Systematic comparison of sequencing-based spatial transcriptomic methods.

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

Glycosylation-related genes mediated prognostic signature contribute to prognostic prediction and treatment options in ovarian cancer: based on bulk and single­cell RNA sequencing data.

BACKGROUND: Ovarian cancer (OC) is a complex disease with significant tumor heterogeneity with the worst prognosis and highest mortality among all gynecological cancers. Glycosylation is a specific post-translational modification that plays an important role in tumor progression, immune escape and metastatic spread. The aim of this work was to identify the major glycosylation-related genes (GRGs) in OC and construct an effective GRGs signature to predict prognosis and immunotherapy. METHODS: AUCell algorithm was used to identify glycosylation-related genes (GRGs) based on the scRNA-seq and bulk RNA-seq data. An effective GRGs signature was conducted using COX and LASSO regression algorithm. The texting dataset and clinical sample data were used to assessed the accuracy of GRGs signature. We evaluated the differences in immune cell infiltration, enrichment of immune checkpoints, immunotherapy response, and gene mutation status among different risk groups. Finally, RT-qPCR, Wound-healing assay, Transwell assay were performed to verify the effect of the CYBRD1 on OC. RESULTS: A total of 1187 GRGs were obtained and a GRGs signature including 16 genes was established. The OC patients were divided into high- and low- risk group based on the median riskscore and the patients in high-risk group have poor outcome. We also found that the patients in low-risk group have higher immune cell infiltration, enrichment of immune checkpoints and immunotherapy response. The results of laboratory test showed that CYBRD1 can promote the invasion, and migration of OC and is closely related to the poor prognosis of OC patients. CONCLUSIONS: Our study established a GRGs signature consisting of 16 genes based on the scRNA-seq and bulk RNA-seq data, which provides a new perspective on the prognosis prediction and treatment strategy for OC.

Target sequencing reveals the association between variants in VAX1 and NSCL/P in Chinese population.

OBJECTIVE: A significant genetic association between rs7078160 in VAX1 and NSCL/P has been established through genome-wide association studies (GWAS), and we previously replicated the association in the Chinese population. The critical issue in the post-GWAS era is to identify functional variations that have a real impact on disease in the susceptible regions highlighted by GWAS. This study aimed to elucidate functional variants in VAX1 fully. MATERIALS AND METHODS: Firstly, target sequencing was performed on 159 NSCL/P patients, followed by association analysis to discover disease-associated single-nucleotide polymorphisms (SNPs); we then replicated the findings using a larger sample (1626 cases, 2255 controls) and investigated how candidate SNPs affect disease occurrence using extensive annotation databases. Additionally, we compared the genetic profiles of NSCL/P subtypes. RESULTS: In this study, 6 SNPs in VAX1 were identified to be associated with NSCL/P in the Western Han Chinese population. Five of them were predicted to influence transcriptional factor-biding ability and were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. CONCLUSION: The previously reported association between rs7078160 and NSCL/P was successfully replicated. Moreover, our findings firstly revealed that 5 SNPs in VAX1 are associated with NSCL/P in the Western Han Chinese population. LEVEL OF EVIDENCE: Original Reports.

Early evidence for mounted horseback riding in northwest China.

Horseback riding was a transformative force in the ancient world, prompting radical shifts in human mobility, warfare, trade, and interaction. In China, domestic horses laid the foundation for trade, communication, and state infrastructure along the ancient Silk Road, while also stimulating key military, social, and political changes in Chinese society. Nonetheless, the emergence and adoption of mounted horseback riding in China is still poorly understood, particularly due to a lack of direct archaeological data. Here we present a detailed osteological study of eight horse skeletons dated to ca. 350 BCE from the sites of Shirenzigou and Xigou in Xinjiang, northwest China, prior to the formalization of Silk Road trade across this key region. Our analyses reveal characteristic osteological changes associated with equestrian practices on all specimens. Alongside other relevant archaeological evidence, these data provide direct evidence for mounted horseback riding, horse equipment, and mounted archery in northwest China by the late first millennium BCE. Most importantly, our results suggest that this region may have played a crucial role in the spread of equestrian technologies from the Eurasian interior to the settled civilizations of early China, where horses facilitated the rise of the first united Chinese empires and the emergence of transcontinental trade networks.

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Integrated Analysis of the Association Between Variants at PAX7 and NSCL/P in the Han Population.

OBJECTIVE: Paired box 7 (PAX7) has been considered as a candidate gene for non-syndromic cleft lip with or without palate (NSCL/P). However, there is no research for the XXX, and previous studies concentrated on limited variants. This study aimed to conduct sufficiently dense and powerful scans of variants at PAX7 and explored the roles of variants at PAX7 in NSCL/P among the XXX. DESIGN: Targeted region sequencing was performed to thoroughly screen variations, followed by a two-phase association analysis. 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. We also explored the roles of variants at PAX7 gene in NSCL/P subtypes. Additionally, indirect associations were found by calculating LD and haplotypes. SETTING: The study was conducted in XXX. PATIENTS, PARTICIPANTS: 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. INTERVENTIONS: Blood samples were collected. MAIN OUTCOME MEASURES: To explore the association analysis between variants at PAX7 and NSCL/P in XXX. RESULTS: The results showed that rs2236810, rs114882979 and rs2236804 were significantly associated with NSCL/P, which were predicted to have regulatory functions. Besides, variants at PAX7 function differently in the NSCL/P subtypes. We also discovered a PAX7 missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T). CONCLUSIONS: In summary, we confirmed 3 SNPs at PAX7 were significantly associated with NSCL/P in XXX and identified a missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T).

Highly Valuable Fish Oil: Formation Process, Enrichment, Subsequent Utilization, and Storage of Eicosapentaenoic Acid Ethyl Esters.

In recent years, as the demand for precision nutrition is continuously increasing, scientific studies have shown that high-purity eicosapentaenoic acid ethyl ester (EPA-EE) functions more efficiently than mixed omega-3 polyunsaturated fatty acid preparations in diseases such as hyperlipidemia, heart disease, major depression, and heart disease; therefore, the market demand for EPA-EE is growing by the day. In this paper, we attempt to review EPA-EE from a whole-manufacturing-chain perspective. First, the extraction, refining, and ethanolysis processes (fish oil and ethanol undergo transesterification) of EPA-EE are described, emphasizing the potential of green substitute technologies. Then, the method of EPA enrichment is thoroughly detailed, the pros and cons of different methods are compared, and current developments in monomer production techniques are addressed. Finally, a summary of current advanced strategies for dealing with the low oxidative stability and low bioavailability of EPA-EE is presented. In conclusion, understanding the entire production process of EPA-EE will enable us to govern each step from a macro perspective and accomplish the best use of EPA-EE in a more cost-effective and environmentally friendly way.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Occurrence of polycyclic aromatic compounds and potentially toxic elements contamination and corresponding interdomain microbial community assembly in soil of an abandoned gas station.

Bacteria, archaea and fungi usually coexist in various soil habitats and play important roles in biogeochemical cycle and remediation of contamination. Despite their significance, their combined bioassembly pattern, ecological interactions and driving factors in contaminated soils still remain obscure. To fill the gap, a systemic investigation on the characteristics of microbial community including bacteria, archaea and fungi, assembly patterns and environmental driving factors was conducted in an abandoned gas station soils which were contaminated by polycyclic aromatic compounds and potentially toxic elements for decades. The results showed that the soils were contaminated excessively by benzo[a]pyrene (0.46-2.00 mg/kg) and Dibenz[a,h]anthracene (0.37-1.30 mg/kg). Multitudinous contaminant-degrading/resistant microorganisms and unigenes were detected, indicating potential of the soils to mitigate the pollution. Compared with fungi and archaea, the bacteria had higher community diversity and were more responsive to seasonal shifts. Functional genes (nidB, nahAb, nahAa, adhP, adh, adhC, etc.) involved in biodegradation were highly enriched in summer (1.96% vs 1.80%). The co-occurrence network analysis showed summer communities exhibit a more robust network structure and positive interactions than winter communities. The fungi Neocucurbitaria, Penicillium, Fusarium, Chrysosporium, Knufia, Filobasidium, Wallemia and Rhodotorula were identified as the keystone taxa, indicating that fungi also had important positions in the interdomain molecular ecological networks of both seasons. The network topological properties and |ßNTI| (66.7%-93.3% greater than 2) results indicated the deterministic assembly processes of the microbial communities in the contaminated soil. Acenaphthylene, benzo[b]fluoranthene, indeno[1,2,3-cd]perylene, benzo[g,h,i]pyrene and 9-fluorenone were the key environmental factors driving the deterministic assembly processes of the interdomain microbial community in the contaminated soil. These findings extended our knowledge of interdomain microbial community assembly mechanisms and ecological patterns in natural attenuation and provide valuable guidance in associated bioremediation strategies.

Occurrence of polycyclic aromatic compounds and interdomain microbial communities in oilfield soils.

Soil polycyclic aromatic compound (PAC) pollution as a result of petroleum exploitation has caused serious environmental problems. The unclear assembly and functional patterns of microorganisms in oilfield soils limits the understanding of microbial mechanisms for PAC elimination and health risk reduction. This study investigated the polycyclic aromatic hydrocarbons (PAHs) and substituted PAHs (SPAHs) occurrence, and their impact on the bacteria-archaea-fungi community diversity, co-occurrence network and functionality in the soil of an abandoned oilfield. The results showed that the PAC content in the oilfield ranged from 3429.03 µg kg-1 to 6070.89 µg kg-1, and risk assessment results suggested a potential cancer risk to children and adults. High molecular weight PAHs (98.9%) and SPAHs (1.0%) contributed to 99.9% of the toxic equivalent concentration. For microbial analysis, the abundantly detected degraders and unigenes indicated the microbial potential to mitigate pollutants and reduce health risks. Microbial abundance and diversity were found to be negatively correlated with health risk. The co-occurrence network analysis revealed nonrandom assembly patterns of the interdomain microbial communities, and species in the network exhibited strong positive connections (59%). The network demonstrated strong ecological linkages and was divided into five smaller coherent modules, in which the functional microbes were mainly involved in organic substance and mineral component degradation, biological electron transfer and nutrient cycle processes. The keystone species for maintaining microbial ecological functions included Marinobacter of bacteria and Neocosmospora of fungi. Additionally, benzo [g,h,i]pyrene, dibenz [a,h]anthracene, indeno [1,2,3-cd]perylene and total phosphorus were the key environmental factors driving the assembly and functional patterns of microbial communities under pollution stress. This work improves the knowledge of the functional pattern and environmental adaptation mechanisms of interdomain microbes, and provides valuable guidance for the further bioremediation of PAC-contaminated soils in oilfields.

[Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis].

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

[Effect of Jinzhen Oral Liquid on cough after lipopolysaccharide-induced infection in rats and mechanism].

This study aims to explore the effect of Jinzhen Oral Liquid(JOL) on cough after infection in rats and the mechanism. To be specific, a total of 60 male SD rats were classified into 6 groups: normal group(equivalent volume of distilled water, ig), model group(equivalent volume of distilled water, ig), Dextromethorphan Hydrobromide Oral Solution group(3.67 mL·kg~(-1), ig), high-, medium-, and low-dose JOL groups(11.34, 5.67, and 2.84 mL·kg~(-1), respectively, ig). Lipopolysaccharide(LPS, nasal drip), smoking, and capsaicin(nebulization) were employed to induce cough after infection in rats except the normal group. Administration began on the 19 th day and lasted 7 days. Capsaicin(nebulization) was used to stimulate cough 1 h after the last administration and the cough frequency and cough incubation period in rats were recorded. The pathological morphology of lung tissue was observed based on hematoxylin-eosin(HE) staining. Immunohistochemistry(IHC) was used to detect the specific expression of transient receptor potential vanilloid 1(Trpv1), nerve growth factor(NGF), tropomyosin receptor kinase A(TrkA), and phosphorylated-p38 mitogen-activated protein kinase(p-p38 MAPK) in lung tissue, Western blot the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and real-time fluorescent quantitative polymerase chain reaction(real-time PCR) the mRNA expression of Trpv1, NGF, and TrkA. The results showed that model group demonstrated significantly high cough frequency, obvious proliferation and inflammatory cell infiltration in lung tissue, significantly enhanced positive protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue and significant increase in the mRNA expression of Trpv1, NGF, and TrkA compared with the normal group. Compared with the model group, JOL can significantly reduce the cough frequency, alleviate the pathological changes of lung tissue, and decrease the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and high-dose and medium-dose JOL can significantly lower the mRNA expression of Trpv1, NGF, and TrkA. This study revealed that JOL can effectively inhibit Trpv1 pathway-related proteins and improve cough after infection. The mechanism is that it reduces the expression of NGF, TrkA, and p-p38 MAPK in lung tissue, thereby decreasing the expression of Trpv1 and cough sensitivity.

Neuronal nitric oxide synthase in dorsal raphe nucleus mediates PTSD-like behaviors induced by single-prolonged stress through inhibiting serotonergic neurons activity.

The pathogenesis of post-traumatic stress disorder (PTSD) remains largely unclear. A large body of evidence suggests that the abnormal level of serotonin (5-HT) is closely related to the onset of PTSD. Several reports reveal that nitric oxide (NO) affects extracellular 5-HT levels in various brain regions, but no consistent direction of change was found and the underlying mechanisms remain unknown. The most of serotonergic neurons in dorsal raphe nucleus (DRN), a major source of serotonergic input to the forebrain, co-expresses neuronal nitric oxide synthase (nNOS), a synthase derived nitric oxide (NO) in the central nervous system. Here, we found that the excessive expression of nNOS and thereby the high concentration of NO followed by single-prolonged stress (SPS) caused suppression of the activity of DRN 5-HT neurons, inducing PTSD-like phenotype including increased anxiety-like behaviors, enhanced contextual fear memory, and fear generalization. Our study uncovered an important role of DRN nNOS-NO pathway in the pathology of PTSD, which may contribute to new understanding of the molecular mechanism of PTSD.

dCA1-NAc shell glutamatergic projection mediates context-induced memory recall of morphine.

Opioid relapse is generally caused by the recurrence of context-induced memory reinstatement of reward. However, the internal mechanisms that facilitate and modify these processes remain unknown. One of the key regions of the reward is the nucleus accumbens (NAc) which receives glutamatergic projections from the dorsal hippocampus CA1 (dCA1). It is not yet known whether the dCA1 projection to the NAc shell regulates the context-induced memory recall of morphine. Here, we used a common model of addiction-related behavior conditioned place preference paradigm, combined with immunofluorescence, chemogenetics, optogenetics, and electrophysiology techniques to characterize the projection of the dCA1 to the NAc shell, in context-induced relapse memory to morphine. We found that glutamatergic neurons of the dCA1 and gamma aminobutyric acidergic (GABA) neurons of the NAc shell are the key brain areas and neurons involved in the context-induced reinstatement of morphine memory. The dCA1-NAc shell glutamatergic input pathway and the excitatory synaptic transmission of the dCA1-NAc shell were enhanced via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) when mice were re-exposed to environmental cues previously associated with drug intake. Furthermore, chemogenetic and optogenetic inactivation of the dCA1-NAc shell pathway decreased the recurrence of long- and short-term morphine-paired context memory in mice. These results provided evidence that the dCA1-NAc shell glutamatergic projections mediated the context-induced memory recall of morphine.

A strategy for enhancing the photoactivity of g-C3N4-based single-atom catalysts via sulphur doping: a theoretical study.

Single-atom catalysts (SACs) have received intense attention owing to their maximum utilization efficiency of metal atoms and high catalytic activity. Although SACs possess many merits, such as high activity, selectivity and stability in photocatalysis, the difficulty of fabricating atomically dispersed atom catalysts with a high level of metal loading limits their practical applications. Here, a sulphur-doping strategy was proposed to enhance the incorporation of single Pt atoms in monolayer graphitic carbon nitride (g-C3N4), and the structural, electronic and optical properties were investigated through density functional theory (DFT) calculations. This work verified that SACs based on sulphur-doped monolayer g-C3N4 (S-g-C3N4) exhibit a lower band gap energy, higher photocatalytic oxidation ability, easier charge separation, lower oxidation state of Pt atoms and wider light absorption range. This work provides a promising path for fabricating efficient g-C3N4-based photocatalytic SACs.

Genetic ancestry does not explain increased atopic dermatitis susceptibility or worse disease control among African American subjects in 2 large US cohorts.

BACKGROUND: Atopic dermatitis (AD) is more common among African American children. Whether there are racial/ethnic difference among adults with AD and the causes for those disparities are unclear. OBJECTIVE: We sought to examine the relationship between self-reported race/ethnicity and AD and determine whether African genetic ancestry is predictive of these outcomes among African American subjects. METHODS: We analyzed data from 2 independent multiethnic longitudinal studies: 86,893 subjects aged 18 to 100 years from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and 5467 subjects aged 2 to 26 years from the national Pediatric Eczema Elective Registry (PEER) cohort. The primary outcomes were physician-diagnosed AD in GERA and repeated measures of self-reported disease control among patients with physician-diagnosed AD at 6-month intervals in PEER. We examined whether self-identified African American race/ethnicity was predictive of these outcomes and then tested whether a continuous measure of African genetic ancestry was associated with outcomes within the African American group. RESULTS: AD was more common among self-identified African American subjects than non-Hispanic white subjects in GERA (4.4% vs 2.1%; odds ratio, 2.06; 95% CI, 1.70-2.48) and less well-controlled in PEER subjects (odds of 1-level worse control, 1.91; 95% CI, 1.64-2.22). However, African genetic ancestry was not associated with AD risk or control among self-identified African American subjects in either cohort, nor did an AD polygenic risk score or genetic skin pigment score explain the AD disparities in patients with AD. CONCLUSION: Ancestry-related genetic effects do not explain increased AD prevalence or poorer disease control among African American subjects.

FBXW10 promotes hepatocarcinogenesis in male patients and mice.

Hepatocellular carcinoma (HCC) is reported to associate with abnormal expression of SCF E3 ubiquitin ligases. FBXW10, an F-box protein of the E3 ubiquitin ligases, was abnormally regulated in HCC patients. However, whether FBXW10 is associated with HCC has not yet been evaluated. Here, we analyzed the associations between overall survival and various risk factors in 191 HCC tissues. Univariate and multivariate analyses demonstrated that FBXW10 was an independent risk factor related to HCC prognosis. The results showed that FBXW10, gender and tumor state were strongly associated with overall survival in HCC patients. Furthermore, high expression of FBXW10 was associated with poor survival among male HCC patients but not female HCC patients. FBXW10 was more highly expressed in male HCC tissues and more strongly related to vascular invasion in male HCC patients. Consistent with these findings, the male FBXW10-Tg(+) mice were more susceptible to tumorigenesis, changes in regenerative capacity, and liver injury and inflammation but not changes in liver function than FBXW10-Tg(-) mice. FBXW10 promoted cell proliferation and migration in HCC cell lines. Our findings reveal that FBXW10, an independent risk factor for HCC, promotes hepatocarcinogenesis in male patients, and is also a potential prognostic marker in male patients with HCC.

Zn stress facilitates nitrate transporter 1.1-mediated nitrate uptake aggravating Zn accumulation in Arabidopsis plants.

Describing the mechanisms of zinc (Zn) accumulation in plants is essential to counteract the effects of excessive Zn uptake in crops grown in contaminated soils. Increasing evidence suggests that there is a positive correlation between nitrate supply and Zn accumulation in plants. However, the role of the primary nitrate transporter NRT1.1 in Zn accumulation in plants remains unknown. In this study, a Zn stress-induced increase in nitrate uptake and an increase in NRT1.1 protein levels in wild-type (Col-0) Arabidopsis plants were measured using microelectrode ion flux and green fluorescent protein (GFP)/ß-glucuronidase (GUS) staining, respectively. Both agar and hydroponic cultures showed that mutants lacking the NRT1.1 function in nrt1.1 and chl1-5 (chlorate resistant 1) exhibited lower Zn levels in the roots and shoots of Zn-stressed plants than the wild-type. A lack of NRT1.1 activity also alleviated Zn-induced photosynthetic damage and growth inhibition in plants. Further, we used a rotation system with synchronous or asynchronous uptakes of nitrate and Zn to demonstrate differences in Zn levels between the Col-0 and nrt1.1/chl1-5 mutants. Significantly lower difference in Zn levels were noted in the nitrate/Zn asynchronous treatment than in the nitrate/Zn synchronous treatment. From these results, it can be concluded that NRT1.1 modulates Zn accumulation in plants via a nitrate-dependent pathway.

Quantitative and Qualitative Evaluation of Breast Cancer Prognosis: A Sonographic Elastography Study.

BACKGROUND Breast cancer is one of the most commonly diagnosed cancers in women worldwide, and sonographic elastography has previously demonstrated good performance in detecting breast malignancies. However, the exact relationship between elastographic measures and clinical prognostic factors is still not well understood. Thus, the aim of this study was to evaluate any associations between major clinical prognostic factors and strain elastography and to validate the diagnostic value of elastography in breast cancer. MATERIAL AND METHODS A total of 373 subjects with breast masses, of which 196 were benign and 177 were malignant, were included in the study. All subjects underwent routine ultrasound examination and strain elastography before biopsy. The elastographic measures - strain ratio (SR) for qualitative measures and Tsukuba score (TS) for quantitative measures - were obtained and compared with prognostic factors, including nuclear grade, lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2). The SR demonstrated the best diagnostic performance in differentiation between malignant and benign lesions. RESULTS With the best cut-off value at 2.42, the SR achieved a sensitivity of 96.0% and specificity of 98.5%. Moreover, higher SRs and TSs were associated with breast lesions with a high nuclear grade and lymph node metastasis and with being ER-negative, PR-negative, and HER-2 negative. CONCLUSIONS Elastography is a useful imaging technique in differentiating benign breast masses from malignant ones. The strong relationship between prognostic factors and elastographic measures also demonstrated its excellent performance in predicting the prognosis of breast malignancies.