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Abstract This open-label, single-arm, phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab combined with anlotinib and chemotherapy, followed by adjuvant sintilimab, for resectable NSCLC. Forty-five patients received anlotinib (10 mg, QD, PO, days 1–14), sintilimab (200 mg, day 1), and platinum-based chemotherapy of each three-week cycle for 3 cycles, followed by surgery within 4–6 weeks. Adjuvant sintilimab (200 mg) was administered every 3 weeks. The primary endpoint was achieving a pathological complete response (pCR). From June 10, 2021 through October 10, 2023, 45 patients were enrolled and composed the intention-to-treat population. Twenty-six patients (57.8%) achieved pCR, and 30 (66.7%) achieved major pathological response (MPR). Forty-one patients underwent surgery. In the per-protocol set (PP set), 63.4% (26/41) achieved pCR, and 73.2% achieved MPR. The median event-free survival was not attained (95% CI, 25.1-NE). During the neoadjuvant treatment phase, grade 3 or 4 treatment-related adverse events were observed in 25 patients (55.6%), while immune-related adverse events were reported in 7 patients (15.6%). We assessed vascular normalization and infiltration of immune-related cells by detecting the expression of relevant cell markers in NSCLC tissues with mIHC. Significant tumor microenvironment changes were observed in pCR patients, including reduced VEGF+ cells and CD4+Foxp3+ Treg cells, and increased perivascular CD4+ T cells, CD39+CD8+ T cells, and M1 macrophages. In conclusion, perioperative sintilimab and neoadjuvant anlotinib plus chemotherapy achieved pCR in a notable proportion of patients with resectable NSCLC and were associated with profound changes in the tumour microenvironment (ClinicalTrials.gov NCT05400070).

Airway management in complex tracheobronchial surgery (TBS) remains a challenge in thoracic surgery. The use of extracorporeal membrane pulmonary oxygenation (ECMO) in thoracic surgery is rather rare, except for lung transplantation. To report the safety and efficacy of ECMO in complex TBS, a total of 5 patients with tracheobronchial and bronchial reconstructive surgery supported by ECMO in the Department of Thoracic Surgery of Tangdu Hospital, Air Force Medical University from May 2019 to June 2024 were collected. Among them, 4 cases of tracheal tumor (including long-segment trachea resection and reconstruction, or carinal resection and reconstruction) and 1 case of acute airway obstruction caused by tracheal rupture were included, all of which were performed in veno-venous ECMO (V-V ECMO) mode. Systemic heparinization was used in 2 patients, and anticoagulation was not performed in 3 patients, which were maintained only by ECMO heparin-coated lines. 4 patients recovered well after surgery, and 1 patient died 1 month after surgery due to immune-related pneumonia. For complex TBS, or in emergency situations (tracheal stenosis with risk of asphyxiation), ECMO can provide adequate support and safeguard.

The utilization of Bacillus sp. for the production of bio-CaCO3 in concrete crack repair and strength enhancement has attracted considerable attention. However, microbial-induced calcium carbonate precipitation (MICP) has yet to be explored as a precedent with activated sludge. Here calcium sourced from concrete slurry waste (CSW) and carbon from sludge microbial β-oxidation under alkaline were used to generate micro/nano CaCO3. The results indicate that the main crystalline form of the generated precipitated particles is calcite, with a particle size ranging from 0.7 to 10 μm. Minimal heavy metals were found in the supernatant following settling. And at the optimum pH of 8.5–9, carbon capture reached 743 mg L−1, and CaCO3 production reached 1,191 mg L−1, and dominant phylum were Proteobacteria and Bacteroidota, with Thauera being a prevalent genus adept in β-oxidation. Mass balance analysis showed that alkali promotes microbial β-oxidation of organisms to produce CO2 and facilitate storage. Thus, the alkaline regulation of metabolism between microbe and CSW provides a novel way of sludge to initiate MICP. HIGHLIGHTS Utilizing concrete slurry waste as a calcium source and sludge β-oxidation as a carbon source can successfully produce bio-CaCO3.; pH 8.5–9 is the optimal alkaline control for Thauera to be the dominant genus undergoing β-oxidation to produce CO2.; Bio-CaCO3 is a 0.7–10 μm calcite particle, which is an excellent material for repairing concrete.; There is no risk of heavy metal leakage during operation.;

Dietary fiber is a key nutritional regulatory factor that has been studied intensively for its role in improving reproduction in sows during gestation. However, the metabolic mechanism underlying the effect of interactions between metabolites and gut microbes on coarse feeding tolerance in indigenous sows remains to be elucidated. Therefore, the present study aimed to investigate the effects of dietary supplementation with alfalfa at different content ratios on the reproductive performance of pregnant Songliao Black sows. In total, 40 Songliao Black sows at 30 days of gestation were allocated to four treatments, which received the following diets: (1) a corn–soybean meal basal diet with no alfalfa meal (CON group), (2) a corn–soybean meal basal diet +10% alfalfa meal (Treatment 1 group), (3) a corn–soybean meal basal diet +20% alfalfa meal (Treatment 2 group), and (4) a corn–soybean meal basal diet +30% alfalfa meal (Treatment 3 group). Untargeted metabolomics, 16S rDNA sequencing, and enzyme-linked immunosorbent assay (ELISA) were performed to determine the possible effects of metabolites, the microbial communities in fecal samples and their functional potential, and the effects of dietary fiber on serum biochemical parameters, oxidative stress, and reproductive hormones in Songliao Black sows during gestation. The results revealed that the meals with 10 and 20% alfalfa had a beneficial effect on sows in terms of improving the reproductive performance of these sows. Bacterial 16S rDNA sequencing of the fecal samples revealed that the 10% alfalfa meal group had a higher α-diversity and higher abundance of probiotics. Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were revealed as the most abundant groups at the phylum level and Lactobacillus, Prevotella, Ruminococcus, Streptococcus, and Clostridium were the most abundant at the genus level in the sows fed with diets containing higher fiber levels. A total of 239 differential metabolites were identified in the sows fed with alfalfa meals. These metabolites were enriched mainly in the cAMP signaling pathway, biosynthesis of amino acids, and steroid biosynthesis. Pearson correlation analysis revealed significant positive correlations between Blautia and Daizein, Fibrobacter and 5-alpha-Cholestanone, Sphaerochaeta, Sutterella, and Metaraminol. Negative correlations were revealed between Sphaerochaeta and Erucic acid, Prevotellaceae and Harmaline, and Streptococcus and 5-alpha-Cholestanone. Collectively, these findings provide novel insights into the application of dietary fiber in sow diets.

Abstract Background The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). Results Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell–cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. Conclusions This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Introduction: Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients. Methods: A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines. Results: Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines. Conclusion: Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy.

Abstract Objective We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. Methods Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. Results Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. Conclusions The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

This study aims to analyze the correlation between Systemic Inflammatory Response Index (SIRI) and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). It also aims to assess the predictive value of SIRI for the severity of coronary artery stenosis. A total of 2990 patients who underwent coronary angiography were included in this study. The Gensini score was used to estimate the severity of coronary vascular lesions. The predictive ability of SIRI for CHD was evaluated using receiver operating characteristic (ROC) curves. Binary multivariate logistic regression analysis was used to predict the likelihood of CHD based on the SIRI index. The results showed that people with higher SIRI index were more likely to have CHD (P < 0.001). After controlling for other risk factors, the highest quartile had a significantly higher incidence of coronary artery disease compared to the lowest quartile (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.73-3.92, P < 0.001). Furthermore, the Gensini score was significantly higher in the fourth quartile group (T4) compared to the first (T1) and second (T2) quartile groups (P < 0.001). Additionally, the SIRI index was significantly higher in the group with severe coronary artery lesions compared to the mild and moderate groups (P < 0.001). The SIRI index also showed a higher predictive ability for the extent of coronary lesions under the ROC curve compared to other commonly used markers, including platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001). Therefore, SIRI index positively correlates with coronary artery stenosis in CHD patients, serving as an effective early screening marker for assessing stenosis severity.

In this study we report, for the first time, the synthesis of Co-doped NiO microspheres assembled by two-dimension nanosheets using a facile solvothermal method. The H2S gas-sensing performance of the as-prepared samples was systematically investigated. The result demonstrates that the Co–NiO sensor with Co/Ni molar ratio of 1% (1% Co–NiO) exhibits high response (12.9) and rapid response speed (110 s) to 20×10−6 H2S at 200 °C in comparison with the pure NiO sensor. Moreover, excellent selectivity, repeatability, and stability were achieved. The sensing mechanism illustrates that the superior gas-sensing properties can be attributed to two factors. (1) The hierarchical microspherical construction with an ultrahigh specific surface area of 163.1 m2 g−1 provides adequate active sites for H2S gas adsorption, porous structures, and an interlayer gap that accelerates the diffusion of H2S gas, resulting in improved sensitivity and response speed of the sensor. (2) Co-doping results in a decrease in the particle sizes (ca. 4 nm) and increase in the number of adsorbed ionized oxygen species, which improves sensitivity and selectivity. Therefore, this study provides a facile approach for the synthesis of hierarchical Co–NiO microspheres with enhanced H2S gas-sensing performance.

Objectives: Present study aims to explore the surgery patterns and survival of T4N2 non-small cell lung cancer (NSCLC) in real-world condition. Materials and methods: Clinical stage T4N2 NSCLC patients in Surveillance, Epidemiology and End Result Program were extracted. Cox regression was used for calculation of hazard ratio (HR) and confidence interval (CI), and landmark analysis was used for survival test at different cut-off time points. Results: There were 1445 eligible patients included, of which 306 patients received surgery alone, 390 patients received induction therapy, and 749 patients received adjuvant therapy. For resection types, 1210 patients received lobectomy and 235 received pneumonectomy. Among patient receiving induction therapy, the overall survival (OS) HRs of pneumonectomy at 1-year, 3-year, 5-year, and 8-year cut-off points were 1.330, 0.972, 1.231, and 1.332 (P ​= ​0.708, 0.972, 0.281 and 0.145), respectively, and cancer-specific survival (CSS) HRs at these landmark points were 2.386, 1.231, 1.455, and 1.480 (P ​= ​0.293, P ​= ​0.409, 0.059 and 0.056), respectively. Among patients receiving adjuvant therapy, the OS HRs of pneumonectomy at 1-year and 8-year cut-off points were 1.570 and 1.274 (P ​= ​0.050 and 0.087), respectively, and CSS HRs at these landmark points were 1.493 and 1.284 (P ​= ​0.096 and 0.094), respectively. Both OS and CSS of patients receiving lobectomy were superior than pneumonectomy at 3-year and 5-year in this cohort. For patients receiving surgery alone, pneumonectomy resulted in inferior survival than lobectomy at all cut-off points (all P ​

Summary: The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

Following the final biological treatment, the oil wastewater is intended for reuse in factory floor cleaning. However, the presence of varying concentrations of oil-in-iron characteristic wastewater has led to a sudden surge in sludge SV to 90%, adversely affecting water treatment efficiency. In this study, we conducted an analysis of microbial community structure and selected pepA and 16S rRNA primers to assess the proportions of zoogloea and total bacteria in sludge bulking. Iron concentration plays a pivotal role, and it should be maintained at or 0.6 mgL−1. By selective discharging of sludge to maintain 1,700 mgL−1, we minimized iron enrichment, thereby enhancing the sludge settling performance. Maintaining dissolved oxygen (DO) at 3.5 mgL−1 supports the aerobic sludge's ability to replenish iron in its system, while the oil content should be controlled at 145.33 mgL−1 to reduce the release of iron into the water. The order of significance is as follows: sludge concentration > Fe amount > DO > oil content. Implementing this approach was applied in the field for 1 week and effectively reduced the SV from 90% to approximately 43%. The interaction between quorum sensing molecules related to sludge bulking and iron, leading to the formation of complexes, underscores the significance of controlling iron levels. This study offers a valuable case for practical application of quorum quenching technology in oil wastewater, presenting a rapid, efficient, and cost-effective solution to address the issue of sludge bulking.

Generally, transition metal-catalyzed stereodivergent transfer semihydrogenation of alkynes realized regulation of stereoselectivity by a Z to E isomerization process. Here, authors report a Ni-catalyzed stereodivergent transfer semihydrogenation of alkynes with a base-assisted metal species modulation mechanism, delivering both olefinic isomers smoothly in orthogonal catalytic pathways using cheap and nontoxic catalysts and additives

The electrocaloric effect (ECE) depends on the sudden change of the polarization field during ferroelectric phase transition near the Curie temperature. Similarly, giant ECE can be found enormously during the domain structure transition from multidomain to monodomain process in ferroelectrics. To reveal the mechanism with the effects of the electric inclusions, the ECE of PbTiO3 (PTO) ferroelectric solids under electric loads is investigated by phase-field simulation. The giant ECEs of ferroelectric materials containing three kinds of electric inclusions, namely, air, silicone oil, and water, are discussed in detail under applied electric fields. The results suggest that an unusual ultrahigh negative ECE (−9.30 K) and a large EC strength (∆T/∆E=0.237 KmMV−1 are achieved near room temperature (about 50°C) in ferroelectrics containing water inclusion. The results indicate that electric inclusions generate high electrostatic energy under electric loads to break through the energy barrier and play an importation role in the ECE. In summary, the works may provide a better way to obtain the giant ECE and large EC strength close to room temperature by effectively regulating the dielectric constant of the electric inclusion and the increment of the applied electric field.

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient’s primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.

Reduced cancer deaths have led to an increase in the number of cancer survivors and the risk of the second primary tumor. This study explored the surgical outcomes of patients with non-small cell lung cancer as the second primary tumor and the impact of previous extra-pulmonary malignancies. Patients’ data were obtained from Surveillance, Epidemiology and End Results database. The patients were divided into lung surgery and non-surgery groups. Propensity-score matching was used to balance potential confounders. Kaplan-Meier curves were generated to test the overall survival and lung-cancer-specific survival. Cox regression analysis was performed to calculate death risk. In total 3054 lung surgery and 1094 non-surgery patients with stage I-II non-small cell lung cancer as the second primary tumor were included. The surgery group showed longer overall survival (68 vs. 22 months) and lung cancer-specific survival (not reached vs. 37 months) than those of non-surgery groups (both P

Abstract Objective To investigate the clinical effect of internal fixation of a Ni–Ti arched shape-memory connector in the treatment of distal tibiofibular syndesmosis ligament injury. Methods From January 2013 to January 2016, 108 cases of ankle fracture with distal tibiofibular syndesmosis ligament injury in our hospital were selected, and all of them were fixed with ASCs or screw fixation. The functional evaluation and efficacy evaluation were performed according to the Olerud Molander Ankle Score (Omas) and SF-36. At the same time, follow-ups recorded the incidence of postoperative complications: osteoarthritis, superficial infection, symptomatic hard and soft tissue irritation, early removal and poor reduction of internal fixation, and later loss of reduction. Results In the ASC(Ni–Ti Arched shape-memory Connector) group, the incidence of symptomatic hardware, soft tissue or superficial infection decreased to 2.77%(from 13.8% or 11.1% in SCREW group). The early removal rate(2.77%) of internal fixation was also lower than that of the screw group. While the incidence of osteoarthritis is 13.8% in SCREW group, the incidence of osteoarthritis in the later follow-up was also as low as 1.38% in ASC group. Loss of fracture reduction due to removal of the fixation device for the distal tibiofibular syndesmosis ligament was not observed in the ASC group. With two postoperative scoring systems (OMAS and SF-36), patients in the ASC group significantly get higher score than that in SCREW group. Conclusion The design of the Ni–Ti arched shape-memory connector can be adapted to the irregular anatomical structure of the malleolus and the ability to continue to contract by body temperature. The use of ASCs in fixation of articular ligaments can preserve a slight range of motion, and the results suggest that ASCs can effectively reduce the incidence of fixation looseness, fracture, infection and other complications.

Approximately 75% of patients with advanced breast cancer develop bone metastasis, which significantly affects both the quality of life and the survival rate of patients. Accurate determination of the status of bone metastases is important for developing treatment strategies and the prognosis of the disease. Here, we report the case of a 33-year-old patient with advanced metastatic breast cancer (MBC) and multiple bone metastases, in which advanced first-line endocrine therapy and second-line chemotherapy were both considered unsuccessful according to the efficacy evaluation by conventional imaging. Considering the possibility of bone pseudoprogression, the original endocrine scheme was reapplied, and bone metastases achieved a great response of non-complete response (CR)/non-progressive disease (PD). This case showed that, in the course of therapy for the disease, if bone scintigraphy (BS) shows increased lesion density or new lesions, this probably indicates a favorable response (osteoblastic repair of osteolytic lesions) to therapy, and not the worsening of metastatic lesions, called bone pseudoprogression. This paper will provide new insights into strategies for the treatment of bone metastasis and shows the significance of distinguishing osteoblastic bone repair from real bone lesion progression in clinical settings.

Waterborne pathogens are the primary concern for the safe reuse of wastewater. Although digital PCR (dPCR) is considered promising for absolutely quantitating genes, the detection efficiency of dPCR is affected by many factors. This study tested eight virulence genes of pathogenic bacteria on a control plasmid and reclaimed water samples with reported primer–probe sets and designed ones on quantitative PCR (qPCR) and dPCR. Probe efficiency, data analysis, and PCR inhibition were found to affect the detection efficiency of dPCR. Firstly, poor probe quality, which is determined by probe quenching and activation efficiencies, was the main cause of PCR failure. Secondly, even if the PCR was successful, the probe quality and signal intensity could still affect the quantitative process. Manual analysis of dPCR data on the weak signal intensity would significantly reduce errors. And lastly, the sensitivity of PCR inhibition was lower in dPCR than qPCR, but inhibition still existed. The dPCR produced various detection efficiencies for different targets in one sample indicating inconstant inhibitory effects. Dilution was still the proper approach to overcome inhibition, but decreased the detection limit. More studies are required to ensure accurate waterborne pathogen quantitation by dPCR. HIGHLIGHTS Successful primers and probes are PCR reagent, protocol, and equipment dependent.; Probe quality is determined by quenching and activation efficiencies.; Peak separation of dPCR is critical and needed manual adjustment sometimes.; dPCR is much more inhibition-tolerant than qPCR.; PCR inhibitory effect is different for different PCR reactions.;

Abstract Transcription factor AP-2α (TFAP2A) was previously regarded as a critical regulator during embryonic development, and its mediation in carcinogenesis has received intensive attention recently. However, its role in lung adenocarcinoma (LUAD) has not been fully elucidated. Here, we tried to investigate TFAP2A expression profiling, clinical significance, biological function and molecular underpinnings in LUAD. We proved LUAD possessed universal TFAP2A high expression, indicating a pervasively poorer prognosis in multiple independent datasets. Then we found TFAP2A was not indispensable for LUAD proliferation, and exogenous overexpression even caused repression. However, we found TFAP2A could potently promote LUAD metastasis possibly by triggering epithelial–mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated TFAP2A could transactivate Pregnancy-specific glycoprotein 9 (PSG9) to enhance transforming growth factor β (TGF-β)-triggering EMT in LUAD. Meanwhile, we discovered suppressed post-transcriptional silencing of miR-16 family upon TFAP2A partly contributed to TFAP2A upregulation in LUAD. In clinical specimens, we also validated cancer-regulating effect of miR-16 family/TFAP2A/PSG9 axis, especially for lymph node metastasis of LUAD. In conclusion, we demonstrated that TFAP2A could pivotally facilitate LUAD progression, possibly through a novel pro-metastasis signaling pathway (miR-16 family/TFAP2A/PSG9/ TGF-β).

Abstract Background Lung adenocarcinoma (LUAD) remains a crucial factor endangering human health. Gene-based clinical predictions could be of great help for cancer intervention strategies. Here, we tried to build a gene-based survival score (SS) for LUAD via analyzing multiple transcriptional datasets. Methods We first acquired differentially expressed genes between tumors and normal tissues from intersections of four LUAD datasets. Next, survival-related genes were preliminarily unscrambled by univariate Cox regression and further filtrated by LASSO regression. Then, we applied PCA to establish a comprehensive SS based on survival-related genes. Subsequently, we applied four independent LUAD datasets to evaluate prognostic prediction of SS. Moreover, we explored associations between SS and clinicopathological features. Furthermore, we assessed independent predictive value of SS by multivariate Cox analysis and then built prognostic models based on clinical stage and SS. Finally, we performed pathway enrichments analysis and investigated immune checkpoints expression underlying SS in four datasets. Results We established a 13 gene-based SS, which could precisely predict OS and PFS of LUAD. Close relations were elicited between SS and canonical malignant indictors. Furthermore, SS could serve as an independent risk factor for OS and PFS. Besides, the predictive efficacies of prognostic models were also reasonable (C-indexes: OS, 0.7; PFS, 0.7). Finally, we demonstrated enhanced cell proliferation and immune escape might account for high clinical risk of SS. Conclusions We built a 13 gene-based SS for prognostic prediction of LUAD, which exhibited wide applicability and could contribute to LUAD management.

Background and objective Electromagnetic navigation bronchoscopy is a tool that can accurately navigation peripheral lung lesions. Because of electromagnetic navigation bronchoscopy (ENB) is too expensive, it has not been widely used in China. It is urgent for us to summarize experience in clinical application, especially in the diagnosis of pulmonary nodules. Methods The clinical data of patients with pulmonary peripheral lesions (PPLs) in our department undergoing ENB biopsy between July 2017 and December 2018 were retrospectively analyzed. Results There were 18 patients with 21 PPLs (10 males and 8 females). Among them, 11 patients got the final pathological diagnosis, 8 cases were diagnosed with adenocarcinoma lung cancer, 1 case was diagnosed with tuberculosis and 2 cases were diagnosed with small cell lung cancer. The positive rate of diagnosis was 61.1%. The sensitivity was 73.3%. The positive diagnosis rate is related to the size of the lesion, the positive diagnosis rate for lesions >2 cm is 100.0% (P=0.04). Conclusion Electromagnetic navigation bronchoscope is safe and effective in clinic. It has a high positive rate for the diagnosis of peripheral lung lesions larger than 2 cm, ENB has broad clinical application prospects.

Sexual maturation provides economically important traits in poultry production. Research on the initiation mechanism of sexual maturity is of great significance for breeding high-yield laying hens. However, the underlying mechanisms are not fully clear. Here, one hundred and fifty Chahua No. 2 laying hens (the CH2 group, which has precocious puberty) and one hundred and fifty Wu Liang Shan black-bone laying hens (the WLS group, a late-maturing chicken breed) with similar weights and ages were randomly selected. ELISA was used to determine the secretion levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in 150-day-old serum and small yellow follicle (SYF) tissues. A histology examination, immunohistochemistry, and quantitative real-time PCR (qPCR) were used to explore the molecular mechanism of how some genes related to oxidative stress affect sexual maturation. The results showed that the secretion levels of LH, E2, and P4 in the CH2 group serum and SYF were higher than those in the WLS group. The results of the real-time PCR of all genes showed that the expression levels of cytochrome P450 family 11 subfamily A member 1, steroidogenic acute regulatory protein, follicle-stimulating hormone receptor, and cytochrome P450 family 19 subfamily A member 1 in the CH2 group were significantly higher than those in the WLS groups (p < 0.001). Untargeted metabolomics combined with multivariate statistical analysis was used to identify biomarkers of SYF tissues in the CH2 and WLS groups. A trajectory analysis of the principal component analysis (PCA) results showed that the samples within the group were clustered and that the samples were dispersed between the CH2 and the WLS groups, indicating that the results of the measured data were reliable and could be used for further research. Further analysis showed that a total of 319 metabolites in small yellow follicles of the CH2 and WLS groups were identified, among which 54 downregulated differential metabolites were identified. These 54 metabolites were found as potential CH2 biomarkers compared with WLS at 150 days, and the different expressions of L-arginine, L-prolinamide, (R)-4-hydroxymandelate, glutathione, and homovanillic acid were more significant. Twenty metabolic pathways were found when significantly differential metabolites were queried in the KEGG database. According to the impact values of the metabolic pathways, eighteen differential metabolites belonged to the mTOR signaling pathway, glutathione metabolism, ABC transporters, the cell ferroptosis pathway, and D-arginine and D-ornithine metabolism. Interestingly, we identified that the cell ferroptosis pathway played an important role in chicken follicle selection for the first time. The histology and immunohistochemistry of SYF showed that the number of granulosa cells increased in the CH2 groups and the expression levels of glutathione peroxidase 4, tumor protein p53, ribosomal protein S6 kinase, and sterol regulatory element binding protein 1 in the granulosa cell layer were upregulated in the CH2 group at the time of sexual maturation. Furthermore, we also speculated that the antioxidant system may play an indispensable role in regulating sexual maturity in chickens. Overall, our findings suggest differentially expressed metabolites and metabolic pathways between CH2 and WLS chickens, providing new insights into the initiation mechanism of sexual maturation.

3D printed external airway splints derived from degradable biopolymers provide a promising way to treat tracheomalacia (TM). However, most of the splints cannot fully reproduce the lumen shapes and the mechanical properties of native tracheas. In this study, biodegradable external airway splints with native-like lumen geometry and mechanical properties were designed and fabricated. Matchable mechanical properties were realized by the combination of different pore shapes and sizes of the splints. A reliable method for the fabrication of the porous polycaprolactone (PCL) splints was demonstrated via selective laser sintering (SLS). Compression results revealed that the SLS-fabricated PCL splints with the diamond pore shape and an inscribed circle diameter of 3 mm possessed similar mechanical properties to those of native tracheas, before and after implantation in dogs with TM for 12 weeks. These SLS-fabricated PCL biodegradable bionic external airway splints might be good candidate for clinical application in future.

AimsSerine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.MethodsSerine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.ResultsSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.ConclusionSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.

Because of the capacity of capturing both the spatial and angular information of the light rays simultaneously, light field images (LFIs) contain richer scene information compared with conventional images, but at the cost of huge volume. This paper proposes a novel LFI sparse compression framework driven by convolutional neural network (CNN). The epipolar plane image (EPI) super-resolution is for compensating the information loss caused by sparse sampling and the decoder-side sub-aperture images (SAIs) quality enhancement is for compensating the information loss caused by lossy compression. Specifically, we choose those SAIs both in odd rows and odd columns as our key SAIs and compress them using standard video encoder. For those non-key SAIs, we predict them using decompressed key SAIs by taking advantage of the special structure of EPI. The low-resolution EPIs generated from the sparse SAIs are super-resolved by a CNN and the outputs, high-resolution EPIs, are used to rebuild the dense SAIs. Moreover, in order to improve the quality of the predicted SAI, we add decoder-side quality enhancement before prediction. We propose a multi-scale dense residual network (MSDRN) to implement both EPI super-resolution and quality enhancement. Transfer learning strategies are used to improve the training performance of quality enhancement. The experimental results show the superior performance of the proposed framework over existing methods in terms of rate-distortion performance.

Background: Overseas imported cases of COVID-19 continue to increase in China, so we conducted this study to review the epidemiological characteristics of these patients.Methods: From February 26 to April 4, 2020, the imported cases from abroad were enrolled in this study. The effect of prevention countermeasures in curbing the spread of COVID-19 was assessed in this study. Moreover, we defined incubation period and confirmed time as from the date of leaving the epicenter to date of symptom onset and date of final diagnosed, respectively, and the interval of symptom onset to final diagnosed time was defined as diagnostic time. Categorical variables were summarized as numbers and percentages, and the difference among the variables were analyzed.Results: For 670 cases imported from abroad, 555 were Chinese and 115 were foreigners. Apparently, confirmed cases had significantly decreased after China was compelled to temporarily suspend the entry of foreign passport holders with valid visas or residence permits; 6 days after implement of controlled measures, the daily new confirmed cases were reduced to 13 cases. Moreover, about 84.3% of patients (166/197) presented symptoms 1 week after leaving the epicenter, and notably seven patients (3.6%) had symptoms 2 weeks after leaving the epicenter. The median incubation period was 3.0 days (inter quartile range, 1.0 to 6.0), the 95th percentile was 11.6 days. Additionally, most of cases (92.9%) were detected positively of nucleic acid after symptom onset with 4 days, the median diagnostic time was 2.0 days (interquartile range, 1.0 to 3.0), and the 95th percentile of the distribution was 5.0 days. Finally, about 5.8% of patients were healthy carriers, and the median confirmed time of asymptomatic patients was 4.0 days (interquartile range, 2.0 to 9.0). The following variables might be associated with confirmed time: symptom type (P = 0.005), exported regions (P < 0.001), and symptom onset time (P < 0.001).Conclusions: The prevention countermeasures for imported cases implemented by the Chinese government played an indispensable role in curbing the spread of COVID-19; the time of departure from epicenter could provide an estimate of the incubation period; and a confirmed time, 2-week quarantine period might need to be prolonged, while asymptomatic patients should be closely monitored.

Immunotherapy is a curable treatment for certain cancers, but it is still only effective in a small subset of patients, partly because of the lack of sufficient immune cells in the tumor. It is reported that targeted lactate dehydrogenase (LDH) to reduce lactic acid production can promote the infiltration and activity of immune cells and turn tumors into hot tumors. Therefore, we constructed a humanized mouse model to evaluate the efficacy of using classical LDH inhibitor oxamate and pembrolizumab alone or in combination in non-small cell lung cancer (NSCLC). We found that both oxamate and pembrolizumab monotherapy significantly delayed tumor growth; moreover, combination therapy showed better results. Immunofluorescence analysis showed that oxamate treatment increased the infiltration of activated CD8+ T cells in the tumor, which might have enhanced the therapeutic effects of pembrolizumab. Treatment of the humanized mice with anti-CD8 abrogated the therapeutic effects of oxamate, indicating CD8+ T cells as the main force mediating the effect of oxamate. In conclusion, Our preclinical findings position that oxamate not only inhibits tumor growth at a high safe dose but also enhances the efficacy of pembrolizumab in Hu-PBMC-CDX mice. Our study also provides a preclinical model for exploring the efficacy of other immune-based combination therapies for NSCLC.

Background: Few studies have reported the transmission characteristics of coronavirus disease (COVID-19) in low-density populations. This study has therefore analyzed the epidemiological characteristics and clinical outcomes of COVID-19 patients in Northwestern China, an area with low population density.Methods: From January 21 to March 11, 2020, data from patients diagnosed with novel coronavirus pneumonia (NCP) in areas of Northwestern China with lower population densities were retrospectively analyzed. Certain variables were categorized as numbers and percentages, with the ratio between resident patients (no history of going out during the epidemic) and imported patients representing the contagiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19. Hospitalization time was also calculated.Results: A total of 617 COVID-19 patients were reported in Northwestern China, and the morbidity and mortality rates of 0.000005 and 0.011, respectively. Further analysis showed that the morbidity was inversely proportional to population density and distance from Wuhan City. This study enrolled 473 confirmed cases; among these patients, there were 248 residents and 225 imported cases with a ratio of 1:1. The youngest and oldest patients were 1 and 94 years of age, respectively, with a median age of 42 years. Fifteen (3.2%) patients were children or infants. Two patients were pregnant, and one patient gave birth to a healthy baby with negative results during her disease course. About 17.3% of patients (82 cases) were healthy carriers without any symptoms during their disease course. One male patient (0.2%) had recurrence of a positive test result 4 days after discharge. The median hospitalization time was 16.0 days, ranging from 2.0 to 43.0 days. Further analysis showed that age (P = 0.03) and severity status (P < 0.001) were significantly correlated with hospitalization time.Conclusions: The morbidity and mortality rates of COVID-19 patients in the regions with a low population density were lower than those of the national average in China. All populations were susceptible to infection by SARS-CoV-2. Asymptomatic patients with positive results should be taken seriously, and the hospitalization time of patients is associated with their age and severity status.

To effectively reduce the mass and simplify the structure of traditional aerial manipulators, we propose novel light cable-driven manipulator for the aerial robots in this article. The drive motors and corresponding reducers are removed from the joints to the base; meanwhile, force and motion are transmitted remotely through cables. Thanks to this design, the moving mass has been greatly reduced. In the meantime, the application of cable-driven technology also brings about extra difficulties for high-precise control of cable-driven manipulators. Hence, we design a nonsingular terminal sliding mode controller using time-delay estimation. The time-delay estimation is applied to obtain lumped system dynamics and found an attractive model-free scheme, while the nonsingular terminal sliding mode controller is utilized to enhance the control performance. Stability is analyzed based on Lyapunov theory. Finally, the designed light cable-driven manipulator and presented time-delay estimation-based nonsingular terminal sliding mode controller are analyzed. Corresponding results show that (1) our proposed cable-driven manipulator has high load to mass ratio of 0.8 if we only consider the moving mass and (2) our proposed time-delay estimation-based nonsingular terminal sliding mode is model-free and can provide higher accuracy than the widely used time-delay estimation-based proportional–derivative (PD) controller.

We explored the face classification processing mechanism in depressed patients, especially the biases of happy faces in face classification processing of depression. Thirty patients with the first episode of depression at the First Affiliated Hospital of Harbin Medical University were selected as the depression group, while healthy people matched for age, gender, and educational level were assigned to the control group. The Hamilton Depression Scale and Hamilton Anxiety Scale were used to select the subjects; then, we used the forced face classification paradigm to collect behavioral (response time and accuracy) and event-related potential (ERP) data of the subjects. The differences between the groups were estimated using a repeated measurement analysis of variance. The total response time of classified faces in the depression group was longer than that in the control group, the correct rate was lower, and the difference was statistically significant (P

Congenital hypothyroidism is a genetic condition in which the thyroid gland fails to produce sufficient thyroid hormone (TH), resulting in metabolic dysfunction and growth retardation. Xb130−/− mice exhibit perturbations of thyrocyte cytoskeleton and polarity, and develop postnatal transient growth retardation due to congenital hypothyroidism, leading ultimately to multinodular goiter. To determine the underlying mechanisms, we performed transcriptomic analyses on thyroid glands of mice at three age points: week 2 (W2, before visible growth retardation), W4 (at the nadir of growth); and W12 (immediately before full growth recovery). Using gene set enrichment analysis, we compared a defined set of thyroidal genes between Xb130+/+ and Xb130−/− mice to identify differentially enriched gene clusters. At the earliest postnatal stage (W2), the thyroid glands of Xb130−/− mice exhibited significantly downregulated gene clusters related to cellular metabolism, which continued to W4. Additionally, mutant thyroids at W4 and W12 showed upregulated gene clusters related to extracellular matrix, angiogenesis, and cell proliferation. At W12, despite nearly normal levels of serum TH and TSH and body size, a significantly large number of gene clusters related to inflammatory response were upregulated. Early postnatal TH deficiency may suppress cellular metabolism within the thyroid gland itself. Upregulation of genes related to extracellular matrix and angiogenesis may promote subsequent thyroid growth. Chronic inflammatory responses may contribute to the pathogenesis of multinodular goiter in later life. Some of the pathoadaptive responses of Xb130−/− mice may overlap with those from other mutations causing congenital hypothyroidism.

Background/Aims: Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. Methods: The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. Results: The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan–Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). Conclusions: Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients.

Underwater long-distance high-voltage direct current transmission system can provide long-term, reliable, and sustainable energy for ocean observatories system which has higher reliability requirement than onshore or conventional underwater equipment. As the main network point for high-voltage direct current transmission system, medium-voltage converter of the primary node is at the top layer of power supply chain and its reliability will directly affect the reliability of high-voltage direct current transmission system. Based on a 2.5 kW medium-voltage converter, this study proposes a method to evaluate the reliability of medium-voltage converter with accuracy using the lifetime model of switch by analysis of component junction temperature providing theoretical foundation and technical guidance for medium-voltage converter design. Owing to the high power density of medium-voltage converter, the heat dissipation space is restricted to pressure vessel. This study proposes a thermal design method to ensure normal operation condition within appropriate temperature for medium-voltage converter and verified using ANSYS finite element analysis software.

New energy storage vehicles which use supercapacitors (SCs) as the unique source of traction power are developing rapidly recently. To satisfy the operating voltage requirement of energy storage vehicle, hundreds of SCs are needed to be connected in series. In this case, there is a voltage imbalance between the energy storage cells during rapid charging, resulting in reduced energy efficiency and service life of the energy storage device. A layered equalisation scheme is proposed to solve the problem of voltage imbalance. A single-input multiple-output synchronous rectification equalising circuit is proposed to ensure voltage consistency of series supercapacitor monomer in bottom module. The proposed circuit resolves the existing slow balancing speed and low-voltage balancing precision problems in the current supercapacitor equalising circuits. Meanwhile, an equalisation strategy based on module SOC is adopted to solve voltage imbalance problem of the upper supercapacitor module. The results of MATLAB/Saber co-simulation and experiment demonstrate that the layered equalisation system achieves the target of fast equilibrium and high precision balance.

Many applications of wireless power transmission (WPT) require high misalignment tolerance. However, the transmission power of WPT is highly susceptible to the misalignment. To solve this problem, the magnetic resonant WPT control method with high misalignment tolerance is proposed here. First, based on the general mutual model, the complex ratio transformer model is established. This model gives an intuitive physical picture in power transmission process and frequency splitting phenomenon. Second, approximately constant voltage gain at frequency splitting point in a wide range of misalignment is analysed. Considering this frequency splitting characteristics of Magnetic resonant WPT, the maximum peak point tracking control methods for wide misalignment, maintaining constant output power is proposed. Finally, the corresponding simulation and experimental validation is given, demonstrating the feasibility of the control method. When the misalignment reached 40%, the fluctuation of the output voltage will be

Backgrounds/Aims: The selective κ-opioid agonist U50,488H protects heart from myocardial ischemia-reperfusion (MI/R) injury. We examined whether U50,488H is also beneficial for MI/R induced heart failure. Methods: Anesthetized male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia via left anterior descending coronary artery (LAD) occlusion, followed by 4 weeks of reperfusion. Infarct size was examined by Evans blue/triphenyl tetrazolium chloride (TTC) staining. Cardiac function and remodeling were examined by echocardiography and histology. HO-1 gene transcription and expression were measured by RT-PCR and western blot. Results: Compared to vehicle-treated MI/R rats, rats administered a single dose of U50,488H at the beginning of reperfusion exhibited reduced myocardial infarct size, oxidative stress, hypertrophy, and fibrosis, improved mechanical function, and greater neovascularization. U50,488H also increased myocardial heme oxygenase (HO)-1 gene transcription and expression, while pharmacological HO-1 inhibition reversed all protective effects of U50,488H. Furthermore, U50,488H protected control cultured cardiomyoctes against simulated I/R-induced apoptosis but not cultures subjected to shRNA-mediated HO-1 knockdown. Inhibition of HO-1 in the subacute phase of reperfusion reversed the U50,488H-induced increase in neovascularization and suppression of oxidative stress. Finally, U50,488H increased Akt phosphorylation and nuclear translocation of Nrf2, a key HO-1 transcription activator, while inhibition of PI3K-Akt signaling abolished U50,488H-induced Nrf2 nuclear translocation, HO-1 upregulation, and cardioprotection. Conclusion: Activation of HO-1 expression through the PI3K-Akt-Nrf2 pathway may mediate the acute and long-term protective effects of U50,488H against heart failure by enhancing cardiomyocyte survival and neoangiogenesis and by reducing oxidative stress.

To improve the degradation ability of anaerobic granular sludge (AGS) toward the iodinated contrast media (ICM) iohexol, biogenic nanoscale palladium (Pd) was formed in AGS via microbial reduction. The Pd hosted in AGS (Pd-AGS) was used for iohexol degradation. The effects of the electron donor, reaction medium, iodide ion fouling, and polymer embedding of the Pd-AGS on the reactivity were investigated. Our results showed the Pd-AGS increased the degradation rate of iohexol, with a conversion rate constant increased by 86.3-fold compared to the AGS control. Various organic compounds were investigated as electron donors to initiate the catalytic activity of Pd-AGS and the promotion achieved with the tested electron donors was in the following order: formate > lactate > ethanol > glucose > acetate. The Pd-AGS had high reactivity in deionized water at mild pH, and almost no reactivity under acidic (pH = 1.2) and alkaline (pH > 11) conditions. The presence of iodide ions in the medium inhibited the catalytic activity of Pd-AGS toward iohexol because of catalyst fouling. Embedding the Pd-AGS in alginate, chitosan, or polyvinyl alcohol (PVA) could prevent Pd loss but it also retarded the iohexol degradation rate. The Pd-AGS, as a combination of Pd catalyst and AGS, provides a novel strategy for iohexol degradation in polluted water and wastewater.

SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice. Lentiviral vector-mediated overexpression of SIRT6 upregulated TERT and TRF1 and increased the survival of mice after TAC. Echocardiography and hemodynamic measurements as well as histological analyses indicated that SIRT6 overexpression attenuated TAC-induced heart dysfunction and decreased TAC-induced cardiac inflammatory responses, reducing cardiac fibrosis and decreasing infarct size. Taken together, our findings indicate that SIRT6 protects the myocardium against damage and this effect may be mediated by the modulation of telomeres. Our findings linking SIRT6 and telomere integrity in the heart warrant further investigation into the underlying mechanisms and support SIRT6 as a promising therapeutic target for the treatment of cardiovascular diseases.

A multi-cavity periodic structure with the characteristic of local resonance was proposed in the paper. The low frequency band-gap structure was comparatively analyzed by the finite element method (FEM) and electric circuit analogy (ECA). Low frequency band-gap can be opened through the dual influence of the coupling’s resonance in the cavity and the interaction among the couplings between structures. Finally, the influence of the structural factors on the band-gap was analyzed. The results show that the structure, which is divided into three parts equally, has a broader effective band-gap below the frequency of 200 Hz. It is also proved that reducing the interval between unit structures can increase the intensity of the couplings among the structures. And in this way, the width of band-gap would be expanded significantly. Through the parameters adjustment, the structure enjoys a satisfied sound insulation effect below the frequency of 500Hz. In the area of low frequency noise reduction, the structure has a lot of potential applications.

Background and objective NOK (Novel Oncogene with Kinase-domain) is a newly identified receptor protein-tyrosine kinases (RPTKs) subfamily, which possesses strong oncogenic potential including enhancing cell transformation, tumorigenesis, invasion and metastasis. However, NOK protein lacks extracellular domain, and how the NOK is activated by the membrane receptor and the expression of NOK in non small cell lung cancer (NSCLC) are not clear. Our aim of this study was to investigate the expressions of NOK, EGFR proteins in NSCLC. Methods The expression rates of NOK, EGFR proteins in 155 cases with NSCLC was deteced by immunohistochemical stain; The clinical correlations between two proteins were analyzed by statistics. Results The NOK positive expression was mainly located in cytoplasm and EGFR was mainly located in the plasma membrane and cytoplasm. NOK, EGFR proteins were high expressed in NSCLC and there were extremely differences comparing the expression of NOK, EGFR proteins in squamous cell lung cancer, lung adenocarcinoma with those in corresponding normal tissue respectively (P < 0.001); and there were no significant differences between the two kinds of the cancers for their comparison of NOK, EGFR expression (P=0.099; P=0.23); however, there were significant differences for NOK and EGFR expression among histological grades and TNM stages in squamous cell lung cancers, lung adenocarcinoma (P < 0.01). There were correlation between positive and intensity of NOK and EGFR expression in whatever total NSCLC or squamous cell lung cancer or lung adenocarcinoma (P < 0.001), while the correlation coefficients(rs) were 0742, 0.722, 0.756 respectively. Conclusion The NOK proteins are highly expressed in the NSCLC, and the expression rates of NOK proteins are correlated with the cancers’ histological grades and TNM stages, which may be concern with tumorgenesis and progression; the positive expression rate and intensity of NOK protein correlate well with the expression of EGFR protein in NSCLC, which the activation of NOK probably owe to EGFR activation, all that would provide evidence for further study on the effective mechanism of NOK in the tumorigenesis or tumor progression.

Background and objective Multidrug resistance (MDR) is the main reason of the failure of chemotherapy in lung cancer. The MDR mechanism in lung cancer is complex, which relates to sorts of drug resistant genes. ABCC10 is a recently identified member of a subset of the C family of ATP-binding cassette (ABC) transporters. The drug resistance capability of ABCC10 has been partly determined. The aim of the study is to investigate the expression of ABCC10 in non small cell lung cancer (NSCLC) and normal tissues, and analyze the relationship between ABCC10 expression level and clinical features, such as TNM stages, histological types and pathological grades. Methods The expression of ABCC10 was detected in squamous cell carcinoma, adenocarcinoma and normal lung tissues by immunohistochemistry. Then the statistical analysis was performed. Results The expression of ABCC10 was mainly located in cell membrane and cytoplasm. There were significant differences between the expression of ABCC10 in NSCLC and normal tissues (P

The repair and regeneration of airway epithelium is important for maintaining homeostasis of the respiratory system. XB130 is an adaptor protein involved in the regulation of cell proliferation, survival and migration. In the human trachea, XB130 is expressed on the apical site of ciliated epithelial cells. We hypothesize that XB130 may play a role in epithelial repair and regeneration after injury. Xb130 knockout (KO) mice were generated, and a mouse isogenic tracheal transplantation model was used. Adult Xb130 KO mice did not show any significant anatomical and physiological phenotypes in comparison with their wild type (WT) littermates. The tracheal epithelium in Xb130 KO mice, however, was significantly thicker than that in WT mice. Severe ischemic epithelial injury was observed immediately after the tracheal transplantation, which was followed by epithelial cell flattening, proliferation and differentiation. No significant differences were observed in terms of initial airway injury and apoptosis. However, at Day 10 after transplantation, the epithelial layer was significantly thicker in Xb130 KO mice, and associated with greater proliferative (Ki67+) and basal (CK5+) cells, as well as thickening of the connective tissue and fibroblast layer between the epithelium and tracheal cartilages. These results suggest that XB130 is involved in the regulation of airway epithelial differentiation, especially during airway repair after injury.

Semiconductors have been widely used in many high-tech fields such as photo- and electro-catalysis, ion batteries, and solar cells. In addition to the earliest discovered elemental and compound semiconductors, such as monocrystalline silicon and metal oxides, new types of compound semiconductors have been discovered. Among them, metal hydroxyfluorides (MOHF) are an emerging type of semiconductor that are easy to synthesize and inexpensive. However, many of their properties and applications are not well understood. Nevertheless, some MOHF materials, such as ZnOHF and CoOHF, have been sufficiently developed, and their applications have been extensively explored. This review focuses on a new compound semiconductor, MOHF, with ZnOHF and CoOHF as the typical. After a short introduction to their physical and chemical properties, their common applications are illustrated with several examples. Subsequently, other less-researched MOHF and MOHF-like materials, as well as their applications, are discussed. Moreover, the expectations and development directions of MOHFs are briefly summarized. [ABSTRACT FROM AUTHOR]