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This study aims to explore the clinical and pathological characteristics, prognosis, diagnosis, and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED) in elderly patients. A total of 16 cases of GAED diagnosed from August 2019 to August 2022 at the First Affiliated Hospital of Nanchang University were retrospectively collected to analyze their clinical and pathological features. A control group of 360 cases of conventional gastric adenocarcinoma diagnosed during the same period was used for comparison. Among the 16 GAED patients, 11 were male and 5 were female, with ages ranging from 64 to 89 years (median age 75.5 years). Clinical manifestations of these patients included symptoms such as abdominal pain, bloating, hematemesis, and melena. The macroscopic classification revealed 11 cases of ulcerative lesions, 4 protruded lesions, and 1 diffusely infiltrative lesion. Tumor sizes varied from 3 to 9.5 cm in diameter, with a median diameter of 4.75 cm. Microscopically, the tumor cells exhibited tubular, papillary, and cribriform arrangements, with cuboidal or columnar morphology, relatively distinct cell boundaries, and cytoplasm that appeared clear or weakly acidophilic. Immunophenotyping analysis revealed the expression of SALL4 (15/16), Glypican-3 (12/16), CDX2 (12/16), CD10 (10/16), and p53 (12 cases exhibiting mutant expression, 4 cases exhibiting wild-type expression) within the tumor cells. There was no loss of mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). The Ki-67 proliferation index ranged from 50% to 95%. In comparison to conventional gastric adenocarcinoma, GAED was frequently found in the gastric antrum (P<0.001) and exhibited a higher incidence of intravascular cancer emboli (P<0.001). Significant differences were noted in the Lauren classification, invasion depth, differentiation degree (P<0.01), and macroscopic type (P<0.05). However, no significant differences were found regarding age, gender, tumor diameter, neural invasion, or lymph node metastasis (P>0.05). The postoperative follow-up ranging from 5 to 29 months revealed one death and 15 cases of disease-free survival. GAED is a special subtype of gastric adenocarcinoma characterized by a combination of embryonal and intestinal differentiation immunophenotypes, as well as its increased propensity for biological invasion. Accurate identification of GAED is crucial in pathological practice, as it helps differentiate between GAED and conventional adenocarcinoma and aids in the evaluation of tumor malignancy. Furthermore, it is imperative to conduct a differential diagnosis that involves hepatoid adenocarcinoma, yolk sac tumor-like adenocarcinoma, and metastatic hepatocellular carcinoma., Competing Interests: None., (AJCR Copyright © 2024.)

The linear ubiquitin chain assembly complex (LUBAC) mediates the linear ubiquitination of various proteins and is involved in NF-κB signaling and immune regulation. However, the function and mechanism of linear ubiquitination in regulating oncogenic signaling and tumor growth have remained poorly understood. Herein, we identified Gli proteins, key transcription factors in the Hedgehog (Hh) signaling pathway, as novel substrates of LUBAC. Linear ubiquitination stabilizes Gli proteins, leading to the noncanonical activation of Hh signaling in CRC cells. Furthermore, LUBAC facilitates tumor growth in CRC cells. Additionally, elevated expression of LUBAC components in CRC tissues was observed, and higher expression levels of these components correlated with poor prognosis in CRC patients. Interestingly, inhibition of LUBAC using either a small molecule agonist or RNA silencing specifically suppressed cell growth in CRC cells but had no effect on normal intestinal cells. Taken together, aberrant expression of LUBAC components activates Hh signaling noncanonically by mediating linear ubiquitination, promoting tumor growth in CRC, demonstrating the novel function of linear ubiquitination in regulating the protein stability of its substrates and highlighting the potential of targeting LUBAC as a therapeutic strategy in CRC., (© 2024. The Author(s).)

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 Fe 3+ and can be used as an effective method for detecting Fe 3+ 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 Fe 3+ 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 Fe 3+ fluorescent probes in the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. Springer Nature Switzerland AG.)

Harmine is present in a variety of medicinal plants, and its effects on colon cancer cells remain unclear. Here, we found that harmine exhibited significant inhibitory effects on the proliferation of colon cancer cells by inhibiting the phosphorylation levels of the FAK/AKT and ERK1/2/CREB. Furthermore, harmine also inhibited the migration of colon cancer cells and suppressed the expression levels of MMP-2, MMP-9, and VEGF. Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.

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., Competing Interests: Competing Interests The authors declare that they have no competing interests., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 (dachshund homolog 1) expression has a detrimental role in numerous disorders, but its role in COPD remains understudied. This study aimed to elucidate the role and underlying mechanism of DACH1 in airway inflammation in COPD by measuring DACH1 expression in lung tissues of patients with COPD. Airway epithelium-specific DACH1-knockdown mice and adenoassociated virus-transfected DACH1-overexpressing mice were used to investigate the role of DACH1 and the potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by CS extract stimulation in vitro . Compared with nonsmokers and smokers without COPD, patients with COPD had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated airway inflammation and lung function decline caused by CS in mice, 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, respectively, in 16HBE human bronchial epidermal cells after CS extract stimulation. NRF2 (nuclear factor erythroid 2-related factor 2) 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 patients with COPD than in nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating the NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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/Fe 3+ @lithium chloride aerogel (SA-TA-5/Fe 3+ @LiCl) with macroporous structure (average pore diameter ∼43.67 μm) and high solar absorbance (∼98.4 %) was fabricated via Fe 3+ -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/Fe 3+ @LiCl aerogel reaching approximately 1.229 g g -1 under dry conditions (relative humidity (RH) ∼ 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/Fe 3+ @LiCl aerogel can reach approximately 4.65 kg kg -1 in conditions close to the real outdoor environment (RH ∼ 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

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 Tyr 270 . 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.

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-β/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-β., 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

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., (© 2024. The Author(s).)

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.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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 ∼ 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 -2 h -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 m 2 sample). We believe that the proposed strategy to fabricate all-in-one evaporators has great significance for scientific research and practical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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 β-Adrenergic receptor (β-AR), which in turn exacerbates the occurrence and development of different types of cancers; however, the molecular mechanisms of β-AR in liver cancer are not fully understood. In the present study, reverse transcription (RT)-PCR and RT-quantitative PCR showed that β-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 β-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 β-adrenergic receptor activation promoted the proliferation of HepG2 cells through ERK1/2/CREB signaling pathways., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Lin et al.)

Carbonized polymer dots (CPDs) have highly potential application value in the field of optoelectronic devices due to their preferable stability, excellent optical properties and low cost. Here, the nitrogen-doped carbonized polymer dots (HNCDs) with self-quenching-resistant fluorescence were prepared via a simple solvothermal method with citric acid, urea and 2-hydroxyethyl methacrylate (HEMA) as raw materials. The structure and optical properties of the HNCDs have been explored in detail by various contrast experiments. The results show that HEMA form the poly(HEMA) to modify on the surface of carbonized core, which can overcome the quenching effect of carbonized core. The nitrogen doping is crucial for the red shift emission of solid-state HNCDs. Furthermore, the HNCDs exhibit concentration-dependent emission and excellent compatibility with silicone sol, which lead to their emission red shifted from blue to red with increasing concentration. The HNCDs were further applied to construct the light-emitting diodes (LEDs), and the multicolor LEDs ranging from blue to red can be prepared by simply varying the type of chips and adjusting the concentration of HNCDs in encapsulating material., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhan, Zou, Wu, Fu, Huang, Lin, Luo and Wang.)

Background: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h., Methods: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia., Results: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s 2 , 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s 2 , P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection., Conclusion: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Wang, Zhan, Liu, Wang, Feng, Li, Chen and Zeng.)

Recurrent infection of chronic wounds remains a major clinical challenge. Recently, the hydrogel antibacterial materials have attracted extensive attention for preventing infection in wound healing. In this study, a hybrid hydrogel made of polyvinyl alcohol - iodine (PAI), sodium carboxymethyl cellulose (CMC), and carbamino quantum dot (CQDs) was prepared by the cross-linking of hydrogen bonds, named as polyvinyl alcohol‑iodine/sodium carboxymethyl cellulose/carbon quantum dots (PAI/CMC/CQDs). The composite hydrogels exhibited the outstanding photothermal conversion efficiency with near infrared (NIR) light irradiation, and the high antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Meanwhile, the elevated temperature of the composite hydrogels up to ∼45 °C was able to stimulate the migration of epidermal cell to accelerate skin repair. Given that PAI and CQDs could respond to different pH values (5-8), the real-time would pH information was provided by the visible light and fluorescent light dual monitoring system by naked eye. Moreover, the visible-fluorescent images could be collected and transformed into RGB signals to quantify the would pH levels, avoiding secondary injuries caused by frequent dressing changes. PAI/CMC/CQDs was demonstrated the significant therapeutic effect on chronic wounds by eliminating bacterial infections and promoting skin repair under the smart RGB monitoring system., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate the predictive performance of end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc) values phototherapy in neonates with significant hyperbilirubinemia., Methods: A prospective study was conducted on neonates with significant hyperbilirubinemia who received phototherapy between 3 and 7 days of life. The breath ETCOc and serum total bilirubin of the recruited infants were measured on admission., Results: The mean ETCOc at admission in 103 neonates with significant hyperbilirubinemia was 1.70 ppm. The neonates were categorized into two groups: phototherapy duration ≤72 h ( n  = 87) and >72 h ( n  = 16) groups. Infants who received phototherapy for >72 h had significantly higher ETCOc (2.45 vs. 1.60, P  = 0.001). The cutoff value of ETCOc on admission for predicting longer phototherapy duration was 2.4 ppm, with a sensitivity of 62.5% and specificity of 88.5%, yielding a 50% positive predictive value and a 92.7% negative predictive value., Conclusion: ETCOc on admission can help predict the duration of phototherapy in neonates with hyperbilirubinemia, facilitate clinicians to judge disease severity, and make clinical communication easier and more efficient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhan, Peng, Jin, Su, Tan, Zhao and Zhang.)

Helitrons , a novel type of mysterious DNA transposons discovered computationally prior to bench work confirmation, are components ubiquitous in most sequenced genomes of various eukaryotes, including plants, animals, and fungi. There is a paucity of empirical evidence to elucidate the mechanism of Helitrons transposition in plants. Here, by constructing several artificial defective Helitron ( dHel ) reporter systems, we aim to identify the autonomous Helitrons ( aHel ) in maize genetically and to demonstrate the transposition and repair mechanisms of Helitrons upon the dHel-GFP excision in maize. When crossing with various inbred lines, several transgenic lines produced progeny of segregated, purple-blotched kernels, resulting from a leaky expression of the C1 gene driven by the dHel -interrupted promoter. Transcription analysis indicated that the insertion of different dHels into the C1 promoter or exon would lead to multiple distinct mRNA transcripts corresponding to transgenes in the host genome. Simple excision products and circular intermediates of dHel-GFP transposition have been detected from the leaf tissue of the seedlings in F 1 hybrids of transgenic lines with corresponding c1 tester, although they failed to be detected in all primary transgenic lines. These results revealed the transposition and repair mechanism of Helitrons in maize. It is strongly suggested that this reporter system can detect the genetic activity of autonomic Helitron at the molecular level. Sequence features of dHel itself, together with the flanking regions, impact the excision activity of dHel and the regulation of the dHel on the transcription level of the host gene.

The Warburg effect indicates that cancer cells survive through glycolysis under aerobic conditions; as such, the topic of cancer metabolism has aroused interest. It is requisite to further explore cancer metabolism, as it helps to simultaneously explain the process of carcinogenesis and guide therapy. The flexible metabolism of cancer cells, which is the result of metabolic reprogramming, can meet the basic needs of cells, even in a nutrition-deficient environment. Glutamine is the most abundant non-essential amino acid in the circulation, and along with glucose, comprise the two basic nutrients of cancer cell metabolism. Glutamine is crucial in non-small cell lung cancer (NSCLC) cells and serves an important role in supporting cell growth, activating signal transduction and maintaining redox homeostasis. In this perspective, the present review aims to provide a new therapeutic strategy of NSCLC through inhibiting the metabolism of glutamine. This review not only summarizes the significance of glutamine metabolism in NSCLC cells, but also enumerates traditional glutamine inhibitors along with new targets. It also puts forward the concept of combination therapy and patient stratification with the aim of comprehensively showing the effect and prospect of targeted glutamine metabolism in NSCLC therapy. This review was completed by searching for keywords including 'glutamine', 'NSCLC' and 'therapy' on PubMed, and screening out articles., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhou et al.)

H. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and β-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and β-catenin pathways in H. pylori -associated gastric tumorigenesis. Immunohistochemical analysis of YAP and β-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and β-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori -induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and β-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and β-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin-gastrin (INS-GAS) mice, whereas silencing of both YAP and β-catenin synergistically inhibited H. pylori- induced cell proliferation and expansion. In addition, YAP was found to directly interact with β-catenin and knockdown of YAP suppressed H. pylori -induced nuclear translocation of β-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and β-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or β-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori -infected mice. Finally, the elevation of gastric YAP was positively correlated with β-catenin expression in human gastric cancer tissues. These findings indicate that YAP and β-catenin synergistically promote H. pylori -induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and β-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis.

Chronic obstructive pulmonary disease (COPD), a small airway disease, is regarded as a metabolic disorder. To further uncover the metabolic profile of COPD patients, it is necessary to identify metabolism-related differential genes in small airway epithelium (SAE) of COPD. Metabolism-related differential genes in SAE between COPD patients and nonsmokers were screened from GSE128708 and GSE20257 datasets. KEGG, GO, and PPI analyses were performed to evaluate the pathway enrichment, term enrichment, and protein interaction of candidate metabolism-related differential genes, respectively. RT-PCR was used to verify the mRNA expression of the top ten differential genes. Western blotting was used to evaluate the protein expression of TXNRD1. TXNRD1 inhibitor auranofin (AUR) was used to assess the impact of TXNRD1 on oxidative stress and inflammation induced by cigarette smoke extraction (CSE). Twenty-four metabolism-related differential genes were selected. ALDH3A1, AKR1C3, CYP1A1, AKC1C1, CPY1B1, and TXNRD1 in the top ten genes were significantly upregulated after CSE simulation for 24 h in human bronchial epithelial (16HBE) cells. Among them, CYP1A1 and TXNRD1 also have a significant upregulation in primary SAE after simulation of CSE for 24 h. The overexpression of protein TXNRD1 has also been detected in 16HBE cells, primary SAE stimulated with CSE, and mouse lung exposed to cigarette smoke (CS). Additionally, inhibition of TXNRD1 with 0.1  μ M AUR alleviated the expression of IL-6 and reactive oxygen species (ROS) induced by CSE by activating the Nrf2/HO-1 pathway in 16HBE cells. This study identified twenty-four metabolism-related differential genes associated with COPD. TXNRD1 might participate in the oxidative stress and inflammation induced by CS by regulating the activation of the Nrf2/HO-1 pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qian Huang et al.)

Background: Nonalcoholic fatty liver disease (NAFLD) poses a substantial socioeconomic burden and is becoming the fastest growing driver of chronic liver disease, potentially accompanied by a poor prognosis., Objective: We aim to elucidate the global and regional epidemiologic changes in NAFLD during the past 30 years and explore the interconnected diseases., Methods: Data on NAFLD incidence, prevalence, death, and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The age-standardized incident rate (ASIR), age-standardized prevalent rate (ASPR), age-standardized death rate (ASDR), and age-standardized DALYs were calculated to eliminate the confounding effects of age when comparing the epidemiologic changes between different geographical regions. In addition, we also investigated the correlation between the NAFLD burden and the sociodemographic index (SDI). Finally, the associations of the 3 common comorbidities with NAFLD were determined., Results: Globally, the incidence and prevalence of NAFLD both increased drastically during the past 3 decades (incidence: from 88,180 in 1990 to 172,330 in 2019, prevalence: from 561,370,000 in 1990 to 1,235,700,000 in 2019), mainly affecting young adults who were aged from 15 to 49 years. The ASIR increased slightly from 1.94 per 100,000 population in 1990 to 2.08 per 100,000 population in 2019, while ASPR increased from 12,070 per 100,000 population in 1990 to 15,020 per 100,000 population in 2019. In addition, the number of deaths and DALYs attributable to NAFLD increased significantly as well from 93,760 in 1990 to 168,970 in 2019 and from 2,711,270 in 1990 to 4,417,280 in 2019, respectively. However, the ASDR and age-standardized DALYs presented decreasing trends with values of estimated annual percentage change equaling to -0.67 and -0.82, respectively (ASDR: from 2.39 per 100,000 population in 1990 to 2.09 per 100,000 population in 2019; age-standardized DALYs: from 63.28 per 100,000 population in 1990 to 53.33 per 100,000 population in 2019). Thereinto, the burden of death and DALYs dominated the patients with NAFLD who are older than 50 years. Moreover, SDI appeared to have obvious negative associations with ASPR, ASDR, and age-standardized DALYs among 21 regions and 204 countries, although there is no marked association with ASIR. Finally, we found that the incidence and prevalence of NAFLD were positively related to those of diabetes mellitus type 2, stroke, and ischemic heart disease., Conclusions: NAFLD is leading to increasingly serious health challenges worldwide. The morbidity presented a clear shift toward the young populations, while the heavier burden of death and DALYs in NAFLD was observed in the aged populations and in regions with relatively low SDI. Comprehensive acquisition of the epidemiologic pattern for NAFLD and the identification of high-risk comorbidities may help policy makers and clinical physicians develop cost-effective prevention and control strategies, especially in countries with a high NAFLD burden., (©Huilong Chen, Yuan Zhan, Jinxiang Zhang, Sheng Cheng, Yuhao Zhou, Liyuan Chen, Zhilin Zeng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 12.12.2022.)

Carbon dots have been widely focused on the field of metal ion detection due to their excellent optical property. Herein, novel orange fluorescent nitrogen and boron co-doped carbon dots (NB-CDs) are obtained by one-pot solvothermal using p-phenylenediamine and boric acid as raw materials. The NB-CDs exhibit excitation-independent emissions and the maximum emission wavelength is 597 nm at 420 nm excitation. The fluorescence can be quenched by Ce 4+ effectively and selectively, and the detection range of Ce 4+ is gained from 0.14 to 180 μM with a detection limit of as low as 0.14 μM. Furthermore, Al 3+ can also recombine with NB-CDs surface functional groups, which shows a detection range from 1.07 to 100 μM and a detection limit of as low as 1.07 μM, accompanied with a blue-shift to 527 nm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The flavan-3-ols of 10 primarily plant food byproducts, including Muscat Hamburg grape seed, hawthorn sarcocarp, litchi pericarp, cocoa bean, peanut skin, lotus seedpod, Xinyang Maojian green tea, Cinnamomi cortex, Sargentodoxa cuneata stem, and Cyperus esculentus, leaves were analyzed. Ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry was used for the analysis. Cyperus esculentus leaves contained a high amount of procyanidin B1 (198.9 mg/100 g), second only to Muscat Hamburg grape seed (292.9 mg/100 g). Unlike grape seed that contained several procyanidin B isomers with very similar retention times, C. esculentus leaves contained primarily procyanidin B1 with few isomers. Procyanidin B1 was enriched in the ethyl acetate fraction of a 70% methanol extract of C. esculentus leaves and purified at 95% purity by two runs of open column chromatography. Direct chromatography of the plant extract on octadecylsilane and Sephadex LH20 open columns improved the yield of the resultant leaf procyanidin B1 (95% purity) to 0.21‰. The present research demonstrated that the leaves of C. esculentus, byproducts of tigernut, are ideal plant sources for isolating and providing high-purity procyanidin B1. PRACTICAL APPLICATION: Procyanidin B1 has a broad range of health benefits. Cyperus esculentus is cultivated in many countries with nearly 6190 square hectares (hm 2 ) in the Spanish Mediterranean region in 2020-2021 and over 16,700 hm 2 in China in recent years, primarily for its tubers. The byproducts, the leaves of C. esculentus, contain high levels of procyanidin B1, with few isomers that interfere with its isolation and purification. Thus, the leaves of this plant provide a viable source for preparing high-purity procyanidin B1., (© 2022 Institute of Food Technologists.)

Aging plays an essential role in the development for chronic obstructive pulmonary disease (COPD). The aim of this study was to identify and validate the potential aging-related genes of COPD through bioinformatics analysis and experimental validation. Firstly, we compared the gene expression profiles of aged and young COPD patients using two datasets (GSE76925 and GSE47460) from Gene Expression Omnibus (GEO), and identified 244 aging-related different expressed genes (DEGs), with 132 up-regulated and 112 down-regulated. Then, by analyzing the data for cigarette smoke-induced COPD mouse model (GSE125521), a total of 783 DEGs were identified between aged and young COPD mice, with 402 genes increased and 381 genes decreased. Additionally, functional enrichment analysis revealed that these DEGs were actively involved in COPD-related biological processes and function pathways. Meanwhile, six genes were identified as the core aging-related genes in COPD after combining the human DEGs and mouse DEGs. Eventually, five out of six core genes were validated to be up-regulated in the lung tissues collected from aged COPD patients than young COPD patients, namely NKG7, CKLF, LRP4, GDPD3 and CXCL9. Thereinto, the expressions of NKG7 and CKLF were negatively associated with lung function. These results may expand the understanding for aging in COPD.

Introduction: Down syndrome (DS) is the leading cause of genetically defined intellectual disability and congenital birth defects worldwide. A large population of people diagnosed with DS globally is posing an enormous socioeconomic burden. However, the global burden and trends of DS have not been reported. Methods: Based on the data from the Global Burden of Disease database in 2019, we analyzed the incidence, prevalence, disability-adjusted life years (DALYs), and death of DS from 1990 to 2019 according to sex, age, regions, and social-demographic index (SDI). Then, age-standardized rates (ASRs) and estimated annual percentage change (EAPC) of these aforementioned indexes were calculated to evaluate the temporal trend of DS. Finally, the association of SDI with DS epidemiological parameters was assessed. Results: In the past 30 years, the incident cases, age-standardized incident rate (ASIR), and age-standardized prevalent rate (ASPR) of DS first decreased slightly and subsequently increased globally. The number of prevalent cases increased steadily, while the number and age-standardized rate (ASRs) of DALYs and deaths decreased gradually from 1990 to 2019. In the meantime, disease burdens were different across various SDI regions. The prevalent cases and ASPR for both sexes were increasing in all SDI regions except for the high-middle SDI region. At the national level, Brunei Darussalam, Ireland, and Haiti were the top three countries with the highest ASIR in 2019. Georgia was in the top three with the highest increase in ASRs of four parameters, while Serbia was consistently ranked in the top three with fastest declining. Furthermore, we found that ASIR and ASPR were positively correlated with SDI, yet the age-standardized DALYs and age-standardized death rate (ASDR) were negatively correlated with SDI. Conclusion: In the past 30 years, the burden and trends of DS were heterogeneous across different regions and countries with different sociodemographic characteristics. Great improvements had been achieved in reducing DALYs and deaths globally. However, the increased number and ASRs of incident and prevalent cases in some regions, especially in low SDI regions, were contributing to numerous challenges to public health. The findings may provide valuable information to the development or implementation of more effective measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wang, Wang, Hu, Zhan, Zeng and Liu.)

This study aimed to investigate the formation mechanism of  Pseudoangiosarcoma squamous cell carcinoma (PASCC). The researchers reviewed ten cases of PASCC and summarize their clinical outcomes, pathological morphological traits, immunophenotypes, treatment plans and the corresponding follow-up data. Results showed that the pathological morphology revealed complex reticular structures, where numerous tracts of anastomose, and lacunar structures lined with atypical neoplastic cells, which resembles the histopathological appearance of angiosarcoma. Particularly, we observed pathologic patterns that resemble Sclerosing Epithelioid Fibrosarcoma (or Myxoid Fibrosarcoma) in the patients who suffered a relapse. All cases present negative results for vascular markers (CD31, ERG) and positive results for epithelial markers (CK-pan, p40). The average age of the participants is 60 years old (range: 48-79), relative aged, and there is no significant difference between male and female participants (6 men and 4 women). The locations of neoplasms involve face (n=3), upper limbs (n=1), waist(n=1), cervix uteri (n=1), lungs (n=2), thyroid (n=1), and breasts (n=1). All participants had received clinical follow-ups that range from 4 to 47 months, during which the researchers observed Lymph Node Metastases developed in three participants (out of 10; 30%); Distant Metastases in five participants (out of 10; 50%); two local recurrences at the site of surgical resection; and four deaths due to disease (out of 10; 40%), with 9.5 months estimated median survival time and 9 months mean survival time. It was concluded that PASCC presents the tendency for recurrence and metastasis. Accurate pathological diagnosis and standardized medical procedures are crucial to the treatment of PASCC. Epithelial-Mesenchymal Transformation (EMT) and P53 gene mutation are involved in the formation of PASCC.

Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients' pulmonary arteries, CS-exposed rat models' pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs' proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs' increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2's promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2's promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Huang, Li, Gu, Zhan, Wang, Chen, Zeng, Lv, Zhao, Xia and Xie.)

As key regulators of gene function, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are generally accepted to be involved in lung cancer pathogenesis and progression. Recent research has clarified the phenomenon of metabolic reprogramming in lung cancer because of its significant role in tumor proliferation, migration, invasion, metastasis, and other malignant biological behaviors. Emerging evidence has also shown a relationship between the aberrant expression of lncRNAs and circRNAs and metabolic reprogramming in lung cancer tumorigenesis. This review provides insight regarding the roles of different lncRNAs and circRNAs in lung cancer metabolic reprogramming, by how they target transporter proteins and key enzymes in glucose, lipid, and glutamine metabolic signaling pathways. The clinical potential of lncRNAs and circRNAs as early diagnostic biomarkers and components of therapeutic strategies in lung cancer is further discussed, including current challenges in their utilization from the bench to the bedside and how to adopt a proper delivery system for their therapeutic use., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Yuhao Zhou et al.)

Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic inflammation and airway remodeling. Human epididymis protein 4 (HE4) plays a critical role in various inflammatory or fibrotic diseases. However, the role of HE4 in COPD remains unidentified., Methods: HE4 expression was determined in the lung tissues from COPD patients and cigarette smoke (CS)-exposed mice using immunohistochemical staining, qPCR, or western blot. The plasma level of HE4 was detected by ELISA. The regulations of HE4 in the expressions of CS extract (CSE)-induced inflammatory cytokines in human bronchial epithelial cells (HBE) were investigated through knockdown or overexpression of HE4. The role of secretory HE4 (sHE4) in the differentiation and proliferation in human pulmonary fibroblast cells (HPF) was explored via qPCR, western blot, CCK8 assay or 5-ethynyl-2'-deoxyuridine (EdU) staining. The probe of related mechanism in CSE-induced HE4 increase in HBE was conducted by administrating N-acetylcysteine (NAC)., Results: HE4 was up-regulated in both the lung tissue and plasma of COPD patients relative to controls, and the plasma HE4 was negatively associated with lung function in COPD patients. The same enhanced HE4 expression was verified in CS-exposed mice and CSE-induced HBE, but CSE failed to increase HE4 expression in HPF. In vitro experiments showed that reducing HE4 expression in HBE alleviated CSE-induced IL-6 release while overexpressing HE4 facilitated IL-6 expression, mechanistically through affecting phosphorylation of NFκB-p65, whereas intervening HE4 expression had no distinctive influence on IL-8 secretion. Furthermore, we confirmed that sHE4 promoted fibroblast-myofibroblast transition, as indicated by promoting the expression of fibronectin, collagen I and α-SMA via phosphorylation of Smad2. EdU staining and CCK-8 assay demonstrated the pro-proliferative role of sHE4 in HPF, which was further confirmed by enhanced expression of survivin and PCNA. Pretreatment of NAC in CSE or H 2 O 2 -induced HBE mitigated HE4 expression., Conclusions: Our study indicates that HE4 may participate in airway inflammation and remodeling of COPD. Cigarette smoke enhances HE4 expression and secretion in bronchial epithelium mediated by oxidative stress. Increased HE4 promotes IL-6 release in HBE via phosphorylation of NFκB-p65, and sHE4 promotes fibroblastic differentiation and proliferation., (© 2022. The Author(s).)

Carbon quantum dots (CDs) have attracted tremendous interest owing to their idiosyncratic functions and wide-ranging applications. However, it remains a great challenge to empolder an integrated CDs combining high luminescence, biocompatibility and luminescence color tunability for bioimaging via simple approach. In this work, pH-responsive carbon quantum dots (Si-CDs) with high luminescence (quantum yield = 74.8%) were fabricated by one-step hydrothermal method using (3-mercaptopropyl) triethoxysilane (KH-580) as modifier for the first time. The optical properties of the as-prepared Si-CDs can be controlled from obvious green-blue-violet transformation by altering the pH. More importantly, the change is reversible and repeatable. In addition, the Si-CDs have good biocompatibility and chemically inert in vitro cell system simulation. Such non-toxic, environmental friendly, low-cost, inert CDs materials are promising candidates for biomedical and pH-sensitive sensors., (© 2022 IOP Publishing Ltd.)

Introduction: Infective endocarditis (IE) presents with increasing incidence and mortality in some regions and countries, as well as serious socioeconomic burden. The current study aims to compare and interpret the IE burden and temporal trends globally and in different regions from 1990 to 2019., Methods: Data on the incidence, deaths and disability-adjusted life years (DALYs) caused by IE were extracted and analyzed from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPC) were adopted to quantify the change trends of age-standardized rates (ASRs). Besides, potential contributors of serious IE burden were also evaluated including age, gender, social-demographic index (SDI), and age-standardized incident rate (ASIR) in 1990., Results: Globally, the number of IE cases and deaths has increased sharply during the past 30 years from 478,000 in 1990 to 1,090,530 in 2019 and from 28,750 in 1990 to 66,320 in 2019, and both presented an upward temporal trend annually (EAPC:1.2 for incidence and 0.71 for death). However, the EAPC of age-standardized DALYs demonstrated a negative temporal trend despite increasing DALYs from 1,118,120 in 1990 to 1,723,590 in 2019. Moreover, older patients and men were more severely affected. Meanwhile, different SDI regions had different disease burdens, and correlation analyses indicated that SDI presented a positive association with ASIR (R = 0.58, P < 0.0001), no association with age-standardized death rate (R = -0.06, P = 0.10), and a negative association with age-standardized DALYs (R = -0.40, P < 0.0001). In addition, the incidence of IE increased in most countries during the past 30 years (190 out of 204 countries). However, the change trends of deaths and DALYs were heterogeneous across regions and countries. Finally, we discovered positive associations of the EAPC of ASRs with the SDI in 2019 among 204 countries and territories but few associations with the ASIR in 1990., Conclusion: Generally, the global burden of IE is increasing, and there is substantial heterogeneity in different genders, ages and regions, which may help policy-makers and medical staff respond to IE and formulate cost-effective interventional measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MY declared a shared affiliation with several of the authors HC, YZ, YG, JZ, ZC, and ZZ, to the handling editor at the time of review., (Copyright © 2022 Chen, Zhan, Zhang, Gao, Chen, Zhan, Chen and Zeng.)

Background: At present, few studies have reported the metabolic profiles of lung tissue in patients with COPD. Our study attempted to analyze the lung metabolome in male COPD patients and to screen the overlapping biomarkers of the lung and plasma metabolomes. Methods: We performed untargeted metabolomic analysis of normal lung tissue from two independent sets (the discovery set: 20 male COPD patients and 20 controls and the replication set: 47 male COPD patients and 27 controls) and of plasma samples from 80 male subjects containing 40 COPD patients and 40 controls. Results: We found glycerophospholipids (GPs) and Amino acids were the primary classes of differential metabolites between male COPD patients and controls. The disorders of GPs metabolism and the valine, leucine and isoleucine biosynthesis metabolism pathways were identified in lung discovery set and then also validated in the lung replication set. Combining lung tissue and plasma metabolome, Phytosphingosine and l-tryptophan were two overlapping metabolites biomarkers. Binary logistic regression suggested that phytosphingosine together with l-tryptophan was closely associated with male COPD and showed strong diagnostic power with an AUC of 0.911 (95% CI: 0.8460-0.9765). Conclusion: Our study revealed the metabolic perturbations of lung tissues from male COPD patients. The detected disorders of GPs and amino acids may provide an insight into the pathological mechanism of COPD. Phytosphingosine and l-tryptophan were two novel metabolic biomarkers for differentiating COPD patients and controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wu, Gu, Wang, Zhan, Chen, Zeng, Lv, Zhao and Xie.)

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro . Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yiya Gu et al.)

Silane-functionalized carbon dots (SiCDs) can be exploited as effective color converting materials for the solid-state light-emitting devices. However, most of SiCDs reported thus far have shown photoluminescence emissions in the blue and green spectral range, which limit them to construct an efficient white light-emitting diodes (WLEDs) due to the lack of long-wavelength emission. Herein, a series of double silane-functionalized carbon dots (DSiCDs) were prepared via a one-step solvothermal method. The results show that the organic functional group of the silane has great influence on the optical properties of DSiCDs and the number of alkoxy group in the silane has great influence on coating properties of DSiCDs. In addition, the DSiCDs prepared by (3-aminopropyl)triethoxysilane and N-[3-(trimethoxysilyl)propyl]ethylenediamine with molar ratio of 7:3 show excellent optical properties with the maximum emission at 608 nm under 570 nm excitation. Furthermore, they can be completely cured within 1 h at room temperature to form fluorescent coating with high stability and strong adhesion to the substrate. Together with their excellent optical and coating properties, they can be directly coated on LED chips to prepare WLEDs, with a CIE coordinate of (0.33,0.31), color rendering index of 81.6, and color temperature of 5774 K., (© 2021 IOP Publishing Ltd.)

We have used a modified-intake plasma-enhanced metal-organic chemical vapor deposition (MIPEMOCVD) system to fabricate gallium-doped zinc oxide (GZO) thin films with varied Ga content. The MIPEMOCVD system contains a modified intake system of a mixed tank and a spraying terminal to deliver the metal-organic (MO) precursors and a radio-frequency (RF) system parallel to the substrate normal, which can achieve a uniform distribution of organic precursors in the reaction chamber and reduce the bombardment damage. We examined the substitute and interstitial mechanisms of Ga atoms in zinc oxide (ZnO) matrix in MIPEMOCVD-grown GZO thin films through crystalline analyses and Hall measurements. The optimal Ga content of MIPEMOCVD-grown GZO thin film is 3.01 at%, which shows the highest conductivity and transmittance. Finally, the optimal MIPEMOCVD-grown GZO thin film was applied to n-ZnO/p-GaN LED as a window layer. As compared with the indium-tin-oxide (ITO) window layer, the n-ZnO/p-GaN LED with the MIPEMOCVD-grown GZO window layer of the rougher surface and higher transmittance at near UV range exhibits an enhanced light output power owing to the improved light extraction efficiency (LEE).

Chronic obstructive pulmonary disease (COPD), primarily attributed to cigarette smoke (CS), is characterized by multiple pathophysiological changes, including oxidative stress and inflammation. Stromal interaction molecule 1 (STIM1) is a Ca 2+ sensor that regulates Ca 2+ entry in different types of cells. The present study aimed to explore the relationship between CS-induced oxidative stress and inflammation, as well as the functional role of STIM1 thereinto. Our results showed that the reactive oxygen species (ROS)/STIM1/Ca 2+ axis played a critical role in CS-induced secretion of interleukin (IL)-8 in human alveolar macrophages. Specifically, smokers with COPD (SC) showed higher levels of ROS in the lung tissues compared with healthy non-smokers (HN). STIM1 was upregulated in the lung tissues of COPD patients. The expression of STIM1 was positively associated with ROS levels and negatively correlated with pulmonary function. The expression of STIM1 was also increased in the bronchoalveolar lavage fluid (BALF) macrophages of COPD patients and PMA-differentiated THP-1 macrophages stimulated by cigarette smoke extract (CSE). Additionally, CSE-induced upregulation of STIM1 in PMA-differentiated THP-1 macrophages was inhibited by pretreatment with N-acetylcysteine (NAC), a ROS scavenger. Transfection with small interfering RNA (siRNA) targeting STIM1 and pretreatment with NAC alleviated CSE-induced increase in intracellular Ca 2+ levels and IL-8 expression. Furthermore, pretreatment with SKF-96365 and 2-APB, the inhibitors of Ca 2+ influx, suppressed CSE-induced secretion of IL-8. In conclusion, our study demonstrates that CSE-induced ROS production may increase the expression of STIM1 in macrophages, which further promotes the release of IL-8 by regulating Ca 2+ entry. These data suggest that STIM1 may play a crucial role in CSE-induced ROS production and inflammation, and participate in the pathogenesis of COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Zhan, Gu, Huang, Wang, Deng and Xie.)

Durio zibethnus is mainly distributed in Southeast Asia. Traditional Chinese medicine believes that durian shells have the effects of clearing heat and purging fire, nourishing yin and moisturizing dryness. Therefore, it is often used as a pharmaceutic food in the Chinese folk to assist treating diseases. At present, the chemical constituents isolated from durian shell include phenolic acids, phenolic glycosides, flavonoids, coumarins, triterpenes, simple glycosides and other compounds. Modern pharmacological studies show that durian shell has many pharmacological activities, such as antioxidant, anti-inflammatory, regulation of glucose and lipid metabolism. The chemical composition and pharmacological effects of durian shells are summarized in order to provide references for the further research and application of durian shell., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Nowadays, great effort has been devoted to fabricate flexible wearable sensor with high stretchability, moderate modulus, favorable durability, excellent transparency, and satisfactory sensitivity. In this work, we report the preparation of a hybrid double-network (DN) hydrogel by a simple one-pot method. First, chitosan was added into an AlCl 3 solution to form Al 3+ -chitosan complex (CS-Al 3+ ). Second, the hybrid CS/Al 3+ -poly(acrylamide) (PAM) DN hydrogels were constructed via in situ polymerization of acrylamide (AM) in present of Al 3+ -chitosan complex. Thanks to the existence of electrically conductive CS-Al 3+ networks, the resulting hybrid DN hydrogel exhibits excellent stretchability, fatigue resistance, transparency, and conductivity. Furthermore, the CS/Al 3+ -PAM DN hydrogel could be used as strain sensor, and demonstrates many desired virtues, including satisfactory sensitivity (gauge factors of 1.7-12.1), wide detection range (up to 1500%), low limit of discernment (1% strain), high reliability, and excellent durability (1000 cycles). More significantly, the manufactured hydrogel-based strain sensor can be employed as wearable devices to precisely detect various human movements.