Emodin induces ferroptosis in colorectal cancer through NCOA4-mediated ferritinophagy and NF-κb pathway inactivation.

Ferroptosis is a new programmed cell death characterized by iron-dependent lipid peroxidation. Targeting ferroptosis is considered a promising strategy for anti-cancer therapy. Recently, natural compound has gained increased attention for their advantage in cancer treatment, and the exploration of natural compounds as ferroptosis inducers offers a hopeful avenue for advancing cancer treatment modalities. Emodin is a natural anthraquinone derivative in many widely used Chinese medicinal herbs. In our previous study, we predicted that the anti-cancer effect of Emodin might related to ferroptosis by using RNA-seq in colorectal cancer (CRC). Thus, in this study, we aim to investigate the molecular mechanism underlying Emodin-mediated ferroptosis in CRC. Cell-based assays including CCK-8, colony formation, EdU, and Annexin V/PI staining were employed to assess Emodin's impact on cell proliferation and apoptosis. Furthermore, various techniques such as FerroOrange staining, C11-BODIPY 581/591 staining, iron, MDA, GSH detection assay and transmission electron microscopy were performed to examine the role of Emodin in ferroptosis. Additionally, specific NCOA4 knockdown cell lines were generated to elucidate the involvement of NCOA4 in Emodin-induced ferroptosis. Moreover, the effects of Emodin on ferroptosis were further confirmed through the application of inhibitors, including Ferrostatin-1, 3-MA, DFO, and PMA. As a results, Emodin inhibited proliferation and induced apoptosis in CRC cells. Emodin could decrease GSH content, xCT and GPX4 expression, meanwhile increasing ROS generation, MDA, and lipid peroxidation, and these effects could reverse by ferroptosis inhibitor, Ferostatin-1, iron chelator DFO, autophagy inhibitor 3-MA and NCOA4 silencing. Moreover, Emodin could inactivate NF-κb pathway, and PMA, an activator of NF-κb pathway could alleviate Emodin-induced ferroptosis in CRC cells. Xenograft mouse model also showed that Emodin suppressed tumor growth and induced ferroptosis in vivo. In conclusion, these results suggested that Emodin induced ferroptosis through NCOA4-mediated ferritinophagy by inactivating NF-κb pathway in CRC cells. These findings not only identified a novel role for Emodin in ferroptosis but also indicated that Emodin may be a valuable candidate for the development of an anti-cancer agent.

RSL1D1 knockdown induces ferroptosis and mediates ferrous iron accumulation in senescent cells by inhibiting FTH1 mRNA stability.

Iron metabolism plays an important role in maintaining cellular multiple biological functions. Dysfunction of iron homeostasis-maintaining systems was observed in many diseases, including cancer. Ribosomal L1 domain-containing 1 (RSL1D1) is an RNA-binding protein involved in multiple cellular processes, including cellular senescence, proliferation and apoptosis. However, the regulatory mechanism of RSL1D1 underlying cellular senescence and its biological process in colorectal cancer (CRC) is not clearly understood. Here, we report that RSL1D1 expression is downregulated by ubiquitin-mediated proteolysis in senescence-like CRC cells. RSL1D1, as an anti-senescence factor, is frequently upregulated in CRC, and elevated RSL1D1 prevents CRC cells from senescence-like phenotype, and correlated with poor prognosis of CRC patients. Knockdown of RSL1D1 inhibited cell proliferation, and induced cell cycle arrest and apoptosis. Notably, RSL1D1 plays important roles in regulating iron metabolism of cancer cells. In RSL1D1-knockdown cells, FTH1 expression was significantly decreased, while transferrin receptor 1 expression was increased, leading to intracellular ferrous iron accumulation, which subsequently promoted ferroptosis, indicated by the increased malondialdehyde and decreased GPX4 levels. Mechanically, RSL1D1 directly bounds with 3' untranslated region of FTH1 and subsequently promoted the mRNA stability. Moreover, RSL1D1-mediated downregulation of FTH1 was also observed in H2O2-induced senescence-like cancer cells. Taken together, these findings support RSL1D1 plays an important role in regulating intracellular iron homeostasis in CRC, and suggest that RSL1D1 could be a potential therapeutic target for cancer treatment.

Synergistic Effect of Surface p-Doping and Passivation Improves the Efficiency, Stability, and Reduces Lead Leakage in All-Inorganic CsPbIBr2 -Based Perovskite Solar Cells.

Wide-bandgap inorganic cesium lead halide CsPbIBr2 is a popular optoelectronic material that researchers are interested in because of the character that balances the power conversion efficiency and stability of solar cells. It also has great potential in semitransparent solar cells, indoor photovoltaics, and as a subcell for tandem solar cells. Although CsPbIBr2 -based devices have achieved good performance, the open-circuit voltage (Voc ) of CsPbIBr2 -based perovskite solar cells (PSCs) is still lower, and it is critical to further reduce large energy losses (Eloss ). Herein, a strategy is proposed for achieving surface p-type doping for CsPbIBr2 -based perovskite for the first time, using 1,5-Diaminopentane dihydroiodide at the perovskite surface to improve hole extraction efficiency. Meanwhile, the adjusted energy levels reduce Eloss and improve Voc of the CsPbIBr2 PSCs. Furthermore, the Cs- and Br-vacancies at the interface are filled, reducing structural disorder and defect states and thus improving the quality of the perovskite film. As a result, the target device achieves a high efficiency of 11.02% with a Voc of 1.33 V, which is among the best values. In addition to the improved performance, the stability of the target device under various conditions is enhanced, and the lead leakage is effectively suppressed.

miR-590-5p/Tiam1-mediated glucose metabolism promotes malignant evolution of pancreatic cancer by regulating SLC2A3 stability.

BACKGROUND: T lymphoma invasion and metastasis 1 (Tiam1) is a tumor related gene that specifically activates Rho-like GTPases Rac1 and plays a critical role in the progression of various malignancies. Glycolysis plays an important role in cancer progression, it is crucial for supplying energy and producing metabolic end products, which can maintain the survival of tumor cells. As yet, however, the mechanism of Tiam1 in glycolysis reprogramming of pancreatic cancer (PC) remains to be clarified. Here, we investigated the functional role of Tiam1 in PC cell proliferation, metastasis and glycolysis reprogramming. It is expected to provide a new direction for clinical treatment. METHODS: The clinical relevance of Tiam1 was evaluated in 66 patients with PC, the effect of Tiam1 on cell proliferation was detected via 5-Ethynyl-2'-deoxyuridine (EdU) and colony formation. The ability of cell migration was detected by the wound healing and Transwell. Quantitative real time polymerase chain reaction (qRT-PCR) and luciferase reporter gene experiments clarify the regulatory relationship of miR-590-5p inhibiting Tiam1. Detection of the molecular mechanism of Tiam1 regulating glucose metabolism reprogramming in PC by glucose metabolism kit. RNA sequencing and Co-Immunoprecipitation (CoIP) have identified glucose transporter protein 3 (SLC2A3) as a key downstream target gene for miR-590-5p/Tiam1. RESULTS: We found that Tiam1 expression increased in PC tissues and was associated with lymph node metastasis. The silencing or exogenous overexpression of Tiam1 significantly altered the proliferation, invasion, and angiogenesis of PC cells through glucose metabolism pathway. In addition, Tiam1 could interact with the crucial SLC2A3 and promote the evolution of PC in a SLC2A3-dependent manner. Moreover, miR-590-5p was found to exacerbate the PC cell proliferation, migration and invasion by targeting Tiam1. Furthermore, the reversing effects on proliferation, migration and invasion were found in PC cells with miR-590-5p/Tiam1 overexpression after applying glucose metabolism inhibition. CONCLUSIONS: Our findings demonstrate the critical role of Tiam1 in PC development and the miR-590-5p/Tiam1/SLC2A3 signaling pathway may serve as a target for new PC therapeutic strategies.

Overexpression of ferritin light chain as a poor prognostic factor for breast cancer.

BACKGROUND: Ferritin light chain (FTL) is involved in tumor progression, but the specific molecular processes by which FTL affects the development of breast cancer (BRCA) have remained unknown. In this research, the clinicopathological significance of FTL overexpression in BRCA was investigated. METHODS: To investigate the role of FTL in BRCA, we utilized multiple online databases to analyse FTL expression levels in BRCA. Next, we reviewed the expression and localization of the FTL protein in BRCA by immunohistochemistry (IHC), Western blot (WB) and immunofluorescence (IF) staining. To assess the impact of FTL on patient prognosis, we conducted Kaplan‒Meier, univariate and multivariate survival analyses. The relationship between FTL and immune infiltration in BRCA was also analysed in the TISCH and SangerBox databases. MTT, malondialdehyde (MDA) and reactive oxygen species (ROS) assays were carried out to investigate the molecular mechanisms of FTL action in BRCA cells. RESULTS: FTL was significantly upregulated in BRCA compared to normal tissues. Its expression significantly linked to histological grade (P = 0.038), PR expression (P = 0.021), Her2 expression (P = 0.012) and Ki-67 expression (P = 0.040) in patients with BRCA. Furthermore, the expression of the FTL protein was higher in the BRCA cell lines than in the normal breast cells and mainly localized in the cytoplasm. Compared to patients with a low level of FTL expression, patients with a high level of FTL expression showed lower overall survival (OS). More convincingly, univariate and multivariate statistical analyses revealed that FTL expression (P = 0.000), ER expression (P = 0.036) and Her2 expression (P = 0.028) were meaningful independent prognostic factors in patients with BRCA. FTL was associated with immune infiltration in BRCA. Functional experiments further revealed that FTL knockdown inhibited the capacity of proliferation and increased the level of oxidative stress in BRCA cells. CONCLUSIONS: Overexpression of FTL was associated with the progression of BRCA. FTL overexpression may become a biomarker for the evaluation of poor prognosis in patients with BRCA.

Perovskite Films Regulation via Hydrogen-Bonded Polymer Network for Efficient and Stable Perovskite Solar Cells.

Perovskite solar cells (PSCs) are considered as a promising photovoltaic technology due to their high efficiency and low cost. However, their long-term stability, mechanical durability, and environmental risks are still unable to meet practical needs. To overcome these issues, we designed a multifunctional elastomer with abundant hydrogen bonds and carbonyl groups. The chemical bonding between polymer and perovskite could increase the growth activation energy of perovskite film and promote the preferential growth of high-quality perovskite film. Owing to the low defect density and gradient energy-level alignment, the corresponding device exhibited a champion efficiency of 23.10 %. Furthermore, due to the formation of the hydrogen-bonded polymer network in the perovskite film, the target devices demonstrated excellent air stability and enhanced flexibility for the flexible PSCs. More importantly, the polymer network could coordinate with Pb2+ ions, immobilizing lead atoms to reduce their release into the environment. This strategy paves the way for the industrialization of high-performance flexible PSCs.

miR-21-5p/Tiam1-mediated glycolysis reprogramming drives breast cancer progression via enhancing PFKL stabilization.

T lymphoma invasion and metastasis 1 (Tiam1) as a tumor-associated gene specifically activates Rho-like GTPases Rac1 and implicates in the invasive phenotype of many cancers. Altering the glycolytic pathway is foreseen as a sound approach to trigger cancer regression. However, the mechanism of Tiam1 in breast cancer (BC) glycolysis reprogramming remains to be clarified. Here, we reported the Tiam1 high expression and prognostic significance in BC. In vitro and in vivo experimental assays identified the functional role of Tiam1 in promoting BC cell proliferation, metastasis and glycolysis reprogramming. Mechanistically, we showed for the first time that Tiam1 could interact with the crucial glycolytic enzyme phosphofructokinase, liver type (PFKL) and promote the evolution of BC in a PFKL-dependent manner. Moreover, miR-21-5p was found to exacerbate the BC proliferation and aggression by targeting Tiam1. Altogether, our study highlights the critical role of Tiam1 in BC development and that the miR-21-5p/Tiam1/PFKL signaling pathway may serve as a target for new anti-BC therapeutic strategies.

Lipid metabolism regulator human hydroxysteroid dehydrogenase-like 2 (HSDL2) modulates cervical cancer cell proliferation and metastasis.

Human hydroxysteroid dehydrogenase-like 2 (HSDL2) is a potent regulator in cancers and is also involved in lipid metabolism, but the role of HSDL2 in cervical cancer and whether it regulates the progress of cervical cancer through lipid metabolism remains unclear. In this study, we found that the overexpression of HSDL2 was in relation with cervical cancer progression including lymph nodes metastasis and recurrence. HSDL2 could serve as a novel marker of early diagnosis in cervical cancer. HSDL2 also gave impetus to tumorigenesis by initiating and promoting proliferation, invasion and migration of cervical cancer cells (Hela, C33A and SiHa) through EMT. Interestingly, we also searched that HSDL2 participated in oncogenesis by regulating lipid metabolism. In sum, our results gave the novel insight of HSDL2 functions which could be the potential for being the biomarker of prognosis and new target of therapy.

Modeling sparse longitudinal data on Riemannian manifolds.

Modern data collection often entails longitudinal repeated measurements that assume values on a Riemannian manifold. Analyzing such longitudinal Riemannian data is challenging, because of both the sparsity of the observations and the nonlinear manifold constraint. Addressing this challenge, we propose an intrinsic functional principal component analysis for longitudinal Riemannian data. Information is pooled across subjects by estimating the mean curve with local Fréchet regression and smoothing the covariance structure of the linearized data on tangent spaces around the mean. Dimension reduction and imputation of the manifold-valued trajectories are achieved by utilizing the leading principal components and applying best linear unbiased prediction. We show that the proposed mean and covariance function estimates achieve state-of-the-art convergence rates. For illustration, we study the development of brain connectivity in a longitudinal cohort of Alzheimer's disease and normal participants by modeling the connectivity on the manifold of symmetric positive definite matrices with the affine-invariant metric. In a second illustration for irregularly recorded longitudinal emotion compositional data for unemployed workers, we show that the proposed method leads to nicely interpretable eigenfunctions and principal component scores. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative database.

Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis.

BACKGROUND AND AIM: Aerobic glycolysis (the Warburg effect) is a distinctive metabolic hallmark of colon adenocarcinoma. Ezrin was a member of the Ezrin-Radixin-Moesin protein family and has been found profoundly implicated in tumorigenesis. However, the specific functional roles of Ezrin in metabolic reprogramming of colon adenocarcinoma remain poorly characterized and need to be explored. METHODS: The expression of Ezrin in colon adenocarcinoma tissues was screened by bioinformatics analysis and immunohistochemical assay. Si-RNA-mediated transfection and overexpression plasmid transfection were performed in colon adenocarcinoma cells. The proliferation viability was measured using MTT, colony formation, and EdU assays. The migration ability was determined using wound healing and transwell assay. The expression of EMT markers and transcriptional factors was detected using immunofluorescence staining and western blot assays. Glucose uptake, lactate production, and ATP assay were performed to validate the effect of Ezrin on glycolysis-mediated colon adenocarcinoma progression. RESULTS: Ezrin was upregulated in colon adenocarcinoma tissues and associated with poor survival. Ezrin stimulated colon adenocarcinoma cell proliferation, migration, and the process of EMT. Ezrin aroused significant increase in glucose uptake, lactate production, and ATP level in colon adenocarcinoma cells. Further investigations demonstrated that treatment with a glycolytic inhibitor 2-deoxy-d-glucose reversed the effects reduced by Ezrin on colon adenocarcinoma cells. CONCLUSIONS: Our results evidenced a novel mechanism for colon adenocarcinoma cells proliferation and migration induced by Ezrin via glycolysis.

Multilevel oxygen-vacancy conductive filaments in ß-Ga2O3 based resistive random access memory.

ß-Ga2O3 has recently attracted considerable attention for its application in resistive switching memory. However, the resistive behaviors and mechanisms of ß-Ga2O3 memory dominated by the oxygen-vacancy (VO) still remain controversial. In this study, we systemically investigated the formation process of VO conductive filaments in ß-Ga2O3 memory. There were at least three kinds of VOs and conductive filaments with different low resistance states (LRSs) in ß-Ga2O3 memory, suggesting their potential for multilevel storage application. Interestingly, these conductive filaments preferred to be formed along the [010] direction and with a single VO cluster rather than a mixed VO cluster due to the lower single VO cluster formation energy and ellipsoid charge distribution. The lowest migration and activation barriers for different kinds of VOs in +2 charge states (V2+Os) were discrepant and lower than the neutral charge states. Meanwhile, the forward migration energy of VO was different from the reversed migration path, so that the conductive filament formation and rupture were not an inverse process in the experiment. The detailed mechanisms were revealed by the charge density and migration process of these VOs. These results not only revealed the function of the VO conductive filaments in ß-Ga2O3 memory but also predicted the potential of ß-Ga2O3 memory for multilevel storage application.

Ezrin promotes hepatocellular carcinoma progression by modulating glycolytic reprogramming.

Ezrin, one of the ezrin-radixin-moesin (ERM) proteins, is involved in the formation of cell membrane processes and has been implicated in the promotion of cancer proliferation and metastasis. However, the possible role of ezrin in hepatocellular carcinoma (HCC) metastasis and glycolysis reprogramming has remained unclear. In this study, we found that ezrin was upregulated in HCC tissues, and its overexpression was linked with HCC patients' aggressive tumor characteristics and poor prognosis. Functional experiments further revealed that ezrin overexpression promoted HCC cell proliferation, epithelial-to-mesenchymal transition (EMT) progression and angiogenesis. In addition, by measuring glucose consumption, lactate production, ATP levels and the expression of glucose metabolism-related markers in HCC cells, we investigated whether ezrin regulated glucose metabolism. Moreover, 2-deoxy-D-glucose (2-DG) affected ezrin-mediated proliferation, migration and EMT of HCC cells, which suggested that ezrin may, at least in part, promote HCC progression by regulating glycolysis reprogramming. Based on our results, we proposed that ezrin was involved in HCC progression and may be a valid prognostic marker.

Cordycepin Inhibits Cancer Cell Proliferation and Angiogenesis through a DEK Interaction via ERK Signaling in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignant tumor that arises from the epithelial cells of the bile duct and is notorious for its poor prognosis. The clinical outcome remains disappointing, and thus more effective therapeutic options are urgently required. Cordycepin, a traditional Chinese medicine, provides multiple pharmacological strategies in antitumors, but its mechanisms have not been fully elucidated. In this study, we reported that cordycepin inhibited the viability and proliferation capacity of CCA cells in a time- and dose-dependent manner determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay. Flow cytometry and Hoechst dye showed that cordycepin induced cancer cell apoptosis via extracellular signal-regulated kinase (ERK) 1/2 deactivation. Moreover, cordycepin significantly reduced the angiogenetic capabilities of CCA in vitro as examined by tube formation assay. We also discovered that cordycepin inhibited DEK expression by using Western blot assay. DEK serves as an oncogenic protein that is overexpressed in various gastrointestinal tumors. DEK silencing inhibited CCA cell viability and angiogenesis but not apoptosis induction determined by Western blot and flow cytometry. Furthermore, cordycepin significantly inhibited tumor growth and angiogenic capacities in a xenograft model by downregulating the expression of DEK, phosphorylated ERK1/2 CD31 and von Willebrand factor (vWF). Taken together, we demonstrated that cordycepin inhibited CCA cell proliferation and angiogenesis with a DEK interaction via downregulation in ERK signaling. These data indicate that cordycepin may serve as a novel agent for CCA clinical treatment and prognosis improvement. SIGNIFICANCE STATEMENT: Cordycepin provides multiple strategies in antitumors, but its mechanisms are not fully elucidated, especially on cholangiocarcinoma (CCA). We reported that cordycepin inhibited the viability of CCA cells, induced apoptosis via extracellular signal-regulated kinase 1/2 deactivation and DEK inhibition, and reduced the angiogenetic capabilities of CCA both in vivo and in vitro.

Mortalin contributes to colorectal cancer by promoting proliferation and epithelial-mesenchymal transition.

This study focused on the expression of mortalin in colorectal cancer (CRC). Mortalin activated the Wnt/ß-catenin pathway to accelerate cell proliferation and the epithelial-mesenchymal transition (EMT) program. Data from online databases displayed that the expression of mortalin was high in CRC, which was further validated using clinical specimens. Meanwhile, high mortalin expression was positively associated with a poor overall survival rate. Suppression of mortalin inhibited CRC cell proliferation as evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, and immunofluorescence staining assays. In addition, depletion of mortalin inhibited CRC cell EMT progression and deactivated the Wnt/ß-catenin pathway. Altogether, mortalin is highly expressed in CRC and may indicate a poor prognosis. Mortalin accelerated CRC progression by stimulating cell proliferation and the EMT program. This study may provide a potential clinical therapeutic target for CRC.

Modulation of the transport properties of metal/MoS2 interfaces using BN-graphene lateral tunneling layers.

Modulating the n- and p-type interfacial charge transport properties of the metal-semiconductor interface is vital to realizing high performance two-dimensional material nanodevices and is still a significant challenge. Here, a boron nitride (BN)-graphene lateral heterostructure (LH) was used as the interfacial tunneling layer to control the Schottky barrier, Fermi level pinning and charge injection efficiency of the metal-MoS2 interface. The BN-graphene LH with graphene-N junction structure decreased the n-type vertical Schottky barrier and enhanced the interfacial tunneling probability, while the graphene-B junction structure decreased the p-type vertical Schottky barrier. Consequently, the n-type Au/LH-MoS2 interface with Ohmic character and high tunneling probability (∼0.242) and the p-type vertical Schottky barrier of about 0.20 eV for the Pt/LH-MoS2 interface were achieved. Compared to other reported BN or graphene tunneling layers, such a BN-graphene LH tunneling layer not only suppressed the charge scattering from the metal electrode to the MoS2 layer and the Fermi level pinning effect, but also reduced the contact resistance between metal electrode and tunneling layer. The underlying mechanisms were revealed to be due to the charge transfer, orbitals and interfacial dipole. This work improves the current understanding of the metal-MoS2 interface and proposes a new way to overcome the current severe contact issues for future nanoelectronic and optoelectronic applications.

Role of Paip1 on angiogenesis and invasion in pancreatic cancer.

Poly(A)-binding protein-interacting protein 1 (Paip1) was discovered as a modulator of translation initiation as a result of binding to PABP. Increasing evidence suggested that Paip1 has been implicated in several pathogenic roles. However, its clinical significance and underlying molecular mechanisms in Pancreatic cancer (PC) remain uncertain. In our present study, we found that Paip1 was over-expressed in human PC tissues. As well as poor survival, the over-expression of Paip1 was associated with lymph node (LN) metastasis of the PC samples analyzed. Paip1 silencing inhibits PC cell proliferation, metastasis, and angiogenesis, whereas over-expression of Paip1 produces the opposite effects. In all, we proposed that Paip1 contributes to PC progression and appears to be a valid prognostic factor of PC.

Ezrin promotes breast cancer progression by modulating AKT signals.

BACKGROUND: Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear. METHODS: Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression. RESULTS: In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC. CONCLUSIONS: In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

Role of community health service programs in navigating the medical ethical slippery slope-a 10-year retrospective study among medical students from southern China.

BACKGROUND: For promoting autonomous learning motivation, the learning effect of community-oriented service is beneficial, because through community participation and service, students can transfer their implicit cognition of ethics into explicit cognition, leading to the cultivation of a sympathetic partnership between the community and medical students. Despite the proven benefits of medical students' community health service (CHS) in Western countries, CHS programs designed for medical students are not well established in mainland China, and their effects on medical students' ethical cognition are largely unknown. This study evaluated the effects of CHS programs on the ethical cognition of medical students. METHODS: A cross-sectional study was conducted on third- and fourth-year medical students and graduates working at Shantou University Medical College by using a self-administered anonymous questionnaire. Through interviews, we applied a thematic approach to analyze the responses of the participating students. The questionnaire adopted in this study was revised based on a review of the literature on medical ethics in medical students and on the CHS environment in China. The reviewed questionnaires included an evaluation questionnaire on cultivating medical ethics in a CHS context, and questionnaires used to explore the cultivation and transformation of medical ethics in medical students during the preclinical period. RESULTS: A total of 361 (54.4%) undergraduate medical students and 302 (45.6%) graduates participated in this survey. Significant differences were observed in self-evaluation of the cognitive development of ethics between those who had participated in CHS programs 1-5 times and those who had participated > 6 times. The successful identification of accepting money from the patients under the table as unethical behavior significantly differed (p = .031) among the graduates but not (p = .567) among the undergraduate students. The participants expressed the positive impact of CHS programs on their self-development. CONCLUSION: CHS programs can be widely applied in medical education in China. This educational strategy, which supports medical professionalism and incorporates humanitarian behavior as a complement to learning, should be encouraged and promoted nationally.

Amino Nitrogen Quantum Dots-Based Nanoprobe for Fluorescence Detection and Imaging of Cysteine in Biological Samples.

Fluorescent amino nitrogen quantum dots (aN-dots) were synthesized by microwave-assisted method using 2-azidoimidazole and aqueous ammonia. The aN-dots have a nitrogen component up to 40%, which exhibit high fluorescence quantum yield, good photostability, and excellent biocompatibility. We further explored the use of the aN-dots combined with AuNPs as a nanoprobe for detecting fluorescently and imaging of cysteine (Cys) in complex biological samples. In this sensing system, the fluorescence of aN-dots was quenched significantly by gold nanoparticles (AuNPs), while the addition of Cys can lead to the fluorescence signal recovery. Furthermore, we have demonstrated that this strategy can offer a rapid and selective detection of Cys with a good linear relationship in the range of 0.3-3.0 µmol/L. As expected, this assay was successfully applied to the detection of Cys in human serum and plasma samples with recoveries ranging from 90.0% to 106.7%. Especially, the nanoprobe exhibits good cell membrane permeability and excellent biocompatibility by CCK-8 assay, which is favorable for bioimaging applications. Therefore, this fluorescent probe ensemble was further used for imaging of Cys in living cells, which suggests our proposed method has strong potential for clinical diagnosis. As a novel member of the quantum-dot family, the aN-dots hold great promise to broaden applications in biological systems.

HBXIP suppression reduces cell proliferation and migration and its overexpression predicts poor prognosis in non-small-cell lung cancer.

Emerging evidence has demonstrated that the high expression of HBXIP has been correlated with many cancers. With evaluation of the functional role of HBXIP in non-small-cell lung cancer, the primary aim of this study is to investigate the correlation between HBXIP expression and the prognosis of non-small-cell lung cancer patients. The protein levels of HBXIP were detected using western blotting in non-small-cell lung cancer cells. Cell proliferation and migration assays were measured to evaluate the function of HBXIP in non-small-cell lung cancer cells. A total of 120 non-small-cell lung cancer patients with strict follow-up and 60 adjacent non-tumor lung tissues were selected for immunohistochemical staining of the HBXIP protein. The localization of the HBXIP protein was detected in A549 non-small-cell lung cancer cells using immunofluorescence staining. The correlation between HBXIP expression and the clinicopathological features of non-small-cell lung cancer patients was analyzed by a chi-squared and Fisher's exact test. The overall survival rates of all of the non-small-cell lung cancer patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In function, we showed that suppression of HBXIP decreased A549 cell proliferation and migration. HBXIP protein showed a mainly cytoplasmic staining pattern in non-small-cell lung cancer using immunohistochemical staining in paraffin-embedded non-small-cell lung cancer tissues and immunofluorescence staining in A549 cells. The HBXIP protein had strong positive staining in the non-small-cell lung cancer tissues, which was significantly higher than the percentage of adjacent non-tumor tissues. The overexpression of HBXIP was closely correlated with histological grade, clinical stage, lymph node metastasis, and lower overall survival rates of patients with non-small-cell lung cancer. Moreover, multivariate analysis suggested that HBXIP emerged as a significant independent prognostic factor along with clinical stage in patients with non-small-cell lung cancer. In conclusion, a high level of expression of HBXIP is associated with the progression of non-small-cell lung cancer and may be a useful biomarker for poor prognostic evaluation and a potential molecular therapy target for patients with non-small-cell lung cancer.