The association between urbanization and depression in the elderly: A network analysis from the complexity science perspective.

IMPORTANCE: The global increase in urbanization has coincided with a rise in depression prevalence. However, the effect of urbanization on depression remains controversial, especially for the elderly. OBJECTIVE: To clarify how urbanization impacts depression in the elderly from a network perspective. DESIGN, SETTING, AND PARTICIPANTS: This sectional cohort study used data from China Health and Retirement Longitudinal Study (CHARLS). MAIN OUTCOMES AND MEASURES: The occurrence of depressive symptoms in urban and rural elderly residents. Network metrics of depressive symptoms. RESULTS: Of the 13,993 participants, lower incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 24.7 %-27.8 %) than in rural (40.4 %, 95 % CI, 39.5 %-41.3 %, P < 0.0001) residents. However, higher incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 25.2 %-28.4 %) than in rural (17.5 %, 95 % CI, 16.1 %-18.9 %, P < 0.0001) residents in a subset of 2898 pairs of participants after PSM. No difference in the network structure and metrics between urban and rural residents before (M = 0.071, p = 0.054, S = 0.037, p = 0.80) and after (M = 0.085, p = 0.133, S = 0.086, p = 0.47) PSM was detected. The networks structure revealed that negative affect was strongly connected to somatic symptoms and that the two anhedonic symptoms were also strongly connected. CONCLUSIONS: The current study indicated the homogeneity of the ultimate nature of depression between rural and urban residents from the network perspective, supporting the viewpoint that urbanization might not impose influence on depression. Further researches delving deeper into the complexity of the issue may provide new insights into our understanding of depression in an urban environment among the elderly.

Regulation of lipid metabolism by APOE4 in intrahepatic cholangiocarcinoma via the enhancement of ABCA1 membrane expression.

Intrahepatic cholangiocarcinoma (ICC) is a malignancy with a dismal prognosis, thus the discovery of promising diagnostic markers and treatment targets is still required. In this study, 1,852 differentially expressed genes (DEGs) were identified in the GSE45001 dataset for weighted gene co-expression network analysis (WGCNA), and the turquoise module was confirmed as the key module. Next, the subnetworks of the 1,009 genes in the turquoise module analyzed by MCODE, MCC, and BottleNeck algorithms identified nine overlapping genes (CAT, APOA1, APOC2, HSD17B4, EHHADH, APOA2, APOE4, ACOX1, AGXT), significantly associated with lipid metabolism pathways, such as peroxisome and cholesterol metabolism. Among them, APOE4 exhibited a potential tumor-suppressive role in ICC and high diagnostic value for ICC in both GSE45001 and GSE32879 datasets. In vitro experiments demonstrated Apolipoprotein E4 (APOE4) overexpression suppressed ICC cell proliferation, migration, and invasion, knockdown was the opposite trend. And in ICC modulated lipid metabolism, notably decreasing levels of TG, LDL-C, and HDL-C, while concurrently increasing the expressions of TC. Further, APOE4 also downregulated lipid metabolism-related genes, suggesting a key regulatory role in maintaining cellular homeostasis, and regulating the expression of the membrane protein ATP-binding cassette transporter A1 (ABCA1). These findings highlighted the coordinated regulation of lipid metabolism by APOE4 and ABCA1 in ICC progression, providing new insights into ICC mechanisms and potential therapeutic strategies.

A two-step electrochemical biosensor based on Tetrazyme for the detection of fibrin.

In this study, an electrochemical biosensor was constructed for the detection of fibrin, specifically by a simple two-step approach, with a novel artificial enzyme (Tetrazyme) based on the DNA tetrahedral framework as signal probe. The multichannel screen-printed electrode with the activated surface cannot only remove some biological impurities, but also serve as a carrier to immobilize a large number of antigen proteins. The DNA tetrahedral nanostructure was employed to ensure the high sensitivity of the probe for biological analysis. The hemin was chimeric into the G-quadruplex to constitute the complex with peroxidase catalytic activity (hemin/G4-DNAzyme), subsequently, Tetrazyme was formed through combining of this complex and DNA tetrahedral nucleic acid framework. The artificial enzyme signal probe formed by the covalent combination of the homing peptide (Cys-Arg-Glu-Lys-Ala, CREKA), which is the aptamer of fibrin and the new artificial enzyme is fixed on the surface of the multichannel carbon electrode by CREKA-specific recognition, so as to realize the sensitive detection of fibrin. The feasibility of sensing platform was validated by cyclic voltammetry (CV) and amperometric i-t curve (IT) methods. Effects of Tetrazyme concentration, CREKA concentrations and hybridization time on the sensor were explored. Under the best optimal conditions of 0.6 µmol/L Tetrazyme, 80 µmol/L CREKA, and 2.5 h reaction time, the immunosensor had two linear detection ranges, 10-40 nmol/L, with linear regression equation Y = 0.01487X - 0.011 (R2 = 0.992), and 50-100 nmol/L, with linear regression equation Y = 0.00137X + 0.6405 (R2 = 0.998), the detection limit was 9.4 nmol/L, S/N ≥ 3. The biosensor could provide a new method with great potential for the detection of fibrin with good selectivity, stability, and reproducibility.

Electrochemical biosensor based on PAMAM functionalized MXene nanoplatform for detection of folate receptor.

The level of folate receptor (FR) has become one of the independent factors for measuring human tumor diseases. The precise quantification of FR is helpful for the early diagnosis and subsequent treatment of tumors. The modification of electrodes is a key issue in ensuring and enhancing the electrochemical biosensing ability. In this study, we in-situ synthesized a nanocomposite material with excellent conductivity and stability by grafting first-generation poly(amidoamine) dendrimers onto the MXene (Ti3C2TX) as the immobilized matrix (PAMAM@MXene). An electrochemical sensor was developed for FR monitor by loading the PAMAM@MXene on screen-printed carbon electrodes (SPCEs). Scanning electron microscopy (SEM) supported the effective synthesis of PAMAM@MXene. Under optimal conditions, the prepared sensor achieved the quantification of FR with a wide range of concentrations from 10 ng/mL to 1000 ng/mL with a detection limit (LOD) of 5.6 ng/mL. It also exhibited satisfactory selectivity, reproducibility, and stability, which provided the possibility for expanding new pathways in the detection of clinical FR.

Nano delivery system for paclitaxel: Recent advances in cancer theranostics.

Paclitaxel is one of the most effective chemotherapeutic drugs which processes the obvious curative effect for a broad range of cancers including breast, ovarian, lung, and head & neck cancers. Though some novel paclitaxel-loaded formulations have been developed, the clinical application of the paclitaxel is still limited due to its toxicity and solubility issues. Over the past decades, we have seen rapid advances in applying nanocarriers in paclitaxel delivery systems. The nano-drug delivery systems offer unique advantages in enhancing the aqueous solubility, reducing side effects, increasing permeability, prolonging circulation half-life of paclitaxel. In this review, we summarize recent advances in developing novel paclitaxel-loaded nano delivery systems based on nanocarriers. These nanocarriers show great potentials in overcoming the disadvantages of pure paclitaxel and as a result improving the efficacy.

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer.

Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy.

Aescin-induced reactive oxygen species play a pro-survival role in human cancer cells via ATM/AMPK/ULK1-mediated autophagy.

Aescin, a natural mixture of triterpene saponins, has been reported to exert anticancer effect. Recent studies show that aescin increases intracellular reactive oxygen species (ROS) levels. However, whether the increased ROS play a role in the anticancer action of aescin remains to be explored. In this study, we demonstrated that aescin (20-80 µg/mL) dose-dependently induced apoptosis and activated mammalian target of rapamycin (mTOR)-independent autophagy in human hepatocellular carcinoma HepG2 cells and colon carcinoma HCT 116 cells. The activation of autophagy favored cancer cell survival in response to aescin, as suppression of autophagy with ATG5 siRNAs or 3-methyladenine (3-MA), a selective inhibitor of autophagy, promoted aescin-induced apoptosis in vitro, and significantly enhanced the anticancer effect of aescin in vivo. Meanwhile, aescin dose-dependently elevated intracellular ROS levels and activated Ataxia-telangiectasia mutated kinase/AMP-activated protein kinase/UNC-51-like kinase-1 (ATM/AMPK/ULK1) pathway. The ROS and ATM/AMPK/ULK1 pathway were upstream modulators of the aescin-induced autophagy, as N-acetyl-L-cysteine (NAC) or ATM kinase inhibitor (KU-55933) remarkably suppressed aescin-induced autophagy and consequently promoted aescin-induced apoptosis, whereas overexpression of ATG5 partly attenuated NAC-induced enhancement in aescin-induced apoptosis. In conclusion, this study provides new insights into the roles of aescin-mediated oxidative stress and autophagy in cancer cell survival. Our results suggest that combined administration of the antioxidants or autophagic inhibitors with aescin might be a potential strategy to enhance the anticancer effect of aescin.

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway.

As an oncogene, MACC1 serves an important function in cancer progression and metastasis. However, the effect of MACC1 in esophageal carcinoma (EC) remains to be fully understood. The present study assessed the association between MACC1 expression and the progression of EC cells. A small interfering (si)RNA was delivered into EC cells to downregulate MACC1 expression. The MTT assay demonstrated that EC cell viability was reduced by siRNA-MACC1. Decreasing MACC1 expression increased the apoptotic rate of EC cells compared with control cells. Transwell and Matrigel assays demonstrated that EC cell migration and invasion, respectively, were downregulated by siRNA-MACC1. Furthermore, knocking down MACC1 suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by upregulating the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor. The results of the present study revealed that MACC1 expression affected cellular functions of the EC cells through the PTEN/PI3K/Akt signaling pathway. Therefore, MACC1 may potentially serve as a novel biomarker and therapeutic target for EC.