SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

BACKGROUND: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights. RESULTS: Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest. CONCLUSIONS: In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP . Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP .

Male germ cell-associated kinase (MAK) is required for axoneme formation during ciliogenesis in zebrafish photoreceptors.

Vertebrate photoreceptors are highly specialized retinal neurons that have cilium-derived membrane organelles called outer segments (OS), which function as platforms for phototransduction. Male germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase, and its genetic mutation causes photoreceptor degeneration in mice and retinitis pigmentosa in humans. However, the role of MAK in photoreceptors is not fully understood. Here, we report that zebrafish mak mutants show rapid photoreceptor degeneration during embryonic development. In mak mutants, both cone and rod photoreceptors completely lack OSs and undergo apoptosis. Interestingly, zebrafish mak mutants fail to generate axonemes during photoreceptor ciliogenesis, whereas basal bodies are specified. These data suggest that MAK contributes to axoneme development in zebrafish, in contrast to mouse Mak mutants, which have elongated photoreceptor axonemes. Furthermore, the kinase activity of MAK is critical in ciliary axoneme development and photoreceptor survival. Thus, MAK is required for ciliogenesis and OS formation in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.

Chip-level mass detection for micro-LED displays based on regression analysis and deep learning.

Though micro-light-emitting diode (micro-LED) displays are regarded as the next-generation emerging display technology, challenges such as defects in LED's light output power and radiation patterns are critical to the commercialization success. Here we propose an electroluminescence mass detection method to examine the light output quality from the on-wafer LED arrays before they are transferred to the display substrate. The mass detection method consists of two stages. In the first stage, the luminescent image is captured by a camera by mounting an ITO (indium-tin oxide) transparent conducting glass on the LED wafer. Due to the resistance of the ITO contact pads and on-wafer n-type electrodes, we develop a calibration method based on the circuit model to predict the current flow on each LED. The light output power of each device is thus calibrated back by multi-variable regression analysis. The analysis results in an average variation as low as 6.89% for devices predicted from luminescent image capturing and actual optical power measurement. We also examine the defective or non-uniform micro-LED radiation profiles by constructing a 2-D convolutional neural network (CNN) model. The optimized model is determined among three different approaches. The CNN model can recognize 99.45% functioning LEDs, and show a precision of 96.29% for correctly predicting good devices.

Downregulated antisense lncRNA ENTPD3-AS1 contributes to the development of lung adenocarcinoma.

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

Upregulated enhancer of rudimentary homolog promotes epithelial­mesenchymal transition and cancer cell migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1­0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non­tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH­correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial­mesenchymal transition and cell migration in vitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.

6-Plex mdSUGAR Isobaric-Labeling Guide Fingerprint Embedding for Glycomics Analysis.

Glycans are vital biomolecules with diverse functions in biological processes. Mass spectrometry (MS) has become the most widely employed technology for glycomics studies. However, in the traditional data-dependent acquisition mode, only a subset of the abundant ions during MS1 scans are isolated and fragmented in subsequent MS2 events, which reduces reproducibility and prevents the measurement of low-abundance glycan species. Here, we reported a new method termed 6-plex mdSUGAR isobaric-labeling guide fingerprint embedding (MAGNI), to achieve multiplexed, quantitative, and targeted glycan analysis. The glycan peak signature was embedded by a triplicate-labeling strategy with a 6-plex mdSUGAR tag, and using ultrahigh-resolution mass spectrometers, the low-abundance glycans that carry the mass fingerprints can be recognized on the MS1 spectra through an in-house developed software tool, MAGNIFinder. These embedded unique fingerprints can guide the selection and fragmentation of targeted precursor ions and further provide rich information on glycan structures. Quantitative analysis of two standard glycoproteins demonstrated the accuracy and precision of MAGNI. Using this approach, we identified 304 N-glycans in two ovarian cancer cell lines. Among them, 65 unique N-glycans were found differentially expressed, which indicates a distinct glycosylation pattern for each cell line. Remarkably, 31 N-glycans can be quantified in only 1 × 103 cells, demonstrating the high sensitivity of our method. Taken together, our MAGNI method offers a useful tool for low-abundance N-glycan characterization and is capable of determining small quantitative differences in N-glycan profiling. Therefore, it will be beneficial to the field of glycobiology and will expand our understanding of glycosylation.

Potential of methacrylated acemannan for exerting antioxidant-, cell proliferation-, and cell migration-inducing activities in vitro.

BACKGROUND: Acemannan is an acetylated polysaccharide of Aloe vera extract with antimicrobial, antitumor, antiviral, and antioxidant activities. This study aims to optimize the synthesis of acemannan from methacrylate powder using a simple method and characterize it for potential use as a wound-healing agent. METHODS: Acemannan was purified from methacrylated acemannan and characterized using high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), and 1H-nuclear magnetic resonance (NMR). 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays were performed to investigate the antioxidant activity of acemannan and its effects on cell proliferation and oxidative stress damage, respectively. Further, a migration assay was conducted to determine the wound healing properties of acemannan. RESULTS: We successfully optimized the synthesis of acemannan from methacrylate powder using a simple method. Our results demonstrated that methacrylated acemannan was identified as a polysaccharide with an acetylation degree similar to that in A. vera, with the FTIR revealing peaks at 1739.94 cm-1 (C = O stretching vibration), 1370 cm-1 (deformation of the H-C-OH bonds), and 1370 cm-1 (C-O-C asymmetric stretching vibration); 1H NMR showed an acetylation degree of 1.202. The DPPH results showed the highest antioxidant activity of acemannan with a 45% radical clearance rate, compared to malvidin, CoQ10, and water. Moreover, 2000 µg/mL acemannan showed the most optimal concentration for inducing cell proliferation, while 5 µg/mL acemannan induced the highest cell migration after 3 h. In addition, MTT assay findings showed that after 24 h, acemannan treatment successfully recovered cell damage due to H2O2 pre-treatment. CONCLUSION: Our study provides a suitable technique for effective acemannan production and presents acemannan as a potential agent for use in accelerating wound healing through its antioxidant properties, as well as cell proliferation- and migration-inducing activities.

Lobectomy Versus Sublobar Resection in Simultaneous Bilateral Thoracoscopic Lung Resection.

BACKGROUND: Simultaneous bilateral thoracoscopic lung resection (SBTLR) has been shown to be a feasible and efficacious approach for a wide range of pulmonary conditions. Our aim was to evaluate the impact of different procedures on surgical outcomes in patients receiving SBTLR. METHODS: Between 2012 and 2021, 207 patients with bilateral lung neoplasms who underwent SBTLR were retrospectively reviewed. Fifty-one patients received ipsilateral plus contralateral lobectomy or sublobectomy (lobar group), whilst 156 patients received bilateral sublobectomy (sublobar group). Propensity scores were calculated and matched. Perioperative and clinicopathologic outcomes were compared. RESULTS: The lobar group had a greater mean age (64.5 vs. 60.0 years, p = 0.008), longer operative time (254 vs. 205 min, p < 0.001), and more blood loss (74 vs. 46 ml, p < 0.001). The sublobar group had fewer complications (6.4 vs. 19.6%, p = 0.006), shorter hospital stay (4.8 vs. 7.4 days, p < 0.001), and lower hospital costs (p = 0.03). Among 50 pairs of matched groups, significant differences were found only in operative time, hospital stay, and costs. Maximum tumor size and pathological features differed significantly before and after matching (all p < 0.05), with the lobar group consistently demonstrating a larger main tumor (median, 2.5 cm) and a higher percentage of primary lung cancer (84%). Multivariate logistic regression analysis showed that a longer operative time was the factor associated with more complications (OR: 1.01; 95% CI 1.00-1.02, p = 0.002). CONCLUSIONS: With regard to SBTLR, our data suggests that sublobectomy may reduce the prolonged recovery, hospital costs, and complications incurred by lobectomy, without compromising oncological outcomes.

Pneumorrhachis with spontaneous pneumomediastinum in pediatric patients: An 11-year retrospective study in Southern Taiwan.

BACKGROUND: Although uncommon, available evidence suggests that pneumorrhachis (PR) with spontaneous pneumomediastinum (SPM) in adulthood is usually benign and self-limiting. This study aimed to review our experience and identify the risk factors of PR in pediatric patients with SPM. METHODS: Between September 2007 and September 2017, SPM in patients aged ≤18 years was retrospectively reviewed and clinical features and outcomes between SPM patients with and without PR were analyzed. RESULTS: In total, thirty consecutive occurrences of SPM in 29 patients were finally identified and classified into SPM (n = 24) and SPM plus PR (n = 6) groups. No significant differences in received interventional exams, prophylactic antibiotic administration or restriction of oral intake between the two groups were found. Both groups were treated with hospitalization predominantly; but the SPM plus PR group tended to have longer length of hospital stay (median 5.5 vs. 3 days, p = 0.08). PR was observed more frequently in patients with abnormal serum C-reactive protein (CRP) levels (>5 mg/L), identified predisposing factors, and those with more severe grade of SPM (p = 0.005, 0.001 and < 0.001, respectively). On multivariable regression analysis, the SPM plus PR group exhibited more predisposing factors than did the SPM group (coefficient: 0.514, standard error: 0.136, p < 0.001). All patients were successfully treated without morbidity and mortality. CONCLUSION: Although patients with pneumorrhachis retained a higher CRP level, more identified predisposing factors and prolonged inpatient care, conservative management without an extensive work-up would be an appropriate and favorable strategy in pediatrics with concurrent SPM and PR.

Air quality health index (AQHI) based on multiple air pollutants and mortality risks in Taiwan: Construction and validation.

The currently used air quality index (AQI) is not able to capture the additive effects of air pollution on health risks and reflect non-threshold concentration-response relationships, which has been criticized. We proposed the air quality health index (AQHI) based on daily air pollution-mortality associations, and compared its validity in predicting daily mortality and morbidity risks with the existing AQI. We examined the excess risk (ER) of daily elderly (≥65-year-old) mortality associated with 6 air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3) in 72 townships across Taiwan from 2006 to 2014 by performing a time-series analysis using a Poisson regression model. Random effect meta-analysis was used to pool the township-specified ER for each air pollutant in the overall and seasonal scenarios. The integrated ERs for mortality were calculated and used to construct the AQHI. The association of the AQHI with daily mortality and morbidity were compared by calculating the percentage change per interquartile range (IQR) increase in the indices. The magnitude of the ER on the concentration-response curve was used to evaluate the performance of the AQHI and AQI, regarding specific health outcomes. Sensitivity analysis was conducted using coefficients from the single- and two-pollutant models. The coefficients of PM2.5, NO2, SO2, and O3 associated with mortality were included to form the overall and season-specific AQHI. An IQR increase in the overall AQHI at lag 0 was associated with 1.90%, 2.96%, and 2.68% increases in mortality, asthma, and respiratory outpatient visits, respectively. The AQHI had higher ERs for mortality and morbidity on the validity examinations than the current AQI. The AQHI, which captures the combined effects of air pollution, can serve as a health risk communication tool to the public.

Nitrogen Adsorption and Characteristics of Iron, Cobalt, and Nickel Oxides Impregnated on SBA-15 Mesoporous Silica.

Hexagonal SBA-15 mesoporous material was used as a catalytic template for impregnation, with the transition metals Fe, Co, and Ni as catalysts for chemical transformation. Nitrogen adsorption/desorption isotherms, scanning electron microscopy, and transmission electron microscopy were conducted to better understand the physicochemical properties of the metal oxide-impregnated SBA-15. The specific surface area of the original SBA-15 was approximately 680 m2/g, and the abundances of the catalysts impregnated ranged from 2 to 8%, corresponding to specific surface areas of 560-470 m2/g for Fe-SBA-15, 440-340 m2/g for Ni-SBA-15, and 410-340 m2/g for Co-SBA-15. The increase in impregnated metal loadings filled the pores and collapsed the silica walls during the metal oxides impregnation on SBA-15 and calcination procedures, resulting in a decrease in the specific surface area and pore volume of the templates. The results showed that the order of nitrogen adsorbed was SBA-15 > Fe-SBA-15 > Ni-SBA-15 > Co-SBA-15 when the metal loading was 5%. In addition, the metal oxides on SBA-15 increased the wall thickness compared with raw SBA-15. Based on the XRD spectrum analysis, Fe2O3, Co3O4, and NiO were the stable crystals on the Fe-SBA-15, Co-SBA-15, and Ni-SBA-15, respectively. The sequence of the average grain size of metal oxides on SBA-15 was Co-SBA-15 > Fe-SBA-15 > Ni-SBA-15, according to XRD spectra and Scherrer's equation. Isopropanol could be decomposed by metal oxide-impregnated SBA-15 to form carbon filament materials. Therefore, these materials have the potential to be employed for pollutant removal, catalytic reactions for organic solvent and bio-oil/biomass reforming, and recycling waste into high-value materials.

Diastole/Body Mass Index Ratio Can Predict Post-Thoracoscopic Surgery Metastasis in Stage I Lung Adenocarcinoma.

BACKGROUND: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. METHODS: Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients' clinical and pathological characteristics were analyzed. RESULTS: Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). CONCLUSIONS: MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Exposure Characteristics and Cumulative Risk Assessment for Phthalates in Children Living near a Petrochemical Complex.

BACKGROUND: School-aged children living near plastics-producing factories may have higher risk of exposure to phthalates released during the manufacturing processes. OBJECTIVES: We aimed to investigate the urinary concentrations of phthalate metabolites in school-aged children living near a petrochemical complex and estimate the cumulative risk of phthalate exposure. METHODS: We used a well-established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-aged children (6-13 years old) living near polyvinyl chloride (PVC) and vinyl chloride monomer (VCM) factories in central Taiwan from October 2013 to September 2014. A total of 257 children were included from five elementary schools: Syu-Cuo Branch (n = 58, school A, ~0.9 km), Feng-An (n = 40, school B, ~2.7 km), Ciao-Tou (n = 58, school C, ~5.5 km), Mai-Liao (n = 37, school D, ~6.9 km), and Lung-Feng (n = 57, school E, ~8.6 km). We analyzed 11 metabolites of seven phthalates (including di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP)) in urine. Daily intakes (DIs) were compared with acceptable intake levels to calculate the hazard quotient (HQ) for individual phthalates, and the cumulative risk for each child was assessed using a hazard index (HI), which was the sum of the the individual HQs. RESULTS: The geometric mean and proportion of participants with HIs exceeding one for hepatic (HIhep) and reproductive (HIrep) effects were 0.33 (13.2%) and 0.24 (7.8%), respectively. The major contributors to phthalate exposure risk were DEHP, di-iso-butyl phthalate (DiBP) and DnBP in all children. Moreover, we observed a U shaped distribution of DEHP exposure by school distance from the PVC and VCM factories (school A: 7.48 µg/kg/day and school E: 80.44 µg/kg/day). This may be due to emissions (closest) and and being located downwind of PVC scrap incineration (farthest). CONCLUSIONS: Our findings suggest that children living near a petrochemical complex were at a greater risk of phthalate exposure than normal school-aged children and that phthalate exposure was mainly attributed to DEHP, DiBP and DnBP. In addition, inhalation may have been a risk factor for people living near to PVC and VCM factories.

Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated. METHODS: Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs). RESULTS: A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE-/-) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE-/- mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis. CONCLUSIONS: The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.

Mechanism and modeling of human disease-associated near-exon intronic variants that perturb RNA splicing.

It is estimated that 10%-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, systematic diagnosis or prediction of splicing variants is yet to be established, especially for the near-exon intronic splice region. The major challenge lies in the redundant and ill-defined branch sites and other splicing motifs therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants that overlapped with branch sites and collected 5,884 variants across the 5' splice region. We found that strong splice sites and exonic features preserve splicing from intronic sequence variation. Whereas the splice-altering mechanism of the 3' intronic variants is complex, that of the 5' is mainly splice-site destruction. Statistical learning combined with these molecular features allows precise prediction of altered splicing from an intronic variant. This statistical model provides the identity and ranking of biological features that determine splicing, which serves as transferable knowledge and out-performs the benchmarking predictive tool. Moreover, we demonstrated that intronic splicing variants may associate with disease risks in the human population. Our study elucidates the mechanism of splicing response of intronic variants, which classify disease-associated splicing variants for the promise of precision medicine.

Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming.

Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 (EIF4A1) and EIF4A2, in developing LUAD, as well as their underlying mechanisms. We found that the expression of EIF4A1, but not EIF4A2, was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of EIF4A1. Functional enrichment analysis revealed that upregulation of EIF4A1 was related to cell cycle regulation and DNA repair. The oncogenic effect of EIF4A1 was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with EIF4A1 was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated EIF4A1 expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with EIF4A1 was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of EIF4A1 might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.

The effect of microwave pyrolysis on product characteristics and bromine migration for a non-metallic printed circuit board.

At present, it is necessary to carry out environmentally friendly treatment of non-metallic fractions (NMFs) of waste printed circuit board (WPCB) to improve resource utilization. NMFs of WPCB are pyrolyzed by microwave heating to determine the effect of different operating conditions on the characteristics of pyrolysis products. The results show that yields for residue, oil and gas are 59.03-67.63, 7.10-28.46 and 4.86-33.88 wt%. A high temperature promotes a decrease in oil yield and an increase in non-condensable gas yield. An increase in the NaOH dose results in a more significant cracking of the oil to gas. Increasing the concentration of NaOH increases the mass fraction of the total Br in residues (from 23.62 to 86.94 %), so the addition of NaOH is beneficial to the fixation of Br. A kinetics study shows that there are two thermal decomposition regions (398-625 K and 675-925 K), and NaOH-catalyzed pyrolysis reduces the activation energy to 18.91 and 31.95 kJ mol-1, respectively. The formation of Br-containing substances in the pyrolysis oil and gas can be inhibited if the bromine fixation in pyrolysis residue increases. NaOH-catalyzed pyrolysis can reduce bromine and also reduce energy recovery efficiency. This pyrolysis process still requires further research to improve the recovery of energy and valuable materials.

Pulmonary completion lobectomy after segmentectomy: An integrated analysis of perioperative outcomes.

BACKGROUND: Completion lobectomy (CL) after anatomical segmentectomy is technically challenging and rarely performed. Here, we aimed to report perioperative outcomes of a single center real-world CL data. METHODS: Seven patients who underwent CL after segmentectomy were retrospectively evaluated between 2015-2021. Additionally, 34 patients were included in the review based on relevant studies in the literature until March 2022. A total of 41 patients were finally analyzed and classified into groups, according to surgical approach (video-assisted thoracic surgery [VATS] and thoracotomy; 12 and 29 patients, respectively) or interval-to-CL following initial segmentectomy (≤8 weeks [short] and >8 weeks [long]; 11 and 30 patients, respectively). RESULTS: There were no significant differences in estimated blood loss, postoperative hospital stay, or complications between the predefined groups. However, a longer operative time was observed in the long interval-to-CL group than in the short interval-to-CL group (267 vs. 226 min, p = 0.02). The rate of severe hilar adhesions was higher in the thoracotomy versus VATS groups (72 vs. 42%, p = 0.06) and in the long versus short interval-to-CL groups (70 vs. 45%, p = 0.15). On multivariable logistic regression analysis of a subgroup (n = 30), completion lobectomy of upper lobes may be associated with severe hilar adhesions (p = 0.02, odds ratio: 13.98; 95% confidence interval [CI]: 1.36-143.71). CONCLUSION: Completion lobectomy after segmentectomy can be performed securely by either VATS or thoracotomy. Although the thoracotomy and long interval-to-CL groups retained a greater percentage of severe hilar adhesions, the perioperative outcomes were similar to those of VATS and short interval-to-CL groups, respectively.

The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy.

Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.

Downregulated ADAMTS1 Incorporating A2M Contributes to Tumorigenesis and Alters Tumor Immune Microenvironment in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) still holds the most dreadful clinical outcomes worldwide. Despite advanced treatment strategies, there are still some unmet needs. Next-generation sequencing of large-scale cancer genomics discovery projects combined with bioinformatics provides the opportunity to take a step forward in meeting clinical conditions. Based on in-house and The Cancer Genome Atlas (TCGA) cohorts, the results showed decreased levels of ADAMTS1 conferred poor survival compared with normal parts. Gene set enrichment analyses (GSEA) indicated the negative correlation between ADAMTS1 and the potential roles of epithelial-mesenchymal transition (EMT), metastasis, and poor prognosis in LUAD patients. With the knockdown of ADAMTS1, A549 lung cancer cells exhibited more aggressive behaviors such as EMT and increased migration, resulting in cancer metastasis in a mouse model. The pathway interaction network disclosed the linkage of downregulated α2-macroglobulin (A2M), which regulates EMT and metastasis. Furthermore, immune components analysis indicated a positive relationship between ADAMTS1 and the infiltrating levels of multiple immune cells, especially anticancer CD4+ T cells in LUAD. Notably, ADAMTS1 expression was also inversely correlated with the accumulation of immunosuppressive myeloid-derived suppressor cells and regulatory T cells, implying the downregulated ADAMTS1 mediated immune adjustment to fit the tumor survival disadvantages in LUAD patients. In conclusion, our study indicates that ADAMTS1 interacts with A2M in regulating EMT and metastasis in LUAD. Additionally, ADAMTS1 contributes to poor prognosis and immune infiltration in LUAD patients.