Spatially organized tumor-stroma boundary determines the efficacy of immunotherapy in colorectal cancer patients.

Colorectal cancer (CRC) patients with mismatch repair (MMR)-deficient (dMMR) but not MMR-proficient (pMMR) tend to benefit from immune checkpoint blockade (ICB) therapy. To profile the tumor microenvironments (TME) underlying these varied therapeutic responses, we integrate spatial enhanced resolution omics-sequencing (Stereo-seq), single-cell RNA sequencing, and multiplexed imaging analysis to create high-definition spatial maps of tumors from treatment-naïve and ICB-treated CRC patients. Our results identify the spatial organization and immune status of the tumor-stroma boundary as a distinctive feature of dMMR and pMMR CRCs, which associates with ICB response.

Stimulation strategies for electrical and magnetic modulation of cells and tissues.

Electrical phenomena play an important role in numerous biological processes including cellular signaling, early embryogenesis, tissue repair and remodeling, and growth of organisms. Electrical and magnetic effects have been studied on a variety of stimulation strategies and cell types regarding cellular functions and disease treatments. In this review, we discuss recent advances in using three different stimulation strategies, namely electrical stimulation via conductive and piezoelectric materials as well as magnetic stimulation via magnetic materials, to modulate cell and tissue properties.

Enhanced hybrid photocatalytic dry reforming using a phosphated Ni-CeO nanorod heterostructure.

Operating the dry reforming reaction photocatalytically presents an opportunity to produce commodity chemicals from two greenhouse gases, carbon dioxide and methane, however, the top-performing photocatalysts presented in the academic literature invariably rely on the use of precious metals. In this work, we demonstrate enhanced photocatalytic dry reforming performance through surface basicity modulation of a Ni-CeO photocatalyst by selectively phosphating the surface of the CeO nanorod support. An optimum phosphate content is observed, which leads to little photoactivity loss and carbon deposition over a 50-hour reaction period.

Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis.

A major challenge in understanding vertebrate embryogenesis is the lack of topographical transcriptomic information that can help correlate microenvironmental cues within the hierarchy of cell-fate decisions. Here, we employed Stereo-seq to profile 91 zebrafish embryo sections covering six critical time points during the first 24 h of development, obtaining a total of 152,977 spots at a resolution of 10 × 10 × 15 μm (close to cellular size) with spatial coordinates. Meanwhile, we identified spatial modules and co-varying genes for specific tissue organizations.

Spatial transcriptome unveils a discontinuous inflammatory pattern in proficient mismatch repair colorectal adenocarcinoma.

The preexistence of immune cells in the tumor microenvironment substantiates the efficacy of immunotherapy in cancer patients. Although the complex intratumoral immune heterogeneity has been extensively studied in single cell resolution, hi-res spatial investigations are limited. In this study, we performed a spatial transcriptome analysis of 4 colorectal adenocarcinoma specimens and 2 paired distant normal specimens to identify the molecular pattern involved in a discontinuous inflammatory response in pathologically annotated cancer regions.

Solar Urea: Towards a Sustainable Fertilizer Industry.

Urea, an agricultural fertilizer, nourishes humanity. The century-old Bosch-Meiser process provides the world's urea. It is multi-step, consumes enormous amounts of non-renewable energy, and has a large CO footprint.

Corrigendum to "Protective Effect of the HIF-1A Pro582Ser Polymorphism on Severe Diabetic Retinopathy".

[This corrects the article DOI: 10.1155/2019/2936962.].

Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis.

Background: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear.

Results: Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4 T cells and CD8 T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq).

Development of double-positive thymocytes at single-cell resolution.

Background: T cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated.

Methods: We applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat.

Landscape and Dynamics of the Transcriptional Regulatory Network During Natural Killer Cell Differentiation.

Natural killer (NK) cells are essential in controlling cancer and infection. However, little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation. In this study, we applied the assay of transposase accessible chromatin with sequencing (ATAC-seq) technique in a home-developed in vitro NK cell differentiation system.

CYP46A1-dependent and independent effects of efavirenz treatment.

Cholesterol excess in the brain is mainly disposed cholesterol 24-hydroxylation catalysed by cytochrome P450 46A1, a CNS-specific enzyme. Cytochrome P450 46A1 is emerging as a promising therapeutic target for various brain diseases with both enzyme activation and inhibition having therapeutic potential. The rate of cholesterol 24-hydroxylation determines the rate of brain cholesterol turnover and the rate of sterol flux through the plasma membranes.

Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes.

Cytochrome P450 46A1 encoded by catalyzes cholesterol 24-hydroxylation and is a CNS-specific enzyme that controls cholesterol removal and turnover in the brain. Accumulating data suggest that increases in cytochrome P450 46A1 activity in mouse models of common neurodegenerative diseases affect various, apparently unlinked biological processes and pathways. Yet, the underlying reason for these multiple enzyme activity effects is currently unknown.

Anchoring Ba to Pd/H WO Nanowires Promotes a Photocatalytic Reverse Water-Gas Shift Reaction.

Surface deposition of Ba on Pd/H WO nanowires was developed by using a solution-phase atomic layer deposition process. The procedure involves the generation of Brønsted surface OH sites by H spillover on Pd/WO , which can then hydrolytically condense with Ba(OEt) to produce surface Ba . At just 0.

Hybrid Photo- and Thermal Catalyst System for Continuous CO Reduction.

Heterogeneous thermal catalytic processes are vital for industrial production of fuels, fertilizers, and other chemicals necessary for sustaining human life. However, these processes are highly energy-intensive, requiring a vast consumption of fossil fuels. An emerging class of heterogeneous catalysts that are thermally driven but also exhibit a photochemically enhanced rate can potentially reduce process energy intensity by partially substituting conventional heat (where fossil fuels are needed) with solar energy.

APEC: an accesson-based method for single-cell chromatin accessibility analysis.

The development of sequencing technologies has promoted the survey of genome-wide chromatin accessibility at single-cell resolution. However, comprehensive analysis of single-cell epigenomic profiles remains a challenge. Here, we introduce an accessibility pattern-based epigenomic clustering (APEC) method, which classifies each cell by groups of accessible regions with synergistic signal patterns termed "accessons".

Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC-derived retinal organoids.

Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered.

Cu Atoms on Nanowire Pd/HWO Bronzes Enhance the Solar Reverse Water Gas Shift Reaction.

Nanowire hydrogen bronzes of WO nanowires decorated with Pd (Pd/HWO) were previously demonstrated to effectively capture broadband radiation across the ultraviolet to near-infrared wavelength range and catalyze the reverse water gas shift reaction (RWGS). Herein, we report a synthetic strategy to enhance the performance of this class of photocatalysts by conformally coating Cu atoms onto the surface of Pd/HWO by anchoring Cu(I)OBu to the Brønsted acidic protons of the bronze. The resulting materials are characterized by a suite of analytical methods, including electron microscopy and X-ray absorption spectroscopy.

Protective Effect of the Pro582Ser Polymorphism on Severe Diabetic Retinopathy.

Objective: Hypoxia is central in the pathogenesis of diabetic retinopathy (DR). Hypoxia-inducible factor-1 (HIF-1) is the key mediator in cellular oxygen homeostasis that facilitates the adaptation to hypoxia. HIF-1 is repressed by hyperglycemia contributing by this to the development of complications in diabetes.

Nickel@Siloxene catalytic nanosheets for high-performance CO methanation.

Two-dimensional (2D) materials are of considerable interest for catalyzing the heterogeneous conversion of CO to synthetic fuels. In this regard, 2D siloxene nanosheets, have escaped thorough exploration, despite being composed of earth-abundant elements. Herein we demonstrate the remarkable catalytic activity, selectivity, and stability of a nickel@siloxene nanocomposite; it is found that this promising catalytic performance is highly sensitive to the location of the nickel component, being on either the interior or the exterior of adjacent siloxene nanosheets.

Pd@H WO Nanowires Efficiently Catalyze the CO Heterogeneous Reduction Reaction with a Pronounced Light Effect.

The design of photocatalysts able to reduce CO to value-added chemicals and fuels could enable a closed carbon circular economy. A common theme running through the design of photocatalysts for CO reduction is the utilization of semiconductor materials with high-energy conduction bands able to generate highly reducing electrons. Far less explored in this respect are low-energy conduction band materials such as WO.

Programmed differentiated natural killer cells kill leukemia cells by engaging SLAM family receptors.

Natural killer (NK) cells are important innate immune cells that can directly kill transformed or virus-infected cells. The adoptive transfer of NK cells has been used to treat hematological malignancies; however, the limited sources and quantities of NK cells have restricted their clinical application. Here, we acquired sufficient quantities of functional NK cells from CD34 cells treated with a cytokine cocktail.

Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease.

Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz.

Heterogeneous catalytic hydrogenation of CO by metal oxides: defect engineering - perfecting imperfection.

Metal oxides with their myriad compositions, structures and bonding exhibit an incredibly diverse range of properties. It is however the defects in metal oxides that endow them with a variety of functions and it is the ability to chemically tailor the type, population and distribution of defects on the surface and in the bulk of metal oxides that delivers utility in different applications. In this Tutorial Review, we discuss how metal oxides with designed defects can be synthesized and engineered, to enable heterogeneous catalytic hydrogenation of gaseous carbon dioxide to chemicals and fuels.

Efficient Electrocatalytic Reduction of CO by Nitrogen-Doped Nanoporous Carbon/Carbon Nanotube Membranes: A Step Towards the Electrochemical CO Refinery.

Herein we introduce a straightforward, low cost, scalable, and technologically relevant method to manufacture an all-carbon, electroactive, nitrogen-doped nanoporous-carbon/carbon-nanotube composite membrane, dubbed "HNCM/CNT". The membrane is demonstrated to function as a binder-free, high-performance gas diffusion electrode for the electrocatalytic reduction of CO to formate. The Faradaic efficiency (FE) for the production of formate is 81 %.