The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile ...of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single‐cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post‐mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.
Synopsis
The transcriptome of human neural retina at a single‐cell level defines the gene expression profile in major cell types in the neural retina and can be used as a benchmark to assess the quality of stem cell‐derived cells or primary retinal cells.
The presented transcriptome atlas of human neural retina comprises single‐cell RNA‐sequencing data from 20,009 human retinal cells.
Unsupervised cell clustering analysis allows identification of 18 transcriptionally distinct cell populations that represent all known neural retinal cell types.
Reduced expression of the long non‐coding RNA MALAT1 correlates with longer post‐mortem time in putative early degenerating rod photoreceptors.
The retina transcriptome atlas can be used to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line.
A comprehensive analysis of the human retinal transcriptome at a single‐cell level defines gene expression profiles of all major retinal cell types.
Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core ...conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
To investigate the physico-chemical properties of aerosols in Taiwan, an observation network was initiated in 2003. In this work, the measurements of the mass concentration and carbonaceous ...composition of PM10 and PM2.5 are presented. Analysis on the data collected in the first 5-years, from 2003 to 2007, showed that there was a very strong contrast in the aerosol concentration and composition between the rural and the urban/suburban stations. The five-year means of EC at the respective stations ranged from 0.9±0.04 to 4.2±0.1 μgC m−3. In rural areas, EC accounted for 2–3% of PM10 and 3–5% of PM2.5 mass loadings, comparing to 4–6% of PM10 and 4–8% of PM2.5 in the urban areas. It was found that the spatial distribution of EC was consistent with CO and NOx across the network stations, suggesting that the levels of EC over Taiwan were dominated by local sources. The measured OC was split into POC and SOC counterparts following the EC tracer method. Five-year means of POC ranged from 1.8±0.1 to 9.7±0.2 μgC m−3 among the stations. It was estimated that the POM contributed 5–17% of PM10 and 7–18% of PM2.5 in Taiwan. On the other hand, the five-year means of SOC ranged from 1.5±0.1 to 3.8±.3 μgC m−3. The mass fractions of SOM were estimated to be 9–19% in PM10 and 14–22% in PM2.5. The results showed that the SOC did not exhibit significant urban-rural contrast as did the POC and EC. A significant cross-station correlation between SOC and total oxidant was observed, which means the spatial distribution of SOC in Taiwan was dominated by the oxidant mixing ratio. Besides, correlation was also found between SOC and particulate nitrate, implying that the precursors of SOA were mainly from local anthropogenic sources. In addition to the spatial distribution, the carbonaceous aerosols also exhibited distinct seasonality. In northern Taiwan, the concentrations of all the three carbonaceous components (EC, POC, and SOC) reached their respective minima in the fall season. POC and EC increased drastically in winter and peaked in spring, whereas the SOC was characterized by a bimodal pattern with the maximal concentration in winter and a second mode in summertime. In southern Taiwan, minimal levels of POC and EC occurred consistently in summer and the maxima were observed in winter, whereas the SOC peaked in summer and declined in wintertime. The discrepancies in the seasonality of carbonaceous aerosols between northern and southern Taiwan were most likely caused by the seasonal meteorological settings that dominated the dispersion of air pollutants. Moreover, it was inferred that the Asian pollution outbreaks could have shifted the seasonal maxima of air pollutants from winter to spring in the northern Taiwan, and that the increases in biogenic SOA precursors and the enhancement in SOA yield were responsible for the elevated SOC concentrations in summer.
A major challenge for organic solar cell (OSC) research is how to minimize the tradeoff between voltage loss and charge generation. In early 2019, we reported a non-fullerene acceptor (named Y6) that ...can simultaneously achieve high external quantum efficiency and low voltage loss for OSC. Here, we use a combination of experimental and theoretical modeling to reveal the structure-property-performance relationships of this state-of-the-art OSC system. We find that the distinctive π-π molecular packing of Y6 not only exists in molecular single crystals but also in thin films. Importantly, such molecular packing leads to (i) the formation of delocalized and emissive excitons that enable small non-radiative voltage loss, and (ii) delocalization of electron wavefunctions at donor/acceptor interfaces that significantly reduces the Coulomb attraction between interfacial electron-hole pairs. These properties are critical in enabling highly efficient charge generation in OSC systems with negligible donor-acceptor energy offset.
Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. We used molecular profiling combined with functional ...assays to investigate the role of these cells in human renal cell carcinoma (RCC). Blood monocytes from RCC patients displayed a tumor-promoting transcriptional profile that supported functions like angiogenesis and invasion. Induction of this protumor phenotype required an interleukin-1 receptor (IL-1R)-dependent mechanism. Indeed, targeting of IL-1-IL-1R axis in a human RCC xenograft model abrogated the protumor phenotype of tumor-associated macrophages (TAMs) and reduced tumor growth in vivo. Supporting this, meta-analysis of gene expression from human RCC tumors showed IL1B expression to correlate with myelomonocytic markers, protumor genes, and tumor staging. Analyzing RCC patient tumors confirmed the protumor phenotype of TAMs. These data provide direct evidence for a tumor-promoting role of monocytes and macrophages in human cancer and indicate IL-1-IL-1R as a possible therapeutic target.
•Monocytes and macrophages show a protumor phenotype in a human cancer setting•The protumor phenotype is regulated by an IL-1 receptor-dependent mechanism•Targeting this mechanism abrogated macrophage protumor phenotype and tumor in vivo
Monocytes and macrophages are major components of the tumor microenvironment, but their contributions to human cancer are poorly understood. Biswas and colleagues provide transcriptional, functional, and mechanistic data demonstrating a tumor-promoting phenotype of these cells in a human cancer setting.
Objective
Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb
Scutellaria baicalensis
, can be ...biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE.
Methods
The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific
Apc
Min/
+
mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model.
Results
HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (
P
< 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (
P
< 0.01,
P
< 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1β, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death.
Conclusion
Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.
We evaluated global and regional burdens of, risk factors for, and epidemiologic trends in pancreatic cancer among groups of different sexes and ages.
We used data from the GLOBOCAN database to ...estimate pancreatic cancer incidence and mortality in 184 countries. We examined the association between lifestyle and metabolic risk factors, extracted from the World Health Organization Global Health Observatory database, and pancreatic cancer incidence and mortality by univariable and multivariable linear regression. We retrieved country-specific age-standardized rates (ASRs) of incidence and mortalities from cancer registries from 48 countries through 2017 for trend analysis by joinpoint regression analysis.
The highest incidence and mortality of pancreatic cancer were in regions with very high (ASRs, 7.7 and 4.9) and high human development indexes (ASRs, 6.9 and 4.6) in 2018. Countries with higher incidence and mortality were more likely to have higher prevalence of smoking, alcohol drinking, physical inactivity, obesity, hypertension, and high cholesterol. From 2008 to 2017, 2007 to 2016, or 2003 to 2012, depending on the availability of the data, there were increases in incidence among men and women in 14 (average annual percent changes AAPCs, 8.85 to 0.41) and 17 (AAPCs, 6.04 to 0.87) countries, respectively. For mortality, the increase was observed in 8 (AAPCs, 4.20 to 0.55) countries among men and 14 (AAPCs, 5.83 to 0.78) countries among women. Although the incidence increased in 18 countries (AAPCs, 7.83 to 0.91) among individuals 50 years or older, an increasing trend in pancreatic cancer was also identified among individuals younger than 50 years and 40 years in 8 (AAPCs, 8.75 to 2.82) and 4 (AAPCs, 11.07 to 8.31) countries, respectively.
In an analysis of data from 48 countries, we found increasing incidence and mortality trends in pancreatic cancer, especially among women and populations 50 years or older, but also among younger individuals. More preventive efforts are recommended for these populations.
Display omitted
Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable ...structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14
+
monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. We use this data to build a
de novo
assembly of eight genomic regions encoding four key components of the immune system, namely the human leukocyte antigen, immunoglobulins, T cell receptors, and killer-cell immunoglobulin-like receptors. Validation of our assembly using k-mer based and alignment approaches suggests that it has high accuracy, with estimated base-level error rates below 1 in 10 kb, although we identify a small number of remaining structural errors. We use the assembly to identify heterozygous and homozygous structural variation in comparison to GRCh38. Despite analyzing only a single individual, we find multiple large structural variants affecting core genes at all three immunoglobulin regions and at two of the three T cell receptor regions. Several of these variants are not accurately callable using current algorithms, implying that further methodological improvements are needed. Our results demonstrate that assessing haplotype variation in these regions is possible given sufficiently accurate long-read and associated data. Continued reductions in the cost of these technologies will enable application of these methods to larger samples and provide a broader catalogue of germline structural variation at these loci, an important step toward making these regions accessible to large-scale genetic association studies.
We tested the hypotheses that kidney cancer incidence was increasing globally whilst its mortality was reducing; and its incidence was positively correlated with country-specific socioeconomic ...development. The incidence and mortality figures of each country were projected to 2030. Data on age-standardized incidence/mortality rates were retrieved from the GLOBOCAN in 2012. Temporal patterns were examined for 39 countries from the Cancer Incidence in Five Continents volumes I-X and other national registries. We evaluated the correlation between the incidence/mortality rates and Human Development Index (HDI)/Gross Domestic Product (GDP). The average annual percent change of its incidence and mortality in the most recent 10 years was obtained from joinpoint regression. The highest incidence rates were observed in Eastern Europe and North America, while its mortality rates were the highest in European countries. Incidence was positively correlated with HDI and GDP per capita. Many countries experienced incidence rise over the most recent 10 years, and a substantial reduction in mortality rates was observed for a significant number of countries, yet increases in mortality rates were observed in Eastern Europe. By 2030, Brazil and Ecuador may have the greatest rise in incidence both in men and women, which requires urgent need for planning healthcare resources.
Pancreatic cancer induces a substantial global burden. We examined its global incidence/mortality rates and their correlation with socioeconomic development (Human Development Index HDI and Gross ...Domestic Product GDP in 2000 as proxy measures). Data on age-standardized incidence/mortality rates in 2012 were retrieved from the GLOBOCAN database. Temporal patterns in 1998-2007 were assessed for 39 countries according to gender. The Average Annual Percent Change (AAPC) of the incidence/mortality trends was evaluated using joinpoint regression analysis. The age-standardized incidence ranged between 0.8-8.9/100,000. When compared among countries, Brazil (AAPC = 10.4, 95%C.I. = 0.8,21) and France (AAPC = 4.7, 95%C.I. = 3.6,5.9) reported the highest incidence rise in men. The greatest increase in women was reported in Thailand (AAPC = 7, 95%C.I. = 2.1,12.1) and Ecuador (AAPC = 4.3, 95%C.I. = 1.3,7.3). For mortality, the Philippines (APCC = 4.3, 95%C.I. = 2,6.6) and Croatia (AAPC = 2, 95% C.I. = 0,3.9) reported the biggest increase among men. The Philippines (AAPC = 5.8, 95% C.I. 4.5,7.2) and Slovakia (AAPC = 3.1, 95% C.I. 0.9,5.3) showed the most prominent rise among women. Its incidence was positively correlated with HDI (men: r = 0.66; women: r = 0.70) and GDP (men: r = 0.29; women: r = 0.28, all p < 0.05), and similarly for mortality (men: r = 0.67; women: r = 0.72 HDI; men: r = 0.23; women: r = 0.28 GDP). In summary, the incidence and mortality of pancreatic cancer were rising in many countries, requiring regular surveillance.