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Dietary cholesterol has been implicated to promote lung cancer. Lung adenocarcinoma (LAC) is a main type of lung cancer, whereas the functional mechanism of cholesterol in LAC remained largely unknown. In the present study, we evidenced that cholesterol promoted cell proliferation and invasion of LAC in vitro as well as LAC metastasis in vivo. Cyp27A1 knockdown reduced the cholesterol-induced LAC cells proliferation and invasion. In contrast, Cyp7B1 knockdown enhanced the effect of cholesterol on LAC cells proliferation and invasion. Furthermore, Cyp27A1 deficiency remarkably reduced high cholesterol-induced LAC metastasis in vivo. Mechanism investigation demonstrated that exposure of LAC cells to 27-hydroxycholesterol induced the phosphorylation of AKT and NFκB p65, and promoted the expression of peptidylprolyl isomerase B (PPIB), especially in the coculture with THP1-derived macrophage. Meanwhile, 27-hydroxycholesterol induced the secretion of FGF2 and IL-6, which contributed to the expression of snail and vimentin. Luciferase report assay and ChIP assay confirmed that NFκB p65 controlled the transcription of PPIB. Inhibiting NFκB p65 activation reduced PPIB expression. PPIB inhibition reduced 27-hydroxycholesterol-induced expression of snail and vimentin. These results indicated that 27-hydroxycholesterol linked high cholesterol and LAC metastasis by regulating NFκB/PPIB axis and the secretion of FGF2 and IL-6.

C-aryl glycosides are an important kind of carbohydrate derivatives for drug discovery, due to their distinctive attributes of resistance to hydrolysis from enzymes. Herein, C-aryl glycosylation was established for the synthesis of 2-sulfur C-aryl glycals and 1,2-dihydrobenzofuran-fused C-aryl glycosides via interrupted Pummerer process, featured with sulfonium-tethered [3,3]-sigmatropic rearrangement between sulfoxide glycals and phenols. This protocol offers a broad substrate scope with diverse glycosyl and phe-nols. Dapagliflozin, Empagliflozin, and Ipragliflozin analogs were straightforward achieved, respectively.

The difference and similarities in the physicochemical and volatile flavor properties were determined in neon flying squid (OB), jumbo squid (DG), and Argentine squid (IA) mantles during 8 days of chilled storage. Physicochemical analysis indicated the chilled conditions induced rapid increases in pH value, total volatile basic nitrogen (TVBN), and carbonyl and malondialdehyde (MDA) content of the three squid species. In addition, myofibrillar protein (MP) content decreased and springiness in the OB, DG, and IA mantle samples declined with the extension of storage time. Importantly, OB mantles presented less chemical stability than the other two squid samples during 8 days of chilled storage. In addition, histological observations suggest DG mantle tissues presented more compact structures than those of the other two samples. Volatile flavor analysis showed propionaldehyde, 3-pentanone, trimethylamine, 3-furanmethanol, 2-methyl butyric acid, and 2-butanone were highly abundant in the squid mantles after storage, likely resulting from decomposition, oxidation, and degradation of proteins and lipids in the squid mantle, which varied with different squid species. The findings provide insight into the performance of three squid species during chilled storage.

Statistical process of grouping and modeling

The legend of Figure S1

Purpose: Effective biomarkers for the diagnosis of non–small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis.Experimental Design: The plasma levels of IDH1, CA125, Cyfra21-1, and CEA were assayed by ELISA. Blood samples were obtained from 1,422 participants (943 patients with NSCLC and 479 healthy controls). The samples were randomly divided into a training set and a test set. Receiver operating characteristic and binary logistic regression analyses were applied to evaluate diagnostic efficacy and establish diagnostic mathematical models.Results: Plasma IDH1 levels were significantly higher in patients with NSCLCs than in healthy controls (P < 0.001). The diagnostic use of IDH1 in lung adenocarcinoma [area under curve (AUC): 0.858 and 0.810; sensitivity: 77.1% and 76.2%; specificity: 82.9% and 76.6%; in the training set and test set, respectively] was significantly greater than that of CA125, Cyfra21-1, or CEA (P < 0.001). The model combining IDH1 with CEA, CA125, and Cyfra21-1 was more effective for lung adenocarcinoma diagnosis than IDH1 alone (sensitivity and specificity in the training set: 75.8%, 89.6%; test set: 86.3%, 70.7%). In addition, the plasma levels of IDH1 could contribute to the diagnostic model of lung squamous cell carcinoma.Conclusions: IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity. Clin Cancer Res; 19(18); 5136–45. ©2013 AACR.

The diagnostic effect of IDH1 after stratification in smokers and non-smokers.

The analysis of the Pearson Correlation between IDH1 levels and smoking history in ADC, SCC, and healthy control groups.

The equations used in the models, which were obtained by binary logistic regression.

Figure S1. IDH1 concentrations in patients with different T stages. (A) IDH1 concentrations in ADC patients with stages T1a-T2a versus stages T2b-T4. (B) IDH1 concentrations in SCC patients with stages T1a-T2a versus stages T2b-T4.

Multi-satellite and buoy observation data were used to systematically analyze the ocean response offshore of Taiwan to Super Typhoon Nepartak in 2016. The satellite data showed that a high sea surface temperature combined with a thick warm water layer and deep mixed layer provided a good thermal environment for continuous intensification of the typhoon. Two high-resolution buoys (NTU1 and NTU2) moored 375 and 175 km offshore of southeastern Taiwan were used to clarify the typhoon–ocean interaction as the typhoon approached Taiwan. The ocean conditions were similar at the two buoys before the typhoon, and both buoys were on the left side of the typhoon track and suffered similar typhoon factors (e.g., typhoon intensity and translation speed) during its passage. However, the ocean response differed significantly at the two buoys. During the forced period, the entire upper ocean was cooled at NTU1. In contrast, there was a clear three-layer vertical structure at NTU2 consisting of cool surface and deep layers with a warmer layer between the two cool layers. These responses can be attributed to strong upwelling of a cold eddy at NTU1 and vertical mixing at NTU2. These results indicate that, under similar preexisting conditions and typhoon factors, the movement of ocean eddies under typhoon forcing is an unexpected mechanism that results in upwelling and thus needs to be considered when predicting changes in the ocean environment and typhoon intensity.

A mixed drug self-delivery system (DSDS) with high drug content (>50%) was developed to regulate pH-triggered drug release, based on two doxorubicin (DOX)-DOX dimmers: D-DOXADH and D-DOXcar conjugated with acid-labile dynamic covalent bonds (hydrazone and carbamate, respectively) and stabilized with PEGylated D-DOXADH (D-DOXADH-PEG). Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them, pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS. Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios, that had a similar DOX content and diameter but different drug releasing rates. The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

The scaling laws have long been used as evidence of science where many fundamental physics laws emerge. As emerging nanomaterials, quantum dots are also sensitive to scaling because of their strong size effect. In this work, we developed the chiral dielectric theory based on the exciton absorption mechanism to explain the increment of the dielectric constant from chirality via its dimensionality. To help researchers discover and develop scaling relevant theories, the Authentic Intelligent Machine (AIM) protocol was developed to generate and interpret experimental data in an analytical and scaling-oriented manner. We show how the AIM protocol interprets spectra such as transient absorption data of chiral quantum dots with theories, where discrepancies concerning the dielectric constant were discovered. Examples for applying the AIM protocol on other spectra, such as absorption spectra and photoluminescence spectra, are also given.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare lung cancer subtype. Studies concerning PSC are limited and controversial; therefore, we analyzed the treatment and outcomes of PSC utilizing a relatively large single-institution database. METHODS: From January 2003 to December 2018, 262 consecutive PSC patients treated at our institution were retrospectively reviewed. The clinical characteristics, treatments, and outcomes were analyzed. RESULTS: The median survival time (MST) was 22.0 months, with 1-, 3-, and 5-year overall survival (OS) rates of 59.9%, 40.1%, and 36.1%, respectively. Patients who underwent surgery had a significantly better prognosis than patients who received nonsurgical treatment (MST, 23.0 vs. 11.0 months, P=0.016). The use of surgery followed by adjuvant therapy significantly prolonged survival in stage III patients (MST, 17.0 vs. 8.0 months, P=0.003) but not in stage I and II patients. Multivariate analysis showed that a systemic inflammation-immune index (SII) value >430.8, TNM stage and necrosis were independent prognostic predictors of OS and disease-free survival (DFS) in radically resected PSC patients (P

This paper explores the rate and severity of plasmonic bubble generation by gold nanoparticles (AuNPs) of different sizes and concentrations under sunlight illumination. An AuNP nanoengine has been...

Background The rate of unplanned return to the operation room (UROR) is an important index for the quality of surgeries. Study of the features and causes of patients who have suffered UROR is key to reduce the risk of it. Methods A retrospective, observational study was conducted among lung cancer patients who have received lung resections and UROR over a 5-year period. The causes, findings, procedures of UROR and recovery of patients were examined. Results Among the 23,345 lung cancer surgeries, 64 underwent UROR with the rate being 0.27%. Lobectomy was performed in 78.1% of the patients. The most common indication was post-operative bleeding, responsible for 82.8% (53/64) of the cases. The median length of stay after the second surgery was 7 days and over 90% of the patients were discharged with proper recovery. The death rate within 90 days after return to operation room (OR) was 1.6% (1/64). In the 53 cases caused by bleeding, 27 (50.9%) occurred in surgical sites, with the raw surface of lymph node dissection being most frequently affected. Bleedings on incisions and unknown origin took up 11.3% and 37.7%, respectively. Conclusions Bleeding is the most common indication which causes over 80% of UROR for lung cancer surgeries. Careful examination and complete hemostasis in surgery is key to reduce the risk of this unwanted complication.

International audience; The synthesis of CdSe/CdS core/shell nanoparticles was revisited with the help of a causal inference machine learning framework. The tadpole morphology with 1–2 tails was experimentally discovered. The causal inference model revealed the causality between the oleic acid (OA), octadecylphosphonic acid (ODPA) ligands, and the detailed tail shape of the tadpole morphology. Further, with the identified causality, a neural network was provided to predict and directly lead to the original experimental discovery of new tadpole-shaped structures. An entropy-driven nucleation theory was developed to understand both the ligand and temperature dependent experimental data and the causal inference from the machine learning framework. This work provided a vivid example of how the artificial intelligence technology, including machine learning, could benefit the materials science research for the discovery.

The trend of digitalization has produced rapidly increasing data interaction and authentication demand in today's internet of things ecosystem. To face the challenge, we demonstrated a micro-scale label by direct laser writing to perform as a passport between the physical and digital worlds. On this label, the user information is encrypted into three-dimensional geometric structures by a tensor network and then authenticated through the decryption system based on computer vision. A two-step printing methodology is applied to code the randomly distributed fluorescence from doped quantum dots, which achieved physical unclonable functions (PUFs) of the passport. The 10

Stereoselective glycosylation is challenging in carbohydrate chemistry. Herein, stereoselective thioglycosylation of glycals via palladium-catalyzed allylic rearrangement yields various substituents on α-isomer thioglycosides. Two comprehensive series of aryl and benzyl thioglycosides were obtained via a combination of thiosulfates with glycals derived from glucose, arabinose, galactose, and rhamnose. Furthermore, diosgenyl α-l-rhamnoside and isoquercitrin achieved selectivity via stereospecific [2,3]-sigma rearrangements of α-sulfoxide-rhamnoside and α-sulfoxide-glucoside, respectively.

Background: Tracheal cancer is a rare malignancy of which previous reports are mostly case reports or small series. Herein, we sought to evaluate the clinical characteristics, surgical treatments, and prognosis of surgically treated primary tracheal cancer patients. Methods: Patients with primary tracheal cancer who had received surgery in our center between January 2000 and December 2020 were enrolled. Clinical and surgical features were collected by retrospective review of medical records and follow-up was done by telephone interview. The statistical tests were two-sided. Results: A total of 128 patients were included in the study, 49.2% of whom were male, and the average age was 49.4 +/- 13.6 years. The most common histological subtype was adenoid cystic carcinoma (ACC; 78/128, 60.9%) followed by squamous cell carcinoma (SCC; 24/128, 18.8%). The percentage of tumors located in the cervical trachea, thoracic trachea, and carina were 50%, 41.4%, and 8.6%, respectively. Among those analyzed, 32.0% of the primary tumors had invaded adjacent organs (E2 disease) and 7.8% of patients had lymph node involvement. Tracheal resection plus reconstruction (with or without thyroidectomy) was the predominant surgical procedure, followed by carinal resection with neocarina. Radical resection (R0) was performed on 61.7% of patients and 63 (49.2%) patients received adjuvant therapy. Compared to ACC, SCC patients had significantly higher risk of tumor of the carina, nodal metastasis, and complications. The 5-year overall survival (OS) for the entire cohort was 84.5% and factors associated with poor prognosis included carinal tumor [hazard ratio (HR) =10.206; P

Hypertension has become a major public health challenge, and previous studies have observed associations between hypertension and sodium, potassium, and sodium to potassium ratio. However, little is known about how the whole continuum of blood pressure (BP) is related to dietary intake of sodium and potassium. This study aims to examine quantile-specific associations of blood pressure with dietary intake of sodium and potassium. It is based on national-level, cross sectional data for US adults aged ≥18 years from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. A total of 11,095 eligible subjects were included in this study. Quantile regression (QR) models were used to investigate distributional effects in the dietary intake of sodium and potassium on blood pressure by adjusting the confounding factors. We observed some evidence indicating distributional effects of dietary intake of sodium and potassium on systolic blood pressure (SBP) and diastolic blood pressure (DBP). QR showed that the consumption of sodium was positively associated with SBP (P10) and DBP (P10) in males, and positively associated with DBP (P80-P90) alone in females. Intake of potassium was, however, negatively associated with SBP (P20-P30, P70-P80) in males, and also negatively associated with SBP (P10-P80) and DBP(P20-P50) in females. Sodium to potassium ratio was positively associated with SBP (P10-P50, P80) and DBP (P70-P90) in males, and was positively associated with SBP(P10-P70, P90) in females. QR models provided a more detailed view on associations of SBP and DBP with the dietary intake of sodium and potassium and uncovered the quantile-related patterns.

A nickel-catalyzed coupling of N-sulfonyl-1,2,3-triazole with various H-phosphine oxides for the construction of C(sp2)–P bonds is established. This unexpected reaction proceeds through a formal nickel-bound ketenimine pathway, representing a previously unknown 1,2-reactivity type of an azavinyl carbene. The method provides an efficient approach to the stereoselective and site-selective synthesis of α-aminovinylphosphoryl derivatives with moderate to good yield. A plausible mechanism is proposed based on experimental and theoretical studies.

A new two-dimensional carbon allotrope, which consists of 18 atoms in a hexagonal cell, is theoretically investigated by performing first-principle method. The allotrope displays a P6/mmm symmetry (termed as hP-C18 carbon). The new 2D carbon phase has an sp2-sp3 network, consisting of hexagons and octagons formed by near-by atoms. The calculations demonstrate that hP-C18 carbon is a metastable 2D carbon phase compared to graphene, but it is more energetically stable than penta-graphene. The dynamical, thermal and mechanical stabilities are demonstrated by phonon dispersion, ab inito MD simulations and elastic constants, respectively. The analysis of electronic band structure shows that hP-C18 is an indirect semiconductor with a band gap of 2.93 eV (HSE06). Besides, its buckled 3D structure, hP-C18-3D carbon, is also predicted. The stability of the new 3D phase is discussed by phonon dispersion and elastic constants. It is found that hP-C18-3D carbon is a super-hard indirect semiconductor with an indirect band gap of 2.24 eV (HSE06). Thus, hP-C18 carbon and its buckled 3D structure may possess not only potential electronic applications but also mechanical applications.

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

Polyprodrugs, in which drug was used as the structural unit by linking with each other via the dynamic covalent bonds in the main chain, are expected to endow excellent drug delivery performance. Here, acid-triggered degradable diblock polyprodrug, poly(doxorubicin)-polyethylene glycol (PDOX-PEG), was designed with DOX as structural unit alternately linked with acid-labile hydrazone and maleic amide groups, by the polycondensation of DOX-based dimers (D-DOXADH or D-DOXMAH) with PEGylated dimer (DOX-ADH-DOX-PEG) as end capping agent. The optimized PDOX-PEG, which was synthesized with D-DOXADH and the PEGylated dimer at a feeding ratio of 10%, possessed a high Mn of 3.1 × 104 g/mol with a high DOX content of 75.42%. It could easily self-assemble into near spherical nanoparticles with average hydrodynamic diameter of 135 nm. They showed excellent pH-triggered sustained drug release owing to the acid-triggered degradation of the polyprodrug block in the tumor intracellular microenvironment, with low premature drug leakage of 4.39 % within 60 h. The MTT results indicated the enhanced antitumor efficacy of the proposed PDOX-PEG nanoparticles than free DOX. The results demonstrated the promising potential of the proposed acid-triggered degradable diblock PDOX-PEG polyprodrug for tumor treatment.

Background Uniportal thoracoscopic sleeve lobectomy is rarely reported owing to its high degree of difficulty. We conducted a comparative study on the safety and efficacy of uniportal versus multiportal thoracoscopic sleeve lobectomy for the treatment of centrally located lung cancer. Methods From January 2016 to December 2018, 30 thoracoscopic sleeve lobectomies (12 by the uniportal approach and 20 by the multiportal approach) for centrally located lung cancer at our institution were retrospectively analyzed. Results The uniportal approach resulted in a significantly shorter chest drainage duration (5.3±1.9 vs. 7.1±2.8 days, P=0.028) and a smaller chest drainage volume (796.7±582.9 vs. 1,667.8±1,154.9 mL, P=0.004) than the multiportal approach. The two groups showed no significant differences in the dissection of lymph nodes, operation time, estimated blood loss, conversion rate, length of postoperative hospital stay and the proportion of patients with postoperative complications. The short-term overall survival (OS) and disease-free survival (DFS) between uniportal and multiportal groups were similar (3-year OS, 100.0% vs. 82.5%, P=0.222; 3-year DFS, 75.8% vs. 84.4%, P=0.641). For the eight cases of the uniportal approach conducted by the same surgeon, the cumulative sum (CUSUM) curve showed its inflection at patient number 4 and divided the series into phase I (learning phase) and phase II (experienced phase). A significant reduction in estimated blood loss (42.5±8.7 vs. 177.5±121.2 mL, P=0.037), chest drainage volume (280.0±155.8 vs. 972.5±464.5 mL, P=0.043) and chest drainage duration (3.8±1.0 vs. 6.8±2.2 days, P=0.027) was also noted in the phase II patients compared with the phase I patients. Conclusions Uniportal thoracoscopic sleeve lobectomy is technically feasible and safe for the treatment of centrally located lung cancer and may achieve superior surgical outcomes compared with the multiportal approach.

Given that robots are being utilized extensively in chemical synthesis research, the potential applications of robots remain to be explored. Along with the remarkable progress of experimental science, circumstances have occurred in which publications were castigated because of irreproducibility, either because of rigorous experimental conditions or because of initial data forgery. Some credit-assignment issues and plagiarism cases also attracted intense attention throughout the community. As a possible solution to authenticity and originality problems, we herein propose a blockchain integrated automatic experiment platform, BiaeP, which attempts to provide solutions for those kinds of problems. As a result of the integration with blockchain, its data irreversibility secures the authenticity and the timestamp helps prove the originality. Two trial experiments are included as examples. We believe the architecture of BiaeP could be widely applicable for future development of scientific research in experimental subjects, such as chemistry, materials science, biology, and so forth.

Microplastics have become an emerging concerned global environmental pollution problem. Their strong adsorption towards the coexisting organic pollutants can cause additional environmental risks. Therefore, the adsorption capacity and mechanisms are necessary information for the comprehensive environmental assessments of both microplastics and organic pollutants. To overcome the lack of adsorption information, five quantitative structure–property relationship (QSPR) models were developed for predicting the microplastic/water partition coefficients (log Kd) of organics between polyethylene/seawater, polyethylene/freshwater, polyethylene/pure water, polypropylene/seawater, and polystyrene/seawater. All the QSPR models show good fitting ability (R2 = 0.811–0.939), predictive ability (Q2ext = 0.835–0.910, RMSEext = 0.369–0.752), and robustness (Qcv2 = 0.882–0.957). They can be used to predict the Kd values of organic pollutants (such as polychlorinated biphenyls, chlorobenzene, polycyclic aromatic hydrocarbons, antibiotics perfluorinated compounds, etc.) under different pH conditions. The hydrophobic interaction has been indicated as an important mechanism for the adsorption of organic pollutants to microplastics. In sea waters, the role of hydrogen bond interaction in adsorption is considerable. For polystyrene, π–π interaction contributes to the partitioning. The developed models can be used to quickly estimate the adsorption capacity of organic pollutants on microplastics in different types of water, providing necessary information for ecological risk studies of microplastics.

Background Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population. Methods Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (, This study revealed the first lncRNA signature that showed powerful predictive value for pathological response in ESCCs with nCRT; The three‐lncRNA signature was the first molecular model to show robust prognostic accuracy in patients with ESCC undergoing nCRT; and the number of cases from multi‐institutions enrolled in this project was considerably larger than any of the previous studiesfruit.

Objective: People have high 10-year cardiovascular disease (CVD) risk should take measures to prevent CVD. Thus, to know which subgroups of the population have high CVD risk is important. This study found out trends and risk factor of CVD risk in the US population.Methods: The population aged 30 years and older who were not diagnosed with CVD came from the National Health and Nutrition Examination Surveys (NHANES) in this study, n=35196. Logistic regression models were used to analyze the trends of CVD risk and estimate association between risk factor and CVD risk.Results: The estimated rate of CVD risk > 10% changed from 1999 to 2016 (from 42.2% to 47.7% for males, from 24.7% to 23.9% for females). The estimated rate increased in males over time (P for trend =0.001), while it was stable in females. Males who did not participate in vigorous recreational activity, the estimated rate of CVD risk> 10% significantly increased (P for trend 10%, 20% and 30% increased with BMI level in males in the multivariable-adjusted model; the odds ratios and 95% confidence intervals (OR [95% CI] ) of obesity was 1.63 [1.41, 1.88] for CVD risk >10%, 1.69[1.45, 1.48] for CVD risk >20%, and 1.56[1.30, 1.87)] for CVD risk >30%. Conclusions: The rate of CVD risk >10% had an increasing trend in American males adults, who did not participate in vigorous recreational activity. In addition, lower annual household income, higher weight status and do not participate in vigorous recreational activity increased the CVD risk.

Qingpeng Zeng,1 Bingzhi Wang,2 Jiagen Li,1 Jun Zhao,1 Yousheng Mao,1 Yushun Gao,1 Qi Xue,1 Shugeng Gao,1 Nan Sun,1 Jie He1 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Jie HeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing 100021, People’s Republic of ChinaEmail prof.jiehe@gmail.comObjective: Spread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas.Patients and Methods: We retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed.Results: Before propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) (p = 0.001) and solid/micropapillary patterns (SMPs) (p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826– 20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis (p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis.Conclusion: We found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma.Keywords: lung adenocarcinoma, spread through air spaces, solid pulmonary nodule

We found a straightforward dependence of plant growth on the sizes of graphene quantum dots. Enormous GQDs, such as graphene with dimensions of micrometers, neither promoted nor inhibited the growth. In contrast, synthesized GQDs with dimensions of about 10 nm best promoted the plant growth. Moreover GQDs synthesized using an "intelligent" chemistry robot yielded even better growth results than did GQDs synthesized conventionally by humans. In addition, a theoretical model was derived for the mechanism of the promotion of plant growth by GQDs.

An intelligent chemistry strategy based automated machine is applied for the study of the phase transition in CsPbBr3 quantum dots (QDs). With an in situ photoluminescence (PL) signal detection and analysis module, oleyl amine (OLA) and oleyl acid (OA) ligand concentration dependent diffusion pictures are well derived, a three-stage power-law scaling is disclosed on the ligand concentration dependent growth, and a phase transformation from CsPbBr3 to Cs4PbBr6 QDs is confirmed. Based on the experimental analysis associated with the G0W0–BSE calculation, we confirmed that there is no significant PL signal in the pure Cs4PbBr6 structure. With a steady temperature control module, we find that the ligand concentration and the Soret effect are isomorphic for the mass flux in the QD nucleation and phase transformation. We find that the activity of surface states can be essential for the size dependence of the Soret effect in a general way.

Lung adenocarcinoma (LUAD) is the predominant subtype of lung cancer, with increasing evidence showing clinical benefits of immunotherapy. However, a lack of integrated profiles of complex LUAD immune microenvironments hampers the application of immunotherapy, resulting in limited eligible patient populations as well as drug resistance problems. Here, we aimed to systematically profile the immune signatures of LUADs and to assess the role of the immune microenvironment in patient outcome. We systematically profiled the immune signatures of LUADs deposited in the TCGA and GEO databases using a total of 730 immune-related genes. Differential expression analysis was used to identify dysregulated genes. Univariate Cox analysis followed by robust likelihood-based survival analysis and multivariate Cox analysis were applied to construct an immune-related prognostic model. We found that differentially expressed immune genes were mainly enriched in immune cell proliferation, migration, activation and the NF-κB and TNF signaling pathways. The 10-immune gene predictive model that we constructed could differentiate LUAD patients with different overall survival times in several datasets, with areas under the curve (AUCs) of 0.67, 0.69, 0.72 and 0.74. LUAD patients with high- or low-risk scores exhibited distinct immune cell compositions, which may explain the prognostic significance of our model. Our results add to the current knowledge of immune processes in LUADs and underscore the critical role of the immune microenvironment in LUAD patient outcome.

Relative to the open Northwest Pacific, the basin-scale South China Sea (SCS) is smaller and semi-enclosed, and the impacts of frequent super typhoons on the entire SCS basin have yet to be fully understood. Using multi-satellite observations and reanalysis data, this study explored biophysical responses of the upper ocean of the SCS induced by a typical super typhoon, Mangkhut (2018), and their regional differences with potential mechanisms. There were three different significant-response regions in the whole SCS, as follows: (1) In the ocean area around the typhoon path, strong vertical mixing, upwelling and cooling were induced, resulting in the surface chlorophyll-a (chl-a) concentration enhancing markedly (three-fold). Particularly, asymmetric distribution of typhoon rainfall induced asymmetric sea surface salinity change over along the path the nearshore. Diurnal peak of chl-a concentration increased obviously, and the daily growth rate of chl-a sped up considerably in non-shore areas after Mangkhut's passage. (2) In the Beibu Gulf (BBG), the peripheral winds of Mangkhut caused a change in direction of the sea surface flow field, transporting the high-temperature and high-salinity surface seawater from the southeastern area to the BBG. This induced dramatic increases in sea surface temperature, salinity and height, and a decrease in chl-a, in most areas of BBG. (3) In the southwest SCS, the southwest monsoon–induced eastward offshore upwelling jet was weakened by the opposite large-scale peripheral wind vector of Mangkhut and gradually disappeared, resulting in accumulation and enhancement of chl-a in the nearshore. In addition, Mangkhut peripheral winds also intensified (weakened), shifting the cold (warm) eddy to the north (south) and blocking the horizontal eastward transport belt of the high-concentration chl-a. In general, our present work sheds light on the new evidence that a supper typhoon can cause basin-wide anomalies in the SCS, which has broad implications for marine biophysical environment.

Facile one-pot approach was established to fabricate chitosan-based supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking of the β-cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter (Dh) of 140 nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio of carrier:DOX at 25:10. They were stable in the simulated physiological medium with premature drug release of only 3% over 60 h, while a high cumulative release up to 82.3% was achieved within 84 h in a sustained manner without initial burst in the simulated tumor intracellular micro-environment. The MTT assays indicated that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced antitumor efficacy in comparison with the free DOX.

The new era with prosperous artificial intelligence (AI) and robotics technology is reshaping the materials discovery process in a more radical fashion. Here we present authentic intelligent robotics for chemistry (AIR-Chem), integrated with technological innovations in the AI and robotics fields, functionalized with modules including gradient descent-based optimization frameworks, multiple external field modulations, a real-time computer vision (CV) system, and automated guided vehicle (AGV) parts. AIR-Chem is portable and remotely controllable by cloud computing. AIR-Chem can learn the parametric procedures for given targets and carry on laboratory operations in standalone mode, with high reproducibility, precision, and availability for knowledge regeneration. Moreover, an improved nucleation theory of size focusing on inorganic perovskite quantum dots (IPQDs) is theoretically proposed and experimentally testified to by AIR-Chem. This work aims to boost the process of an unmanned chemistry laboratory from the synthesis of chemical materials to the analysis of physical chemical properties, and it provides a vivid demonstration for future chemistry reshaped by AI and robotics technology.

Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis. A total of 2326 AS events in 1738 genes and 1812 AS events in 1360 genes were determined to be significantly associated with overall survival (OS) of patients in the EAC and ESCC cohorts, respectively, including some essential participants in the oncogenic process. The predictive model of each splice type performed reasonably well in distinguishing good and poor outcomes of patients with esophageal cancer, and values for the area under curve reached 0.942 and 0.815 in the EAC exon skip predictive model and the ESCC alternate acceptor site predictive model, respectively. The splicing regulation networks revealed an interesting correlation between survival-associated splicing factors and prognostic AS genes. In summary, we created prognostic models for patients with esophageal cancer based on AS signatures and constructed novel splicing correlation networks.

A facile one-pot approach has been developed to prepare novel pH-responsive ionic nanohydrogels with high drug-loading capacity and desirable size for tumor-specific intracellular triggered release of anticancer drug DOX, in which the ionic crosslinking of alginate (AL) or its derivatives (oxidized alginate (OAL) or PEGylated OAL (mPEG-OAL)) and the DOX-loading ocurred simultaneously. It was found that the modification was benificial to the formation of the DOX-loaded ionic nanohydrogels with smaller diameter and narrower size distribution, even with similar DOX loading capacity. Especially for the mPEG-OAL, the resultant mPEG-OAL/DOX ionic nanohydrogels showed a hydrodynamic diameter of 135 nm with very narrow size distribution. All the three DOX-loaded ionic nanohydrogels (AL/DOX, OAL/DOX, and mPEG-OAL/DOX) showed the pH-responsive characteristic, and the last one exhibited the best capacity for controlled release, in a sustained release mode.

Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. NMR was methylated by NSUN2 and might competitively inhibit methylation of potential mRNAs. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functions as an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.

PEGylated multi-walled carbon nanotubes (PEG-MWCNTs) were optimized as versatile vector for tumor-specific intracellular triggered release of doxorubicin (DOX), based on the effect of their length and PEGylation degree on the cytotoxicity and DOX-loading capacity. The length and surface carboxyl groups of the carboxylated multi-walled carbon nanotubes (CMWCNTs) were easily tailored by adjusting the oxidation time. The longer CMWCNTs or those with high carboxyl group content showed obvious cytotoxicity, while the PEG-MWCNTs ≤ 300 nm showed better cytocompatibility. The PEG-MWCNTs-3 of about 300 nm was selected as drug delivery vector, possessing a high drug-loading capacity of 0.55 mg/mg. They released DOX rapidly under lower pH media mimicking the tumor microenvironment with cumulative release of 57% within 24 h, while the premature leakage under the simulated physiological condition was only 10%. The WST-1 assays demonstrated the DOX-loaded PEG-MWCNTs-3 exhibited the enhanced inhibitory efficiency against HepG2 cells, in comparison with free DOX.

Liquid hydrogenated nitrile-butadiene rubber (LH-NBR), hydrogenated nitrile-butadiene rubber (H-NBR) with number-averaged molecular weight of C C groups instead of the C N ones in the liquid nitrile-butadiene rubber (L-NBR) with narrow molecular weight distribution was conducted with palladium nanoparticles supported on macroporous hollow silica microspheres (Pd/MHS) catalyst, with the hydrogenation degree (HD%) > 95% for the 5th reuse.

Ligand-induced chirality in semiconductor nanocrystals (NCs) has attracted attention because of the tunable optical properties of the NCs. Induced circular dichroism (CD) has been observed in CdX (X = S, Se, Te) NCs and their hybrids, but circularly polarized luminescence (CPL) in these fluorescent nanomaterials has been seldom reported. Herein, we describe the successful preparation of l- and d-cysteine-capped CdSe-dot/CdS-rods (DRs) with tunable CD and CPL behaviors and a maximum anisotropic factor ( glum) of 4.66 × 10-4. The observed CD and CPL activities are sensitive to the relative absorption ratio of the CdS shell to the CdSe core, suggesting that the anisotropic g-factors in both CD and CPL increase to some extent for a smaller shell-to-core absorption ratio. In addition, the molar ratio of chiral cysteine to the DRs is investigated. Instead of enhancing the chiral interactions between the chiral molecules and DRs, an excess of cysteine molecules in aqueous solution inhibits both the CD and CPL activities. Such chiral and emissive NCs provide an ideal platform for the rational design of semiconductor nanomaterials with chiroptical properties.

Background At present, it has not yet been determined whether metastasis can be transferred cross-lobe to peripheral lymph nodes (LNs) from other lobes in early stages of lung cancer, especially without any direct involvement to the pleura and parenchyma of the lobe. This study was conducted to investigate this issue. Methods A retrospective analysis was conducted at the Chinese Academy of Medical Sciences. Patients undergoing right middle and lower lobectomy with lymphadenectomy for preoperative clinical stage Ia-IIIa from 2014 to 2015 were identified. To avoid interference, cases were limited to tumors within the primary lobe. When a tumor is completely located in the lower lobe, no direct invasion occurs into the visceral pleura/bronchus/parenchyma of the middle lobe and tumor cell metastasis into the peripheral LNs (stations 12-14) in the middle lobe is defined as cross-lobe lymph node metastasis (CLM). Results A total of 68 patients were identified, of which nine (13.2%) had CLM. Seven had squamous cell carcinoma, one adenocarcinoma, and one small cell carcinoma. Seven cases (77.8%) had intermediate bronchus invasion, and seven cases (77.8%) intermediate bronchus adjacent lymph node involvement (station 11). Compared to non-CLM patients, tumor diameter (5.2 vs. 3.2; P = 0.28), N2 lymph node metastasis rate (66.7% vs. 28.8%; P = 0.03), late stage (IIIa 77.8% vs. 35.6%; P = 0.04), and invasion of intermediate bronchus (77.8% vs. 45.8%; P = 0.07) relatively increased. Conclusion Non-primary lobe peripheral LN metastasis exists in lung cancer and requires greater attention and further study.