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Wen-Yu Zhai,1,2,* Fang-Fang Duan,3,* Yao-Bin Lin,1,2,* Yong-Bin Lin,1,2 Ze-Rui Zhao,1,2 Jun-Ye Wang,1,2 Bing-Yu Rao,1,2 Lie Zheng,4 Hao Long1,2 1Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Medical oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Medical Imaging Division, Department of Medical Imaging and Interventional Radiology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Long, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, and Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email longhao@sysucc.org.cn Lie Zheng, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, and Medical Imaging Division, Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhenglie@sysucc.org.cnBackground: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients’ selection.Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan–Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR.Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response.Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.Keywords: non-small-cell lung cancer, pan-immune-inflammatory value, neoadjuvant immunochemotherapy, pathological complete response, survival benefits

Objectives: To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood., Methods: Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode., Results: The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect., Conclusions: This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.

Costimulatory molecules are an indispensable signal for activating immune cells. However, the features of many costimulatory molecule genes (CMGs) in lung adenocarcinoma (LUAD) are poorly understood. This study systematically explored expression patterns of CMGs in the tumor immune microenvironment (TIME) status of patients with LUAD. Their expression profiles were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Two robust TIME subtypes ("hot" and "cold") were classified by K-means clustering and estimation of stromal and immune cells in malignant tumor tissues using expression data. The "hot" subtype presented higher infiltration in activated immune cells and enrichments in the immune cell receptor signaling pathway and adaptive immune response. Three CMGs (CD80, LTB, and TNFSF8) were screened as final diagnostic markers by means of Least Absolute Shrinkage Selection Operator and Support Vector Machine-Recursive Feature Elimination algorithms. Accordingly, the diagnostic nomogram for predicting individualized TIME status showed satisfactory diagnostic accuracy in The Cancer Genome Atlas training cohort as well as GSE31210 and GSE180347 validation cohorts. Immunohistochemistry staining of 16 specimens revealed an apparently positive correlation between the expression of CMG biomarkers and pathologic response to immunotherapy. Thus, this diagnostic nomogram provided individualized predictions in TIME status of LUAD patients with good predictive accuracy, which could serve as a potential tool for identifying ideal candidates for immunotherapy., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Ground glass opacity (GGO) is associated with favorable survival in lung cancer. However, the relevant evidence of the difference in prognostic factors between GGO and pure-solid nodules for pathological stage I invasive adenocarcinoma (IAC) is limited. We aimed to identify the impact of GGO on survival and find prognostic factor for part-GGO and pure-solid patients., Methods: Between December 2007 and August 2018, patients with pathological stage I IAC were retrospectively reviewed and categorized into the pure-GGO, part-GGO, and pure-solid groups. Survival curves were analyzed by the Kaplan-Meier method and compared by log-rank tests. Least absolute shrinkage and selection operator and Cox regression models were used to obtained prognostic factors for disease-free survival (DFS) and overall survival (OS)., Results: The number of patients with pure-GGO, part-GGO, and pure-solid was 134, 540, and 396, respectively. Part-GGO patients with consolidation-tumor-ratio (CTR) > 0.75 had similar outcome to those with pure-solid nodules. In part-GGO patients, CTR was negatively associated with OS (P = 0.007) and solid tumor size (STS) was negatively associated with DFS (P < 0.001). Visceral pleural invasion (VPI) was negatively associated with OS (P = 0.040) and DFS (P = 0.002). Sublobectomy was negatively associated with OS (P = 0.008) and DFS (P = 0.005), while extended N1 stations examination was associated with improved DFS (P = 0.005) in pure-solid patients., Conclusions: Though GGO component is a positively prognostic factors of patients with pathological stage I IAC, a small proportion of GGO components is not associated with favorable survival. VPI, STS and CTR are the significant predictors for part-GGO patients. Sublobectomy, especially wedge resection should be used cautiously in pure-solid patients., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (Copyright 2022, Zhai et al.)

A new visible imaging system characterizing a flexible optical design and delivering high resolution frames is established on the HL-2A tokamak. It features a modular configuration, consisting of a front-end imaging lens, a set of bilateral telecentric relay lenses, and a camera. To avoid the effects of plasma radiation (x and gamma-rays) and magnetic field variation on the camera, it should be away from the coils. Therefore, the length of the relay lenses determines the total size of the imaging system. The main feature of this imaging system is to realize the variation of field of view (FOV) by interchanging the front-end prime lenses or by using a zoom lens directly rather than designing the optical system afresh, which lowers the cost drastically. The primary purpose of varying FOV is to enrich the versatility of this system, i.e., focusing on a narrow FOV such as gas puff imaging or a wide FOV such as the plasma cross sections. During the HL-2A experiments, this visible imaging system is used to provide high quality pictures of the plasma-wall interaction, divertor detachment, pellet injections, and so on. The frames confirmed that a strong radiation close to the X point is correlated with the completely detached inner target.

Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly., (© 2022 John Wiley & Sons Ltd.)

Aging is an inevitable process characterized by a decline in many physiological activities, and has been known as a significant risk factor for many kinds of malignancies, but there are few studies about aging-related genes (ARGs) in lung squamous carcinoma (LUSC). We designed this study to explore the prognostic value of ARGs and establish an ARG-based prognosis signature for LUSC patients. RNA-sequencing and corresponding clinicopathological data of patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The ARG risk signature was developed on the basis of results of LASSO and multivariate Cox analysis in the TCGA training dataset ( n = 492). Furthermore, the GSE73403 dataset ( n = 69) validated the prognostic performance of this ARG signature. Immunohistochemistry (IHC) staining was used to verify the expression of the ARGs in the signature. A five ARG-based signature, including A2M, CHEK2, ELN, FOS, and PLAU, was constructed in the TCGA dataset, and stratified patients into low- and high-risk groups with significantly different overall survival (OS) rates. The ARG risk score remained to be considered as an independent indicator of OS in the multivariate Cox regression model for LUSC patients. Then, a prognostic nomogram incorporating the ARG risk score with T-, N-, and M-classification was established. It achieved a good discriminative ability with a C-index of 0.628 (95% confidence interval [CI]: 0.586-0.671) in the TCGA cohort and 0.648 (95% CI: 0.535-0.762) in the GSE73403 dataset. Calibration curves displayed excellent agreement between the actual observations and the nomogram-predicted survival. The IHC staining discovered that these five ARGs were overexpression in LUSC tissues. Besides, the immune infiltration analysis in the TCGA cohort represented a distinctly differentiated infiltration of anti-tumor immune cells between the low- and high-risk groups. We identified a novel ARG-related prognostic signature, which may serve as a potential biomarker for individualized survival predictions and personalized therapeutic recommendation of anti-tumor immunity for patients with LUSC., 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 Zhai, Duan, Chen, Wang, Zhao, Wang, Rao, Lin and Long.)

Inflammation is an important hallmark of cancer and plays a role in both neogenesis and tumor development. Despite this, inflammatory-related genes (IRGs) remain to be poorly studied in lung adenocarcinoma (LUAD). We aim to explore the prognostic value of IRGs for LUAD and construct an IRG-based prognosis signature. The transcriptomic profiles and clinicopathological information of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression were applied in the TCGA set to generate an IRG risk signature. LUAD cases with from the GSE31210 and GSE30219 datasets were used to validate the predictive ability of the signature. Analysis of the TCGA cohort revealed a five-IRG risk signature consisting of EREG, GPC3, IL7R, LAMP3, and NMUR1. This signature was used to divide patients into two risk groups with different survival rates. Multivariate Cox regression analysis verified that the risk score from the five-IRG signature negatively correlated with patient outcome. A nomogram was developed using the IRG risk signature and stage, with C-index values of 0.687 (95% CI: 0.644-0.730) in the TCGA training cohort, 0.678 (95% CI: 0.586-0.771) in GSE30219 cohort, and 0.656 (95% CI: 0.571-0.740) in GSE30219 cohort. Calibration curves were consistent between the actual and the predicted overall survival. The immune infiltration analysis in the TCGA training cohort and two GEO validation cohorts showed a distinctly differentiated immune cell infiltration landscape between the two risk groups. The IRG risk signature for LUAD can be used to predict patient prognosis and guide individual treatment. This risk signature is also a potential biomarker of immunotherapy., 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 Zhai, Duan, Chen, Wang, Lin, Wang, Rao, Zhao and Long.)

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m 2 for adenocarcinoma) or nab-paclitaxel (260 mg/m 2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4-5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248)., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Two-dimensional transition metal dichalcogenides are of particular interest in high-performance photothermal conversion, yet there remains a huge challenge in their practical application in smart textiles for healthcare, energy, and personal protection. Herein, we controllably prepared MoS 2 hollow nanospheres with a high photothermal conversion efficiency of 36% via a microemulsion-hydrothermal method, which was further applied to construct photothermal fibers for personal thermal management after a hot-blast dip-drying process. Because of the prominent photothermal effect, the temperature of the photothermal fibers sharply increases from the room temperature value of 25.0 to 55.5 °C in 60 s under near-infrared illumination with a power density of 500 W/cm 2 . Furthermore, the photothermal fiber pad demonstrated an obvious temperature enhancement of 38.0 °C from a skin temperature of 22.0 °C after it was irradiated by natural sunlight for 60 s. Significantly, the antibacterial elimination rates of the photothermal fibers for Escherichia coli and Staphylococcus aureus are ∼99.9 and ∼99.8%, respectively. This strategy affords an avenue toward the practical application of photothermal materials in smart fibers for personal thermoregulation.

Background: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear., Methods: Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and β-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression., Results: Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21., Conclusions: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.

Stray laser light is a serious problem that interrupts the measurement of electron temperature and density in Thomson scattering (TS) systems. This paper presents a ray-tracing simulation of stray laser light in HL-2M TS systems. A model including (i) a simplified laser-beam injection system, (ii) the scattered-light collection systems for central-point TS (CPTS) and edge TS (ETS), and (iii) the HL-2M vessel is built using the TracePro and CATIA software packages based on measurements of the bidirectional scattering distribution function at a wavelength of 532 nm. The simulation results show that no stray laser light reaches the injection surface of the collection lens of the CPTS system, and only a few stray laser rays of all the rays reaching the injection surface of the collection lens of the ETS system can be collected when the energy threshold per ray is 1 × 10 -16 . The stray laser rays that reach the scattered-light collection systems are mainly from the first and second parts of the slides of the beam dump, so decreasing the roughness of those parts could be effective in reducing the level of stray laser light.

Background: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear., Methods: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics., Results: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%., Conclusions: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5525). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with oesophageal squamous cell carcinoma (ESCC) who underwent left transthoracic oesophagectomy is still unclear., Methods: Patients with ESCC who underwent left transthoracic oesophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival (OS). The association between ELN count and nodal status was investigated through scatter plot and binary logistic regression analyses. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression., Results: Among the 1826 included patients, greater ELNs were associated with a higher rate of nodal metastasis (adjusted OR = 1.018). When the ELN count increased, the omission rate of positive lymph nodes (LNs) decreased. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted HR = 0.983), especially in those with node-negative disease (adjust HR = 0.972). In patients with node-negative disease, cut point analysis showed a threshold ELN count of 18., Conclusions: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 18 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease in the left thoracic approach., Competing Interests: Declaration of competing interest No conflict., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Lobectomy has long been regarded as the standard treatment for operable non-small cell lung cancer (NSCLC). Recent studies suggested that segmentectomy could achieve a good prognosis for early-stage NSCLC and might be an alternative to lobectomy in this cohort. Until now, on the issue of comparison between lobectomy and segmentectomy, there remains no published randomized controlled trial (RCT), and all existing evidence is low. Recently, a categorization of lower-level evidence has been proposed, namely, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The aim of this meta-analysis is to compare the oncologic outcome between lobectomy and segmentectomy in NSCLC with the clinical T1N0M0 stage according to the GRADE system., Methods: PubMed, the PMC database, EMBASE, Web of Science, and the Cochrane library were searched prior to May 2019 to identify studies that compared the prognosis between lobectomy and segmentectomy for clinical T1N0M0 NSCLC. The evidence level of the included studies was assessed according to the GRADE system, including level IIA, probably not confounded nonrandomized comparison; level IIB, possibly confounded nonrandomized comparison; and level IIC, probably confounded nonrandomized comparison. The predefined outcomes included overall survival (OS) and disease-free survival (DFS). Univariable and multivariable hazard ratios (HRs) with 95% confidence intervals (95% CI) were pooled using a random-effects model., Results: Twelve nonrandomized studies involving 8,072 participants were included. Of these studies, two were classified as IIA level (16.7%), six as IIB level (50.0%), and four as IIC level (33.3%). When crude HRs were included, compared with lobectomy, segmentectomy was associated with shorter OS but comparable DFS in the entire cohort (OS, pooled HR =1.45, 95% CI, 1.23 to 1.67; DFS, pooled HR =1.03, 95% CI, 0.65 to 1.82) and in patients with nodules ≤2 cm (OS, pooled HR =1.55, 95% CI, 1.33 to 1.80; DFS, pooled HR =0.98, 95% CI, 0.55 to 1.77). When adjusted HRs were included, the impact of segmentectomy on OS and DFS was comparable to that of lobectomy in the entire cohort (OS, pooled HR =1.39, 95% CI, 0.92 to 2.10; DFS, pooled HR =0.83, 95% CI, 0.66 to 1.03) and in patients with nodules ≤2 cm (OS, pooled HR =1.61, 95% CI, 0.87 to 3.00; DFS, pooled HR =0.90, 95% CI, 0.63 to 1.27)., Conclusions: Based on our results, although shorter OS is observed in patients received segmentectomy, it is necessary to wait for more results from RCT to draw a valid conclusion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3802). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Amyloid β peptide 1-42 (Aβ 1-42 ) could induce cognitive deficits through oxidative stress, inflammation, and neuron death in Alzheimer's disease (AD). MAPK pathways have been thought to mediate Aβ 1-42 -induced neuroinflammation responses, neuron death and cognitive decline in AD. The α7 nicotinic acetylcholine receptor (α7nAChR) exerts a neuroprotective effect. However, whether α7nAChR alleviates Aβ 1-42 -induced neurotoxicity through MAPKs (p38, ERK, JNK) in vivo remains unclear. In our study, memory was assessed in C57BL/6 mice using a Y-maze test. Cell death was assessed by Nissl and Hoechst staining and Bax, Bcl-2, Caspase 3, and Cytochrome C levels using Western blotting. Oxidative stress was assayed by superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. Inflammation was examined with GFAP and Iba1 using immunohistochemistry. The Aβ degrading enzymes insulin degrading enzyme (IDE) and neprilysin (NEP) were tested using Western blotting. We found that activating α7nAChR or inhibiting p38 or JNK pathway alleviated Aβ 1-42 -induced cognitive deficits and neuron loss and death by reducing oxidative stress. In addition, activating α7nAChR or inhibiting p38 or JNK pathway also reduced inflammation, which was observed as reduced GFAP and Iba1 levels with different effects on Aβ degrading enzymes. Finally, we found that the activation of α7nAChR led to the downregulation of pp38 and pJNK levels. Conversely, the inhibition of p38 or JNK resulted in the upregulation of α7nAChR levels in the hippocampus and cortex. Our data indicate that the activation of α7nAChR alleviates Aβ 1-42 -induced neurotoxicity, and this protective effect might act through the downregulation of p38 and JNK MAPKs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. Intracellular β-amyloid protein (Aβ) is an early event in AD. It induces the formation of amyloid plaques and neuron damage. The α7 nicotinic acetylcholine receptor (α7nAChR) has been suggested to play an important role in Aβ caused cognition. It has high affinity with Aβ and could mediate Aβ internalization in vitro. However, whether in mouse brain the p38 MAPK signaling pathway is involved in the regulation of the α7nAChR mediated Aβ internalization and their role in mitochondria remains little known. Therefore, in this study, we revealed that Aβ is internalized by cholinergic and GABAergic neurons. The internalized Aβ were found deposits in lysosomes/endosomes and mitochondria. Aβ could form Aβ-α7nAChR complex with α7nAChR, activates the p38 mitogen activated protein kinase (MAPK). And the increasing of α7nAChR could in return mediate Aβ internalization in the cortex and hippocampus. In addition, by using the α7nAChR agonist PNU282987, the p38 phosphorylation level decreases, rescues the biochemical changes which are tightly associated with Aβ-induced apoptosis, such as Bcl2/Bax level, cytochrome c (Cyt c) release. Collectively, the p38 MAPK signaling pathway could regulate the α7nAChR-mediated internalization of Aβ. The activation of α7nAChR or the inhibition of p38 MAPK signaling pathway may be a beneficial therapy to AD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

With the construction of the Three Gorges Dam, the river flow pattern and sediment dynamics are expected to be affected. As a consequence, the sediment traits could be impacted by these changes. The temporal and spatial variation characteristics of the nutrient content from 2000 to 2015 in surface sediment were analyzed in the main stream from Jiangjin to the dam site section of the Yangtze River and in the estuaries of the representative input tributaries of the Three Gorges Reservoir, such as the Jialing River, Yulin River, Wujiang River, Xiaojiang River, Daning River, and Xiangxi River. Then, the state of the pollution was assessed. Results revealed that the average concentrations of total phosphorus (TP) in the surface sediments of the main stream ranged from 678.2 to 928.6 mg·kg -1 , the average contents of total nitrogen (TN) ranged from 0.203% to 0.362%, the average contents of potassium ranged from 1.74% to 2.37%, and the average contents of organic matter ranged from 0.94% to 1.54%. The average concentrations of TP in the estuaries of the representative input tributaries ranged from 490.1 to 832.3 mg·kg -1 , the average contents of TN ranged from 0.257% to 0.495%, the average contents of potassium ranged from 1.69% to 2.32%, and the average contents of organic matter ranged from 1.21% to 2.27%. The concentrations of TP and potassium in the study sections were generally within background concentration ranges, while the concentrations of TN were obviously above background levels, and the concentrations of organic matter were obviously below background levels. The nutrient contents in the surface sediment did not display significant differences among the study sites; however, the distributions of different nutrient contents along the river varied widely. Although the nutrient contents in the surface sediments fluctuated somewhat during different flow periods, they were seemingly unaffected by the impoundment, since no obvious enrichment was observed throughout the impoundment. The evaluation of organic index indicated a clean state for the surface sediments in the majority of the study area, while there was a moderately polluted state in some local sections. The evaluation of nitrogen pollution indicated a polluted state for most sections. Overall, the nutrients in the surface sediments of the Three Gorges Reservoir showed moderate ecological risks, possibly caused by TP and TN.

Objective: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs)., Methods: Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma., Results: PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 µg/ml) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs., Conclusion: The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.

Flower-like nanostructured hydroxyapatite hollow spheres (NHHS) assembled with nanosheets with a hierarchical morphology are fabricated by a rapid microwave-assisted hydrothermal route. The presence and concentration of block copolymer poly(lactide)-block-poly(ethylene glycol) (PLA-PEG) are important parameters for the formation of the hollow structure. The possible formation mechanism of NHHS is proposed. The NHHS are explored as anticancer drug carriers for cellular delivery of mitoxantrone (MIT). The MIT-loaded NHHS exhibit sustained-drug-release behavior in vitro and the intracellular drug-distribution tests indicate that the MIT loaded in NHHS carriers can enter the cells efficiently. The experiments also show that the NHHS have a good biocompatibility, and therefore, they are promising anticancer drug carriers in cancer chemotherapy.

Electrospinning has been recognized as an efficient technique for fabricating polymer nanofibrous biomaterials. However, the study of electrospun inorganic biomaterials with well-designed three-dimensional (3-D) structures is still limited and little reported. In this study hydroxyapatite (HAp) nanorods with an average diameter of approximately 7 nm and length of approximately 27 nm were synthesized through a simple precipitation method and used for the fabrication of inorganic/organic [poly(vinyl pyrolidone) (PVP)] composite nanofibers by electrospinning in ethanol solution. 3-D fabrics and aligned nanofiber arrays of the HAp nanorods/PVP composite were obtained as precursors. Thereafter, 3-D single phase HAp fabrics, tubular structures and aligned nanofiber arrays were obtained after thermal treatment of the corresponding composite precursors. Cytotoxicity experiments indicated that the HAp fabric scaffold had good biocompatibility. In vitro experiments showed that mesenchymal stem cells could attach to the HAp fabric scaffold after culture for 24h., (Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Zinc-containing glass is prepared by the substitution of CaO in 58S bioactive glass with 0.5 and 4 wt% ZnO, and glass-ceramics are obtained by heat-treating the glass at 1,200 C. The bending strength and in vitro bioactivity of the glass and glass-ceramics are evaluated. The results indicate that Zn promotes the crystallization of SiO(2) and wollastonite in glass-ceramics, and proper crystallization can enhance the bending strength of the glass-ceramic. The in vitro results show that ZnO in glass retards the hydroxyapatite (HA) nucleation at the initial stage of simulated body fluid (SBF) soaking, but does not affect the growth of HA after long periods of soaking, and the ionic products of 58S4Z glass can stimulate the proliferation of osteoblast at certain concentrations. Osteoblasts attach well on both glass samples and glass-ceramic samples, but the high Si ion concentration released from glass samples restrains the proliferation of osteoblasts after 3 days of culture. In contrast, osteoblasts show good proliferation on glass-ceramic samples, and ZnO in glass-ceramics promotes the proliferation rate. The results in this study suggest that the glass and glass-ceramics with different ZnO content might be used as bioactive bone implant materials in different applications.