Abstract
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer ...in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that
NF2
loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.
The formation of PtSe2‐layered films is reported in a large area by the direct plasma‐assisted selenization of Pt films at a low temperature, where temperatures, as low as 100 °C at the applied ...plasma power of 400 W can be achieved. As the thickness of the Pt film exceeds 5 nm, the PtSe2‐layered film (five monolayers) exhibits a metallic behavior. A clear p‐type semiconducting behavior of the PtSe2‐layered film (≈trilayers) is observed with the average field effective mobility of 0.7 cm2 V−1 s−1 from back‐gated transistor measurements as the thickness of the Pt film reaches below 2.5 nm. A full PtSe2 field effect transistor is demonstrated where the thinner PtSe2, exhibiting a semiconducting behavior, is used as the channel material, and the thicker PtSe2, exhibiting a metallic behavior, is used as an electrode, yielding an ohmic contact. Furthermore, photodetectors using a few PtSe2‐layered films as an adsorption layer synthesized at the low temperature on a flexible substrate exhibit a wide range of absorption and photoresponse with the highest photocurrent of 9 µA under the laser wavelength of 408 nm. In addition, the device can maintain a high photoresponse under a large bending stress and 1000 bending cycles.
Phase‐engineered PtSe2‐layered films by a plasma‐assisted selenization process to highly sensitive, flexible, and wide‐spectrum photoresponse photodetectors are demonstrated. A full PtSe2 field effect transistor is also demonstrated where the thinner PtSe2, exhibiting a semiconducting behavior, is used as the channel material, and the thicker PtSe2, exhibiting a metallic behavior, is used as an electrode.
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct ...disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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•First deep proteogenomic landscape of non-smoking lung adenocarcinoma in East Asia•Identified age, sex-related endogenous, and environmental carcinogen mutagenic processes•Proteome-informed classification distinguished clinical features within early stages•Protein networks identified tumorigenesis hallmarks, biomarkers, and druggable targets
Deep proteogenomic landscape of early stage lung adenocarcinoma in a cohort of mostly non-smokers reveals unique drivers and biomarkers, as well as gender-associated mutagenesis.
Recently, interest in aluminium ion batteries with aluminium anodes, graphite cathodes and ionic liquid electrolytes has increased; however, much remains to be done to increase the cathode capacity ...and to understand details of the anion-graphite intercalation mechanism. Here, an aluminium ion battery cell made using pristine natural graphite flakes achieves a specific capacity of ∼110 mAh g
with Coulombic efficiency ∼98%, at a current density of 99 mA g
(0.9 C) with clear discharge voltage plateaus (2.25-2.0 V and 1.9-1.5 V). The cell has a capacity of 60 mAh g
at 6 C, over 6,000 cycles with Coulombic efficiency ∼ 99%. Raman spectroscopy shows two different intercalation processes involving chloroaluminate anions at the two discharging plateaus, while C-Cl bonding on the surface, or edges of natural graphite, is found using X-ray absorption spectroscopy. Finally, theoretical calculations are employed to investigate the intercalation behaviour of choloraluminate anions in the graphite electrode.
Water pollution and freshwater shortage have deteriorated the global water crisis. Developing sustainable methods to alleviate contaminated water has become an urgent affair. Herein, inspired by ...water transportation and transpiration of natural trees, the authors report an ultralong hydroxyapatite nanowires‐based biomimetic aerogel with vertically aligned channels and multiple functions for continuous flow catalysis, water disinfection, solar energy‐driven water purification, and seawater desalination. Ultralong hydroxyapatite nanowires act as carriers to immobilize catalyst nanoparticles and serve as building blocks to assemble with chitosan to form the biomimetic aerogel with structure‐function integration. Benefiting from the interconnected cellular structure, unidirectional aligned channels, nanowire‐interwoven networked pore wall, and evenly distributed catalyst nanoparticles, the biomimetic aerogel exhibits high catalytic activity (97.6% treatment efficiency) and permeability (1786 L m−2 h−1), excellent recyclability and stability in continuous flow catalytic degradation of methylene blue solely driven by gravity. The biomimetic aerogel exhibits excellent performance for bacteria removal and anti‐biofouling. The superior photothermal conversion and heat confinement properties enable the biomimetic aerogel with a high efficiency (86.7%) for solar energy‐driven seawater desalination and wastewater purification under one sun irradiation. The multifunctional biomimetic aerogel has promising applications in catalytic reactions, wastewater remediation, and environmental engineering.
A tree‐inspired multifunctional aerogel with vertically aligned channels is fabricated from ultralong hydroxyapatite nanowires, immobilized palladium nanoparticles, and chitosan through a unidirectional freeze‐drying approach. The biomimetic aerogel exhibits high performances in gravity‐driven continuous flow catalytic reactions, water disinfection, and solar energy‐driven water purification and seawater desalination.
Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. The molecular mechanisms underlying the role of JAM3 in placental dysfunction remain ...unclear. We hypothesized that JAM3 expression regulates trophoblast fusion, differentiation, proliferation, and apoptosis. Our results revealed that JAM3 was expressed in the cytotrophoblasts and syncytiotrophoblasts of first-trimester and term placental villi. JAM3 expression in cell–cell junctions decreased with the formation of syncytiotrophoblasts. Using trophoblasts as an in vitro model, we observed that forskolin and JAM3 knockdown significantly reduced JAM3 expression and increased syncytium formation. JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. Increased expression of BIM, NOXA, XAF1, cytochrome c, and cleaved caspase-3 further indicated trophoblast apoptosis. Overexpression of JAM3 or recombinant JAM3 protein enhanced trophoblast adhesion and migration, which were inhibited by JAM3 knockdown. JAM3 knockdown induced reactive oxygen species and syncytin 2 expression in trophoblasts. Furthermore, H2O2-induced oxidative stress reduced JAM3 expression in trophoblasts and cell culture supernatants. H2O2 simultaneously induced trophoblast apoptosis. JAM3 expression was significantly decreased in the plasmas and placentas of patients with early-onset severe preeclampsia. Thus, our results show that JAM3 may not only be a structural component of trophoblast cell junctions but also regulates trophoblast fusion, differentiation, proliferation, apoptosis, and motility. Dysregulated trophoblast JAM3 expression is crucial in preeclampsia development. Graphical Abstract
Efficient and economical delivery of pharmaceuticals to patients is critical for effective therapy. Here we describe a multiorgan (lung, liver, and breast cancer) microphysiological system ...(“Body‐on‐a‐Chip”) designed to mimic both inhalation therapy and/or intravenous therapy using curcumin as a model drug. This system is “pumpless” and self‐contained using a rocker platform for fluid (blood surrogate) bidirectional recirculation. Our lung chamber is constructed to maintain an air‐liquid interface and contained a “breathable” component that was designed to mimic breathing by simulating gas exchange, contraction and expansion of the “lung” using a reciprocating pump. Three cell lines were used: A549 for the lung, HepG2 C3A for the liver, and MDA MB231 for breast cancer. All cell lines were maintained with high viability (>85%) in the device for at least 48 hr. Curcumin is used to treat breast cancer and this allowed us to compare inhalation delivery versus intravenous delivery of the drug in terms of effectiveness and potentially toxicity. Inhalation therapy could be potentially applied at home by the patient while intravenous therapy would need to be applied in a clinical setting. Inhalation therapy would be more economical and allow more frequent dosing with a potentially lower level of drug. For 24 hr exposure to 2.5 and 25 µM curcumin in the flow device the effect on lung and liver viability was small to insignificant, while there was a significant decrease in viability of the breast cancer (to 69% at 2.5 µM and 51% at 25 µM). Intravenous delivery also selectively decreased breast cancer viability (to 88% at 2.5 µM and 79% at 25 µM) but was less effective than inhalation therapy. The response in the static device controls was significantly reduced from that with recirculation demonstrating the effect of flow. These results demonstrate for the first time the feasibility of constructing a multiorgan microphysiological system with recirculating flow that incorporates a “breathable” lung module that maintains an air‐liquid interface.
Efficient and economical delivery of pharmaceuticals to patients is critical for effective therapy. Here we describe a multiorgan (lung, liver, and breast cancer) microphysiological system (“Body‐on‐a‐Chip”) designed to mimic both inhalation therapy and/or intravenous therapy using curcumin as a model drug.
Carbon coating is a simple, effective and common technique for improving the conductivity of active materials in lithium ion batteries. However, carbon coating provides a strong reducing atmosphere ...and many factors remain unclear concerning the interface nature and underlying interaction mechanism that occurs between carbon and the active materials. Here, we present a size-dependent surface phase change occurring in lithium iron phosphate during the carbon coating process. Intriguingly, nanoscale particles exhibit an extremely high stability during the carbon coating process, whereas microscale particles display a direct visualization of surface phase changes occurring at the interface at elevated temperatures. Our findings provide a comprehensive understanding of the effect of particle size during carbon coating and the interface interaction that occurs on carbon-coated battery material--allowing for further improvement in materials synthesis and manufacturing processes for advanced battery materials.
Tumor cells metabolize in distinct pathways compared with most normal tissue cells. The resulting tumor microenvironment would provide characteristic physiochemical conditions for selective tumor ...modalities. Here we introduce a concept of sequential catalytic nanomedicine for efficient tumor therapy by designing and delivering biocompatible nanocatalysts into tumor sites. Natural glucose oxidase (GOD, enzyme catalyst) and ultrasmall Fe
O
nanoparticles (inorganic nanozyme, Fenton reaction catalyst) have been integrated into the large pore-sized and biodegradable dendritic silica nanoparticles to fabricate the sequential nanocatalyst. GOD in sequential nanocatalyst could effectively deplete glucose in tumor cells, and meanwhile produce a considerable amount of H
O
for subsequent Fenton-like reaction catalyzed by Fe
O
nanoparticles in response to mild acidic tumor microenvironment. Highly toxic hydroxyl radicals are generated through these sequential catalytic reactions to trigger the apoptosis and death of tumor cells. The current work manifests a proof of concept of catalytic nanomedicine by approaching selectivity and efficiency concurrently for tumor therapeutics.The specific metabolism of cancer cells may allow for selective tumor therapeutics. Here, the authors show that a suitable combination of an enzyme and iron nanoparticles loaded on dendritic silica induces apoptosis of cancer cells in response to the glucose-reliant and mild acidic microenvironment.
Illumina sequencing of a marker gene is popular in metagenomic studies. However, Illumina paired-end (PE) reads sometimes cannot be merged into single reads for subsequent analysis. When mergeable PE ...reads are limited, one can simply use only first reads for taxonomy annotation, but that wastes information in the second reads. Presumably, including second reads should improve taxonomy annotation. However, a rigorous investigation of how best to do this and how much can be gained has not been reported.
We evaluated two methods of joining as opposed to merging PE reads into single reads for taxonomy annotation using simulated data with sequencing errors. Our rigorous evaluation involved several top classifiers (RDP classifier, SINTAX, and two alignment-based methods) and realistic benchmark datasets. For most classifiers, read joining ameliorated the impact of sequencing errors and improved the accuracy of taxonomy predictions. For alignment-based top-hit classifiers, rearranging the reference sequences is recommended to avoid improper alignments of joined reads. For word-counting classifiers, joined reads could be compared to the original reference for classification. We also applied read joining to our own real MiSeq PE data of nasal microbiota of asthmatic children. Before joining, trimming low quality bases was necessary for optimizing taxonomy annotation and sequence clustering. We then showed that read joining increased the amount of effective data for taxonomy annotation. Using these joined trimmed reads, we were able to identify two promising bacterial genera that might be associated with asthma exacerbation.
When mergeable PE reads are limited, joining them into single reads for taxonomy annotation is always recommended. Reference sequences may need to be rearranged accordingly depending on the classifier. Read joining also relaxes the constraint on primer selection, and thus may unleash the full capacity of Illumina PE data for taxonomy annotation. Our work provides guidance for fully utilizing PE data of a marker gene when mergeable reads are limited.
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