnosis/statistics & numerical data , Adult , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Retrospective Studies , Beijing , Surveys and Questionnaires , Aged , China , Logistic Models , Adolescent , Risk Factors , Young AdultABSTRACT
The design and development of high-performance and long-life Pt-free catalysts for the oxygen reduction reaction (ORR) is of great important with respect to metal-air batteries and fuel cells. Herein, a new low-cost covalent organic frameworks (COFs)-derived CoNC single-atoms catalyst (SAC) is fabricated and compared with the engineered nanoparticle (NP) counterpart for ORR activity. The ORR performance of the SAC catalyst (CoSA@NC) surpasses the NP counterpart (CoNP-NC) under the same operation condition. CoSA@NC also achieves improved long-term durability and better methanol tolerance compared with the Pt/C. The zinc-air battery assembled by the CoSA@NC cathode delivers a higher power density and energy density than that of commercial Pt/C catalyst. Molecular dynamics (MD) is performed to explain the spontaneous evolution from clusters to single-atom metal configuration and density functional theory (DFT) calculations find that CoSA@NC possesses lower d-band center, resulting in weaker interaction between the surface and the O-containing intermediates. Consequently, the reductive desorption of OH*, the rate-determine step, is further accelerated.
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Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances. IMPORTANCE: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.
Subject(s)
Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Gastrointestinal Microbiome/drug effects , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Mice , Male , Diet, High-Fat/adverse effects , Dysbiosis/drug therapy , Dysbiosis/microbiology , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Bile Acids and Salts/metabolism , Fatty Acids, Volatile/metabolism , Lipid Metabolism/drug effects , Signal Transduction/drug effects , Plant ExtractsABSTRACT
Artificial diets for silkworms overcome the seasonal limitations of traditional rearing methods with fresh mulberry leaves. However, the current wet artificial diets, steamed at high temperatures, are not favored by silkworms, and they are cumbersome and challenging to preserve. These conditions adversely affected the development of artificial diet-based sericulture production. In this study, we disinfected dry powder diets with radiation and added distilled water without steaming before use. Then, the nutritional value of finished diets and their impact on silkworm development was assessed. Compared with steamed diets, nonsteamed diets were more attractive to silkworms. Chemical assays showed significantly more essential nutrients for silkworms, including l-ascorbic acid, vitamin B1, vitamin B2, and urease in nonsteamed diets than in steamed diets. Feeding fifth-instar silkworm larvae with nonsteamed diets significantly improved the ammonia utilization efficiency of the diet and increased the cocoon shell rate and diet/silk protein conversion efficiency by 5.9% and 13.3%, respectively. When fed with nonsteamed diets, the abundance of aerobic microorganisms in silkworm intestines increased and the abundance of pathogenic bacteria decreased. Furthermore, the vitality of the silkworm, measured by the dead worm cocoon rate, significantly improved by 16.90%. In summary, preparing sterile wet diets without high-temperature steaming effectively improved the nutritional value of the diet and enhanced silkworm growth.
Subject(s)
Bombyx , Morus , Animals , Silk/metabolism , Diet , Larva , Nutritive ValueABSTRACT
Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.
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A rapid analytical method for simultaneous determination of 32 kinds of multi-residue veterinary drugs in eggs was developed using a modified QuEChERS technique based on a reduced graphene oxide-coated melamine sponge(r-GO@MeS)by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The influences of graphene oxide(GO)concentrations,sponge dosages,and purification modes on drug recoveries were investigated during the purification process.The optimal purification conditions involved using a GO concentration of 0.5 mg/mL,a sponge dosage of 6.0 cm3/mL,and a dynamic purification mode of 5 extrusion cycles.Separation was achieved using an Agilent Eclipse Plus C18 RRHD column(100 mm×2.1 mm,1.8 μm),and quantitative analysis was performed by the external standard method using an electrospray ionization source(ESI)in multiple reaction monitoring(MRM)mode.The results showed that all 32 kinds of veterinary drugs exhibited good linear correlation with coefficients greater than 0.999,and matrix effects(MEs)ranging from?7.8%to 18.9%.The limits of detection(LODs)and quantification(LOQs)ranged from 0.2 to 10.2 μg/kg and from 0.6 to 28.0 μg/kg,respectively.The recoveries for the three spiked levels were in the range of 66.5%?117.5%,with intra-day and inter-day precision(Relative standard deviation)below 13.3%and 16.3%,respectively.The synthetic r-GO@MeS exhibited efficient matrix purification without the need of high-speed centrifugation or strong magnetic field assistance.This significantly shorted the sample pretreatment time and improved the convenience of the matrix purification process.Combined with UPLC-MS/MS,the method was suitable for the rapid determination of multi-residue veterinary drugs in eggs.
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Rutin, a flavonoid glycoside phytochemical compound, has a remarkable antiobesity effect. However, its therapeutic potential is hindered by its poor water solubility and low oral bioavailability. In this study, rutin was loaded into liposomes (LR) through the self-assembly of lecithin and cholesterol. It was discovered that liposomes improved the water solubility and cellular uptake of rutin in adipocytes. These rutin-loaded liposomes were then incorporated into a microneedle patch (MP) system formed by polyvinylpyrrolidone and poly(vinyl alcohol), and the MP-LR showed an increased release percentage in the adipose tissue microenvironment of pH 6.5 and achieved local delivery of rutin into adipocytes. Next, the therapeutic potentials of rutin, LR, and MP-LR were investigated in a high-fat diet (HFD)-induced obese mouse model. The MP-LR formulation decreased the weight of the HFD mice the most significantly. The antilipogenesis mechanisms of MP-LR are downregulating the lipid synthesis-related proteins (PPAR γ and C/EBP α) in adipocytes and promoting the expression of the beige adipogenesis-related proteins (UCP 1 and Cyt C). The MP systems further promote the local penetration of LR into the adipose tissue specifically, which again elevates their antiobesity effect. Overall, this study suggests that MP-delivered liposome-based formulation is a promising approach to enhance the antiobesity efficacy of antilipogenesis bioactive compounds.
Subject(s)
Liposomes , Rutin , Mice , Animals , Rutin/pharmacology , Rutin/metabolism , Rutin/therapeutic use , Liposomes/metabolism , Obesity/drug therapy , Obesity/metabolism , Adipose Tissue/metabolism , Water/metabolismABSTRACT
Goats rarely move and forage randomly. They tend to move in ways generally influenced by biotic and abiotic factors, respectively. However, few studies have explored the foraging behaviour of goats in the absence of predation and human disturbance. Based on step selection function modelling framework, Normalised Difference Vegetation Index, vegetation surveys, and Global Positioning System tracking of 124 free-ranging domestic adult male Zhongwei goats over one year (2016-2017) were used to assess how biotic and abiotic environmental factors affected their spatiotemporal distribution, and developed a conceptual model to represent the goats' trade-off between forage quantity and preference at different seasons, in the semi-arid grassland of Loess Plateau of 1 178 hectare. The results showed that spatial distributions of goats responded to spatiotemporal variation of biotic factors rather than abiotic factors of elevation, slope and solar radiation, which indicated that biotic factors were of priority to abiotic factors in the foraging process for the goats. According to the season changing, the goats positively used areas with higher forage quantity in the spring and winter, areas of higher forage quantity and preferred species in summer, and areas of abundance of preferred species in autumn. We developed a model to describe the phenomenon that the goats selected areas with higher preferred species only when the forage quantity was plentiful, otherwise they selected areas with higher forage quantity. Better understanding of the patterns and drivers of spatiotemporal distribution of the goats can improve our ability to predict foraging behaviour of livestock in heterogeneous environment and lead to better management practices and policies for the sustainability of these semi-arid landscapes and associated ecosystem services.
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CONTEXT: nanoKAZ is a compact luciferase that exhibits intense blue light emission when it catalyzes the substrate Furimazine (FMZ) as a luciferin, making it an excellent candidate as a reporter protein. However, the specific catalytic residues and mechanism of nanoKAZ have not been revealed. Recently, the structure of nanoKAZ was determined, and it was observed that the luminescent properties changed when FMZ analogs with naphthalene replacing benzene were used. It is speculated that the substituted naphthalene may influence the interaction between the catalytic residues and luciferins, thereby affecting the energy of the emitted light signal. METHOD: Therefore, the primary objective of this study is to analyze and compare the molecular recognition between nanoKAZ and FMZ along with its four activity-altered naphthalene analogs, with aiming to identify the catalytic residues. Molecular docking was employed to construct all nanoKAZ-luciferin models, followed by a 500 ns molecular dynamics simulation. The simulation trajectory was subjected to MM/PBSA analysis to identify crucial residues that contribute significantly to luciferin binding. In the result, two polar residues Y109, and R162 were identified as active residues as their notable contributions to the binding energy. Subsequently, an oxygen molecule was introduced into the local region of the nanoKAZ-FMZ complex and followed with quantum chemical calculations (semiempirical and DFT methods were used) to investigate the catalysis details. The results illustrated the involvement of Y109 and R162 in the oxygenation of FMZ, leading to the formation of dioxetanone, which has been suggested as an important intermediate in the oxidation process among various luciferins sharing the same functional group as FMZ.
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Nonphotosynthetic microorganisms are typically unable to directly utilize light energy, but light might change the metabolic pathway of these bacteria indirectly by forming intermediates such as reactive oxygen species (ROS). This work investigated the role of light on nitrogen conversion by anaerobic ammonium oxidation (anammox) consortia. The results showed that high intensity light (>20000 lx) caused ca. 50% inhibition of anammox activity, and total ROS reached 167% at 60,000 lx. Surprisingly, 200 lx light was found to induce unexpected promotion of the nitrogen conversion rate, and ultraviolet light (<420 nm) was identified as the main contributor. Metagenomic and metatranscriptomic analyses revealed that the gene encoding cytochrome c peroxidase was highly expressed only under 200 lx light. 15N isotope tracing, gene abundance quantification, and external H2O2 addition experiments showed that photoinduced trace H2O2 triggered cytochrome c peroxidase expression to take up electrons from extracellular nonfermentative organics to synthesize NADH and ATP, thereby expediting nitrogen dissimulation of anammox consortia. External supplying reduced humic acid into a low-intensity light exposure system would result in a maximal 1.7-fold increase in the nitrogen conversion rate. These interesting findings may provide insight into the niche differentiation and widespread nature of anammox bacteria in natural ecotopes.
Subject(s)
Anaerobic Ammonia Oxidation , Cytochrome-c Peroxidase , Electrons , Hydrogen Peroxide , Reactive Oxygen Species , NitrogenABSTRACT
Background and Aims: In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them. Methods: We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers. Results: We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers. Conclusions: AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.