Single-cell RNA sequencing (scRNA-seq) identifies cell subpopulations within tissue but does not capture their spatial distribution nor reveal local networks of intercellular communication acting in ...situ. A suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding, can help address this issue. However, no method currently provides as complete a scope of the transcriptome as does scRNA-seq, underscoring the need for approaches to integrate single-cell and spatial data. Here, we review efforts to integrate scRNA-seq with spatial transcriptomics, including emerging integrative computational methods, and propose ways to effectively combine current methodologies.
Nanometer‐sized rutile shows much higher electroactivity towards Li insertion than micrometer‐sized rutile. Up to 0.8 mol of Li per mole of TiO2 can be inserted into nanometer‐sized rutile at room ...temperature (see figure), which is able to reversibly accommodate Li up to Li0.5TiO2 with excellent capacity retention and high rate capability on cycling, rendering it a promising anode material for high‐power lithium‐ion batteries.
An optimized nanostructure design of electrode material for high power, high energy lithium batteries is realized. Highly Li‐permeable materials are obtained by introducing hierarchical mixed ...conducting networks on both nanoscale and microscale levels (see figure). A mesoporous TiO2:RuO2 composite is selected as an example of this new design.
Summary
Background
Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in ...various autoimmune and liver diseases.
Aim
To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA).
Methods
Consecutive PBC patients were retrospectively reviewed. 25‐hydroxyvitamin D 25(OH)D levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris‐I and Barcelona criteria. Logistic regressions were performed to identify the treatment response‐associated parameters.
Results
Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris‐I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02–15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023).
Conclusions
25(OH)D level is associated with biochemical and histological features in PBC. Pre‐treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.
The biexciton cascade process in self-assembled quantum dots (QDs) provides an ideal system for realizing deterministic entangled photon-pair sources, which are essential to quantum information ...science. The entangled photon pairs have recently been generated in experiments after eliminating the fine-structure splitting (FSS) of excitons using a number of different methods. Thus far, however, QD-based sources of entangled photons have not been scalable because the wavelengths of QDs differ from dot to dot. Here, we propose a wavelength-tunable entangled photon emitter mounted on a three-dimensional stressor, in which the FSS and exciton energy can be tuned independently, thereby enabling photon entanglement between dissimilar QDs. We confirm these results via atomistic pseudopotential calculations. This provides a first step towards future realization of scalable entangled photon generators for quantum information applications.
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging ...from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
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•Profiling of 10 human skin SCCs and matched normals via scRNA-seq, ST, and MIBI•Tumor-specific keratinocytes (TSKs) reside within a fibrovascular niche at leading edges•Distinct ligand-receptor and spatial niche associations for tumor and stromal cells.•Subpopulation essential tumorigenic gene networks defined by in vivo CRISPR screening
Integration of high-dimensional multi-omics approaches to characterize human cutaneous squamous cell carcinoma identifies a tumor-specific keratinocyte population as well as the immune infiltrates and heterogeneity at tumor leading edges.
Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 ...SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.
By using nanometer‐sized RuO2 to “metalize” tiny pores and even “repair” incomplete electronically conducting (carbon) networks in porous carbon‐containing LiFePO4 (see figure), the kinetics and rate ...capability of the composite are significantly improved. The key lies in the bonding properties of RuO2, which enables good contact to both the oxidic storage material as well as the carbon structures used as current collector.
Previously we showed that pure struvite could be recovered from wastewater at neutral pH. This omits the need for adding alkalinity to the process. However, at a neutral pH value the reaction is ...relatively slow making it practically not a good system from an engineering point of view. In this study, electrochemical deposition was evaluated as a means to improve the formation of pure struvite at a neutral pH value. An electrolytic cell with an inert Pt (or graphite) anode and a nickel cathode was set up for the experiment. The generation of OH
− via electrochemical reduction of dissolved oxygen slightly increased the interfacial pH near the cathode, resulting in rapid formation of the precipitates. The structure, morphology, composition and thermal properties of the harvested precipitate were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), microscopic analysis, infrared (IR) spectra, energy-dispersive spectrometry (EDS), element analysis (EA) and thermo-gravimetric analysis (TGA). All the analyses support formation of pure struvite in the precipitate.
Ketosis is one of the most prevalent and complex metabolic disorders in high-producing dairy cows and usually detected through analyses of β-hydroxybutyrate (BHB) concentration in blood. Our main ...objectives were to evaluate genetic parameters for blood BHB predicted based on Fourier-transform mid-infrared spectra from 5 to 305 d in milk, and estimate the genetic relationships of blood BHB with 7 reproduction traits and 6 longevity traits in Holstein cattle. Predicted blood BHB records of 11,609 Holstein cows (after quality control) were collected from 2016 to 2019 and used to derive 4 traits based on parity number, including predicted blood BHB in all parities (BHBp), parity 1 (BHB1), parity 2 (BHB2), and parity 3+ (BHB3). Single- and multitrait repeatability models were used for estimating genetic parameters for the 4 BHB traits. Random regression test-day models implemented via Bayesian inference were used to evaluate the daily genetic feature of BHB variability. In addition, genetic correlations were calculated for the 4 BHB traits with reproduction and longevity traits. The heritability estimates of BHBp, BHB1, BHB2, and BHB3 ranged from 0.100 ± 0.026 (± standard error) to 0.131 ± 0.023. The BHB in parities 1 to 3+ were highly genetically correlated and ranged from 0.788 (BHB1 and BHB2) to 0.911 (BHB1 and BHB3). The daily heritability of BHBp ranged from 0.069 to 0.195, higher for the early and lower for the later lactation periods. A similar trend was observed for BHB1, BHB2, and BHB3. There are low direct genetic correlations between BHBp and selected reproductive performance and longevity traits, which ranged from −0.168 ± 0.019 (BHBp and production life) to 0.157 ± 0.019 (BHBp and age at first calving) for the early lactation stage (5 to 65 d). These direct genetic correlations indicate that cows with higher BHBp (greater likelihood of having ketosis) in blood usually have shorter production life (−0.168 ± 0.019). Cows with higher fertility and postpartum recovery, such as younger age at first calving (0.157 ± 0.019) and shorter interval from calving to first insemination in heifer (0.111 ± 0.006), usually have lower BHB concentration in the blood. Furthermore, the direct genetic correlations change across parity and lactation stage. In general, our results suggest that selection for lower predicted BHB in early lactation could be an efficient strategy for reducing the incidence of ketosis as well as indirectly improving reproductive and longevity performance in Holstein cattle.
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