Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Factors related to tumor response rate from TCGA three omics data-variants, expression, methylation.

The Cancer Genome Atlas (TCGA) and its patient-derived multi-omics datasets have been the backbone of cancer research, and with novel approaches, it continues to shed new insight into the disease. In this study, we delved into a method of multi-omics integration of patient datasets and the association of biological pathways related to the disease. First, across thirty-three types of cancer present in TCGA, we merged genomic mutations and drug response datasets and filtered for the viable variant-drug response combinations available in TCGA, containing more than three samples for each drug response label with RNA sequencing (RNA-seq) and genomic methylation data available for each patient. We identified two distinct combinations in TCGA, one being pancreatic adenocarcinoma patients with/without rs121913529 variant in KRAS gene treated with gemcitabine, and the other low-grade glioma with/without rs121913500 variant in IDH1 gene administered with temozolomide. In these two groups, different patterns of gene expression were observed in the pathways often associated with cancer progression, such as mTOR and PDGF between the patients with complete response and progressive disease. Our result will provide yet another example of the relevance of these biological pathways in cancer drug response and a way for multi-omics integration in cancer datasets.

Highly Catalytic Pt Nanoparticles Grown in Two-Dimensional Conducting Polymers at the Air-Water Interface.

We report a new approach to the synthesis of uniform, high areal density Pt nanocrystals supported by conducting polymers. The key strategy is the use of ice-templated, two-dimensional polyaniline nanosheets at the air-water interface as a platform for expediting Pt nucleation. Highly crystalline Pt nanoparticles with a narrow size distribution of 2.7 ± 0.3 nm and a high electrochemically active surface area of 94.57 m2 g-1 were obtained. Pt NPs were strongly anchored to the polyaniline nanosheets, and demonstrated high current densities, good durability for the methanol oxidation reaction, and excellent carbon monoxide tolerance, all of which are unprecedented. The idea established in this study could be applied to the production of a wide range of other catalysts with enhanced activities.

Synthesis of three-dimensionally interconnected sulfur-rich polymers for cathode materials of high-rate lithium-sulfur batteries.

Elemental sulfur is one of the most attractive cathode active materials in lithium batteries because of its high theoretical specific capacity. Despite the positive aspect, lithium-sulfur batteries have suffered from severe capacity fading and limited rate capability. Here we report facile large-scale synthesis of a class of organosulfur compounds that could open a new chapter in designing cathode materials to advance lithium-sulfur battery technologies. Porous trithiocyanuric acid crystals are synthesized for use as a soft template, where the ring-opening polymerization of elemental sulfur takes place along the thiol surfaces to create three-dimensionally interconnected sulfur-rich phases. Our lithium-sulfur cells display discharge capacity of 945 mAh g(-1) after 100 cycles at 0.2 C with high-capacity retention of 92%, as well as lifetimes of 450 cycles. Particularly, the organized amine groups in the crystals increase Li(+)-ion transfer rate, affording a rate performance of 1210, mAh g(-1) at 0.1 C and 730 mAh g(-1) at 5 C.

High-Conductivity Two-Dimensional Polyaniline Nanosheets Developed on Ice Surfaces.

A new method to develop two-dimensional PANI nanosheets using ice as a removable hard template is presented. Distinctly high current flows of 5.5 mA at 1 V and a high electrical conductivity of 35 S cm(-1) were obtained for the polyaniline (PANI) nanosheets, which marked a significant improvement from previously values on other PANIs reported over the past decades. These improved electrical properties of ice-templated PANI nanosheets were attributed to the long-range ordered edge-on π-stacking of the quinoid ring, ascribed to the ice surface-assisted vertical growth of PANI. The unprecedented advantages of the ice-templated PANI nanosheets are two-fold. First, the PANI nanosheet can be easily transferred onto various types of substrates via float-off from the ice surfaces. Second, PANI can be patterned into any shape using predetermined masks, and this is expected to facilitate the eventual convenient and inexpensive application of conducting polymers in versatile electronic device forms.

A pH-responsive molecular switch with tricolor luminescence.

We developed a new ratiometric pH sensor based on poly(N-phenylmaleimide) (PPMI)-containing block copolymer that emits three different fluorescent colors depending on the pH. The strong solvatochromism and tautomerism of the PPMI derivatives enabled precise pH sensing for almost the entire range of the pH scale. Theoretical calculations have predicted largely dissimilar band gaps for the keto, enol, and enolate tautomers of PPMI owing to low-dimensional conjugation effects. The tunable emission wavelength and intensity of our sensors, as well as the reversible color switching with high-luminescent contrast, were achieved using rational molecular design of PPMI analogues as an innovative platform for accurate H(+) detection. The self-assembly of block copolymers on the nanometer length scale was particularly highlighted as a novel prospective means of regulating fluorescence properties while avoiding the self-quenching phenomenon, and this system can be used as a fast responsive pH sensor in versatile device forms.

Blue-emitting self-assembled polymer electrolytes for fast, sensitive, label-free detection of Cu(II) ions in aqueous media.

We have developed a light-emitting material based on nonconjugated block copolymers that contain polystyrene sulfonate (PSS) chains. The confinement of the PSS chains within nanosized domains appeared to be a powerful means of achieving enhanced fluorescence signals. High fluorescence quantum yield, with a maximum value of 37%, was obtained by adjusting the types of self-assembled morphologies of PSS-containing block copolymers; in contrast, the fluorescence quantum yield was merely 5% for the PSS homopolymer lacking organization. The wavelength of fluorescence emission was tunable by rational molecular design. In addition, significant self-quenching behavior was not noticed in diverse forms of this material such as solutions, thin films, and free-standing membranes. Notably, the light-emitting self-assembled block copolymer electrolytes exhibited high sensitivity toward Cu(2+) ions, with a detection limit of parts per billion levels, rapid response time of ≤1 min, and insignificant interference of other competitive metal ions.

Simple Route for Tuning the Morphology and Conductivity of Polymer Electrolytes: One End Functional Group is Enough.

We have investigated a new means to control the morphology and conductivity of block copolymer electrolytes by the inclusion of ionic units at the chain ends. A set of poly(styrene-b-ethylene oxide) (PS-b-PEO) block copolymers having dissimilar PEO end groups (-OH, -SO3H, and -SO3Li) exhibited various self-assembled morphologies including disordered, lamellar, and hexagonal cylindrical phases. Strikingly, the addition of Li salts to PS-b-PEO with sulfonate terminal groups afforded enriched nanostructures with significant differences in their conductivities depending on the salt concentration. In particular, a gyroid morphology with a 2-fold-enhanced normalized ionic conductivity was found for the sulfonate-terminated PS-b-PEO when compared to disordered PS-b-PEO-OH. This is closely related to the structural advantages of gyroid having cocontinuous ionic channels, which enable efficient transport of Li+ ions via less tortuous ion conduction pathways. This work presents fascinating experimental insights on the enhancement of ion transport efficiencies by modulating the self-assembly nature of polymer electrolytes by substituting with a single end-functional group.

Nanotopography-guided migration of T cells.

T cells navigate a wide variety of tissues and organs for immune surveillance and effector functions. Although nanoscale topographical structures of extracellular matrices and stromal/endothelial cell surfaces in local tissues may guide the migration of T cells, there has been little opportunity to study how nanoscale topographical features affect T cell migration. In this study, we systematically investigated mechanisms of nanotopography-guided migration of T cells using nanoscale ridge/groove surfaces. The velocity and directionality of T cells on these nanostructured surfaces were quantitatively assessed with and without confinement, which is a key property of three-dimensional interstitial tissue spaces for leukocyte motility. Depending on the confinement, T cells exhibited different mechanisms for nanotopography-guided migration. Without confinement, actin polymerization-driven leading edge protrusion was guided toward the direction of nanogrooves via integrin-mediated adhesion. In contrast, T cells under confinement appeared to migrate along the direction of nanogrooves purely by mechanical effects, and integrin-mediated adhesion was dispensable. Therefore, surface nanotopography may play a prominent role in generating migratory patterns for T cells. Because the majority of cells in periphery migrate along the topography of extracellular matrices with much lower motility than T cells, nanotopography-guided migration of T cells would be an important strategy to efficiently perform cell-mediated immune responses by increasing chances of encountering other cells within a given amount of time.

Binder-free Ge nanoparticles-carbon hybrids for anode materials of advanced lithium batteries with high capacity and rate capability.

We present a facile synthetic route toward binder-free, highly-dispersed Ge nanoparticles in carbon matrices using one-step pyrolysis of self-assembled Ge-polymer hybrids. 3-Dimensionally arranged Ge-carbon exhibits remarkably enhanced cycling properties and rate capability compared with carbon sheathed Ge lacking organization.

Facile one-pot synthesis of functional gold nanoparticle-polymer hybrids using ionic block copolymers as a nanoreactor.

A highly versatile approach to fabricate functional gold nanoparticle (AuNP)-polymer hybrids is demonstrated by employing sulfonated block copolymers. The 3-5 nm sized ionic domain of the sulfonated poly(styrene-block-methylbutylene) (S(n) MB(m) ) copolymers can be utilized as a nanoreactor where the Au ions can be selectively sequestered and reduced to AuNPs using a simple photochemical method. The size of the AuNPs can be adjusted in fine-steps from 2.0 ± 0.3 to 3.9 ± 0.5 nm by changing the sulfonation levels of the S(n) MB(m) copolymers. Remarkably, significantly improved methanol oxidation properties are achieved with the hybrid materials owing to the ion conducting-SO(3) H groups and the interconnected network of AuNPs confined within the self-assembled microstructures, which provides electronic conductivity.