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Depositing an adhering diamond film on stainless steel is still challenging. In this work, Mo/Mo-N film is used as an interlayer to solve the problem. The results show that diamond film with good adhesion is obtained when the interlayer with the N 2 /Ar ratios of 50 %–100 % is used. It is ascribed to the formation of Mo 2 N phase in the interlayer through which it is more difficult for carbon atoms to diffuse than Mo phase. On the Mo/Mo-N interlayer, carbon atoms are easily gathered and a new phase MoC appeared as well as Mo 2 C phase at the interface of diamond/interlayer. Thermal expansion of MoC is obviously lower than that of Mo 2 C, resulting in the lower stress of diamond film. And MoC offers higher bond strength between the diamond and the interlayer compared to Mo 2 C phase. As a result, the diamond film presents good adhesion. • Adherent diamond films were prepared on the steel using Mo/Mo-N interlayers. • The stress of diamond films on stainless steel is lower using Mo/Mo-N interlayers. • The high adhesion of diamond film is ascribed to the formation of Mo 2 N. [ABSTRACT FROM AUTHOR]

• A fig–like Li 2 S–Mo@C nanocomposites is designed and prepared for Li–S batteries. • The fig–like Li 2 S–Mo@C exhibits excellent electrochemical performance. • The role of carbon shell, Mo nanodots and fig–like structure is revealed. Lithium sulfide (Li 2 S) is considered as a promising alternative for the intercalation–type cathode materials because of its high theoretical specific capacity (1166 mAh g–1). However, the large–scale application of Li 2 S is limited by its intrinsic low electronic/ionic conductivity and severe shuttle effect of polysulfides. Herein, we report a facile and green method to the in–situ synthesis of Li 2 S–molybdenum (Mo) nanocomposites at room temperature by mechanochemical reaction of lithium hydride with molybdenum sulfide. The fig–like carbon coated Li 2 S–Mo (Li 2 S–Mo@C) nanocomposite with core–shell structure exhibits a low initial activation barrier of 2.51 V, high reversible capacity of 742 mAh g −1 after 70 cycles at 0.2 A g −1 and excellent cycling stability over 500 cycles at 1.0 A g −1. According to density functional theory calculation and experimental studies, the excellent electrochemical performance of fig–like Li 2 S–Mo@C nanocomposite can be attributed to the increased electronic/ionic conductivity, strong adsorption ability and catalytic conversion of lithium polysulfides, resulting from the synergistic effects of Mo nanodots and, carbon shell and their nanostructure. This work provides a new idea for developing large–scale applications of Li 2 S–based electrodes. [Display omitted] [ABSTRACT FROM AUTHOR]

It is a key challenge to synthesize large-area n-type diamond, which significantly obstacles its application in electronic devices. Here we find that monoatomic tantalum (Ta) lets graphite transform to diamond under normal pressure, subverting the common sense that this transition needs high temperature and high pressure, opening an era for preparing large-area diamond based on large-sized graphite. This phase transition removes non-diamond component in grain boundaries forming closely-packed nanocrystalline diamond films and terminates the grains by Ta, producing high mobility n-type conductivity. First principle calculations reveal that Ta supplies electrons to the adjacent graphene layer, transforming sp2 electronic configuration to sp3 state with energy barrier of −5.38 eV/unit cell. Ta terminated diatomic layer diamond forms a shallow donor energy level of ∼0.4 eV. This supplies important significance in the fabrication of diamond-based electronic devices and gives a way for the sp2/sp3 hybridized matter to realize the phase transition under ordinary pressure. [Display omitted] [ABSTRACT FROM AUTHOR]

• F1 protein of FAdV-4 could nucleus localization in LMH cells, and the P 26 in NLS was required for F1 protein nucleus entry. • We elucidated the time rule of F1 protein subcellular localization in nucleus of LMH cells. • The importin alpha 1 is required for F1 protein nucleus entry. • F1 protein subcellular localization in nucleus was conducive to the proliferation of FAdV-4. Fiber-1 protein (F1) is the structural protein of Fowl Adenovirus serotype 4 (FAdV-4), which could recondite the receptors of host cytomembrane. In this study, we firstly determined that F1 protein located in nucleus of LMH cells after infection with FAdV-4. We additionally revealed that F1 protein had a classic NLS, and the NLS was required for F1 nucleus entry, which was intently associated to the 26th Pro in NLS. The time rule result indicated that some F1 proteins firstly positioned in the nucleus 6 h posttranfection, and it entirely located in the nucleus 12 h posttranfection, then it ordinarily placed in cytoplasm 18 h posttranfection by means of microscopic fluorescence observation and Western Blotting. Then after transfection with pCI-neo-flag-F1 or infection with FAdV-4, the importin alpha 1 was once investigated whether or not it was required for F1 protein nucleus entry through immunofluorescence and/or Co-IP, results demonstrated that the F1 protein and importin alpha 1 co-located in the nucleus 6 h and 12 h posttranfection. The tiers of F1 protein vicinity in nucleus have been additionally investigated after knockdown expression or overexpression of importin alpha 1, and the results further revealed that importin alpha 1 used to be required for F1 protein nucleus entry. Finally, the function of F1 protein nucleus entry was investigated by qPCR, RT-PCR and Western Blotting, and the results revealed that F1 protein nucleus location was conducive to the proliferation of FAdV-4. In summary, we firstly reveal that the F1 protein of FAdV-4 locates in nucleus infected with FAdV-4, and confirm that importin alpha 1 binds to the NLS of F1 protein to nucleus localization, which promotes the proliferation of FAdV-4. [ABSTRACT FROM AUTHOR]

The superconducting radio frequency performance of Nb 3 Sn is significantly impacted by its near-surface composition and nanostructure. In this study, an innovative polishing technique for Nb 3 Sn thin films with nanoscale precision is proposed. Systematic angle-resolved X-ray photoelectron spectroscopy (ARXPS) analysis reveal that the mechanism of this polishing process involves the formation of a few nanometer-thick oxide layer on the film's surface, followed by the uniform removal of the oxide layers with HF rinse. It is approximated that the polishing depth achieved in a single cycle can reach several nanometers. Advanced material characterization demonstrates that optimized polishing process effectively eliminates compulsive tin droplets and potential tin-rich phases with poor superconductivity generated on the surface during the preparation of Nb 3 Sn thin films. Simultaneously, no additional impurity phase will be formed on the surface, and the surface roughness will remain undamaged. Meanwhile, the results of magnetic and electrical analysis show that the superconducting properties of the polished films are not affected. This polishing technique is anticipated to ease the stringent coating conditions for the preparation of high-performance Nb 3 Sn thin film superconducting cavity, and will be a valuable addition to the post-treatment process of Nb 3 Sn thin films. • An innovative polishing technique of Nb 3 Sn thin films with nanoscale precision is proposed. • Mechanism of uniform removing of the outermost surface layer of Nb3Sn film is revealed through systematic analysis. • Impurity phases on the surface could be effectively removed without damaging the roughness by using optimized polishing parameters. • The polishing technique is expected to ease the stringent coating conditions for the high quality Nb3Sn thin film cavities. [ABSTRACT FROM AUTHOR]

Background: Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions. Results: Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm. Conclusions: Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions. [ABSTRACT FROM AUTHOR]

Constructing more efficient air/solid/solution tri-interface for carbon-based oxygen reduced reaction (ORR) electrodes and evaluating the effects of layer numbers of graphene supporter loaded with defects on ORR performance are never explored before. We have successfully assembled vertical graphene sheets (VGs) with edge defects as catalyst centers on separated papillary granules formed (SPF) nanocrystalline diamond films (NCD) and firstly prepared high hydrophobic and high sticky carbon-based electrodes with highly efficient ORR performance. The results show that we regulate the VGs from lying to erect, providing hydrophobic surface to super-hydrophobic surface with high sticky. As the surfaces with medium static contact angle (SCAs)(130°∼140°) and high stickiness produce appropriate negative pressure to drag enough electrolyte to soak the VGs and still leave air pockets among SPF to form quantities of air/solid/liquid tri-interface, the VG-on-SPF-NCD electrodes possess better ORR performance. We firstly combine the I D' , I 2D /I G and FWHM 2D values from Raman spectra to express the defects loaded on fewer layers of graphene. It is a more precise way to assess the ORR catalytic active defects on carbon materials. Our results supply a simple way to construct catalytically active VGs on SPF nanocrystalline diamond films. Image 1 [ABSTRACT FROM AUTHOR]

Background: Epigenetic alterations are involved in most cancers, but its application in cancer diagnosis is still limited. More practical and intuitive methods to detect the aberrant expressions from clinical samples using highly sensitive biomarkers are needed. In this study, we developed a novel approach in identifying, visualizing, and quantifying the biallelic and multiallelic expressions of an imprinted gene panel associated with cancer status. We evaluated the normal and aberrant expressions measured using the imprinted gene panel to formulate diagnostic models which could accurately distinguish the imprinting differences of normal and benign cases from cancerous tissues for each of the ten cancer types. Results: The Quantitative Chromogenic Imprinted Gene In Situ Hybridization (QCIGISH) method developed from a 1013-case study which provides a visual and quantitative analysis of non-coding RNA allelic expressions identified the guanine nucleotide-binding protein, alpha-stimulating complex locus (GNAS), growth factor receptor-bound protein (GRB10), and small nuclear ribonucleoprotein polypeptide N (SNRPN) out of five tested imprinted genes as efficient epigenetic biomarkers for the early-stage detection of ten cancer types. A binary algorithm developed for cancer diagnosis showed that elevated biallelic expression (BAE), multiallelic expression (MAE), and total expression (TE) measurements for the imprinted gene panel were associated with cell carcinogenesis, with the formulated diagnostic models achieving consistently high sensitivities (91–98%) and specificities (86–98%) across the different cancer types. Conclusions: The QCIGISH method provides an innovative way to visually assess and quantitatively analyze individual cells for cancer potential extending from hyperplasia and dysplasia until carcinoma in situ and invasion, which effectively supplements standard clinical cytologic and histopathologic diagnosis for early cancer detection. In addition, the diagnostic models developed from the BAE, MAE, and TE measurements of the imprinted gene panel GNAS, GRB10, and SNRPN could provide important predictive information which are useful in early-stage cancer detection and personalized cancer management. [ABSTRACT FROM AUTHOR]

Abstract Silicon-vacancy (SiV) centred diamond exhibits near infrared emission at 738 nm with narrower zero-phonon line and shorter lifetime comparative with nitrogen-vacancy (NV) centre, considered as a promising room-temperature single-photon source. However, unlike NV centred nanodiamonds easily obtained by detonation, man-made synthesis of ultrafine SiV nanodiamonds is a key challenge. Here, we provide a controllably method for synthesizing nanodiamonds with one or few SiV emitters by reducing their size to the near minimum via oxygen plasma treatments. The size of nanodiamond is uniformly reduced from 11 to 1.7 nm under different treatment durations. It is found that nanodiamonds of a size between 2.1 and 4 nm contain fewer than three emitters. Size dependence of microstructure and photoluminescence suggests that SiV centres exist in the outer shell of nanodiamonds with diameter larger than ∼2 nm. This material has significant applications in nanophotonics platform, quantum communications and quantum photonics. Graphical abstract Diamond grains in size 10 nm with many silicon-vacancy centres (red dot) was etched with oxygen plasma to reduce both the nanodiamond grains size and the quantity of silicon-vacancy centres. After etched to minimum size about 3 nm, nanodiamond grains contained less than three emitters. Image [ABSTRACT FROM AUTHOR]

Background and objectives To improve lung nodule classification efficiency, we propose a lung nodule CT image characterization method. We propose a multi-directional feature extraction method to effectively represent nodules of different risk levels. The proposed feature combined with pattern recognition model to classify lung adenocarcinomas risk to four categories: Atypical Adenomatous Hyperplasia (AAH), Adenocarcinoma In Situ (AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). Methods First, we constructed the reference map using an integral image and labelled this map using a K-means approach. The density distribution map of the lung nodule image was generated after scanning all pixels in the nodule image. An exponential function was designed to weight the angular histogram for each component of the distribution map, and the features of the image were described. Then, quantitative measurement was performed using a Random Forest classifier. The evaluation data were obtained from the LIDC-IDRI database and the CT database which provided by Shanghai Zhongshan hospital (ZSDB). In the LIDC-IDRI, the nodules are categorized into three configurations with five ranks of malignancy (“1” to “5”). In the ZSDB, the nodule categories are AAH, AIS, MIA, and IA. Results The average of Student's t -test p -values were less than 0.02. The AUCs for the LIDC-IDRI database were 0.9568, 0.9320, and 0.8288 for Configurations 1, 2, and 3, respectively. The AUCs for the ZSDB were 0.9771, 0.9917, 0.9590, and 0.9971 for AAH, AIS, MIA and IA, respectively. Conclusion The experimental results demonstrate that the proposed method outperforms the state-of-the-art and is robust for different lung CT image datasets. [ABSTRACT FROM AUTHOR]

Thermal oxidation treatment was executed on boron-doped nano-crystalline diamond (B-NCD) films to change both the microstructure and the terminal groups of grains and grain boundaries. Their contributions to the electrochemical activity and electrical properties were investigated. The grain boundaries become narrowing, with ordered graphite phase firstly, and then they become disordered for long time oxidized treatment. This causes that the mobility of the B-NCD electrodes increases to 84.97 cm 2 /V s after 30 min oxidation and then it decreases obviously with oxidation time further increasing. Nanocrystalline diamond grains with high carrier concentration are growing larger and naked on the B-NCD electrode’s surface after oxidization. Also, part of the terminal C H groups on the grain phases turn to C O groups with positive electron affinity, which is prone to attract electrons from nearby anions. These results lead to larger electrochemical activity area with quick charge transfer rate in the surface of B-NCD electrode. The silane is used to shield the OH sites from electrochemical activity. The covered area become less with the oxidized time, further confirming that the electrochemical reaction mainly occurs on the grain phases and the OH groups is mainly growing in grain boundaries. [ABSTRACT FROM AUTHOR]

High pressure high temperature (HPHT) was conventionally required for the phase transition from graphite to diamond. Here, we deposited monodispersed Ta atoms on pressed pure graphite substrate in hot filament chemical vapor deposition system and then performed annealing on the sample under ordinary pressure, letting graphite transit to diamond. Specifically, along the longitudinal direction the unannealed sample is divided into three regions of TaC particles, amorphous carbon and graphite, and 2–3 nm sized diamond grains are only observed among the TaC particles. After annealing the sample under 1000 °C for 15 min, diamond grains not only form among TaC particles, but also appear in amorphous carbon region. It is observed that more diamond grains with larger size of 3–10 nm and diamond variant structures i-Carbon (i-C) with the size larger than 30 nm are formed in amorphous carbon region. And more monodispersed Ta atoms are distributed in the amorphous carbon region of the annealed sample. This suggests that monodispersed Ta atoms firstly change graphite into amorphous carbon and then induce its transformation into i-C and diamond. Our results give a different way from HPHT method to prepare diamond based on graphite under ordinary pressure. [Display omitted] [ABSTRACT FROM AUTHOR]

Cr/Cr Al N films were chosen as an interlayer to deposit an adherent diamond film on stainless steels by using hot filament chemical vapor deposition (HFCVD). The results show that diamond film with good adhesion is successfully deposited on 3Cr13 stainless steel when the interlayer with Al content from 0 to 18 at.%, which is ascribed to high chemical adhesion by a certain amount of chromium carbide. When Al content in the interlayer further increases, an excessive Al 2 O 3 is formed on the surface of the interlayer, carbon supersaturation is easily arrived, so that the amount of the carbide at the diamond/interlayer interface decreases evidently. This decreases the strength of the covalent bonding from the carbide, producing poor adhesion. Moreover, with the raise of Al content in the interlayer, the hardness of the multilayer coated stainless steel increases due to the increase of the interlayer's hardness and the slight increase of the diamond content in the film. • An adherent diamond film was prepared on stainless steel using Cr/Cr Al N interlayer. • Diamond film becomes thick with interlayer's Al content increasing. • The adhesion becomes poor when applying Cr Al N interlayer with high Al content. [ABSTRACT FROM AUTHOR]

The difficulties in asymmetrical doping of wide band gap materials, especially for the n-type diamond challenge, hamper their application in electronic devices. Here, we propose doping diamond polytypes with reasonable band structures to solve this problem. Various elements are doped into six diamond polytypes, and their doping behaviors are investigated. The results show that pure hexagonal (2H) diamond has the band gap with a value of 4.42 eV and the smallest carrier effective masses among six calculated diamond polytypes, exhibiting high electron mobility and hole mobility up to 4250 and 5840 cm 2 ·V -1 ·s -1 , respectively. Compared to cubic (3C) diamond, the impurity formation energy in 2H-diamond is reduced, which is attributed to its C 3v symmetry. More importantly, 2H-diamond exhibits favorable doping symmetry with a donor level of 0.14 eV for phosphorus and an acceptor level of 0.19 eV for boron, respectively, which originate from smaller effective masses and stronger delocalization at the band edge in 2H-diamond. These ionization energies are smaller than those in 3C-diamond of 0.32 and 0.58 eV, respectively. This reveals that phosphorus and boron in 2H-diamond are more easily excited at room temperature, producing good n- and p-type conductivities. All of these make 2H-diamond a potential candidate for the replacement of 3C-diamond as a wide band gap material theoretically. These provide a way to realize high-quality n-type diamond, giving significant insights into the realization of diamond-based electronic devices. This also supplies a solution for the difficulties in asymmetric doping of other wide band gap materials.

Hsp70-Bim protein-protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10 , the most potent Hsp70-Bim PPI inhibitor thus far. Through structure-activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15 with a 5.6-fold improvement in Hsp70-Bim PPI suppression ( K d = 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 μg/mL) compared to S1g-10 . It maintains comparable apoptosis induction capability with S1g-10 against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1 H- 15 N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a "hot spot" in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

Metabolic reprogramming is one of the essential features of tumors that may dramatically contribute to cancer metastasis. Employing liquid chromatography-tandem mass spectrometry-based metabolomics, we analyzed the metabolic profile from 12 pairwise serum samples of NSCLC brain metastasis patients before and after CyberKnife Stereotactic Radiotherapy. We evaluated the histopathological architecture of 144 surgically resected NSCLC brain metastases. Differential metabolites were screened and conducted for functional clustering and annotation. Metabolomic profiling identified a pathway that was enriched in the metabolism of branched-chain amino acids (BCAAs). Pathologically, adenocarcinoma with a solid growth pattern has a higher propensity for brain metastasis. Patients with high BCAT1 protein levels in lung adenocarcinoma tissues were associated with a poor prognosis. We found that brain NSCLC cells had elevated catabolism of BCAAs, which led to a depletion of α-KG. This depletion, in turn, reduced the expression and activity of the m6A demethylase ALKBH5. Thus, ALKBH5 inhibition participated in maintaining the m6A methylation of mesenchymal genes and promoted the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC cells and the proliferation of NSCLC cells in the brain. BCAA catabolism plays an essential role in the metastasis of NSCLC cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The Sitophilus zeamais (maize weevil) and Sitophilus oryzae (rice weevil) are two insect pests that have caused huge economic losses to stored grains worldwide. It is urgent to develop an environmentally friendly strategy for the control of these destructive pests. Here, the olfactory-mediated selection preference of the two weevil species to three stored grains was analyzed, which should help establish a pull-push system in managing them. Bioassays showed that maize weevil adults prefer to select maize, followed by paddy and wheat, while rice weevil adults mainly migrate towards wheat. Volatile analyses revealed that 2-ethylhexanol, piperitone, and (+)-Δ-cadiene are the major components in volatiles from both maize and wheat, but the abundance of these chemicals is much lower in maize than that in wheat. The volatile limonene was only detected in paddy. Y-tube bioassays suggest that 2-ethylhexanol, piperitone, and (+)-Δ-cadiene were all attractive to both weevils, whereas limonene was attractive only to rice weevils. Overall, maize weevil appeared more sensitive to the tested volatiles based on having much lower effective concentrations of these volatiles needed to attract them. The differences in volatile profiles among the grains and the sensitivity of the two species towards these volatiles may explain the behavioral differences between maize and rice weevils in selecting host grains. The differences in sensitivity of maize and rice weevils towards host volatile components with abundance differences are likely determinants driving the two insect species to migrate towards different host grains., Competing Interests: The authors declare no conflicts of interest.

Selectively targeting the cancer-specific protein - protein interaction (PPI) between Hsp70 and Bim has been discovered as a promising strategy for treating chronic myeloid leukemia (CML). The first Hsp70 - Bim PPI inhibitor, S1g-2 , has been identified to overcome the on-target toxicity of known Hsp70 inhibitors when it induces apoptosis of CML cells. Herein, we carried out a hit-to-lead optimization of S1g-2 , yielding S1g-10 , which exhibited a 10-fold increase in Hsp70/Bim suppressing potency. Furthermore, S1g-10 not only exhibited a 5- to 10-fold stronger antitumor activity in the sub-μM range against CML cells than S1g-2 in vitro, but it also overcame BCR-ABL-independent tyrosine kinase inhibitor resistance in CML in vivo depending on the Hsp70 - Bim signaling pathway. Moreover, through structure - activity relationship analysis, TROSY-HSQC NMR, molecular dynamics simulation, and point mutation validation, two hydrophobic pockets composed of eight key residues were demonstrated to produce predominant interactions with either Bim or S1g-10 , regarded as the "hot-spots" in the Hsp70 - Bim PPI interface.

The development of high-throughput omics technology has greatly promoted the development of biomedicine. However, the poor reproducibility of omics techniques limits their application. It is necessary to use standard reference materials of complex RNAs or proteins to test and calibrate the accuracy and reproducibility of omics workflows. The transcriptome and proteome of most cell lines shift during culturing, which limits their applicability as standard samples. In this study, we demonstrated that the human hepatocellular cell line MHCC97H has a very stable transcriptome (r = 0.983~0.997) and proteome (r = 0.966~0.988 for data-dependent acquisition, r = 0.970~0.994 for data-independent acquisition) after 9 subculturing generations, which allows this steady standard sample to be consistently produced on an industrial scale in long term. Moreover, this stability was maintained across labs and platforms. In sum, our study provides omics standard reference material and reference datasets for transcriptomic and proteomics research. This helps to further standardize the workflow and data quality of omics techniques and thus promotes the application of omics technology in precision medicine., (© 2023. The Author(s).)

Background: Previous studies have evaluated the expression of programmed cell death ligand 1 (PD-L1) in terms of genetic mutation in lung adenocarcinoma (LUAD). However, there are no corresponding large-sample studies in Chinese patients with LUAD with solid components (LUAD-SC). Furthermore, it remains unknown whether the relationship that exists between PD-L1 expression levels and clinicopathological and molecular profiles in small biopsy specimens is consistent with that in surgically-resected specimens. The present study explored the clinicopathological features and genetic correlation of PD-L1 expression in LUAD-SC., Methods: We collected 1,186 LUAD-SC specimens from Fudan University, Zhongshan Hospital. The tumors were divided into PD-L1 negative, low, and high groups according to the tumor proportion score (TPS)-assessed expression of PD-L1. The mutational information of all specimens was assessed. Each group's clinicopathological features were also assessed. The relationship between PD-L1 expression levels and clinicopathological features, the overlap with driver genes and the prognostic value were analyzed., Results: In 1,090 resected specimens, a high PD-L1 expression level was more prevalent in the group with predominant SCs, which was remarkably correlated with lymphovascular invasion and a more advanced clinical stage. In addition, the PD-L1 expression level was significantly related to EGFR , KRAS , and BRAF mutations and ROS1 fusions. Meanwhile, in 96 biopsy specimens, the solid-dominant type and EGFR showed a significant difference in PD-L1 expression. Furthermore, compared with their resected counterparts, the biopsy specimens were significantly associated with solid predominant, advanced tumor-node-metastasis (TNM) stage, and high PD-L1 expression. Finally, high PD-L1 expression can be considered a poor prognostic factor for overall survival (OS)., Conclusions: LUAD-SC with high PD-L1 expression levels is linked to unique clinicopathologic characteristics as well as driver mutations. It is important to evaluate the percentage of solid components in both punctured and excised specimens, which may help identify cases of high PD-L1 expression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1095/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

High pressure and high temperature are normally required for the transformation of graphite to diamond; thus, finding a method that allows the transformation to occur under ordinary pressure will be extremely promising for diamond synthesis. Here, it is found that graphite spontaneously transforms into diamond without any pressure by adding monodispersed transition metals, and the universal rules that will help predict the role of certain elements in the phase transition were studied. The results show that the favorable transition metals possess an atomic radius of 0.136-0.160 nm and an unfilled d-orbital of d 2 s 2 -d 7 s 2 , which allow more charge transfer and accumulation at the proper position between the metal and dangling C atoms, leading to stronger metal-C bonds and a lower energy barrier for the transition. This provides a universal method to prepare diamond from graphite under ordinary pressure and also provides a way for the synthesis from sp 2 to sp 3 bonded materials.

Human microproteins encoded by long non-coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493-encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA-binding protein PABPC4 and transferred to ribosomes for translation of a 95-amino-acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N-terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK-mediated AKT phosphorylation. Moreover, the formation of the SMIM26-AGK-SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493-encoded microprotein SMIM26 and establishes its anti-metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers., (© 2023 The Authors.)

Introduction: High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary (MIP), solid (SOL), or both patterns in lymph node (LN) metastases has prognostic value., Methods: Patients who underwent lobectomy for pathologic stages II to III lung ADC with N1 or N2 LN metastases (N = 360; 2000-2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases. Multivariable Cox regression analysis was used to quantify the association between MIP/SOL patterns and outcomes., Results: MIP and SOL in LN metastases were associated with a higher incidence of smoking history (p = 0.004), tumor necrosis (p = 0.013), and spread of tumor through air spaces (p < 0.0001), a higher prevalence of MIP or SOL in the primary tumor (p < 0.0001), shorter OS (5-y OS, 40% [95% confidence interval or CI: 29%-56%] versus 63% [48%-83%] for no MIP/SOL in LNs, p = 0.03), higher LC-CID (5-y, 43% [29%-56%] versus 14% [4%-29%], p = 0.013), and higher CIR (5-y, 65% [50%-77%] versus 43% [25%-60%], p = 0.057). MIP and SOL in LN metastases were independently associated with poor outcomes: OS (hazard ratio [HR] = 1.81 [95% CI: 1.00-3.29], p = 0.05), LC-CID (HR = 3.10 [1.30-7.37], p = 0.01), and CIR (HR = 2.06 [1.09-3.90], p = 0.026)., Conclusions: MIP/SOL histologic patterns in N1 or N2 LN metastases are associated with worse outcomes in patients with stages II to III lung ADC. MIP/SOL histologic patterns in LN metastases can stratify patients with high-risk stages II to III lung ADC., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The pro- and inflammatory cytokines fail to effectively inhibit FAdV-4, which has always puzzled us. In the current study, the data determined that the mRNA levels of interferons were significantly enhanced in the livers and LMH cells from 24 h to 72 h post FAdV-4 infection. But the viral load of FAdV-4 was still significantly increased, which meant that FAdV-4 evaded innate immune response. We additionally revealed that the protein levels not mRNA levels of PKR were degraded in host cell at 48 h post FAdV-4 infection. Moreover, the results of over expression and silent expression of PKR revealed that PKR could inhibit FAdV-4 proliferation. These results indicated that FAdV-4 degraded the protein levels of PKR to evade innate immune response. We also found that the protein degradation levels of PKR induced by FAdV-4 were recovery in LHM cells after treatment with proteasome inhibitor MG132, and ubiquitin-specific proteases inhibitor DUB-IN-1. Furthermore, our current data presented that FAdV-4 52/55 K protein directly interacted with PKR and degraded it determined by Co-immunoprecipitation and immunofluorescence. We also determined that 52/55 K protein triggered PKR degradation, and the degradation of PKR could be recovery in LHM cells after treatment with MG132, or DUB-IN-1, respectively. Finally, our data demonstrated that 52/55 K protein was a ubiquitylase that could directly degrade PKR protein in host cells via the ubiquitin-proteasome pathway. Therefore, the current study firstly revealed that FAdV-4 52/55 K protein played the key role in triggering PKR degradation by ubiquitin-proteasome system pathway to escape from innate immunity response., Competing Interests: Declaration of Competing Interest All the authors have read and approved the manuscript and its submission to Veterinary Microbiology. The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Chronic obstructive pulmonary disease (COPD) was the third leading cause of global death in 2019, causing a huge economic burden to society. Therefore, it is urgent to identify specific phenotypes of COPD patients through early detection, and to promptly treat exacerbations. The field of phosphoproteomics has been a massive advancement, compelled by the developments in mass spectrometry, enrichment strategies, algorithms, and tools. Modern mass spectrometry-based phosphoproteomics allows understanding of disease pathobiology, biomarker discovery, and predicting new therapeutic modalities., Areas Covered: In this article, we present an overview of phosphoproteomic research and strategies for enrichment and fractionation of phosphopeptides, identification of phosphorylation sites, chromatographic separation and mass spectrometry detection strategies, and the potential application of phosphorylated proteomic analysis in the diagnosis, treatment, and prognosis of COPD disease., Expert Opinion: The role of phosphoproteomics in COPD is critical for understanding disease pathobiology, identifying potential biomarkers, and predicting new therapeutic approaches. However, the complexity of COPD requires the more comprehensive understanding that can be achieved through integrated multi-omics studies. Phosphoproteomics, as a part of these multi-omics approaches, can provide valuable insights into the underlying mechanisms of COPD.

We presented a strategy for enhancing the sensitivity of terahertz glucose sensing with a hydrogel platform pre-embedded with Au nanoparticles. Physiological-level glucose solutions ranging from 0 to 0.8 mg/mL were measured and the extracted absorption coefficients can be clearly distinguished compared to traditional terahertz time domain spectroscopy performed directly on aqueous solutions. Further, Isotherm models were applied to successfully describe the relationship between the absorption coefficient and the glucose concentration (R 2  = 0.9977). Finally, the origin of the sensitivity enhancement was investigated and verified to be the pH change induced by the catalysis of Au nanoparticles to glucose oxidation., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma., Objectives: To identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma., Method: Data-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients., Result: Four candidate biomarkers were identified from DIA and PRM analysis-i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)-and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count., Conclusion: DIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma., Competing Interests: Author TP is employed by Guangdong South China Vaccine Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Lu, Wang, Liang, Dong, Zhang, Qiu, Ou, Zeng, Lan, Hu, Tan, Peng, Zhang and Long.)

Alternative splicing (AS) isoforms create numerous proteoforms, expanding the complexity of the genome. Highly similar sequences, incomplete reference databases and the insufficient sequence coverage of mass spectrometry limit the identification of AS proteoforms. Here, we demonstrated full-length translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) sequencing (RNC-seq) strategy to sequence the entire translating mRNA using next-generation sequencing, including short-read and long-read technologies, to construct a protein database containing all translating AS isoforms. Taking the advantage of read length, short-read RNC-seq identified up to 15,289 genes and 15,906 AS isoforms in a single human cell line, much more than the Ribo-seq. The single-molecule long-read RNC-seq supplemented 4,429 annotated AS isoforms that were not identified by short-read datasets, and 4,525 novel AS isoforms that were not included in the public databases. Using such RNC-seq-guided database, we identified 6,766 annotated protein isoforms and 50 novel protein isoforms in mass spectrometry datasets. These results demonstrated the potential of full-length RNC-seq in investigating the proteome of AS isoforms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Lu, Lu, Wang, Li, Zhao, Jin, Sun, He, Chen and Zhang.)

Well-preserved molecular cargo in circulating extracellular vesicles (EVs) offers an ideal material for detecting oncogenic gene alterations in cancer patients, providing a noninvasive diagnostic solution for detection of disease status and monitoring treatment response. Therefore, technologies that conveniently isolate EVs with sufficient efficiency are desperately needed. Here, a lipid labeling and click chemistry-based EV capture platform ("Click Beads"), which is ideal for EV message ribonucleic acid (mRNA) assays due to its efficient, convenient, and rapid purification of EVs, enabling downstream molecular quantification using reverse transcription digital polymerase chain reaction (RT-dPCR) is described and demonstrated. Ewing sarcoma protein (EWS) gene rearrangements and kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation status are detected and quantified using EVs isolated by Click Beads and matched with those identified in biopsy specimens from Ewing sarcoma or pancreatic cancer patients. Moreover, the quantification of gene alterations can be used for monitoring treatment responses and disease progression., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

It is a key challenge to prepare large-area diamonds by using the methods of high-pressure high-temperature and normal chemical vapor deposition (CVD). The formation mechanism of thermodynamically metastable diamond compared to graphite in low-pressure CVD possibly implies a distinctive way to synthesize large-area diamonds, while it is an intriguing problem due to the limitation of in situ characterization in this complex growth environment. Here, we design a series of short-term growth on the margins of cauliflower-like nanocrystalline diamond particles, allowing us to clearly observe the diamond formation process. The results show that vertical graphene sheets and nanocrystalline diamonds alternatively appear, in which vertical graphene sheets evolve into long ribbons and graphite needles, and they finally transform into diamonds. A transition process from graphite (200) to diamond (110) verifies the transformation, and Ta atoms from hot filaments are found to atomically disperse in the films. First principle calculations confirm that Ta-added H- or O-terminated bilayer graphene spontaneously transforms into diamond. This reveals that in the H, O, and Ta complex atmosphere of the CVD environment, diamond is formed by phase transformation from graphite. This subverts the general knowledge that graphite is etched by hydrogen and sp3 carbon species pile up to form diamond and supplies a way to prepare large-area diamonds based on large-sized graphite under normal pressure. This also provides an angle to understand the growth mechanism of materials with sp2 and sp3 electronic configurations.

Quantitative detection of neurotransmitters in aqueous environment is crucial for the early diagnosis of many neurological disorders. Terahertz waves, as a non-contact and non-labeling tool, have demonstrated large potentials in quantitative biosensing. Although the detection of trace-amount analyte has been achieved with terahertz metamaterials in the recent decades, most studies have been focused on dried samples. Here, a hexagonal asymmetric metamaterial sensor was designed and fabricated for aqueous solution sensing with terahertz waves in the reflection geometry. An absorption enhancement of 43 was determined from the simulation. Dilute adrenaline solutions ranging from 30 µM to 0.6 mM were measured on our sensor using a commercial terahertz time-domain spectroscopy system, and the effective absorption was found to be linearly correlated with the concentration (R 2  = 0.81). Furthermore, we found that as the concentration becomes higher (>0.6 mM), a non-linear relationship starts to take place, which confirmed the previous theory on the extended solvation shell that can be probed on the picosecond scale. Our sensor, without the need of high-power and stable terahertz sources, has enabled the detection of subtle absorption changes induced by the solvation dynamics.

Herein, we explore the potential applications of the experimentally synthesized ZrO 2 monolayer as the cathode catalyst for nonaqueous lithium-oxygen batteries. First, we show that a new peroxide-like adsorption geometry is the most stable configuration for LiO 2 , which is distinct from the previously known O-Li-O triangular geometry. The proposed most stable adsorption configuration is because the Zr atoms in the substrate play a critical role in stabilizing the LiO 2 cluster. Second, our ab initio calculations indicate that both the ORR and OER catalytic activities are most likely to adopt the four-electron mechanism with a considerably low overpotential of only 0.44 and 0.76 V, respectively. Finally, we show that the adsorption energy of Li 2 O 2 is a good descriptor for both ORR and OER catalytic activities, and weak Li 2 O 2 adsorption behavior is positively related to low overpotentials and satisfactory catalytic performance.

The electrocatalytic overall water splitting and the corresponding reverse reaction play a vital role in future renewable energy systems and, hence, are frontiers of catalysis research. In this work, we identify a heretofore unknown two-dimensional palladium carbide using the structure swarm intelligence algorithm. The proposed monolayer, named α-PdC, consists of fully dispersed Pd atoms and a rigid carbon backbone, exhibiting high mechanical, dynamical, and thermal stability with desirable electrical conductivity. Further calculations show that the proposed monolayer is an intrinsic multifunctional electrocatalyst. It possesses an excellent catalytic performance toward the hydrogen evolution reaction (HER), the oxygen evolution reaction (OER), and the oxygen reduction reaction (ORR) with low overpotentials. Specifically, the overpotential for the HER is only -0.01 V, and the significantly low activation energy barrier (0.16 eV) on α-PdC elucidates the fast kinetics. Moreover, α-PdC could also be highly active towards the OER and ORR with comparable overpotentials (0.38 and 0.27 V, respectively). This study identifies an intrinsic versatile electrocatalyst with potential applications in the fields of energy conversion and storage.

Introduction: Asthma is the most common chronic respiratory disease and has been declared a global public health problem by the World Health Organization. Due to the high heterogeneity and complexity, asthma can be classified into different 'phenotypes' and it is still difficult to assess the phenotypes and stages of asthma by traditional methods. In recent years, mass spectrometry-based proteomics studies have made significant progress in sensitivity and accuracy of protein identification and quantitation, and are able to obtain differences in protein expression across samples, which provides new insights into the mechanisms and classification of asthma., Areas Covered: In this article, we summarize research strategies in quantitative proteomics, including labeled, label-free and targeted quantification, and highlight the advantages and disadvantages of each. In addition, new applications of quantitative proteomics and the current status of research in asthma have also been discussed. In this study, online resources such as PubMed and Google Scholar were used for literature retrieval., Expert Opinion: The application of quantitative proteomics in asthma has an important role in identifying asthma subphenotypes, revealing potential pathogenesis and therapeutic targets. But the proteomic studies on asthma are not sufficient, as most of them are in the phase of biomarker discovery.

We propose a novel polymorph of a hexagonal B 3 S monolayer by combing structure swarm intelligence and first-principles calculations. Phonon spectrum analysis and ab initio molecular dynamics simulation indicate that the new structure is dynamically and thermally stable. Furthermore, the structure is mechanically stable and has a satisfactory elastic modulus. Our results show that the B 3 S monolayer is a semiconductor with strong visible-light optical absorption. More importantly, the electronic properties of the structure are tunable via surface functionalization. For example, hydrogenation or fluorination could transform the monolayer from the semiconducting to metallic state. On the other hand, surface oxidation could significantly enhance both carrier mobility and near-infrared optical absorption. Furthermore, we also discovered that the monolayer possesses satisfactory storage capacity for H 2 .

A great number of non-coding RNAs (ncRNAs) account for the majority of the genome. The translation of these ncRNAs has been noted but seriously underestimated due to both technological and theoretical limitations. Based on the development of ribosome profiling (Ribo-seq), full length translating RNA analysis (RNC-seq) and mass spectrometry technology, more and more ncRNAs are being found to be translated in different organism, and some of them can produce functional peptides. While recently, not only individual new functional proteins, but also a new proteome have been experimentally discovered to be encoded by endogenous lncRNAs and circRNAs. These new proteins are of biological significance, suggesting the connection of the translation of ncRNAs to human physiology and diseases. Therefore, an in-depth and systematic understanding of the coding capabilities of ncRNAs is necessary for basic biology and medicine. In this review, we summarize the advances in the field of discovering this new proteome, i.e. "ncRNA-coded" proteins.

Introduction: In patients with stage IA lung adenocarcinoma (ADC), sublobar resection and tumor spread through air spaces (STAS) are associated with high rates of locoregional recurrence, half of which occur within the regional lymph nodes (LNs). Our objectives were to investigate the association between occult LN metastasis (ONM) and STAS and to assess their prognostic value in patients with clinical stage IA lung ADC., Methods: The association between STAS and ONM was analyzed in patients who underwent lobectomy and LN dissection for clinical stage IA lung ADC (n = 809). Multivariable logistic regression analysis was carried out to identify predictors of ONM. Site-specific recurrence by surgical procedure was investigated in patients with pathologic node-negative disease (n = 1055) using a competing risk approach., Results: ONM was identified in 129 patients (16%)-one-third of ONMs were located only in intrapulmonary nodes. STAS was more common in patients with ONM than in those without ONM (67% versus 39%; p < 0.001) and in patients with multiple ONMs than in those with a single ONM (86%-89% versus 60%-67%). STAS was a significant predictor of ONM (p = 0.004) on multivariable analysis, independent of tumor size, maximum standardized uptake value, and lymphovascular invasion. In patients with STAS-positive ADC (high ONM risk), the risk of recurrence in the treated lobe and regional LNs increased as the extent of resection decreased (recurrence risk: lobectomy < segmentectomy < wedge resection). In patients with STAS-negative ADC, the risk of locoregional recurrence did not differ by procedure type., Conclusions: Presence of STAS predicts ONM in patients with clinical stage IA lung ADC and can help stratify risk of recurrence by extent and type of resection., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

In past decades, there have been great achievements on theoretical prediction and experimental fabrication of two-dimensional transition metal carbides. In this work, we report a hitherto unknown atomic-thin planar-structured transition metal carbide sheet denoted as MC6 (M = Cu, Ag, Au) via a structure-swarm intelligence algorithm. The proposed 2D crystals are both statically and dynamically stable, and could maintain their structure integrity at temperatures up to 1500 K. The calculated specific capacities of lithium-ion batteries employing such materials reach 1188 mA h g-1, which is 26.38% higher than previously reported highest MXene material with Mn+1Xn atomic configuration. Our results present the potential application of MC6 in Li-ion batteries.

Introduction: This work was performed to develop and validate procedure-specific risk prediction for recurrence following resection for early-stage lung adenocarcinoma (ADC) and investigate risk prediction utility in identifying patients who may benefit from adjuvant chemotherapy (ACT)., Methods: In patients who underwent resection for small (≤2 cm) lung ADC (lobectomy, 557; sublobar resection, 352), an association between clinicopathologic variables and risk of recurrence was assessed by a competing risks approach. Procedure-specific risk prediction was developed based on multivariable regression for recurrence. External validation was conducted using cohorts (N = 708) from Japan, Taiwan, and Germany. The accuracy of risk prediction was measured using a concordance index. We applied the lobectomy risk prediction approach to a propensity score-matched cohort of patients with stage II-III disease (n = 316, after matching) with or without ACT and compared lung cancer-specific survival between groups among low- or high-risk scores., Results: Micropapillary pattern, solid pattern, lymphovascular invasion, and necrosis were involved in the risk prediction following lobectomy, and micropapillary pattern, spread through air spaces, lymphovascular invasion, and necrosis following sublobar resection. Both internal and external validation showed good discrimination (concordance index in lobectomy and sublobar resection: internal, 0.77 and 0.75, respectively; and external, 0.73 and 0.79, respectively). In the stage II-III propensity score-matched cohort, among high-risk patients, ACT significantly reduced the risk of lung cancer-specific death (subhazard ratio 0.43, p = 0.001), but not among low-risk patients., Conclusions: Procedure-specific risk prediction for patients with resected small lung ADC can be used to better prognosticate and stratify patients for further interventions., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Spread through air spaces (STAS) is a form of invasion wherein tumor cells extend beyond the tumor edge within the lung parenchyma. In lung adenocarcinoma (ADC), we investigated the (1) association between STAS and procedure-specific outcomes (sublobar resection and lobectomy), (2) effect of surgical margin-to-tumor diameter ratio in STAS-positive patients, and (3) potential utility of frozen sections (FSs) for detecting STAS intraoperatively., Methods: We investigated 1497 patients who underwent lobectomy (n = 970) or sublobar resection (n = 527) for T1N0M0 lung ADC after propensity score matching. Outcomes were analyzed by using a competing risks approach. The effect of margin-to-tumor ratio on recurrence pattern (locoregional and distant) was investigated in patients who underwent sublobar resection. Five pathologists evaluated the feasibility of intraoperatively identifying STAS by using FSs (sensitivity, specificity, and interrater reliability)., Results: On multivariable analysis after propensity score matching (349 pairs/procedure), sublobar resection was significantly associated with recurrence (subhazard ratio = 2.84 [p < 0.001]) and lung cancer-specific death (subhazard ratio = 2.63 [p = 0.021]) in patients with STAS but not in those without STAS. Patients with STAS who underwent sublobar resection had a higher risk of locoregional recurrence regardless of margin-to-tumor ratio (for a margin-to-tumor ratio of ≥1 versus <1, the 5-year cumulative incidence of recurrence rates were 16% and 25%, respectively); among patients without STAS, locoregional recurrences occurred in patients with margin-to-tumor ratio lower than 1 (a 5-year cumulative incidence of recurrence rate of 7%). The sensitivity and specificity for detecting STAS by use of FSs were 71% and 92%, with substantial interrater reliability (Gwet's AC1, 0.67)., Conclusions: In patients with T1 lung ADC with STAS, lobectomy was associated with better outcomes than sublobar resection was. Pathologists can recognize STAS on FSs., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: The eighth edition of the TNM staging system included the proposal that the T descriptor be determined according to the invasive component, excluding lepidic component, for nonmucinous lung adenocarcinomas. We sought to conduct a clinicopathologic comparative analysis of the newly proposed classification using invasive size versus total tumor size., Methods: Patients who underwent lung resection for primary lung adenocarcinoma with pathologic stage (p-Stage) I-IIA (based on total size [t]) were reviewed (n = 1704). Pathologic invasive size was measured, and tumors were reclassified using invasive size (i). Cumulative incidence of recurrence and lung cancer-specific cumulative incidence of death were analyzed using a competing-risks approach. Prognostic discrimination by p-Stage(t) and p-Stage(i) was evaluated using a concordance index (C-index)., Results: The use of invasive size resulted in downstaging in 377 of 1704 patients (22%), with twice as many patients with p-Stage IA1 (IA1[i] versus IA1[t]: 389 [23%] versus 195 [11%]). However, outcomes were similar between the two groups (IA1[i] versus IA1[t]: 5-year cumulative incidence of recurrence, 11% versus 13%; 5-year lung cancer-specific cumulative incidence of death, 5% versus 7%). Prognostic discrimination by p-Stage(i) was better than by p-Stage(t) (C-index for p-Stage[i] versus p-Stage[t]: recurrence, 0.614 versus 0.593; lung cancer-specific death, 0.634 versus 0.621)., Conclusions: When invasive size, rather than total size, was used for the T descriptor, a larger number of patients were classified with a favorable prognosis (p-Stage IA1) and better prognostic discrimination of p-Stage I-IIA nonmucinous lung adenocarcinomas was achieved., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

By means of ab initio computations and the global minimum structure search method, we have investigated structural, mechanical, and electronic properties of D-carbon, a crystalline orthorhombic sp 3 carbon allotrope (space group Pmma [ D 2 h 5 ] with 6 atoms per cell). Total-energy calculations demonstrate that D-carbon is energetically more favorable than the previously proposed T 6 structure (with 6 atoms per cell) as well as many others. This novel phase is dynamically, mechanically, and thermally stable at zero pressure and more stable than graphite beyond 63.7 GPa. D-carbon is a semiconductor with a bandgap of 4.33 eV, less than diamond's gap (5.47 eV). The simulated X-ray diffraction pattern is in satisfactory agreement with previous experimental data in chimney or detonation soot, suggesting its possible presence in the specimen.

We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas (BAs) and analyzed their clinicopathologic and molecular features. All BAs were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range, 0.2 to 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No postsurgical recurrences were observed for any lesions (median follow-up, 11 mo). Twenty-one BAs underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal-type and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as BAs, and that lesions currently designated CMPTs represent a subgroup of this family.

Aim: High-resolution magic-angle spinning proton nuclear magnetic resonance (HRMAS 1 H NMR) spectroscopy technique was employed to analyze the metabonomic characterizations of lung cancer tissues in hope to identify potential diagnostic biomarkers for malignancy detection and staging research of lung tissues., Methods: HRMAS 1 H NMR spectroscopy technique can rapidly provide important information for accurate diagnosis and staging of cancer tissues owing to its noninvasive nature and limited requirement for the samples, and thus has been acknowledged as an excellent tool to investigate tissue metabolism and provide a more realistic insight into the metabonomics of tissues when combined with multivariate data analysis (MVDA) such as component analysis and orthogonal partial least squares-discriminant analysis in particular., Results: HRMAS 1 H NMR spectra displayed the metabonomic differences of 32 lung cancer tissues at the different stages from 32 patients. The significant changes (P < 0.05) of some important metabolites such as lipids, aspartate and choline-containing compounds in cancer tissues at the different stages had been identified. Furthermore, the combination of HRMAS 1 H NMR spectroscopy and MVDA might potentially and precisely provided for a high sensitivity, specificity, prediction accuracy in the positive identification of the staging for the cancer tissues in contrast with the pathological data in clinic., Conclusion: This study highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for the diagnosis and staging prediction of lung cancer in future., (© 2016 John Wiley & Sons Australia, Ltd.)

It is known that plant viruses can change the performance of their vectors. However, there have been no reports on whether or how a semipersistent plant virus manipulates the feeding behaviors of its whitefly vectors. Cucurbit chlorotic yellows virus (CCYV) (genus Crinivirus , family Closteroviridae ) is an emergent plant virus in many Asian countries and is transmitted specifically by B and Q biotypes of tobacco whitefly, Bemisia tabaci (Gennadius), in a semipersistent manner. In the present study, we used electrical penetration graph (EPG) technique to investigate the effect of CCYV on the feeding behaviors of B. tabaci . The results showed that CCYV altered feeding behaviors of both biotypes and sexes of B. tabaci with different degrees. CCYV had stronger effects on feeding behaviors of Q biotype than those of B biotype, by increasing duration of phloem salivation and sap ingestion, and could differentially manipulate feeding behaviors of males and females in both biotype whiteflies, with more phloem ingestion in Q biotype males and more non-phloem probing in B biotype males than their respective females. With regard to feeding behaviors related to virus transmission, these results indicated that, when carrying CCYV, B. tabaci Q biotype plays more roles than B biotype, and males make greater contribution than females., Competing Interests: The authors declare no conflict of interest.

Objective: To analyze the prognostic value of the new classification (proposed by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society) in stage I pulmonary adenocarcinoma., Methods: Pathological slides of 328 cases of stage I pulmonary invasive adenocarcinoma were reviewed according to the new classification. The patients received operation in Department of Thoracic Surgery of Zhongshan Hospital affiliated to Fudan University from January 2005 to December 2009. There were 145 male and 183 female patients with an average age of (59 ± 10) years (ranging from 34 to 82 years). Clinical, pathological, and survival data were retrospectively analyzed. Kaplan-Meier method was used for analysis of survival, and Cox regression analysis was used for finding out prognostic factors., Results: Five-year progression-free survival rate and overall survival rate of lepidic-predominant subtype were both 100%. Five-year progression-free survival rate of patients with micropapillary component (49.3%) was significantly lower than that of patients without micropapillary component (75.4%, χ² = 8.154, P = 0.004). Regression analysis showed that tumor size is an independent prognostic factor of death (HR = 1.967, 95% CI: 1.507 to 2.567, P = 0.000) and recurrence (HR = 1.796, 95% CI: 1.469 to 2.198, P = 0.000). In subgroup analysis, the presence of solid component (HR = 1.985, 95% CI: 1.013 to 3.888, P = 0.046) and tumor size (HR = 1.941, 95% CI: 1.455 to 2.589, P = 0.000) were independent prognostic factors of recurrence for stage IB pulmonary adenocarcinoma., Conclusions: The new classification of adenocarcinoma is of prognostic value in stage I pulmonary adenocarcinoma. The presence of solid or micropapillary component impacts on survival. Detailed record of each component in tumor is necessary.

Background: Lung cancers are classified as squamous cell carcinoma (SQ), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). SQ is the major subtype of lung cancer. Currently, there are no targeted therapies for SQ due to lack of understanding its driving oncogenes. In this study, we validated an SQ specific biomarker hsa-miR-205 in Chinese patients with lung cancer and screened its candidate target genes for further functional studies to enrich knowledge in SQ target therapies., Methods: Quantitative reverse-transcription PCR (quantitative RT-PCR) was performed on 197 macro-dissected (cancerous cells >75%) surgical lung tissues (45 SQ, 44 AC, 54 SCLC and 54 adjacent normal tissues) to validate the expression profiles of miR-205. Furthermore, the targets of this microRNA were predicted through the gateway miRecords and mapped to lung cancer-associated pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Then quantitative RT-PCR was performed on an independent cohort of 44 snap-frozen surgical lung tissues to concurrently assess the expression profiles of miR-205 and its 52 putative targeted genes., Results: MicroRNA-205 yielded high diagnostic accuracy in discriminating SQ from AC with an area under the curve (AUC) of 0.985, and discriminating SQ from SCLC with an AUC of 0.978 in formalin-fixed paraffin-embedded (FFPE) surgical lung tissues. Predicted targets of miR-205 were associated with 52 key members of lung cancer signaling pathways. Ten target genes (ACSL1, AXIN2, CACNA2D2, FOXO3, PPP1R3A, PRKAG3, RUNX1, SMAD4, STK3 and TBL1XR1) were significantly down-regulated in SQ and had a strong negative correlation with miR-205, while one target gene (CDH3) was up-regulated in SQ and exhibited a strong positive correlation with miR-205., Conclusions: We confirmed the high diagnostic accuracy of miR-205 in discriminating SQ from AC and SCLC in Chinese patients. Moreover, we identified 11 significant target genes of miR-205 which could be used for further functional studies as the basis for the development of SQ targeted therapies.