The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.

PURPOSE: The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth. METHODS: Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting. RESULTS: Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth. CONCLUSION: Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.

DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways, it is characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 expression has a detrimental role in numerous disorders. However, its role in COPD remains understudied. This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated mice airway inflammation and lung function decline caused by CS, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion in 16 HBE cells after CSE simulation, respectively. Nuclear factor erythroid 2-related factor 2 (NRF2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking COPD patients when compared to nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

Nitrogen-doped carbon dots as fluorescent probes for sensitive and selective determination of Fe3.

At present, the contamination of water resources by heavy metal ions has posed a significant threat to human survival. Therefore, it is particularly critical to develop low-cost, easy-to-use, and highly efficient heavy metal detection technologies. In this work, a fast and cost-effective fluorescent probe for nitrogen-doped carbon dots (N-CDs) was prepared using one-step hydrothermal method with citric acid (CA) as carbon source, and melamine as nitrogen source. The structural and optical characterizations of the resulting N-CDs were investigated in details. The results showed that the quantum yield of the prepared fluorescent probe was as high as 45 %, and an average fluorescence lifetime was about 7.80 ns. N-CDs have excellent water solubility and dispersibility, with an average size of 2.58 nm. N-CDs exhibited excellent specific responsiveness to Fe3+ and can be used as an effective method for detecting Fe3+ at low-concentrations (the concentrations of N-CDs as low as 0.24 µg/mL) using fluorescent probes. The linear response of the fluorescent probe N-CDs to Fe3+ was formed in the concentration range of 20-80 µM, and the detection limit was 3.18 µM. In addition, in the actual water samples analysis, the recovery rate reached 97.05-100.58 %. The prepared of N-CDs provide available Fe3+ fluorescent probes in the environment.

CT-based radiomics research for discriminating the risk stratification of pheochromocytoma using different machine learning models: a multi-center study.

OBJECTIVES: The purpose of this study was to explore and verify the value of various machine learning models in preoperative risk stratification of pheochromocytoma. METHODS: A total of 155 patients diagnosed with pheochromocytoma through surgical pathology were included in this research (training cohort: n = 105; test cohort: n = 50); the risk stratification scoring system classified a PASS score of < 4 as low risk and a PASS score of ≥ 4 as high risk. From CT images captured during the non-enhanced, arterial, and portal venous phase, radiomic features were extracted. After reducing dimensions and selecting features, Logistic Regression (LR), Extra Trees, and K-Nearest Neighbor (KNN) were utilized to construct the radiomics models. By adopting ROC curve analysis, the optimal radiomics model was selected. Univariate and multivariate logistic regression analyses of clinical radiological features were used to determine the variables and establish a clinical model. The integration of radiomics and clinical features resulted in the creation of a combined model. ROC curve analysis was used to evaluate the performance of the model, while decision curve analysis (DCA) was employed to assess its clinical value. RESULTS: 3591 radiomics features were extracted from the region of interest in unenhanced and dual-phase (arterial and portal venous phase) CT images. 13 radiomics features were deemed to be valuable. The LR model demonstrated the highest prediction efficiency and robustness among the tested radiomics models, with an AUC of 0.877 in the training cohort and 0.857 in the test cohort. Ultimately, the composite of clinical features was utilized to formulate the clinical model. The combined model demonstrated the best discriminative ability (AUC, training cohort: 0.887; test cohort: 0.874). The DCA of the combined model showed the best clinical efficacy. CONCLUSION: The combined model integrating radiomics and clinical features had an outstanding performance in differentiating the risk of pheochromocytoma and could offer a non-intrusive and effective approach for making clinical decisions.

Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study.

BACKGROUND: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. OBJECTIVES: This study aimed to investigate the association of prior PTB with the risk of COPD. DESIGN: Prospective cohort study. METHODS: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). RESULTS: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26-2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02-5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16-2.81, p = 0.008), male with aHR of 2.37 (1.47-3.83, p < 0.001), obesity with aHR of 3.35 (2.16-5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39-3.72, p < 0.001), current drinking with aHR of 1.98 (1.47-3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30-5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61-6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15-5.14, p = 0.019). CONCLUSION: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

Associations of prior pulmonary tuberculosis with the incident COPDPrior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.

DNA hypomethylation-mediated upregulation of GADD45B facilitates airway inflammation and epithelial cell senescence in COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typically characterized by chronic airway inflammation, with emerging evidence highlighting the driving role of cellular senescence-related lung aging. Accelerated lung aging and inflammation mutually reinforce each other, creating a detrimental cycle that contributes to disease progression. Growth arrest and DNA damage-inducible (GADD45) family has been reported to involve in multiple biological processes, including inflammation and senescence. However, the role of GADD45 family in COPD remains elusive. OBJECTIVES: To investigate the role and mechanism of GADD45 family in COPD pathogenesis. METHODS: Expressions of GADD45 family were evaluated by bioinformatic analysis combined with detections in clinical specimens. The effects of GADD45B on inflammation and senescence were investigated via constructing cell model with siRNA transfection or overexpression lentivirus infection and animal model with Gadd45b knockout. Targeted bisulfite sequencing was performed to probe the influence of DNA methylation in GADD45B expression in COPD. RESULTS: GADD45B expression was significantly increased in COPD patients and strongly associated with lung function, whereas other family members presented no changes. GADD45B upregulation was confirmed in mice exposed by cigarette smoke (CS) and HBE cells treated by CS extract as well. Moreover, experiments involving bidirectional modulation of GADD45B expression in HBE cells further substantiated its positive regulatory role in inflammatory response and cellular senescence. Mechanically, GADD45B-facilitated inflammation was directly mediated by p38 phosphorylation, while GADD45B interacted with FOS to promote cellular senescence in a p38 phosphorylation-independent manner. Furthermore, Gadd45b deficiency remarkably alleviated inflammation and senescence of lungs in CS-exposed mice, as well as improved emphysema and lung function. Eventually, in vivo and vitro experiments demonstrated that GADD45B overexpression was partially mediated by CS-induced DNA hypomethylation. CONCLUSION: Our findings have shed light on the impact of GADD45B in the pathogenesis of COPD, thereby offering a promising target for intervention in clinical settings.

CT-Based Radiomics Analysis of Different Machine Learning Models for Discriminating the Risk Stratification of Pheochromocytoma and Paraganglioma: A Multicenter Study.

RATIONALE AND OBJECTIVES: Using different machine learning models CT-based radiomics to integrate clinical radiological features to discriminating the risk stratification of pheochromocytoma/paragangliomas (PPGLs). MATERIALS AND METHODS: The present study included 201 patients with PPGLs from three hospitals (training set: n = 125; external validation set: n = 45; external test set: n = 31). Patients were divided into low-risk and high-risk groups using a staging system for adrenal pheochromocytoma and paraganglioma (GAPP). We extracted and selected CT radiomics features, and built radiomics models using support vector machines (SVM), k-nearest neighbors, random forests, and multilayer perceptrons. Using receiver operating characteristic curve analysis to select the optimal radiomics model, a combined model was built using the output of the optimal radiomics model and clinical radiological features, and its accuracy and clinical applicability were evaluated using calibration curves and clinical decision curve analysis (DCA). RESULTS: Finally, 13 radiomics features were selected to construct machine learning models. In the radiomics model, the SVM model demonstrated higher accuracy and stability, with an AUC value of 0.915 in the training set, 0.846 in external validation set, and 0.857 in external test set. Combining the outputs of SVM models with two clinical radiological features, a combined model constructed has demonstrated optimal risk stratification ability for PPGLs with an AUC of 0.926 for the training set, 0.883 for the external validation set, and 0.899 for the external test set. The calibration curve and DCA show good calibration accuracy and clinical effectiveness for the combined model. CONCLUSION: Combined model that integrates radiomics and clinical radiological features can discriminate the risk stratification of PPGLs.

Multicolor melting curve analysis discloses high carrier frequency of hearing loss-associated variants among neonates in Jiangsu province.

BACKGROUND: Genetic disorders ascribe to half of cases of congenital hearing loss. Hearing screening is significant in detecting hearing loss (HL) but weak at diagnosis, which can be complemented by genetic screening. METHODS: To find a feasible method to accomplish genetic screening and evaluate its advantage when combined with hearing screening, between 1 January 2022, and 10 December 2023, we performed an observational cohort study based on 2488 neonates from the Han population at three hospitals in Jiangsu province. Genetic screening for 20 variants in four common HL-associated genes by multicolor melting curve analysis (MMCA) and hearing screening were offered concurrently to all participants. RESULTS: In total, 170 (6.8%) of 2488 eligible neonates were detected at least one variant and among them, the proportion of referral was higher (p < 0.05). Genetic screening combined with hearing screening was associated with a 25.0% increase (2 of 8) in discovering cases of diagnosed hearing loss that were missed by hearing screening. CONCLUSION: This study suggests that genetic screening combined with hearing screening by MMCA is effective at finding potential HL cases and practical to be validated in other places.

Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress.

TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway.

Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration both in vitro and in vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reduced O-glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment of N-acetyl-d-glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP.

Alpinetin ameliorates bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-ß/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-ß. CONCLUSION: In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.

Novel molecular classification and prognosis of papillary renal cell carcinoma based on a large-scale CRISPR-Cas9 screening and machine learning.

Papillary renal cell carcinoma (PRCC) is a highly heterogeneous cancer, and PRCC patients with advanced/metastatic subgroup showed obviously shorter survival compared to other kinds of renal cell carcinomas. However, the molecular mechanism and prognostic predictors of PRCC remain unclear and are worth deep studying. The aim of this study is to identify novel molecular classification and construct a reliable prognostic model for PRCC. The expression data were retrieved from TCGA, GEO, GTEx and TARGET databases. CRISPR data was obtained from Depmap database. The key genes were selected by the intersection of CRISPR-Cas9 screening genes, differentially expressed genes, and genes with prognostic capacity in PRCC. The molecular classification was identified based on the key genes. Drug sensitivity, tumor microenvironment, somatic mutation, and survival were compared among the novel classification. A prognostic model utilizing multiple machine learning algorithms based on the key genes was developed and tested by independent external validation set. Our study identified three clusters (C1, C2 and C3) in PRCC based on 41 key genes. C2 had obviously higher expression of the key genes and lower survival than C1 and C3. Significant differences in drug sensitivity, tumor microenvironment, and mutation landscape have been observed among the three clusters. By utilizing 21 combinations of 9 machine learning algorithms, 9 out of 41 genes were chosen to construct a robust prognostic signature, which exhibited good prognostic ability. SERPINH1 was identified as a critical gene for its strong prognostic ability in PRCC by univariate and multiple Cox regression analyses. Quantitative real-time PCR and Western blot demonstrated that SERPINH1 mRNA and protein were highly expressed in PRCC cells compared with normal human renal cells. This study exhibited a new molecular classification and prognostic signature for PRCC, which may provide a potential biomarker and therapy target for PRCC patients.

Blood glucose and lipids are associated with sarcoidosis: findings from observational and mendelian randomization studies.

BACKGROUND: Several researches have demonstrated that patients with sarcoidosis accompanied with the abnormality in blood glucose and/or lipids, however, the causal relationship between them remains uncertain. To elucidate the potential association and causality of blood glucose and lipids with sarcoidosis, we conducted a propensity score matching (PSM)-based observational study combined with mendelian randomization (MR) analysis. METHODS: All subjects in this study were retrospectively collected from Tongji Hospital during 2010 and 2023. 1:1 PSM was employed to control the potential confounders as appropriate. Univariable and multivariable logistic regression analyses were performed to estimate the associations of sarcoidosis with fasting glucose, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and total triglyceride (TG). The further subtype analysis was also conducted. Afterwards, a bidirectional MR analysis based on public data deeply explored the causality among the 5 candidate traits and sarcoidosis, for which the inverse-variance weighted (IVW) method was utilized as the main inferring approach. RESULTS: In the observational study, a total number of 756 subjects were enrolled, with 162 sarcoidosis patients and 594 non-sarcoidosis participants, while 160 pairs of subjects were matched after PSM. Multivariable logistic regression analysis indicated that HDLC (OR: 0.151; 95% CI: 0.056-0.408; P < 0.001) and TC (OR: 3.942; 95% CI: 2.644-5.877; P < 0.001) were strongly associated with sarcoidosis. Subtype analysis showed that low HDLC was independently correlated to risk of lesions in bronchus and lungs, and mediastinal lymph nodes, while high TC was to cervical lymph nodes. In MR analysis, high fasting glucose, low HDLC, and high TC were identified as the causal factors of sarcoidosis. CONCLUSION: HDLC and TC had the potential to influence the risk of sarcoidosis, which could be regarded as predictors and may provide new diagnostic and therapeutic targets for sarcoidosis.

Macro-porous structured aerogel with enhanced ab/desorption kinetics for sorption-based atmospheric water harvesting.

Sorption-based atmospheric water harvesting (SAWH) has been proven to be a promising method to alleviate the impact of the water crisis on human activities. However, the low water-sorption capacity and sluggish ab/desorption kinetics of current SAWH materials make it difficult to achieve high daily water production. In this study, a photothermal porous sodium alginate-tannic acid-5/Fe3+@lithium chloride aerogel (SA-TA-5/Fe3+@LiCl) with macroporous structure (average pore diameter ∼43.67 µm) and high solar absorbance (∼98.4 %) was fabricated via Fe3+-induced crosslinking and blackening methods. When it is employed for SAWH, moisture can enter the inner space of the aerogel and contact highly hygroscopic lithium chloride (LiCl) more easily via macroporous channels, resulting in the water uptake for the SA-TA-5/Fe3+@LiCl aerogel reaching approximately 1.229 g g-1 under dry conditions (relative humidity (RH) âˆ¼ 45 %, 25 °C) after a short time (4 h) moisture absorption, and releasing as much as 97.7 % of the absorbed water under 1 sun irradiation within 2 h. As a proof of concept, it is estimated that the daily water yield of the fabricated SA-TA/Fe3+@LiCl aerogel can reach approximately 4.65 kg kg-1 in conditions close to the real outdoor environment (RH âˆ¼ 45 %, 25 °C), which satisfies the daily minimum water consumption of two adults. This study demonstrates a novel strategy for developing advanced solar-driven SAWH materials with enhanced ab/desorption kinetics and efficient water sorption-desorption properties.

ß­adrenergic receptor activation promotes the proliferation of HepG2 cells via the ERK1/2/CREB pathways.

Primary liver cancer is one of the most frequently diagnosed malignant tumors seen in clinics, and typically exhibits aggressive invasive behaviors, a poor prognosis, and is associated with high mortality rates. Long-term stress exposure causes norepinephrine (NE) release and activates the ß-Adrenergic receptor (ß-AR), which in turn exacerbates the occurrence and development of different types of cancers; however, the molecular mechanisms of ß-AR in liver cancer are not fully understood. In the present study, reverse transcription (RT)-PCR and RT-quantitative PCR showed that ß-AR expression was upregulated in human liver cancer cells (HepG2) compared with normal liver cells (LO2). Moreover, NE treatment promoted the growth of HepG2 cells, which could be blocked by propranolol, a ß-AR antagonist. Notably, NE had no significant effect on the migration and epithelial-mesenchymal transition in HepG2 cells. Further experiments revealed that NE increased the phosphorylation levels of the extracellular signal-regulated kinase 1/2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB), while inhibition of ERK1/2 and CREB activation significantly blocked NE-induced cell proliferation. In summary, the findings of the present study suggested that ß-adrenergic receptor activation promoted the proliferation of HepG2 cells through ERK1/2/CREB signaling pathways.

Neuroendoscopy surgery for hypertensive intracerebral hemorrhage with concurrent brain herniation: a retrospective study of comparison with craniotomy.

Background: Hypertensive intracerebral hemorrhage combined with cerebral hernia (HIH-CH) is a serious condition. Neuroendoscopy can effectively remove intracranial hematoma, but there is no relevant research support for its utility in patients with HIH-CH. The purpose of this study is to investigate the efficacy and safety of neuroendoscopy in patients with HIH-CH. Methods: Patients with HIH-CH who received craniotomy or neuroendoscopy treatment were included. The patients were divided into craniotomy (CHE) group and neuroendoscopy (NEHE) group. Clinical data and follow-up outcome of the two groups were collected. The primary outcome was hematoma clearance. Results: The hematoma clearance rate (%) of patients in NEHE group was 97.65 (92.75, 100.00), and that of patients in CHE group was 95.00 (90.00, 100.00), p > 0.05. The operation time and intraoperative bleeding volume of patients in NEHE group were significantly less than those in CHE group (p < 0.05). There was no significant difference in the volume of residual hematoma and the incidence of rebleeding between the two groups (p > 0.05). The length of stay in ICU in NEHE group was significantly shorter than that in CHE group (p < 0.05). Conclusion: Neuroendoscopy can safely and effectively remove the intracranial hematoma in patients with hypertensive intracerebral hemorrhage and cerebral hernia, significantly shorten the operation time, reduce the amount of intraoperative hemorrhage, shorten the ICU stay.

Quantum Photonic Circuits Integrated with Color Centers in Designer Nanodiamonds.

Diamond has emerged as a leading host material for solid-state quantum emitters, quantum memories, and quantum sensors. However, the challenges in fabricating photonic devices in diamond have limited its potential for use in quantum technologies. While various hybrid integration approaches have been developed for coupling diamond color centers with photonic devices defined in a heterogeneous material, these methods suffer from either large insertion loss at the material interface or evanescent light-matter coupling. Here, we present a new technique that enables the deterministic assembly of diamond color centers in a silicon nitride photonic circuit. Using this technique, we observe Purcell enhancement of silicon vacancy centers coupled to a silicon nitride ring resonator. Our hybrid integration approach has the potential for achieving the maximum possible light-matter interaction strength while maintaining low insertion loss and paves the way toward scalable manufacturing of large-scale quantum photonic circuits integrated with high-quality quantum emitters and spins.

The incidence of tuberculous pleurisy in mainland China from 2005 to 2018.

Background: Currently, tuberculous pleurisy (TP) remains a serious problem affecting global public health, including in China. Our purpose was to comprehensively understand and identify the incidence of TP in mainland China between 2005 and 2018. Methods: The data on registered TP cases from 2005 to 2018 were acquired from the National Tuberculosis Information Management System. We analyzed the demographics, epidemiology, and time-space distribution of TP patients. Then, the effects of potentially influential factors on TP incidences, such as medical expenses per capita, GDP per capita, and population density, were assessed using the Spearman correlation coefficient. Results: The incidence of TP increased in mainland China from 2005 to 2018, with a mean incidence of 2.5 per 100,000 population. Interestingly, spring was the peak season for TP, with more notified cases. Tibet, Beijing, Xinjiang, and Inner Mongolia had the highest mean annual incidence. A moderate positive relationship was found between TP incidence, medical expenses per capita, and GDP per capita. Conclusions: The notified incidence of TP had an elevated trend from 2005 to 2018 in mainland China. The findings of this study provide insight into the knowledge of TP epidemiology in the country, which can help optimize resource allocation to reduce the TP burden.

One-step fabrication of all-in-one three-dimensional porous polypyrrole/polydopamine structure for efficient solar vapor generation.

High-quality solar evaporators with all-in-one design are highly desirable for vapor generation, but relevant research is scarce. In this study, a three-dimensional (3D) porous polypyrrole/polydopamine (PPY/PDA) structure was fabricated via a simple heating-assisted rapid oxidative polymerization method. The obtained evaporator has multiple features, and can simultaneously provide rapid water transport channels (average pore sizes âˆ¼ 18.37 nm), low thermal conductivity (0.071 W m-1 K-1), high solar absorbance (97.08%), and good mechanical properties. When it is employed as an evaporator, the calculated water evaporation rate is approximately 2.12 kg m-2h-1, which is comparable to other reported 3D evaporators. Additionally, the evaporator displays great potential for purification toward various nonpotable water, as well as reliable pure water yields in an outdoor application (from 8:00 am to 5:00 pm, the evaporator can produce at least 13.95 L of drinkable water for a 1 m2 sample). We believe that the proposed strategy to fabricate all-in-one evaporators has great significance for scientific research and practical applications.