ABSTRACT
OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.
ABSTRACT
Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.
Subject(s)
Bombyx , Insect Proteins , Larva , Silk , Transcriptome , Animals , Bombyx/genetics , Bombyx/metabolism , Silk/metabolism , Larva/metabolism , Larva/genetics , Transcriptome/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Cell Nucleus/metabolism , Receptors, Steroid/metabolism , Receptors, Steroid/genetics , Gene Expression Regulation, Developmental , Gene Expression ProfilingABSTRACT
Purpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions. Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models. Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI. Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.
ABSTRACT
Objective: Waste sorting has received considerable attention in recent decades. However, research on the mechanisms underlying the relationships among cultural worldview, environmental risk perception, and waste sorting is rather scarce. This study aims to explore the cultural worldviews, environmental risk perception, and waste sorting among urban Chinese and their mechanisms. Methods: This was a cross-sectional study involving 744 urban Chinese residents (371 men and 373 women). A questionnaire was utilized to measure cultural worldviews, environmental risk perception, and waste sorting. Pearson correlation analysis and structural equation modeling were used to examine the relationship between cultural worldviews, perceptions of environmental risk, and waste sorting. Results: Waste sorting had a relatively insignificant negative relationship with fatalism and individualism. The correlation between environmental risk perception and cultural worldviews was negative except for egalitarianism, and the correlation between hierarchy and environmental risk perception was higher than the others, while individualism was higher than fatalism. Heightened environmental risk perception mediates the relationship between egalitarianism and waste sorting. Reduced environmental risk perception mediates the relationship between hierarchy and waste sorting, and mediates the relationship between individualism and waste sorting. Conclusion: These new findings provide initial support for the mediating role of environmental risk perception in the relationship between cultural worldviews and waste sorting. Both theoretical and practical implications for understanding the psychological mechanisms of waste sorting are discussed.
Subject(s)
Urban Population , Humans , Male , Female , China , Cross-Sectional Studies , Adult , Surveys and Questionnaires , Middle Aged , Urban Population/statistics & numerical data , Perception , Culture , East Asian PeopleABSTRACT
Microbiota-derived catabolism of nutrients is closely related to ulcerative colitis (UC). The level of indole-3-acetic acid (IAA), a microbiota-dependent metabolite of tryptophan, was decreased significantly in the feces of UC patients. Thus supplementation with IAA could be a potential therapeutic method for ameliorating colitis. In this work, the protective effect of supplementation with IAA on dextran sulfate sodium (DSS)-induced colitis was evaluated, and the underlying mechanism was elucidated. The results indicated that the administration of IAA significantly relieved DSS-induced weight loss, reduced the disease activity index (DAI), restored colon length, alleviated intestinal injury, and improved the intestinal tight junction barrier. Furthermore, IAA inhibited intestinal inflammation by reducing the expression of proinflammatory cytokines and promoting the production of IL-10 and TGF-ß1. In addition, the ERK signaling pathway is an important mediator of various physiological processes including inflammatory responses and is closely associated with the expression of IL-10. Notably, IAA treatment induced the activation of extracellular signal-regulated kinase (ERK), which is involved in the progression of colitis, while the ERK inhibitor U0126 attenuated the beneficial effects of IAA. In summary, IAA could attenuate the clinical symptoms of colitis, and the ERK signaling pathway was involved in the underlying mechanism. Supplementation with IAA could be a potential option for preventing or ameliorating UC.
Subject(s)
Colitis, Ulcerative , Colitis , Indoleacetic Acids , Humans , Animals , Mice , Interleukin-10/metabolism , Dextran Sulfate/toxicity , Dextran Sulfate/metabolism , Colon/metabolism , Extracellular Signal-Regulated MAP Kinases/adverse effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Signal Transduction , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
OBJECTIVE: This study aimed to compare the clinical efficacy of laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) in treating solitary hepatocellular carcinoma (HCC) of the hepatic caudate lobe. METHODS: Patients with hepatic caudate lobe HCC who underwent LLR or RFA at three hospitals in China between February 2015 and February 2021 were included. In total, 112 patients met the inclusion criteria, of whom 52 underwent RFA and 60 underwent LLR. The outcomes of the two groups were compared and analyzed using propensity score matching (PSM) method. RESULTS: There were no significant differences between the two groups in terms of sex, HBV/HCV positivity, AFP positivity (>100 ng/mL), tumor position, Child-Pugh score, or preoperative liver function tests (ALT, AST, TBIL, ALB, and PT) (p > 0.05). Compared to the LLR group, the RFA group had a shorter operation time, less intraoperative bleeding, and shorter postoperative hospital stay (p < 0.05). There was no statistically significant difference in overall postoperative complications between the two groups (p > 0.05). Despite the larger tumor size, the LLR group had better postoperative recurrence-free survival (RFS) (p = 0.00027) and overall survival (OS) (p = 0.0023) than the RFA group. After one-to-one PSM, 31 LLR patients and 31 RFA patients were selected for further analyses. The advantages of LLR over RFA were observed in terms of RFS (p < 0.0001) and OS (p = 0.00029). CONCLUSION: LLR should probably be recommended as the preferred method for solitary caudate lobe HCC.
Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Laparoscopy , Liver Neoplasms , Radiofrequency Ablation , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Propensity Score , Retrospective Studies , Catheter Ablation/adverse effects , Catheter Ablation/methods , Treatment Outcome , Hepatectomy/adverse effects , Hepatectomy/methods , Radiofrequency Ablation/adverse effects , Laparoscopy/adverse effects , Laparoscopy/methodsABSTRACT
Formal Thought Disorder (FTD) is a defining feature of schizophrenia, which is often assessed through patients' speech. Meanwhile, the written language is less studied. The aim of the present study is to establish and validate a comprehensive clinical screening scale, capturing the full variety of empirical characteristics of writing in patients with schizophrenia. The 16-item Screening Instrument for Schizophrenic Features in Writing (SISFiW) is derived from detailed literature review and a "brainstorming" discussion on 30 samples written by patients with schizophrenia. One hundred and fifty-seven participants (114 patients with an ICD-10 diagnoses of schizophrenia; 43 healthy control subjects) were interviewed and symptoms assessed with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Thought, Language, and Communication (TLC). Article samples written by each participant were rated with the SISFiW. Results demonstrated significant difference of the SISFiW-total between the patient group and healthy controls [(3.61 ± 1.72) vs. (0.49 ± 0.63), t = 16.64, p<0.001]. The inter-rater reliability (weighted kappa = 0.72) and the internal consistency (Cronbach's alpha coefficient = 0.613) were acceptable, but correlations with the criterion (PANSS and TLC) were unremarkable. The ROC analysis indicated a cutoff point at 2 with the maximal sensitivity (93.0 %)/specificity (93.0 %). Discriminant analysis of the SISFiW items yielded 8 classifiers that discriminated between the diagnostic groups at a perfect overall performance (with 90.4 % of original and 88.5 % cross-validated grouped cases classified correctly). This instrument appears to be practicable and reliable, with relatively robust discriminatory power, and may serve as a complementary tool to existing FTD rating scales.
Subject(s)
Frontotemporal Dementia , Schizophrenia , Humans , Schizophrenia/diagnosis , Reproducibility of Results , Psychiatric Status Rating Scales , Language , PsychometricsABSTRACT
Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.
ABSTRACT
Purpose: To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence. Patients and Methods: A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence. Results: A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%). Conclusion: Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.
ABSTRACT
BACKGROUND: Body composition parameters (BCPs) are associated with mortality in patients with hepatocellular carcinoma (HCC). Our purpose was to develop a practical scoring model by BCP and the CRAFITY score to predict the overall survival (OS) and tumor response of patients with HCC who received targeted therapy plus immunotherapy. METHODS: This retrospective study included 265 patients with HCC who received targeted therapy plus immunotherapy at 2 centers in China from August 2018 to February 2022. Univariate and multivariate Cox regression analyses were applied to analyze clinical factors and BCP. A scoring model based on independent risk factors was developed to predict OS and tumor response. Moreover, the model's prediction was further validated by an external cohort. RESULTS: A total of 150 patients (55.5 ± 10.8 years) and 115 patients (55.0 ± 8.9 years) treated with lenvatinib or bevacizumab biosimilar plus anti-programmed death-1 (PD-1) antibody were included in training and validation cohorts, respectively. In the training cohort, independent predictive factors for OS included macrovascular invasion (p = 0.016), ChildâPugh class (A vs. B, p = 0.001; A vs. C, p < 0.001), sarcopenia (p = 0.034), and the CRAFITY score (p = 0.011). Based on independent risk factors (MAcrovascular invasion, ChildâPugh class, Sarcopenia, and the CRAFITY score) identified by multivariate analysis, a novel efficacy predictive tool named the MAPS-CRAFITY score was developed to predict OS. In all the training and validation cohorts, the OS differed significantly across the three groups based on the MAPS-CRAFITY score (< 2.1, 2.1-2.3, ≥ 2.4; p < 0.001). Moreover, the C-index of the MAPS-CRAFITY score was 0.720 and 0.761 in the training and validation cohorts, respectively. In both the validation and training cohorts, the MAPS-CRAFITY score was predictive of tumor response and disease control (p < 0.001). The AUCs of the MAPS-CRAFITY score for predicting disease control were 0.752 in the training cohort and 0.836 in the validation cohort. CONCLUSIONS: The MAPS-CRAFITY score based on sarcopenia and the CRAFITY score is a reliable and practical tool for predicting the efficacy of targeted therapy plus immunotherapy in patients with unresectable HCC, and may help hepatologists and oncologists in clinical decision-making.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Sarcopenia , Humans , Carcinoma, Hepatocellular/drug therapy , Retrospective Studies , Liver Neoplasms/drug therapy , ImmunotherapyABSTRACT
Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease, and its pathological development is closely related to the gut-liver axis. The intestinal barrier, an important component of the gut-liver axis, can prevent gut microbes and endotoxins from entering the liver. Intestinal barrier function is impaired in patients with NAFLD. Baicalein, which is the main flavonoid in Scutellariae Radix, can improve NAFLD. However, whether baicalein alleviates NAFLD by ameliorating intestinal barrier dysfunction remains unclear. In this study, a methionine-choline deficient (MCD) diet-induced NAFLD mouse model is used. The effects of baicalein on lipid accumulation, inflammation and the intestinal barrier in MCD-fed mice were evaluated by detecting blood lipid levels, lipid accumulation, liver pathological changes, inflammatory factors, inflammatory signaling pathways, the three main short-chain fatty acids (acetate, propionate and butyrate), intestinal permeability and intestinal tight junction protein expression. Compared with the MCD-only group, baicalein intake decreased the serum and liver lipid levels. Moreover, the accumulation of lipid droplets and steatosis in the liver were also alleviated; all these results demonstrated that baicalein could alleviate NAFLD. Meanwhile, the levels of inflammatory cytokines decreased in the baicalein group. Further investigation of the mucosal permeability to 4 kDa fluorescein isothiocyanate-dextran, concentrations of short-chain fatty acids in feces, and the expression of intestinal zonula occluden 1 and claudin-1 indicated that a baicalein diet could decrease the intestinal permeability caused by a MCD diet. Moreover, the protein levels of p-NF-κB p65 and the ratio of p-NF-κB p65/NF-κB p65 increased, and IκB-α and PPARα decreased in NAFLD mice, while the administration of baicalein could alleviate these changes. The above results indicated that the mechanism of baicalein in the alleviation of NAFLD lies in the regulation of the intestinal barrier.
Subject(s)
Flavanones , Gastrointestinal Diseases , Intestinal Diseases , Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , NF-kappa B/metabolism , Liver/metabolism , Flavanones/pharmacology , Choline/metabolism , Intestinal Diseases/metabolism , Methionine/metabolism , Mice, Inbred C57BLABSTRACT
Winter jujube (Ziziphus jujuba Mill. cv. Dongzao) is a major fresh-eating jujube fruit with various important nutrients for humans. It can absorb heavy metals from polluted air, water and soils and applied pesticides, which may pose potential threats to consumers. Here, to evaluate the content of heavy metals in winter jujube and systematically evaluate the potential risks, we collected 212 winter jujube samples from four main producing areas in China and determined the contents of eight heavy metals (Cd, Cr, Pb, Ni, Cu, Zn, As, and Mn) using inductively coupled plasma mass spectrometer (ICP-MS). Based on the integrated pollution index (IPI) evaluation standard, more than 99.06% of samples were at safe levels. Moreover, clustering analysis divided the eight heavy metals into four groups, namely Cr/Ni, Cd/Pb, Cu/Mn/Zn, and As. Importantly, none of the analyzed heavy metals posed risks to adults as indicted by the average carcinogenic and non-carcinogenic risks. Notably, Cr and Cd could pose low carcinogenic risks to children (≤12 age group) when their concentration reached the 90th percentile. This study systematically assessed the health risks associated with heavy metal intake through winter jujube consumption and highlighted the necessity of constant heavy metal monitoring in winter jujube.
Subject(s)
Metals, Heavy , Soil Pollutants , Ziziphus , Adult , Child , Humans , Cadmium/analysis , Lead/analysis , Environmental Monitoring , Metals, Heavy/analysis , China , Risk Assessment , Soil Pollutants/analysisABSTRACT
The present study aimed to explore the role of histone chaperone antisilencing function 1B (ASF1B) in pancreatic cancer and the underlying mechanism. The biological function of ASF1B was investigated in pancreatic cancer cell lines (PANC1 and SW1990) and a mouse xenograft model. Chromatin immunoprecipitation was used to detect the effect of ASF1B on the transcriptional activity of cMyc. ASF1B was highly expressed in pancreatic adenocarcinoma (PAAD) samples from The Cancer Genome Atlas. ASF1B expression was positively associated with poor survival rates in patients with PAAD. Silencing of ASF1B in PANC1 and SW1990 cells inhibited cell proliferation, migration and invasion, and induced apoptosis. Mechanistically, ASF1B increased H3K56 acetylation (H3K56ac) in a CREBbinding protein (CBP)dependent manner. ASF1B promoted H3K56ac at the cMyc promoter and increased cMyc expression. In PANC1 and SW1990 cells, the CBP inhibitor curcumin and the cMyc inhibitor 10058F4 reversed the promoting effects of ASF1B on cell proliferation, migration and invasion. In the mouse xenograft model, ASF1B silencing inhibited tumor growth, and was associated with low H3K56ac and cMyc expression. ASF1B promoted pancreatic cancer progression by activating cMyc via CBPmediated H3K56ac.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Mice , Animals , Pancreatic Neoplasms/genetics , Pancreas , Acetylation , Disease Models, Animal , Cell Cycle ProteinsABSTRACT
BACKGROUND: Pancreatic cancer (PC) is the most lethal malignant tumor, with average survival period of about 10 months. C-X-C ligand 5 (CXCL5), an important chemokine for immune cell accumulation in tumor tissues, has been reported to be involved in a variety of human cancers. However, the exact role of CXCL5 in PC progression has not been well defined. METHODS: The expression of CXCL5 in PC was analyzed based on online databases and clinical specimens immunohistochemical staining, and Western blotting of CXCL5 in PC cell lines and patient samples. The correlation between CXCL5 expression and prognosis in PC was explored. The role of CXCL5 in PC was investigated through in vitro and in vivo experiments. RESULTS: The expression of CXCL5 was significantly increased in PC tissues compared with that in pancreas tissues, and CXCL5 high expression predicts poor prognosis in PC patients. Further analyses demonstrated that overexpression of CXCL5 in PC cells was positively related to higher proliferation rate, higher migration ability, and higher EMT markers including SNAI2 and TWIST1 of tumor cells in vitro. Consistently, the knockdown of CXCL5 in PC cells harmed the proliferation rate, migration ability, and expression of EMT indexes of tumor cells in vitro. Importantly, knockdown of CXCL5 inhibited the growth of xenograft tumors in vivo. CONCLUSION: CXCL5 high expression predicts poor prognosis in PC patients. CXCL5 promotes PC cell growth and EMT process. Inhibition of CXCL5 may be a potential therapeutic approach for PC.
Subject(s)
Epithelial-Mesenchymal Transition , Pancreatic Neoplasms , Humans , Heterografts , Cell Proliferation , Cell Line, Tumor , Pancreatic Neoplasms/metabolism , Pancreas/pathology , Chemokine CXCL5/genetics , Chemokine CXCL5/metabolism , Pancreatic NeoplasmsABSTRACT
The individual and combined effects of abiotic factors on pollinator-mediated selection on floral traits are not well documented. To examine potential interactive effects of water and nutrient availability on pollinator-mediated selection on three floral display traits of Primula tibetica, we manipulated pollination and nutrient availability in a factorial experiment, conducted at two common garden sites with different soil water content (natural vs addition). We found that both water and nutrient availability affected floral trait expression in P. tibetica and that hand pollination increased seed production most when both nutrient content and water content were high, indicating joint pollen and resource limitation. We documented selection on all floral traits, and pollinators contributed to directional and correlational selection on plant height and number of flowers. Soil water and nutrient availability interactively influenced the strength of both pollinator-mediated directional and correlational selection, with significant selection observed when nutrient or water availability was high, but not when none or both were added. The results suggest that resource limitation constrains the response of P. tibetica to among-individual variation in pollen receipt, that addition of nutrients or water leads to pollinator-mediated selection and that effects of the two abiotic factors are nonadditive.
Subject(s)
Flowers , Primula , Flowers/physiology , Pollen/physiology , Pollination/physiology , Primula/anatomy & histology , Selection, Genetic , Soil/chemistry , Water/analysis , Nutrients/analysis , Nutrients/metabolismABSTRACT
Yinqiao powder, with significant anti-inflammatory and antiviral effects, is a classical formula for the treatment of febrile diseases in China. During the SARS period in 2003, Yinqiao powder showed a good antipyretic effect. It also plays a major role in the treatment for COVID-19 in China. Although there are many studies on the chemical compositions and pharmacological effects of Yinqiao powder, there are few studies on the quality standard system of it. In our study, a systematic quality evaluation method of Yinqiao powder combining HPLC fingerprint with quantitative analysis of multi-components by single marker (QAMS) based on network pharmacology and UPLC-Q-Exactive-Orbitrap-MS was established for the first time. In the UPLC-Q-Exactive-Orbitrap-MS experiment, a total of 53 compounds were identified in the extract solution of Yinqiao powder. In addition, 33 blood components were characterized, 23 of which were prototypes. The results of network pharmacology analysis showed that Yinqiao powder may inhibit inflammatory responses by suppressing IL-6, CXCL2, TNFα, NF-κB, etc., in the treatment of COVID-19. The HPLC fingerprint analysis of Yinqiao powder was conducted at 237 nm and 29 characteristic peaks were matched, 11 of which were identified. Forsythoside A was selected as the internal standard reference and double-wavelength (237 nm and 327 nm) was established in QAMS experiment. The repeatability was well under different conditions, and the results measured by QAMS were consisted with that of the external standard method (ESM), indicating that the QAMS method was reliable and accurate. The quality evaluation method of Yinqiao powder would be helpful to evaluate the intrinsic quality of Yinqiao powder more comprehensively, which is conducive to improve the quality standard of Yinqiao powder and provide a beneficial guarantee for the clinical treatment of COVID-19.
ABSTRACT
BACKGROUND: Paraneoplastic neurological syndrome (PNS) is an unusual event. PNS caused by cystitis glandularis (CG) or a bladder tumor is extremely rare; hence, missed diagnosis or misdiagnosis can easily occur. To date, approximately 21 cases have been reported in PubMed. CASE SUMMARY: We report a case of PNS caused by CG and describe the clinical and imaging features. The main clinical feature was advanced cognitive impairment, and early clinical features were memory impairment, decreased computational ability, and abnormal behavior. Later clinical features were dementia, vomiting, inability to eat and walk, urinary incontinence, and hematuria. Imaging features on cranial magnetic resonance imaging were diffuse white matter lesions. Paraneoplastic tumor markers were normal. A total abdominal computed tomography scan showed multiple thickened areas on the bladder wall with local prominence. Cystoscopy revealed a volcanic protuberance on the posterior wall of the bladder with a diameter of 6 cm and no pedicle. The postoperative pathological diagnosis was CG. The patient recovered well following resection of CG. PNS cases caused by previous bladder tumors can be retrieved from PubMed to describe the clinical signs and prognosis of PNS. CONCLUSION: The main clinical feature of PNS caused by CG was dementia, and the imaging features were diffuse cerebral white matter lesions. Resection of CG lesions is the fundamental treatment for PNS induced by CG. This case highlights the importance of etiological treatment.
ABSTRACT
The electrochemical CO2 reduction reaction (ECRR) is a promising method to reduce excessive CO2 emissions and achieve a sustainable carbon cycle. Due to the high reaction kinetics and efficiency, copper-based catalysts have shown great application potential for preparing multicarbon (C2+) products. C2+ alcohols have high economic value and use-value, playing an essential role in modern industry. Therefore, we summarize the latest research progress of the ECRR to synthesize C2+ alcohols on Cu-based catalysts and discuss the state-of-the-art catalyst design strategies to improve CO2 reduction performance. Moreover, we analyzed in detail the specific reaction pathways for the conversion of CO2 to C2+ alcohols based on DFT calculations. Finally, we propose the problems and possible solutions for synthesizing C2+ alcohols with copper-based catalysts. We hope that this review can provide ideas for devising ECRR catalysts for C2+ alcohols.