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DNA double-strand breaks (DSBs) play an important role in promoting genomic instability and cell death. The precise repair of DSBs is essential for maintaining genome integrity during cancer progression, and inducing genomic instability or blocking DNA repair is an important mechanism through which chemo/radiotherapies exert killing effects on cancer cells. The two main pathways that facilitate the repair of DSBs in cancer cells are homologous recombination (HR) and non-homologous end-joining (NHEJ). Accumulating data suggest that the acetylation and deacetylation of DSB repair proteins regulate the initiation and progression of the cellular response to DNA DSBs, which may further affect the chemosensitivity or radiosensitivity of cancer cells. Here, we focus on the role of acetylation/deacetylation in the regulation of ataxia-telangiectasia mutated, Rad51, and 53BP1 in the HR pathway, as well as the relevant roles of PARP1 and Ku70 in NHEJ. Notably, several histone deacetylase (HDAC) inhibitors targeting HR or NHEJ have been demonstrated to enhance chemo/radiosensitivity in preclinical studies. This review highlights the essential role of acetylation/deacetylation in the regulation of DSB repair proteins, suggesting that HDAC inhibitors targeting the HR or NHEJ pathways that downregulate DNA DSB repair genes may be worthwhile cancer therapeutic agents., Graphical Abstract

The integrity of the epidermal barrier and the maintenance of barrier homeostasis depend on the dynamic balance between the proliferation and differentiation of keratinocytes. Calcium (Ca2+) plays a crucial role in maintaining a balance of these two processes as well as in the formation of an epidermal permeability barrier. In this study, we showed that topical application of oat β-glucan (OG) could ameliorate epidermal hyperplasia and accelerate the recovery of the epidermal barrier by promoting epidermal differentiation. Mechanistic studies revealed a positive interaction between OG and the dectin-1 receptor, and this interaction could lead to an upregulated expression of the calcium-sensing receptor (CaSR) via activation of the downstream ERK and p38 pathways. This consequently increased the sensitivity of keratinocytes to extracellular Ca2+ under the condition of calcium loss following the disruption of the epidermal barrier, resulting in the maintenance of normal keratinocyte differentiation in the epidermis, and ultimately promoting the recovery of the epidermal barrier. These findings clearly demonstrated the healing effect of OG on a physically damaged epidermal barrier. Thus, OG could be considered a valuable component in the development of skin repair agents.

Ferroptosis is a newly identified cell death mechanism and potential biomarker for hepatocellular carcinoma (HCC) therapy; however, its clinical relevance and underlying mechanism remain unclear. In this study, transcriptome and methylome data from 374 HCC cases were investigated for 41 ferroptosis‐related genes to identify ferroptosis activity‐associated subtypes. These subtypes were further investigated for associations with clinical and pathological variables, gene mutation landscapes, deregulated pathways and tumour microenvironmental immunity. A gene expression signature and predictive model were developed and validated using an additional 232 HCC cases from another independent cohort. Two distinct ferroptosis phenotypes (Ferroptosis‐H and Ferroptosis‐L) were identified according to ferroptosis gene expression and methylation in the patients with HCC. Patients with the Ferroptosis‐H had worse overall and disease‐specific survival, and the molecular subtypes were significantly associated with different clinical characteristics, mRNA expression patterns, tumour mutation profiles and microenvironmental immune status. Furthermore, a 15‐gene ferroptosis‐related prognostic model (FPM) for HCC was developed and validated which demonstrated accurate risk stratification ability. A nomogram included the FPM risk score, ECOG PS and hepatitis B status was developed for eventual clinical translation. Our results suggest that HCC subtypes defined by ferroptosis gene expression and methylation may be used to stratify patients for clinical decision‐making.

Metabolic syndrome (MetS) is characterized by a group of metabolic disturbances which leads to the enhanced risk of cancer development. Elucidating the mechanisms between these two pathologies is essential to identify the potential therapeutic molecular targets for colorectal cancer (CRC). 716 colorectal patients from the First and Second Affiliated Hospital of Wenzhou Medical University were involved in our study and metabolic disorders were proven to increase the risk of CRC. The prognostic value of the MetS factors was analyzed using the Cox regression model and a clinical MetS-based nomogram was established. Then by using multi-omics techniques, the distinct molecular mechanism of MetS genes in CRC was firstly systematically characterized. Strikingly, MetS genes were found to be highly correlated with the effectiveness of targeted chemotherapy administration, especially for mTOR and VEGFR pathways. Our results further demonstrated that overexpression of MetS core gene IL6 would promote the malignancy of CRC, which was highly dependent on mTOR-S6K signaling. In conclusion, we comprehensively explored the clinical value and molecular mechanism of MetS in the progression of CRC, which may serve as a candidate option for cancer management and therapy in the future.

Rapid industrialization has inevitably led to serious air pollution problems, thus it is urgent to develop detection and treatment technologies for qualitative and quantitative analysis and efficient removal of harmful pollutants. Notably, the employment of functional nanomaterials, in sensing and photocatalytic technologies, is promising to achieve efficient in situ detection and removal of gaseous pollutants. Among them, carbon dots (CDs) have shown significant potential due to their superior properties, such as controllable structures, easy surface modification, adjustable energy band, and excellent electron-transfer capacities. Moreover, their environmentally friendly preparation and efficient capture of solar energy provide a green option for sustainably addressing environmental problems. Here, recent advances in the rational design of CDs-based sensors and photocatalysts are highlighted. An overview of their applications in air pollutants detection and photocatalytic removal is presented, especially the diverse sensing and photocatalytic mechanisms of CDs are discussed. Finally, the challenges and perspectives are also provided, emphasizing the importance of synthetic mechanism investigation and rational design of structures.

Intrahepatic cholangiocarcinoma (ICC) is a malignancy with a hidden onset, high metastasis recurrence rate, and poor prognosis. Research on effective drugs for ICC is important for improving the prognosis of patients in the clinic. Brusatol is a quassinoid extracted from the seeds of Brucea sumatrana and has been shown to have the potential to inhibit tumor metastasis and proliferation. There has been no scientific research on the therapeutic effect of brusatol on ICC. Our study offers a novel strategy for the therapy of ICC.Explore effects of brusatol treatment on ICC and clarify the possible mechanism.Various cell functional experiments and basic experimental techniques were applied to ICC cell lines to explore the influences of brusatol on ICC cells; this conclusion was further verified in animal models.The anti-cancer effects of the drug on the cell, protein, and RNA level were verified by cell functional experiments, WB blotting and transcriptome sequencing experiments, respectively. Finally, the experimental results were verified using subcutaneous tumor experiments in nude mice.The consequences exhibited that the levels of epithelial markers of ICC cells increased after brusatol treatment, and the levels of interstitial indicators decreased, suppressing the epithelial-mesenchymal transition (EMT) process. Brusatol inhibited proliferation, induced apoptosis, and suppressed the migration and invasion abilities of Hucc-T1 and RBE oncocytes via activating PI3K/Akt pathway. It also suppressed the growth of Hucc-T1 xenografts in nude mice.Brusatol inhibits the proliferation and EMT process in ICC oncocytes by the PI3K/Akt pathway and promotes apoptosis in oncocytes.

Background: Lipid metabolism has a profound impact on gastric cancer (GC) progression and is a newly targetable vulnerability for cancer therapy. Given the importance of lipids in cancer cellular processes, in this study we employed lipidomic clinical and transcriptomic data of GC to connect the variations of lipid metabolism changes.Method: We constructed a clinical nomogram based on the lipid factors and other clinical items. Then by using multi-omics techniques, we established a lipid-related gene signature for individualized prognosis prediction in patients with GC. Moreover, a total of 1357 GC cases were then applied to evaluate the robustness of this model. WGCNA was used to identify co-expression modules and enriched genes associated with GC lipid metabolism. The role of key genes ACLY in GC was further investigated.Results: The prognostic value of the lipidomic signature was analyzed using Cox regression model, and clinical nomogram was established. Among them, we observed overexpression of ACLY significantly increased the levels of intracellular free fatty acid and triglyceride, and activate AKT/mTOR pathway to promote cancer development.Conclusions: In conclusion, our findings delineated a GC clinical and lipidomic signature and revealed that GC exhibited a reprogramming of lipid metabolism in association with an altered expression of lipid metabolism-associated genes. Among them, ACLY significantly promoted GC lipid metabolism and increased cancer cell proliferation, suggesting that this pathway can be targetable as a metabolic vulnerability in future GC therapy.

Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases. Recent advances in three-dimensional cell culture technology (organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.

Background Intrahepatic cholangiocarcinoma (ICC) is a malignant neoplasm with a poor prognosis. Prediction of prognosis is critical for the individualized clinical management of patients with ICC. The purpose of this study is to establish a nomogram based on the psoas muscle index (PMI) and prognostic nutritional index (PNI) to identify the high risk-patient with ICC after curative resection. Methods ICC Patients after hepatectomy in multi-hospital from August 2012 to October 2019 were enrolled. The overall survival (OS) and recurrence-free survival (RFS) rates were analyzed by Kaplan-Meier. The independent factors were identified by univariate and multivariate Cox regression analyses. A nomogram based on independent factors was established to predict ICC patient prognosis. Results 178 ICC patients were included. The OS was worst in the patients with a combination of low PMI combined low PNI (p p༜0.001). Conclusion The nomogram based on the PMI and PNI can identify patients with the highest risk of poor prognosis after curative hepatectomy. It is a good decision-making tool for individualized treatment.

BACKGROUND: Exposure to ultraviolet (UV) radiation (UVB and UVA) is the most well-known extrinsic factor that induces skin aging. Fucoidan has been shown to possess antiphotoaging effects against UV irradiation and can be used as an ingredient in the pharmaceutical industry. The present study evaluated the photoprotective effect of fucoidan purified from Undaria pinnatifida (UPF) on UV-induced skin photoaging and explored its potential molecular mechanism. METHODS: To evaluate the effect of UPF on UV-induced skin aging, HaCaT cells and HFF-1 cells were pretreated with or without UPF and then exposed to UVB and UVA radiation, respectively, and the levels of cellular senescence, reactive oxygen species (ROS) production and mitochondrial dysfunction were evaluated. The mitochondrial ROS (mROS) was stained through MitoSOX, and the confocal microscope was used to capture the images. For further exploration of AMPK/SIRT-1/PGC-1α signaling, western blot was employed. RESULTS: The results demonstrated that pretreatment of HaCaT and HFF-1 cells with UPF ameliorated cellular senescence, ROS and mROS overproduction, and mitochondrial dysfunction caused by UV exposure. This research also revealed that UPF could activate the AMPK/SIRT-1/PGC-1α signaling pathway to promote mitochondrial biogenesis. CONCLUSIONS: UPF can ameliorate UV-induced skin photoaging through inhibition of ROS production via the alleviation of mitochondrial dysfunction by regulating the SIRT-1/PGC-1α signaling pathway.

Background Liver cancer stem cells (LCSCs) play key roles in the metastasis, recurrence, and chemotherapeutic resistance of hepatocellular carcinoma (HCC). Our previous research showed that the POSTN gene is closely related to the malignant progression and poor prognosis of HCC. This study aimed to elucidate the role of POSTN in generating LCSCs and maintaining their stemness as well as the underlying mechanisms. Methods Human HCC tissues and matched adjacent normal tissues were obtained from 110 patients. Immunohistochemistry, western blotting (WB), and RT-PCR were performed to detect the expression of POSTN and stemness factors. The roles of transforming growth factor (TGF)-β1 and AP-2α in the POSTN-induced stemness transformation of HCC cells were explored in vitro and in vivo using LCSCs obtained by CD133+ cell sorting. Results The high expression of POSTN was correlated with the expression of various stemness factors, particularly CD133, in our HCC patient cohort and in TCGA and ICGC datasets. Knockdown of POSTN expression decreased the abilities of HCC cell lines to form tumours in xenograft mouse models. Knockdown of POSTN expression also suppressed cell viability and clone formation, invasion, and sphere formation abilities in vitro. Knockdown of AP-2α attenuated the generation of CD133+ LCSCs and their malignant behaviours, indicating that AP-2α was a critical factor that mediated the POSTN-induced stemness transformation and maintenance of HCC cells. The role of AP-2α was verified by using a specific αvβ3 antagonist, cilengitide, in vitro and in vivo. Activation of POSTN could release TGFβ1 from the extracellular matrix and initiated POSTN/TGFβ1 positive feedback signalling. Furthermore, we found that the combined use of cilengitide and lenvatinib suppressed the growth of HCC cells with high POSTN expression more effectively than the use of lenvatinib alone in the patient-derived xenograft (PDX) mouse model. Conclusions The POSTN/TGFβ1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.

Background: Chemotherapeutic resistance remains a major challenge for treating Pancreatic ductal adenocarcinoma (PDAC) with gemcitabine, which is a classical anticancer agent used to induce apoptosis. Ferroptosis, a recently recognised regulated mechanism of necrotic cell death, plays an important role in overcoming resistance to current chemotherapy. Methods: DPP4 expression status was evaluated in PDAC tissues using tissue chip immunohistochemistry. The effects of DPP4 re-expression on cell proliferation, the cell cycle and energy metabolism were determined. DPP4-related cancer pathways by RNA-seq analyses, and DPP4 interacting protein was identified by Co-IP and His pull-down. The clinical impact of DPP4 in driving ferroptosis and enhancing gemcitabine resistance was assessed in wild-type and DPP4 knock-down (KD) mice orthotopic xenograft models of PDAC. Findings: In this study, DPP4 was expressed at low levels in PDAC. DPP4 significantly inhibited cell proliferation by causing G1–S cell cycle arrest, inhibiting energy metabolism, and promoting PDAC cells death in vitro ; it also suppressed xenograft tumour growth in orthotopic pancreatic cancer transgenic mouse models. Importantly, DPP4-overexpressing cells showed decreased sensitivity to gemcitabine induced apoptosis, however increased sensitivity to erastin induced ferroptosis. Mechanistically, DPP4 increased the levels of Bcl-2 and decreased caspase-3 and BAX in apoptosis, meanwhile facilitated ferroptosis by binding ACSL4, and the DPP4–ACSL4 interaction stabilized ACSL4 by inhibiting its ubiquitin-mediated degradation and subsequent lipid peroxidation. Interpretation: Collectively, these findings identify a novel role of DPP4 in ferroptosis and suggest a potential therapeutic strategy to overcome gemcitabine resistance in PDAC. Funding: This study was supported by the Zhejiang Provincial Natural Science Foundation of China under Grant No. LQ20H160015 to WM Wang. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethics Review Board at the First Affiliated Hospital of Wenzhou University Hospital.

Aims The functions and molecular mechanisms of miR-340-3p in lung adenocarcinoma (LUAD) progression remain unclear. On the other hand, the role of HUS1 in LUAD progression should be further explored. Main methods Data from cancer database were subjected to bioinformatics analysis. Quantitative real-time PCR and western blot were performed to detect gene expression. Colony formation and MTT assay were performed to examine cell growth in vitro. Wound healing assays and transwell assays were performed to examine cell migration. Key findings Here, our results showed that miR-340-3p was lower expressed in LUAD tissues and LUAD-derived cell lines. And miR-340-3p suppressed the proliferation and migration ability of LUAD cells. Further, miR-340-3p inhibits HUS1 expression, which was higher expressed in LUAD tissues and promoted the proliferation and migration ability of LUAD cells. Moreover, higher HUS1 expression was associated with poor survival rate and shorter survival time in patients with LUAD, and HUS1 expression was negative correlated with that of miR-340-3p in clinical samples. In addition, overexpression of HUS1 counteracted the downregulation of cell growth by miR-340-3p. Significance The study mainly indicated that miR-340-3p may play a tumor suppressor role in the progression of LUAD, with the function of restraining HUS1 expression, highlighting a potential therapeutic target for LUAD.

Background: Macrophages can selectively recognize and eliminate senescent cells, but this function is impaired with age, resulting in excessive accumulation of senescent cells in the skin, which ultimately causes skin aging. Therefore, enhancing the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts from aging skin may be an effective skin rejuvenation strategy.Methods: In this study, a macrophage and senescent skin cell co-culture model was established whereby THP-1-derived macrophages and tert-butyl hydroxide-induced senescent skin cells (HaCaT and HFF-1) were grown in the same culture. Senescent skin cells were detected by the SPiDER-βgal assay, and the expression of secretory phenotype factors related to senescence was assayed by qPCR. The effect of carnosine on the number of SA-β-gal positive skin cells in the macrophage-senescent skin cell co-culture was evaluated and compared with that in the senescent skin cell monoculture.Results: Carnosine promoted macrophage-mediated elimination of senescent skin cells in the co-culture. Through the AKT2 signaling pathway, carnosine upregulated the expression of CD36 and receptors for advanced glycation end products and elevated the phagocytic capacity of the macrophages, thereby promoting the ability of the macrophages to eliminate the senescent skin cells.Conclusions: Carnosine could boost the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts in the macrophage-senescent skin cell co-culture by activating the AKT2 signaling pathway, suggesting the possibility of using carnosine as an agent to reverse skin aging.

Acute pancreatitis (AP) is characterized by excessive release of pro-inflammatory cytokines and provokes multiorgan dysfunction. Disruption of the intestinal epithelium often occurs during and following acute pancreatitis and may aggravate systemic organ injuries. Although it has been widely investigated, to date, there is no satisfactory clinical therapy to restore the inflammatory damage. BML-111 is an endogenous lipid mediator that is analogous to LipoxinA4. It has been shown that BML-111 has a stable and potent anti-inflammatory ability. However, it is unclear whether BML-111 is involved in the process of relieving acute pancreatitis and its induced intestinal barrier damage, and the underlying mechanism of this effect. Here, we demonstrated that BML-111 could enhance the expression of E-cadherin, alleviate apoptosis, and mitigate the accumulation of reactive oxygen species in intestinal epithelial cells, thereby contributing to the anti-inflammatory efficacy in vitro and in vivo. Mechanistically, BML-111 upregulates the expression of Nrf2, which is a key regulator of the antioxidant response, and activates its downstream HO-1/NQO-1 pathway to protect against oxidative stress-induced cell death and tissue injury, consequently ameliorating pancreatitis and intestinal epithelium injury. In Nrf2-deficient cell and Nrf2-knockout mouse models, the depletion of Nrf2 blocked BML-111-induced antioxidant effects and thus was unable to exert protective effects in tissue. Taken together, BML-111 attenuated AP-related intestinal injury via an Nrf2-dependent antioxidant mechanism. Targeting this pathway is a potential therapeutic approach for AP-related intestinal injury.

Purpose Recent studies have determined that long non-coding RNAs (lncRNAs) are potential prognostic biomarkers for non-small cell lung cancers (NSCLCs). The purpose of this study was to analyze the function and associated pathways of zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) in NSCLC cells. Methods We used qRT-PCR to analyze ZFPM2-AS1’s transcription level. Its proliferation, migration, and invasion capacities were determined using MTT, colony forming, wound healing, and transwell assays. We additionally analyzed the correlation between ZFPM2 and immune infiltration using the Tumor Immune Estimation Resource (TIMER) database, and the protein expression levels using Western blots. Results We found that ZFPM2-AS1 expression in NSCLC specimens and cell lines was elevated compared to the control group. ZFPM2-AS1 is an oncogene and independent prognostic predictor of poor survival in NSCLCs, and its expression had a positive correlation with tumor size and lymph node metastasis in our clinical data. MTT, colony forming, wound healing, and transwell assays showed a positive correlation between ZFPM2-AS1 expression and the proliferation, migration, and invasion of NSCLC cells in the presence and absence of interferon- (IFN-γ). Using the TIMER database, we hypothesized that ZFPM2 was negatively correlated with ZFPM2-AS1 expression, as well as the immune infiltration levels in lung adenocarcinoma (LUAD). Finally, we found that ZFPM2-AS1 negatively regulated ZFPM2 expression, and had a positive correlation with PD-L1 expression through the JAK-STAT and AKT pathways. Conclusion Our study confirmed that ZFPM2-AS1 promotes the proliferation, migration, and invasion of NSCLC cells via the JAK-STAT and AKT pathways. Further research on the ZFPM2-AS1 pathway regulation mechanism is needed.

Intrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer with dismal survival rates. This study aimed to explore the prognostic value of sarcopenia combine with hepatolithiasis in surgically treated ICC patients and develop a prognostic nomogram to help make clinical decisions.A prospective cohort study was conducted including patients who underwent hepatectomy for ICC between August 2012 and October 2019. The association between the sarcopenia combined with hepatolithiasis and survival, including overall survival (OS) and recurrence-free survival (RFS) was investigated using the Kaplan-Meier (K-M) method. Univariable and multivariable Cox regression analysis was performed to determine the independent prognostic factors and a nomogram establishment was undertaken based on the multivariable analysis.A total of 121 ICC patients were included in the study. K-M analysis revealed that ICC patients with sarcopenia and hepatolithiasis have worse OS and RFS than those without sarcopenias and/or hepatolithiasis (p 0.01). Multivariable analysis showed that age, serum CEA, hepatolithiasis, sarcopenia and diabetes were independent prognostic factors for OS(p 0.05). Finally, a nomogram with good performance in survival prediction was established (C-index was 0.721; the area under the curve of OS was 0.837). The stratified analysis based on the nomogram disclosed that the median OS was 11.9 months in high-risk patients and 51.2 months in low-risk patients (p 0.001).ICC patients with sarcopenia and hepatolithiasis have worse OS and RFS. The nomogram we developed is a practical tool that can provide a more individualized risk assessment for surgically treated ICC patients.

Breast cancer threatened the health of millions of people around the world. Here we explored the influence of TCDD on the expression of circRNA_BARD1 (circ_0001098) in breast cancer and studied the potential molecular mechanism of circRNA_BARD1. The data from GSE76608 was applied to analyze differentially expressed circRNAs and mRNAs. The expressions of circRNA_BARD1, BARD1, miR-3942-3p, miR-4760-3p and apoptosis-related protein p53 were detected by qRT-PCR or western blot. Circinteractome, TargetScan, CIRCNET and dual luciferase reporter assay were employed to uncover the target relationship between circRNA_BARD1/BARD1 and miR-3942-3p/miR-4760-3p. Flow cytometric analysis was used to reveal cell cycle and cell apoptosis. Immunofluorescence was applied to determinate γ-H2AX level. Xenograft assay and in vivo 3-D imaging was implemented to further verify the conclusions in vitro. CircRNA_BARD1 (circ_0001098) was up-regulated in breast cancer with the treatment of TCDD and the up-regulation of circRNA_BARD1 could restrain cell proliferation, block cell cycle and promote cell apoptosis. Moreover, the target relationship between circRNA_BARD1/BARD1 and miR-3942-3p was confirmed. In addition, miR-3942-3p overexpression promoted the disease progression and BARD1 up-regulation inhibited the disease progression in the breast cancer. Similarly, circRNA_BARD1 overexpression induced by TCDD suppressed the growth and metastasis of tumor in vivo. In conclusion, TCDD induced circ_0001098 overexpression and then suppressed breast cancer tumorigenesis via miR-3942-3p/BARD1 axis. The finding of TCDD-circRNA-miRNA-mRNA axis might bring a new perspective for cure strategy of breast cancer.

Intrinsic cancer cells and the tumor-infiltrating immune cells (TIICs) recruited to the immune microenvironment define the malignant phenotype of lung squamous cell carcinoma (LUSC). Understanding more about the immune microenvironment of LUSC enables the selection of high-risk patients who would derive benefit from immunotherapy. Based on large public LUSC cohorts obtained from TCGA and GEO datasets, 22 types of infiltrating immune cell subgroups were evaluated by CIBERSORT. Meta-analysis, principal component analysis (PCA), single-sample gene set enrichment analysis (ssGSEA), and hierarchical clustering analysis were used to evaluate specific immune responses of LUSC. The distribution of TIICs of LUSC was entirely different from normal. TIIC subpopulations were also found to be closely associated with clinical features and molecular subtypes. Unsupervised clustering analysis revealed that three distinct TIIC subgroups existed with different survival patterns. TIICs are extensively implicated in the pathogenesis and development of LUSC. Characterizing the composition of TIICs influences the metabolism, pathological stage, and survival of tumor patients. It is hoped that this immune landscape could provide a more accurate understanding of the development and immunotherapy of LUSC.

Cardiac epithelioid hemangioendothelioma (EHE) is a very rare tumour of endothelial origin with the lung and liver as the most easily metastatic organs. We describe herein a patient with hemoptysis, severe anaemia, and diffuse pulmonary nodules with halo signs that represented metastasis of cardiac EHE; these radiologic manifestations are relatively uncommon. During the initial workup for the patient's pulmonary nodules, echocardiography missed the cardiac mass. However, positron emission tomography-computed tomography revealed increased fluorodeoxyglucose intake in the right atrial wall, and cardiac magnetic resonance imaging (MRI) revealed an irregular nodule with normal T1-weighted signal intensity and hyperintense T2-weighted signal intensity. Enhanced abdominal computed tomography (CT) revealed micronodular liver metastases. Video-assisted thoracic surgery was performed to make a definitive diagnosis. Immunohistochemistry staining proved the diagnosis of EHE with positive results for cluster of differentiation (CD) 34, CD31, erythroblast transformation-specific-related gene and Ki-67. The patient started chemotherapy with docetaxel (75 mg/m2 ) and gemcitabine (900 mg/m2 ), but this failed to control his disease and he died from an opportunistic infection related to his immunocompromised status 5 months later. For the work out process of bilateral diffuse pulmonary nodules suspicious for cardiac origin, especially with atrial deviation, echocardiography alone is not sufficient to exclude atrial origin. Cardiac CT or MRI might be a better choice.

Background: RUFY3 (RUN and FYVE domain-containing protein 3) has been shown to participate in cell migration, membrane transportation, and cellular signaling and is dysregulated in several cancer processes. However, the role of RUFY3 in lung cancer remains unclear. In the present study, we aimed to study the expression of RUFY3 and assess its clinical significance in lung adenocarcinoma. Materials and Methods: We used immunohistochemistry to detect RUFY3 protein expression in human lung adenocarcinoma and adjacent normal lung tissue from 125 patients who underwent surgical resection of the lung cancer. RUFY3 expression was assessed in association with clinicopathological characteristics and clinical prognosis of lung adenocarcinoma patients. The expression of RUFY3 in three different lung adenocarcinoma cell lines and one normal lung epithelial cell (BEAS-2B) was detected by western blot. RNAi technique was used to silence RUFY3. We assessed cell migration by Trans-well assay and wound healing assay. Results: In lung adenocarcinoma tissues, RUFY3 protein was significantly upregulated compared to paired normal lung tissues. High cytoplasmic RUFY3 levels were associated with lymph node metastasis, TNM staging, and survival status. Patients with the highest expression level of RUFY3 had a shorter survival time than patients with the lowest expression. Inhibition of RUFY3 by siRNA inhibited cell migration. Furthermore, silence of RUFY3 lead to up-regulation of E-cadherin, but down-regulation of N-cadherin, Vimentin and Slug. Conclusions: Our study is first to demonstrated that abnormal expression of RUFY3 indicates poor prognosis in lung adenocarcinoma and also indicates that RUFY3 may be related to EMT process. This highlights the potential of RUFY3 as a novel prognostic biomarker for lung adenocarcinoma.

Background Atrial fibrillation (AF) is a common complication after radical surgery of esophageal cancer. The aim of this study was to explore AF risk factors after radical surgery of esophageal carcinoma. Method The data of 335 patients with esophageal cancer who were admitted in our hospital from January 2014 to August 2016 for the first time were retrospectively analyzed. We retrieved the papers in some data banks using the search terms including English and Chinese search terms, and obtained 13 factors which were mentioned in more than 6 papers. The 13 factors including age, gender, history of smoking, history of hypertension, history of peripheral vascular disease, history of cardiac stents or angina pectoris, preoperative pulmonary infection, preoperative brain natriuretic peptide (BNP) level, preoperative left ventricular diastolic dysfunction, operative method, lesion location, intraoperative blood transfusion, adhesion between lymph nodes and pericardium, underwent univariate and multivariate analyses. Results Of the 335 patients with esophageal cancer, 48 had AF within one week after operation. Univariate analysis indicated that the age (OR: 4.89; CI: 2.53–9.47, P: 0.000), gender (OR: 2.26; CI: 1.17–4.37, P: 0.013), history of peripheral vascular disease (OR: 2.29; CI: 1.06–4.92, P: 0.030), history of cardiac stents or angina pectoris (OR: 27.30; CI: 12.44–59.91, P: 0.000), preoperative BNP level (OR: 27.13; CI: 10.97–67.06, P: 0.000), preoperative left ventricular diastolic dysfunction (OR: 2.22; CI: 1.19–4.14, P: 0.012), operative method (OR: 2.09; CI: 1.002–4.380, P: 0.046), intraoperative blood transfusion (OR: 20.24; CI: 8.39–48.82, P: 0.000), and adhesion between lymph nodes and pericardium were risk factors (OR: 2.05; CI: 1.08–3.87, P: 0.024). Furthermore, multivariate analysis displayed that advanced age (OR: 5.044; CI: 1.748–14.554, P: 0.003), male (OR: 6.161; CI: 2.143–17.715, P: 0.001), history of cardiac stents or angina pectoris (OR: 48.813; CI: 13.674–174.246, P: 0.000), preoperative BNP > 100 (OR: 41.515; CI: 9.380–183.732, P: 0.000), open surgery (OR: 3.357; CI: 1.026–10.983, P: 0.045), intraoperative blood transfusion (OR: 58.404; CI: 10.777–316.509, P: 0.000), and adhesion between lymph nodes and pericardium (OR: 3.954; CI: 1.364–11.459, P: 0.011) were risk factors which could increase the incidence of postoperative AF. Conclusion We should pay attention to the above risk factors in order to reduce the incidence of postoperative AF.

Background Exposure to ultraviolet (UV) radiation (UVB and UVA) is the most well-known extrinsic factor that induces skin aging. Fucoidan has been shown to possess antiphotoaging effects against UV irradiation and can be used as an ingredient in the pharmaceutical industry. The present study evaluated the photoprotective effect of fucoidan purified from Undaria pinnatifida (UPF) on UV-induced skin photoaging and explored its potential molecular mechanism. Methods To evaluate the effect of UPF on UV-induced skin aging, HaCaT cells and HFF-1 cells were pretreated with or without UPF and then exposed to UVB and UVA radiation, respectively, and the levels of cellular senescence, reactive oxygen species (ROS) production and mitochondrial dysfunction were evaluated. The mitochondrial ROS (mROS) was stained through MitoSOX, and the confocal microscope was used to capture the images. For further exploration of AMPK/SIRT-1/PGC-1α signaling, western blot was employed. Results The results demonstrated that pretreatment of HaCaT and HFF-1 cells with UPF ameliorated cellular senescence, ROS and mROS overproduction, and mitochondrial dysfunction caused by UV exposure. This research also revealed that UPF could activate the AMPK/SIRT-1/PGC-1α signaling pathway to promote mitochondrial biogenesis. Conclusions UPF can ameliorate UV-induced skin photoaging through inhibition of ROS production via the alleviation of mitochondrial dysfunction by regulating the SIRT-1/PGC-1α signaling pathway.

Background Fibroblast growth factor (FGF) 14 is a member of the FGF family that is mainly expressed in the central nervous system. FGF14 has a close association with the occurrence of neurodegenerative conditions; however, its significance in Alzheimer's disease (AD) has yet to be evaluated. Therefore, we sought to obtain a large amount of exogenous FGF14 protein and explore its effect in a cellular model of AD. Methods FGF14 protein was expressed in an Escherichia coli system using gene recombination technology. Purified protein was obtained through washing and renaturation of inclusion bodies combined with nickel column affinity chromatography. The AD model was established via Aβ25-35-induced injury in PC12 cells. Changes in the levels of lactate dehydrogenase and malondialdehyde were detected, and the neuroprotective effect of recombinant human FGF14 (rhFGF14) was evaluated through double-fluorescence staining and flow cytometry apoptosis detection. For further exploration of rhFGF14-mediated regulation of mitogen-activated protein kinase (MAPK) signaling, western blot was employed. Results We successfully induced large amounts of insoluble rhFGF14. Following solubilization and refolding of the rhFGF14 from inclusion bodies, high purity rhFGF14 was purified by Nickel affinity column chromatography. The results showed that rhFGF14 alleviated Aβ25-3-induced PC12 cell injury by inhibiting the phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, thus suppressing the MAPK signaling pathway. Conclusions FGF14 performed a neuroprotective role in our in vitro AD model via its inhibition of MAPK signaling, highlighting its potential as a therapeutic drug for neurodegenerative conditions.

The aim of this study was to prepare a promising drug carrier for treatment of lung cancer. The self-assembly nanoparticles of SDP-GEM/PEI-PEG-anti-EGFR with chemotherapeutic drug of gemcitabine (GEM), Magnetic resonance imaging (MRI) guided- imaging and targeting of anti- Epidermal Growth Factor Receptor (anti-EGFR) were designed. The imaging capacity, targeting feasibility and anti-tumor function were evaluated respectively. SDP-GEM/PEI-PEG-anti-EGFR exhibited contrast enhancement under T2 Weight Image (T2WI) and a liner relationship was found between the concentration and relaxation rate of R2 and R2* in vitro. With the targeting of anti-EGFR, the endocytosis of nanoparticles increased significantly, which effectively killed lung cancer cells in vitro, and importantly it can be accurately delivered to tumor site within 3 h in vivo. Prolonged lifetime and smaller tumor volume demonstrated that SDP-GEM/PEI-PEG-anti-EGFR efficiently inhibited tumor growth in vivo. Therefore, SDP-GEM/PEI-PEG-anti-EGFR was an effective and safe drug carrier, which had a great potential application in MRI-guided lung cancer therapy.

Fine TiO2 has been widely used as a white pigment, but the aggregation of TiO2 particles related to the high specific surface area makes it a challenge to modify its surface. In this paper, NaOH and Na2SiO3 were adopted as regulators for the pH of TiO2 aqueous dispersion. It was discovered that when the pH is 12, the TiO2 particles have the maximum zeta potential and the repulsive force between two TiO2 particles is also at the maximum, which is favourable for the dispersion of TiO2. In terms of the modifying the surface, it was proved that a continuous and compact film of hydrous silica on the surface of TiO2 particles is produced by coprecipitation of Na2SiO3 and H2SO4 when the TiO2 particles are adequately dispersed by ultrasound at pH 12. Furthermore, it was found that the morphology of SiO2 is different when Na2SiO3 and H2SO4 solutions are added in different ways.

Carbon dots (CDs) attract great interests from scientists for their low toxicity and biocompatibility properties and their important applications in the fields of photocatalysts, batteries, bio-images and supercapacitors. Most strategies of making CDs contain several steps, which can be a time-consuming and costly procedure. In this study, nitrogen-doped CDs have been prepared by a one-step hydrothermal strategy with sodium citrate and ethylenediamine as precursors. It is found that fluorescence intensity of CDs is enhanced with the increased content of doped nitrogen, which implies that nitrogen-doped element plays an important role to improve the fluorescence intensity of CDs. Most importantly, those CDs yielded high selectivity of Fe3+, with good linearity, precision and accuracy. Hence, the as-prepared nitrogen-doped CDs could be used as probes for quantitative analysis of Fe3+ in environmental applications.

Sulfur-doped carbon dots (S-doped C-dots)were synthesized using a simple and straightforward hydrothermal method. The as-prepared S-doped C-dots exhibit significant fluorescence quantum yield (67%) and unique emission behavior. The spherical S-doped C-dots have an average diameter of 4.6 nm and the fluorescence of S-doped C-dots can be effectively and selectively quenched by Fe3+ ions. Thus, S-doped C-dots were applied as probes toward Fe3+ detection, exhibiting a limit of detection of 0.1 μM.