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1.
Environ Sci Pollut Res Int ; 31(23): 34446-34458, 2024 May.
Article En | MEDLINE | ID: mdl-38703318

Underground coal gasification (UCG) is a promising technology, but the groundwater pollution caused by UCG is a potential risk to the environment. The measured results of the stratum in the combustion cavity resulting from UCG had proven that the combustion cavity would be filled with some UCG residues and caving rocks when UCG was finished. The pollutants in underground water around the combustion cavity include organic pollutants, inorganic pollutants, and ammonia nitrogen, and one of the primary organic pollutants is phenol. The migration and diffusion characteristics of organic pollutants (taking phenol as a representative) in the groundwater of the combustion cavity were investigated by breakthrough experiments and numerical simulations. The results show that the hydraulic conductivity of the coarse UCG residues is much higher than that of fine residues, and the hydraulic conductivity of the UCG residues with the size of - 0.15 mm and 0.15-0.3 mm are 4.68 × 10-6 m/s and 1.91 × 10-4 m/s respectively. The dispersivity λ for the migration of organic pollutants will be influenced significantly by the size of UCG residues in fractures of the combustion cavity, while the distribution coefficient Kd will not. The dispersivity of organic pollutants in the fine UCG residues is more significant than that in the coarse residues, and the λ for the two kinds of residues are 3.868 cm and 1.765 cm, respectively. The shape of the migration path slightly affects the pollutant concentration distribution along the path, but the width of a path has a more pronounced influence on the concentration distribution. In this research, the influence was formulated by a new technical term, MPWIT, which is related to transverse dispersion. Specifically, while the transverse dispersion values account for 20% and 10% of the longitudinal dispersion, respectively, the corresponding MPWIT values are 39.48 mm and 33.96 mm.


Coal , Groundwater , Water Pollutants, Chemical , Groundwater/chemistry , Water Pollutants, Chemical/analysis , Environmental Monitoring
2.
J Tissue Eng ; 15: 20417314241253290, 2024.
Article En | MEDLINE | ID: mdl-38818510

The rising prevalence of diabetes has underscored concerns surrounding diabetic wounds and their potential to induce disability. The intricate healing mechanisms of diabetic wounds are multifaceted, influenced by ambient microenvironment, including prolonged hyperglycemia, severe infection, inflammation, elevated levels of reactive oxygen species (ROS), ischemia, impaired vascularization, and altered wound physicochemical properties. In recent years, hydrogels have emerged as promising candidates for diabetic wound treatment owing to their exceptional biocompatibility and resemblance to the extracellular matrix (ECM) through a three-dimensional (3D) porous network. This review will first summarize the microenvironment alterations occurring in the diabetic wounds, aiming to provide a comprehensive understanding of its pathogenesis, then a comprehensive classification of recently developed hydrogels will be presented, encompassing properties such as hypoglycemic effects, anti-inflammatory capabilities, antibacterial attributes, ROS scavenging abilities, promotion of angiogenesis, pH responsiveness, and more. The primary objective is to offer a valuable reference for repairing diabetic wounds based on their unique microenvironment. Moreover, this paper outlines potential avenues for future advancements in hydrogel dressings to facilitate and expedite the healing process of diabetic wounds.

3.
Front Pharmacol ; 15: 1138251, 2024.
Article En | MEDLINE | ID: mdl-38708079

Background and aims: To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome. Methods: In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2 h pre-modeling and 2 and 4 h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD. Results: Serum levels of amylase, TNF-α, IL-1ß, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (p < 0.05). DCQD treatment significantly attenuated rat pancreas damage (p < 0.05) and reduced tissue capillary permeability compared to the SAP group (p < 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (p < 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (p < 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression in vitro (p < 0.05). Conclusion: DCQD can improve capillary permeability in both in vivo and in vitro models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.

4.
Opt Lett ; 49(10): 2577-2580, 2024 May 15.
Article En | MEDLINE | ID: mdl-38748109

We demonstrate an optical fiber-based, multiple-access frequency transmission using two optical frequency combs. The experimental results using the Allan deviation analysis show that with the phase compensation technique, the frequency instabilities at the remote site are 8.7 × 10-15/1 s and 1.0 × 10-17/103 s, and at the accessing node along the fiber link, the frequency instabilities are 6.9 × 10-15/1 s and 1.1 × 10-17/103 s. Similarly, the power spectral density of phase noise was analyzed in the frequency domain. These experimental results demonstrate that the compensation scheme improved the performance by two to three orders of magnitude. Thus, the proposed frequency transmission technique has potential application for disseminating ultrastable frequency references in the optical fiber network.

5.
J Am Chem Soc ; 146(19): 12901-12906, 2024 May 15.
Article En | MEDLINE | ID: mdl-38701349

Cholesterol-rich membranes play a pivotal role in cancer initiation and progression, necessitating innovative approaches to target these membranes for cancer inhibition. Here we report the first case of unnatural peptide (1) assemblies capable of depleting cholesterol and inhibiting cancer cells. Peptide 1 self-assembles into micelles and is rapidly taken up by cancer cells, especially when combined with an acute cholesterol-depleting agent (MßCD). Click chemistry has confirmed that 1 depletes cell membrane cholesterol. It localizes in membrane-rich organelles, including the endoplasmic reticulum, Golgi apparatus, and lysosomes. Furthermore, 1 potently inhibits malignant cancer cells, working synergistically with cholesterol-lowering agents. Control experiments have confirmed that C-terminal capping and unnatural amino acid residues (i.e., BiP) are essential for both cholesterol depletion and potent cancer cell inhibition. This work highlights unnatural peptide assemblies as a promising platform for targeting the cell membrane in controlling cell fates.


Cholesterol , Peptides , Humans , Cholesterol/chemistry , Cholesterol/metabolism , Peptides/chemistry , Peptides/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Proliferation/drug effects
6.
Heliyon ; 10(7): e28497, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38689980

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan-Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan-Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

7.
Proc Natl Acad Sci U S A ; 121(21): e2322501121, 2024 May 21.
Article En | MEDLINE | ID: mdl-38748578

Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during Drosophila spermatogenesis. Bromotyrosine is not evident when Drosophila express a native flavin-dependent dehalogenase that is homologous to the enzyme responsible for iodide salvage from iodotyrosine in mammals. Deletion or suppression of the dehalogenase-encoding condet (cdt) gene in Drosophila allows bromotyrosine to accumulate with no detectable chloro- or iodotyrosine. The presence of bromotyrosine in the cdt mutant males disrupts sperm individualization and results in decreased fertility. Transgenic expression of the cdt gene in late-staged germ cells rescues this defect and enhances tolerance of male flies to bromotyrosine. These results are consistent with reversible halogenation affecting Drosophila spermatogenesis in a process that had previously eluded metabolomic, proteomic, and genomic analyses.


Drosophila Proteins , Fertility , Spermatogenesis , Tyrosine , Animals , Male , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Tyrosine/metabolism , Tyrosine/analogs & derivatives , Drosophila melanogaster/metabolism , Drosophila melanogaster/genetics , Drosophila/genetics , Drosophila/metabolism , Animals, Genetically Modified , Hydrolases/metabolism , Hydrolases/genetics
9.
Nat Commun ; 15(1): 3848, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719794

Fixation and functionalisation of N2 by main-group elements has remained scarce. Herein, we report a fixation and cleavage of the N ≡ N triple bond achieved in a dinitrogen (N2) matrix by the reaction of hydrogen and laser-ablated silicon atoms. The four-membered heterocycle H2Si(µ-N)2SiH2, the H2SiNN(H2) and HNSiNH complexes are characterized by infrared spectroscopy in conjunction with quantum-chemical calculations. The synergistic interaction of the two SiH2 moieties with N2 results in the formation of final product H2Si(µ-N)2SiH2, and theoretical calculations reveal the donation of electron density of Si to π* antibonding orbitals and the removal of electron density from the π bonding orbitals of N2, leading to cleave the non-polar and strong NN triple bond.

10.
Food Funct ; 15(10): 5566-5578, 2024 May 20.
Article En | MEDLINE | ID: mdl-38712886

Free radical damage and oxidative stress are thought to play a crucial role in the development of neurodegenerative diseases. Walnut peptides, especially walnut oligopeptides, have been shown to protect nerve cells from oxidative stress and inflammatory damage, as well as improve memory function. In this study, walnut peptides were obtained from walnut meal through enzymatic hydrolysis, ultrafiltration, and gel filtration chromatography. A novel oligopeptide called AQ was successfully isolated and its chemical structure was identified as AASCDQ using ESI-MS/MS. AQ demonstrated remarkable scavenging activity against O2- free radicals (81.00%), DPPH free radicals (79.40%), and ABTS free radicals (67.09%) at a concentration of 1 mg mL-1. Furthermore, AQ exhibited strong neuroprotective effects against hydrogen peroxide-induced damage in SH-SY5Y cells, reducing cell injury and apoptosis. AQ also effectively inhibited the secretion of pro-inflammatory factors NO (IC50 = 46.03 ± 0.32 µM) and suppressed the expression of IL-6 and TNF-α in RAW264.7 cells stimulated by LPS. In vivo experiments demonstrated that AQ promoted angiogenesis in the quail chick chorioallantoic membrane assay and reduced ROS accumulation in Caenorhabditis elegans, thereby extending its lifespan. The anti-inflammatory mechanism of AQ was further confirmed by western blotting. In summary, the novel oligopeptide AQ possesses potential neuroprotective effects, including antioxidant, anti-inflammatory, angiogenic, and anti-aging properties, making it a promising candidate for the development of functional foods and pharmaceutical products.


Caenorhabditis elegans , Juglans , Neuroprotective Agents , Oligopeptides , Animals , Juglans/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Mice , Caenorhabditis elegans/drug effects , RAW 264.7 Cells , Humans , Oligopeptides/pharmacology , Oligopeptides/chemistry , Oxidative Stress/drug effects , Apoptosis/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Protein Hydrolysates/pharmacology , Protein Hydrolysates/chemistry , Reactive Oxygen Species/metabolism , Nuts/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry
11.
Sci Adv ; 10(20): eadm7694, 2024 May 17.
Article En | MEDLINE | ID: mdl-38748795

Past intervals of warming provide the unique opportunity to observe how the East Asia monsoon precipitation response happened in a warming world. However, the available evaluations are primarily limited to the last glacial-to-interglacial warming, which has fundamental differences from the current interglacial warming, particularly in changes in ice volume. Comparative paleoclimate studies of earlier warm interglacial periods can provide more realistic analogs. Here, we present high-resolution quantitative reconstructions of temperature and precipitation from north-central China over the past 800 thousand years. We found that the average precipitation increase, estimated by the interglacial data, was only around one-half of that estimated for the glacial-to-interglacial data, which is attributed to the amplification of climate change by ice volume variations. Analysis of the interglacial data suggests an increase in monsoon precipitation of ~100 mm for a warming level of 2°C on the Chinese Loess Plateau.

12.
Sci Total Environ ; 934: 173256, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38763195

Green manuring is a conservation agricultural practice that improves soil quality and crop yield. However, increasing the active nitrogen (N) and carbon (C) pools during green manure (GM) amendment may accelerate soil N transformation and stimulate N loss. Previous studies have reported the effects of cover crop incorporation on N2O emission; however, the driving mechanisms and other N losses remain unclear. Therefore, we conducted a comprehensive meta-analysis of 109 published articles (517 paired observations) to clarify the effects of GM amendment on soil reactive N (Nr) losses (N2O emissions, NH3 volatilization, and N leaching and runoff), N pools, and N cycling functional gene abundance. The results showed that green manuring increased soil microbial biomass N (MBN) and NO3--N concentrations and stimulated N2O emission but significantly lowered N leaching and yield-scaled NH3 volatilization. Practices of green manuring made a dominant contribution to the variation in N2O emissions and NH3 volatilization after GM application. Furthermore, applying legume-based GM, using N derived from GM (GMN) as an additional input, and short-term GM amendment each stimulated N2O emissions. In contrast, adopting non-legume GM, using GMN to partially substitute mineral N, and applying GM to the soil surface or paddy field mitigated NH3 loss during GM amendment. Additionally, the variation in NH3 volatilization was positively related to soil pH and N application rate (NAR) but had a negative relationship with mean annual precipitation (MAP). This study highlighted the marked effects of green manuring on soil N retention and loss. Agricultural operations that adopt GM amendment should select suitable GM species and optimize mineral N inputs to minimize N loss.

13.
Article En | MEDLINE | ID: mdl-38819181

Objective: The purpose of this study was to investigate the clinical benefits of implementing enhanced recovery after surgery (ERAS) protocols in managing congenital malformations in newborns. Methods: Sixty infants diagnosed with congenital malformations admitted to the Anqing Municipal Hospital between October 2020 and April 2022 were selected for this study. They were randomly assigned to either the observation group, receiving ERAS management, or the control group, receiving routine management, or the control group, receiving routine management. Each group consisted of 30 patients. Outcome measures included operative duration, intraoperative bleeding volume, intravenous nutrition maintenance duration, length of hospital stay, and hospital costs, complications, and readmission. Results: The duration of the procedure did not show any notable variances, and there were no reports of bleeding during or after surgery in relation to the operative time, intraoperative bleeding, postoperative complications, or readmission. The implementation of ERAS management resulted in notably shorter periods of intravenous nutrition maintenance and hospitalization and reduced costs compared to standard management. Furthermore, ERAS management resulted in significantly lower scores on the Modified Faces, Legs, Activity, Cry, and Consolability Scale at 2, 12, and 24 hours after surgery. However, this difference became insignificant after 48 hours. All study participants experienced elevated levels of cortisol and C-peptide following interventions, with lower levels observed in the observation group. Additionally, all study participants exhibited increased levels of susceptible C-reactive protein and interleukin (IL)-6 and decreased serum albumin levels after interventions, with lower serum IL-6 levels observed in the observation group. Conclusion: Implementing ERAS management for neonatal congenital malformations is safe and feasible, and it can potentially accelerate postoperative recovery in children. It shows promise for wider clinical adoption.

14.
Eur J Pharmacol ; 975: 176646, 2024 May 17.
Article En | MEDLINE | ID: mdl-38762157

Severe acute pancreatitis (SAP) is a complicated inflammatory reaction that impacts the pancreas, often resulting in damage to numerous organs. This disorder encompasses a range of processes such as inflammation, oxidative stress, and pancreatitis. The hormone melatonin (MT) is primarily secreted by the pineal gland and plays a crucial role in mitigating inflammation, countering the harmful effects of free radicals, and regulating oxidative stress. The aim of this research was to investigate the potential protective impact and the underlying mechanism of melatonin in mice afflicted with SAP. The biochemical and histological assessments unequivocally demonstrated that melatonin effectively inhibited necrosis, infiltration, edema and cell death in pancreatic tissues, thereby suppressing acute pancreatitis. Notably, melatonin also alleviated the consequent harm to distant organs, notably the lungs, liver, and kidneys. Furthermore, both preventive and therapeutic administration of melatonin prompted nuclear factor E2-related factor 2 (Nrf2) activation followed by Nrf2 target gene expression. Nrf2 initiates the activation of antioxidant genes, thereby providing defense against oxidative stress. Conversely, Nrf2 reduction may contribute to impaired antioxidant protection in SAP. The beneficial impact of Nrf2 on antioxidants was absent in Nrf2-knockout mice, leading to the accumulation of LDH and exacerbation of cell death. This deterioration in both pancreatitis and injuries in distant organs intensified significantly. The results indicate that melatonin has an enhanced ability to protect against multiorgan damage caused by SAP, which is accomplished through the increase in Nrf2 expression. Additionally, Nrf2 initiates the activation of antioxidant genes that offer defense against cell death.

15.
Ren Fail ; 46(1): 2356021, 2024 Dec.
Article En | MEDLINE | ID: mdl-38785301

OBJECTIVE: This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis. METHODS: 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis. RESULTS: The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p < 0.05). Scr, BUN, and UA levels decreased while eGFR levels increased in both groups (p < 0.05), with a greater magnitude of change observed in the RG + CHF group. Urinary AKI biomarkers decreased more in RG + CHF group (p < 0.05). No serious adverse events occurred during the trial. 58 different lipid metabolites and 48 lipid biomarkers were identified. According to the KEGG database, the possible metabolic pathways involved triglyceride metabolic pathway and fat digestion and absorption metabolic pathways. CONCLUSION: CHF-II effectively alleviated kidney injury and improved TCM syndrome scores in patients with A on C. Lipid differential metabolites could serve as diagnostic indicators for AKI in patients with CKD. The possible metabolic pathways might be implicated in therapeutic action of CHF-II in the prevention and treatment of patients with A on C.


Acute Kidney Injury , Biomarkers , Drugs, Chinese Herbal , Lipidomics , Renal Insufficiency, Chronic , Humans , Male , Acute Kidney Injury/etiology , Acute Kidney Injury/drug therapy , Female , Middle Aged , Drugs, Chinese Herbal/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Aged , Biomarkers/blood , Biomarkers/urine , Adult , Lipids/blood , Glomerular Filtration Rate/drug effects , Treatment Outcome , Medicine, Chinese Traditional/methods
16.
Front Neurol ; 15: 1364952, 2024.
Article En | MEDLINE | ID: mdl-38699054

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.

17.
Front Public Health ; 12: 1351479, 2024.
Article En | MEDLINE | ID: mdl-38803810

Background: While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. Objective: This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. Methods: In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. Results: After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 µg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Conclusion: Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 µg/L.


Manganese , Nutrition Surveys , Sarcopenia , Humans , Sarcopenia/blood , Male , Adult , Manganese/blood , Female , Middle Aged , Adolescent , Young Adult , Cross-Sectional Studies , United States
18.
Chem Sci ; 15(15): 5573-5580, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38638207

Palladium-catalyzed enantioselective domino Heck/intramolecular C-H functionalization reaction, as a valuable strategy for creating molecular diversity, has remained a prominent challenge. Here, we describe a Pd/XuPhos catalyst for asymmetric domino Heck/intermolecular C-H alkylation of unactivated alkenes with diverse polyfluoro- and heteroarenes in a highly chemo- and enantioselective manner. This process enables efficient synthesis of various dihydrobenzofurans, indolines and indanes, which are of interest in pharmaceutical research and other areas. Late-stage modifications of the core structures of natural products are also well showcased. Moreover, synthetic transformations create a valuable platform for preparing a series of functionalized molecules. Several control experiments for mechanistic study are conducted to pursue a further understanding of the reaction.

19.
Poult Sci ; 103(6): 103719, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38603936

Lipopolysaccharide (LPS) from Gram-negative bacteria initially induces liver inflammation with proinflammatory cytokines expressions. However, the underlying hepatoprotective mechanism of quercetin on LPS-induced hepatic inflammation remains unclear. Specific pathogen-free chicken embryos (n = 120) were allocated control vehicle, PBS with or without ethanol vehicle, LPS (125 ng/egg) with or without quercetin treatment (10, 20, or 40 nmol/egg, respectively), quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated abovementioned solutions via the allantoic cavity. At embryonic d 19, the livers of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, and immunohistochemistry investigation. We found that the liver presented inflammatory response (heterophils infiltration) after LPS induction. The LPS-induced mRNA expressions of inflammation-related factors (TLR4, TNFα, IL-1ß, IL-10, IL-6, MYD88, NF-κB1, p38, and MMP3) were upregulated after LPS induction when compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. Quercetin significantly decreased the immunopositivity to TLR4 and MMP3 in the treatment group when compared with the LPS group. Quercetin could significantly downregulate the mRNA expressions of autophagy-related genes (ATG5, ATG7, Beclin-1, LC3A, and LC3B) and necroptosis-related genes (Fas, Bcl-2, Drp1, and RIPK1) after LPS induction. Quercetin significantly decreased the immunopositivity to LC3 in the treatment group when compared with the LPS group; meanwhile, quercetin significantly decreased the protein expressions of LC3-I, LC3-II, and the rate of LC3-II/LC3-I. In conclusions, quercetin can alleviate hepatic inflammation induced by LPS through modulating autophagy and necroptosis.

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