ABSTRACT
Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.
Subject(s)
Endothelial Cells/metabolism , Hepatocytes/metabolism , Intercellular Signaling Peptides and Proteins/physiology , Liver Cirrhosis/metabolism , Liver/metabolism , Receptors, TIE/metabolism , Animals , Biomarkers/metabolism , Capillaries/metabolism , Endothelial Cells/cytology , Endothelial Cells/pathology , HEK293 Cells , Hepatocytes/cytology , Hepatocytes/pathology , Humans , Intercellular Signaling Peptides and Proteins/blood , Liver/blood supply , Liver/pathology , Liver Cirrhosis/diagnosis , Mice, Inbred C57BLABSTRACT
A convenient method for the synthesis of perdeuterated alkyl amides/amines is disclosed. Perdeuterated acetyl amides can be achieved by a hydrogen-deuterium (H/D) exchange protocol with Pt/C as a catalyst and D2O as a deuterium source under mild conditions. After removal or reduction of the acetyl group, this protocol can provide perdeuterated primary, secondary, and tertiary amines, which are difficult to achieve via other methods.
ABSTRACT
Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.
ABSTRACT
BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.
Subject(s)
Carcinoma , Stomach Neoplasms , Humans , Lymphatic Metastasis , Retrospective Studies , Dietary SupplementsABSTRACT
Organosulfates (OSs) could be potentially important compounds in marine organic aerosols, while their formation in marine atmospheres is far from clear due to a lack of cruise observations. In this work, shipboard atmospheric observations were conducted over the Yellow Sea and Bohai Sea to investigate the abundance and formation of biogenic isoprene/monoterpene-OSs in marine aerosols. The quantified OSs and NOSs accounted for 0.04-6.9% of marine organic aerosols and were 0.07-2.2% of the non-sea-salt (nss) sulfate in terms of sulfur content. Isoprene-related (nitrooxy-)OSs occupied 27-87% of the total quantified OSs, following the abundance order of summer > autumn > spring or winter. This order was driven by the marine phytoplankton biomass and sea surface temperature (SST), which controlled the seawater and atmospheric isoprene concentration levels. Under the severe impacts of anthropogenic pollutants from the East Asia continent in winter, monoterpene nitrooxy-OSs, generated with NOx involved in, increased to 34.4 ± 35.5 ng/m3 and contributed 68% of the quantified (nitrooxy-)OSs. Our results highlight the notable roles of biogenic OSs in marine organic aerosols over regions with high biological activity and high SST. The formation of biogenic OSs and their roles in altering marine aerosol properties calls for elaboration through cruise observations in different marine environments.
Subject(s)
Air Pollutants , Environmental Pollutants , Phytoplankton , Air Pollutants/analysis , Monoterpenes , Aerosols/analysisABSTRACT
A quinoline derivative 7-((2-aminoethyl)amino)-5-bromo-6-hydroxy-1-methylquinolin-1-ium-3-sulfonate (QEt) containing quinoline ring, -[Formula: see text] sulfonate, -OH phenol, and amine groups was synthesized and studied luminescence properties. The aqueous solutions QEt 10µM change luminescence color from green (λem = 490 nm) to yellow (λem = 563 nm) as increasing pH and the intensity at a peak of 563 nm is linearly proportional with pH value in the range of pH = 3,0-4,0. The QEt solution can be used as a chemosensor for Cu2+ with an LOD value at 0.66 [Formula: see text]. Along with the experiment, the structure, absorption and emission spectra of QEt have been investigated by TD-DFT calculation. The result shows that the absorption band centered at 420 nm is due to the electron transition from HOMO to LUMO (π â π*). The results also help to assign emission band centered at 490 nm is due to the S1 â S0 transition (LUMO â HOMO singlet transition), at 563 nm is due to the T1 â S0 transition (LUMO â HOMO triplet transition). The dependence of the relative intensity of each emission peak on pH, which is experimentally recorded, is explained based on the results of theoretical TD-DFT calculation.
ABSTRACT
The Pacific Ocean plays an important role in regulating the budget of climatically active gases and the burden of sulfate aerosols. Here, a field investigation was conducted to clarify the key processes and factors controlling climatically active gases, including dimethyl sulfide (DMS), carbonyl sulfide (OCS), carbon disulfide (CS2), and carbon dioxide (CO2), in both surface seawater and the lower atmosphere of the western Pacific. In addition, the relative contributions of different sources to atmospheric sulfate aerosols were quantitatively estimated, and their causes were explored. The maximum concentrations of DMS, OCS and CS2 and the minimum partial pressure of CO2 (pCO2) were observed in the Kuroshio-Oyashio Extension. Kuroshio-induced mesoscale eddies brought abundant nutrients and organic matter from the subsurface layer of Oyashio into the euphotic layer, thus enhancing primary productivity and accelerating the photoreaction of organic matter. These processes led to higher concentrations of DMS, OCS and CS2 and lower pCO2. However, the oligotrophic subsurface layer in the subtropical gyre and the strong barrier layer in the equatorial waters suppressed the upward fluxes of nutrients and organic matter, resulting in lower surface concentrations of DMS, OCS, and CS2 in these areas. Being far from the continents, atmospheric concentrations of DMS, OCS and CS2 and pCO2 in the western Pacific generally were observed to depend on the local sea-to-air exchange and may be regulated by atmospheric oxidation and mixing of air masses. In general, oceanic DMS emissions played an important role in the formation of sulfate aerosols in the western Pacific (accounting for â¼19.5% of total sulfate aerosols), especially in the Kuroshio-Oyashio Extension (â¼32.3%). These processes in seawater may also determine the variations and emissions of other climatically active gases from biogenic and photochemical sources.
Subject(s)
Carbon Dioxide , Gases , Sulfates , Pacific Ocean , AerosolsABSTRACT
BACKGROUND: Immunosenescence occurs as people age, leading to an increased incidence of age-related diseases. The number of senescent T cells also rises with age. T cell senescence and immune response dysfunction can result in a decline in immune function, especially in anti-tumor immune responses. Metformin has been shown to have various beneficial effects on health, such as lowering blood sugar levels, reducing the risk of cancer development, and slowing down the aging process. However, the immunomodulatory effects of metformin on senescent T cells still need to be investigated. METHODS: PBMCs isolation from different age population (n = 88); Flow Cytometry is applied to determine the phenotypic characterization of senescent T lymphocytes; intracellular staining is applied to determine the function of senescent T cells; Enzyme-Linked Immunosorbent Assay (ELISA) is employed to test the telomerase concentration. The RNA-seq analysis of gene expression associated with T cell senescence. RESULTS: The middle-aged group had the highest proportion of senescent T cells. We found that metformin could decrease the number of CD8 + senescent T cells. Metformin affects the secretion of SASP, inhibiting the secretion of IFN-γ in CD8 + senescent T cells. Furthermore, metformin treatment restrained the production of the proinflammatory cytokine IL-6 in lymphocytes. Metformin had minimal effects on Granzyme B secretion in senescent T cells, but it promoted the production of TNF-α in senescent T cells. Additionally, metformin increased the concentration of telomerase and the frequency of undifferentiated T cells. The results of RNA-seq showed that metformin promoted the expression of genes related to stemness and telomerase activity, while inhibiting the expression of DNA damage-associated genes. CONCLUSION: Our findings reveal that metformin could inhibit T cell senescence in terms of cell number, effector function, telomerase content and gene expression in middle-aged individuals, which may serve as a promising approach for preventing age-related diseases in this population.
ABSTRACT
Root-knot nematodes (RKNs) are highly specialized parasites that cause significant yield losses worldwide. In this study, we isolated Bacillus pumilus strain S1-10 from the rhizosphere soil of Zingiber officinale Rosc. plants and evaluated its fumigant activity against Meloidogyne incognita. S1-10 exhibited a strong repellent effect on second-stage juveniles (J2s) of M. incognita, and in vitro assays indicated that S1-10 volatile organic compounds (VOCs) suppressed J2 activity and egg hatching. Under greenhouse conditions, 71 and 79% reductions of nematodes and eggs were detected on plants treated with S-10 VOCs compared with controls. Ten VOCs were identified through gas chromatography and mass spectrometry (GC-MS), of which 2-(methylamino)-ethanol (2-ME) had strong fumigant activity against J2s of M. incognita, with an LC50 value of 1.5 mM at 12 h. These results indicate that S1-10 represents a potential novel biocontrol agent for RKNs.
Subject(s)
Bacillus pumilus , Pesticides , Tylenchoidea , Volatile Organic Compounds , Animals , Volatile Organic Compounds/pharmacology , Volatile Organic Compounds/chemistry , EthanolABSTRACT
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
Subject(s)
Asthma , Biological Products , Nasal Polyps , Rhinitis , Sinusitis , Humans , Asthma/drug therapy , Biological Products/therapeutic use , Chronic Disease , Consensus , Nasal Polyps/complications , Nasal Polyps/drug therapy , Omalizumab/therapeutic use , Quality of Life , Rhinitis/complications , Rhinitis/drug therapy , Sinusitis/complications , Sinusitis/drug therapy , Steroids/therapeutic useABSTRACT
Despite several synthetic approaches that have been developed for α-deuterated amino acids, the synthesis of ß-deuterated amino acids has remained a challenge. Herein, we disclose a palladium catalyzed H/D exchange protocol for a ß-deuterated N-protected amino amide, which can be converted to a ß-deuterated amino acid simply by removal of protecting groups. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of many amino amides. In addition, deuterium labeling of phenylalanine derivatives was also successful when pivalic acid served as an additive to promote the H/D exchange process.
Subject(s)
Amino Acids , Palladium , Deuterium , Amides , CatalysisABSTRACT
We disclose a silver catalyzed H/D exchange reaction, which can introduce the deuterium atom at the ß position of thiophene rings without the assistance of any coordinating groups. The advantages of this reaction include operation in open air, usage of D2O as the deuterium source, good tolerance to a range of functional groups and obtaining high atom% deuterium incorporation. In addition, this H/D exchange reaction is employed for direct deuteration of a thiophene based monomer, which is usually prepared by multistep synthesis from expensive deuterated starting materials.
ABSTRACT
Aberrant differentiation of keratinocytes disrupts the skin barrier and causes a series of skin diseases. However, the molecular basis of keratinocyte differentiation is still poorly understood. In the present study, we examined the expression of C7ORF41 using tissue microarrays by immunohistochemistry and found that C7ORF41 is specifically expressed in the basal layers of skin epithelium and its expression is gradually decreased during keratinocytes differentiation. Importantly, we corroborated the pivotal role of C7ORF41 during keratinocyte differentiation by C7ORF41 knockdown or overexpression in TPA-induced Hacat keratinocytes. Mechanismly, we first demonstrated that C7ORF41 inhibited keratinocyte differentiation mainly through formatting a complex with IKKα in the cytoplasm, which thus blocked the nuclear translocation of IKKα. Furthermore, we also demonstrated that inhibiting the PKCα/ERK signaling pathway reversed the reduction in C7ORF41 in TPA-induced keratinocytes, indicating that C7ORF41 expression could be regulated by upstream PKCα/ERK signaling pathway during keratinocyte differentiation. Collectively, our study uncovers a novel regulatory network PKCα/ERK/C7ORF41/IKKα during keratinocyte differentiation, which provides potential therapeutic targets for skin diseases.
Subject(s)
Epidermis/metabolism , I-kappa B Kinase/metabolism , Keratinocytes/cytology , Signal Transduction/physiology , Active Transport, Cell Nucleus , Cell Differentiation , Cell Line, Transformed , Down-Regulation , Extracellular Signal-Regulated MAP Kinases/physiology , Gene Expression Regulation , Gene Knockdown Techniques , Humans , Keratinocytes/metabolism , Protein Kinase C-alpha/physiology , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacologyABSTRACT
Tree peony (Paeonia suffruticosa Andr.; Paeoniaceae) is highly valued in Chinese culture for their ornamental and medicinal benefits in anti-inflammation, anti-arrhythmia, activating the immune system and protecting the cardiovascular system (Zhai et al. 2020). In May from 2019 to 2021, leaf spot symptoms were observed on tree peony in an area of 0.8 hm2 in Bozhou, Anhui Province, China; with a disease incidence of 35%. Initially, black-brown spots (0.5-2.4 mm) appeared on the leaves, as the disease developed, the spots enlarged to form round, black lesions. Small pieces of tissue taken from the margins of lesions were surface-disinfected by 75% ethanol for 20 s followed by 0.1% mercuric chloride for 3 min, rinsed with distilled sterile water for three times, placed on potato dextrose agar (PDA) at 25 ºC for 7 days in the dark.Fifteen single spore isolates were obtained as described (Dong 2009). When cultured on PDA for 10 days, colonies were white, villose, then became gray-brown, with the reverse side becoming reddish-brown; Chlamydospores globose or irregular shaped, dark brown, unicellular or multicellular (4.3 to 12.2 × 13.1 to 33.7 µm) (n = 200). Pycnidia were black-brown, mostly spheroid, and 86 to 128 × 110 to 197 µm (n = 50); Conidia were hyaline, ellipsoidal, unicellular, aseptate, and 4.1 to 5.2 × 1.8 to 2.4 µm (n = 200) . The DNA of a representative isolate AF21-1-2 was extracted using the CTAB protocol (Doyle and Doyle 1987). The rDNA internal transcribed spacer (ITS), ß-tubulin (TUB) and 28s nrDNA (LSU) genes were amplified and sequenced using the primers ITS1/ITS4 (White et al. 1990), Bt2a/Bt2b (Glass et al. 1995), and LR5/LR0R (Vilgalys and Hester, 1990), respectively (OK485136, OK631973, and ON358331). BLASTn analysis showed that the ITS, TUB, and LSU sequences had 99% (497/501 bp), 98% (530/539 bp), and 99% (878/882 bp) identity with the Epicoccum sorghinum isolates ESCZO20 (MN944541), CZ01 (MT254851) and Dl16-338 (LN907481), respectively. Maximum likelihood phylogenetic tree revealed that AF21-1-2 clustered with E. sorghinum isolates. For pathogenicity test, leaves of 3-year-old healthy tree peony plant in the field were inoculated with 105 conidia/ml spore suspension (prepared with 30-day-old cultures on PDA), added with 0.1% (v/v) Tween-80. Ten surface-sterilized leaves per plant were sprayed with 30 ml suspension until runoff, a total of 3 plants were inoculated. Leaves sprayed with sterilized water serve as a negative control. Each plant was covered with a plastic bag to maintain high relative humidity at 15 to 23°C and was monitored daily for symptom development. Typical symptoms appeared on more than 80% of the leaves after 7 days of inoculation, while control leaves remained symptomless. Cultures isolated from inoculated leaves had the same morphological and molecular traits as those that were previously used to test Koch's postulates. Based on the morphological and molecular characteristics, the causal agent on tree peony was identified as E. sorghinum (Aveskamp et al. 2010). To our knowledge, this is the first report of E. sorghinum causing leaf spot on tree peony in China. The disease will cause serious economic loss for tree peony if it is not managed properly. This report may provide the basis for diagnosis and control of the disease.
ABSTRACT
This paper presents a low-area 8-bit flash ADC that consumes low power. The flash ADC includes four main blocks-an analog multiplexer (MUX), a comparator, an encoder, and an SPI (Serial Peripheral Interface) block. The MUX allows the selection between eight analog inputs. The comparator block contains a TIQ (Threshold Inverter Quantization) comparator, a control circuit, and a proposed architecture of a Double-Tail (DT) comparator. The advantage of using the DT comparator is to reduce the number of comparators by half, which helps reduce the design area. The SPI block can provide a simple way for the ADC to interface with microcontrollers. This mixed-signal circuitry is designed and simulated using 180 nm CMOS technology. The 8-bit flash ADC only employs 128 comparators. The applied input clock is 80 MHz, with the input voltage ranging from 0.6 V to 1.8 V. The comparator block outputs 127 bits of thermometer code and sends them to the encoder, which exports the seven least significant bits (LSB) of the binary code. The most significant bit (MSB) is decided by only one DT comparator. The design consumes 2.81 mW of power on average. The total area of the layout is 0.088 mm2. The figure of merit (FOM) is about 877 fJ/step. The research ends up with a fabricated chip with the design inserted into it.
ABSTRACT
Access to sufficient water, sanitation, and hygiene (WASH) services is a crucial requirement for patients during therapy and general well-being in the hospital. However, in low- and middle-income countries, these services are often inadequate, resulting in increased morbidity and mortality of patients. This study aimed at assessing the current situation of WASH services in six District Health Care Facilities (DHCFs) in rural areas of the Mekong Delta provinces, Vietnam. The results showed that these services were available with inappropriate quality, which did not compromise the stakeholders' needs. The revealed WASH infrastructures have raised concerns about the prolonged hospital stays for patients and push nosocomial infections to a high level. The safety of the water supply was doubted as the high E. coli (> 60%) and total coliform incidence (86%) was observed with very low residual chlorine concentration (< 0.1 mg/L) in water quality assessment. Moreover, water supply contained a high concentration of iron (up to 15.55 mg/L) in groundwater in one DHCF. Technical assessment tool analysis proved that the improper management and lack of knowledge by human resources were the primary roots of the observed status WASH services. Improvement of the perceptions of WASH should be done for the hospital staff with collaboration and support from the government to prevent incidents in the future.
Subject(s)
Escherichia coli , Sanitation , Humans , Sanitation/methods , Chlorine , Vietnam , Environmental Monitoring , Hygiene , Water Supply , Iron , Delivery of Health CareABSTRACT
Starting from eugenol (4-allyl-2-methoxyphenol) three new quinoline derivatives, namely 5-bromo-7-(carboxymethoxy)-6-hydroxy-1-methylquinolin-1-ium-3-sulfonate (Q2, C12H10BrNO7S), 5-amino-7-(carboxymethoxy)-6-hydroxyquinolin-1-ium-3-sulfonate (Q4, C11H10N2O7S) and 7-(carboxymethoxy)-5,6-dihydroxylquinolin-1-ium-3-sulfonate (Q6, C11H9NO8), have been synthesized and crystallised as dihydrate. The best planes through the quinoline ring and the carboxymethoxy substituent is 6.60 (14), 7.28 (6) and 4.73 (7)° for Q2, Q4 and Q6, respectively. The crystal packing of Q2 is characterised by O-H O, π π and Br pyridine interactions. The two water molecules bridge three sulphate groups. Infinite chains of Q4 running in the direction [021] are formed by O/N-H O hydrogen bonds at both ends of the molecule. Parallel chains interact by O/N-H O hydrogen bonds and π π and C=O phenyl stacking. The -NH2 substituent bridges two sulphate groups, while the two water molecules bridge the other functional groups. The packing of Q6 consists of sheets of molecules interaction through O/N-H O hydrogen bonds while the two water molecules bridge all function groups present. Parallel sheets interact through π π and C=O pyridine stacking. An aqueous solution of Q2 and its precursor 7-(carboxymethoxy)-6-hydroxyquinolin-1-ium-3-sulfonate (Q) exhibits fluorescence which is pH dependent. The fluorescence intensity of a 10 µM solution of Q containing Zn2+ reaches its maximum for a [Zn2+]:[Q] ratio of 1:1. The fluorescence properties of Q, Q2, Q4 and Q6 were further investigated by DFT calculation methods.
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is an expanding health problem worldwide. Although many studies have made great efforts to elucidate the pathogenesis of NAFLD, the molecular basis remains poorly understood. Here, we showed that hepatic C7ORF41, a critical regulator of innate immune response, was markedly decreased in diet or genetic-induced NAFLD model. We also demonstrated that C7ORF41 overexpression significantly ameliorated hepatic inflammation and lipid accumulation in palmitic acid (PA)-treated hepatocytes, whereas C7ORF41 knockdown showed the opposite effects. Mechanistically, we found the anti-inflammatory role of C7ORF41 was attributed to the suppression of NF-κB p65-mediated induction of inflammatory cytokines. Moreover, we demonstrated that the suppression of C7ORF41 expression in hepatocytes is due to JNK activation, which promotes c-Jun-mediated transcriptional repression of C7ORF41. In conclusion, our findings suggested that a c-Jun/C7ORF41/NF-κB regulatory network controls the inflammatory response and lipid accumulation in NAFLD and may benefit the development of novel and promising therapeutic targets for NAFLD.
Subject(s)
Inflammation/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Cytokines/metabolism , Disease Models, Animal , Hepatocytes/pathology , Immunity, Innate , Lipid Metabolism , Liver/pathology , Mice , NF-kappa B/metabolism , Signal TransductionABSTRACT
The COVID-19 health disaster has had a dramatic impact on the global hospitality industry, affecting millions of people. The aim of this study is to examine the impact of job insecurity on hotel employees' anxiety and depression, and whether these psychological strains could influence employees' self-rated task performance during the COVID-19 pandemic. We also examine the moderating role of hotel employees' resilience in this context. The hypotheses were examined by collecting data from 353 hotel employees currently working in the Canary Islands (Spain). The results highlight the significant effects of job insecurity on employees' anxiety and depression levels. However, hotel employees' task performance was not affected by their job insecurity or by their anxiety and depression. In addition, employees' resilience has a moderating effect as it reduces the negative influence of job insecurity on depression. Finally, the discussion section sets out various theoretical and practical implications of the findings.
ABSTRACT
BACKGROUND: Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored. METHODS: Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS. RESULTS: The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo. CONCLUSIONS: Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.