Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
Low‐dimensional luminescent lead halide perovskites have attracted tremendous attention for their fascinating optoelectronic properties, while the toxicity of lead is still considered a drawback. ...Herein, we report a novel lead‐free zero‐dimensional (0D) indium‐based perovskite (Cs2InBr5⋅H2O) single crystal that is red‐luminescent with a high photoluminescence quantum yield (PLQY) of 33 %. Experimental and computational studies reveal that the strong PL emission might originate from self‐trapping excitons (STEs) that result from an excited‐state structural deformation. More importantly, the in situ transformation between hydrated Cs2InBr5⋅H2O and the dehydrated form is accompanied with a switchable dual emission, which enables it to act as a PL water‐sensor in humidity detection or the detection of traces of water in organic solvents.
Unleaded and unleashed: A highly emissive lead‐free indium‐based perovskite single crystal, Cs2InBr5⋅H2O, was successfully prepared. The versatile material is the first reversible metal halide perovskite photoluminescence water sensor and paves the way for the application of metal halide perovskites in water detection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
As a sodium superionic conductor, Mn‐rich phosphate of Na
3.4
Mn
1.2
Ti
0.8
(PO
4
)
3
is considered as one of the promising cathodes for sodium‐ion batteries owing to its good thermodynamic ...stability and high working voltage. However, Na
3.4
Mn
1.2
Ti
0.8
(PO
4
)
3
is faced with low electronic conductivity, poor cycling stability and complex phase transition caused by multi‐electron transfers, which limits its practical application. Herein, an anion‐regulated strategy is proposed to optimize the Mn‐rich Na
3.4
Mn
1.2
Ti
0.8
(PO
4
)
3
phosphate cathode. After introducing F anions into the lattice, the rate performance is improved from 60.5 to 72.8 mAh g
−1
at 20 C. Ascribed to unique structure design, the reaction kinetics of Na
3.4
Mn
1.2
Ti
0.8
(PO
4
)
3
are significantly improved, as demonstrated by cyclic voltammetry at varied scan rates and galvanostatic intermittent titration technique. The generated M‐F bond inhibits Jahn–Teller effect with an improved cycle stability (85.8 mAh g
−1
after 1000 cycles at 5 C with 94.3% capacity retention). Interestingly, reaction mechanism of Na
3.4
Mn
1.2
Ti
0.8
(PO
4
)
3
with the complex two‐phase and solid solution reactions changes to the whole solid solution reaction after fluorine substitution, and leads to a smaller volume change of 5.41% during reaction processes, which is verified by in situ X‐ray diffraction. This anion regulation strategy provides a new method for designing the high‐performance phosphate cathode materials of sodium‐ion batteries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). ...However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
Promoter is a fundamental DNA element located around the transcription start site (TSS) and could regulate gene transcription. Promoter recognition is of great significance in determining ...transcription units, studying gene structure, analyzing gene regulation mechanisms, and annotating gene functional information. Many models have already been proposed to predict promoters. However, the performances of these methods still need to be improved. In this work, we combined pseudo k-tuple nucleotide composition (PseKNC) with position-correlation scoring function (PCSF) to formulate promoter sequences of Homo sapiens (H. sapiens), Drosophila melanogaster (D. melanogaster), Caenorhabditis elegans (C. elegans), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli). Minimum Redundancy Maximum Relevance (mRMR) algorithm and increment feature selection strategy were then adopted to find out optimal feature subsets. Support vector machine (SVM) was used to distinguish between promoters and non-promoters. In the 10-fold cross-validation test, accuracies of 93.3%, 93.9%, 95.7%, 95.2%, and 93.1% were obtained for H. sapiens, D. melanogaster, C. elegans, B. subtilis, and E. coli, with the areas under receiver operating curves (AUCs) of 0.974, 0.975, 0.981, 0.988, and 0.976, respectively. Comparative results demonstrated that our method outperforms existing methods for identifying promoters. An online web server was established that can be freely accessed (http://lin-group.cn/server/iProEP/).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Sordariomycetes is one of the largest classes of Ascomycota that comprises a highly diverse range of fungi mainly characterized by perithecial ascomata and inoperculate unitunicate asci. Freshwater ...Sordariomycetes play an important role in ecosystems and some of them have the potential to produce bioactive compounds. This study documents and reviews the freshwater Sordariomycetes, which is one of the largest and important groups of fungi in aquatic habitats. Based on evidence from DNA sequence data and morphology, we introduce a new order Distoseptisporales, two new families, viz. Ceratosphaeriaceae and Triadelphiaceae, three new genera, viz.
Aquafiliformis
,
Dematiosporium
and
Neospadicoides
, 47 new species, viz.
Acrodictys fluminicola
,
Aquafiliformis lignicola
,
Aquapteridospora fusiformis
,
Arthrinium aquaticum
,
Ascosacculus fusiformis
,
Atractospora aquatica
,
Barbatosphaeria lignicola
,
Ceratosphaeria aquatica
,
C. lignicola
,
Chaetosphaeria aquatica
,
Ch. catenulata
,
Ch. guttulata
,
Ch. submersa
,
Codinaea yunnanensis
,
Conioscypha aquatica
,
C. submersa
,
Cordana aquatica
,
C. lignicola
,
Cosmospora aquatica
,
Cylindrotrichum submersum
,
Dematiosporium aquaticum
,
Dictyochaeta cangshanensis
,
D. ellipsoidea
,
D. lignicola
,
D. submersa
,
Distoseptispora appendiculata
,
D. lignicola
,
D. neorostrata
,
D. obclavata
,
Hypoxylon lignicola
,
Lepteutypa aquatica
,
Myrmecridium aquaticum
,
Neospadicoides aquatica
,
N. lignicola
,
N. yunnanensis
,
Ophioceras submersum
,
Peroneutypa lignicola
,
Phaeoisaria filiformis
,
Pseudostanjehughesia lignicola
,
Rhodoveronaea aquatica
,
Seiridium aquaticum
,
Sporidesmiella aquatica
,
Sporidesmium lageniforme
,
S. lignicola
,
Tainosphaeria lunata
,
T. obclavata
,
Wongia aquatica
, two new combinations, viz.
Acrodictys aquatica
,
Cylindrotrichum aquaticum
, and 9 new records, viz.
Chaetomium globosum
,
Chaetosphaeria cubensis
,
Ch. myriocarpa
,
Cordana abramovii
,
Co. terrestris
,
Cuspidatispora xiphiago
,
Sporidesmiella hyalosperma
,
Stachybotrys chartarum
,
S. chlorohalonata
. A comprehensive classification of the freshwater Sordariomycetes is presented based on updated literature. Phylogenetic inferences based on DNA sequence analyses of a combined LSU, SSU, RPB2 and TEF1α dataset comprising species of freshwater Sordariomycetes are provided. Detailed information including their habitats distribution, diversity, holotype, specimens collected and classification are provided.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying ...mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic ...examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Photocleavage of H2O into clean and storable H2 fuel by photoelectrochemical (PEC) cell is a vital part of the sustainable hydrogen economy. However, thus far one of the limitations confronted by PEC ...cell to preferable performance is the insufficient behavior of photoanode for water oxidation half‐reaction. One of the strategies to elevate the photoanode performance is integrating with an oxygen evolution catalyst (OEC) to remove the bottleneck of the water oxidation kinetics. Herein, an ultrafine cobalt iron oxide (CIO) nanocrystalline is reported as a novel OEC for photoelectrochemical water splitting. The CIO evenly distributing on the surface of hematite nanorod arrays not only greatly facilitates the surface hole injection, but also promotes the charge separation along with passivating the surface states. Such combined effects of CIO finally lead to an impressive 1.71 fold enhancement on the photocurrent density at 1.23 VRHE and ≈170 mV negative shift of onset potential, even overwhelms the commonly utilized Co‐Pi. Along with its excellent long‐term stability, the CIO possesses a great potential application in PEC water splitting devices.
One design for multiple effects: ultrafine CoFe2O4 (CIO) nanoparticles are synthesized as an efficient water oxidation co‐catalyst for α‐Fe2O3 photoelectrode to achieve comprehensive promotions on photoelectrochemical water splitting performances.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nanostructural modification and chemical composition tuning are paramount to developing effective non-noble hydrogen evolution reaction (HER) catalysts for water splitting. Herein, we report a novel ...excellent porous molybdenum tungsten phosphide (Mo-W-P) hybrid nanosheet catalyst for hydrogen evolution, which is synthesized via in situ phosphidation of molybdenum tungsten oxide (Mo-W-O) hybrid nanowires grown on carbon cloth. The three-dimensional (3D) hierarchical hybrid electrocatalyst exhibits impressively high electrocatalytic activity with a low overpotential of 138 mV required to achieve a high current density of 100 mA cm-2 and a small Tafel slope of 52 mV dec-1 in 0.5 M H2SO4, which are significantly higher than those of single MoP nanosheets and WP2 nanorods. Such an outstanding performance of the Mo-W-P hybrid electrocatalyst is attributed to the 3D conductive scaffolds, porous nanosheet structure, and strong synergistic effect of W and Mo atoms in Mo-W-P, making it a very promising catalyst for hydrogen production. Our findings demonstrate that careful control over the morphology and composition of the electrocatalyst can achieve highly efficient hybrid electrocatalysts.
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