A compendium of genetic regulatory effects across pig tissues.

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

circPTK2 promotes proliferation, migration and invasion of trophoblast cells through the miR-619/WNT7B pathway in preeclampsia.

It has been shown that the circular RNA (circRNA) circPTK2 modulates many types of diseases. However, the possible functions as well as the molecular mechanisms of circPTK2 in preeclampsia (PE) and their effects on trophoblast are unknown. Herein, we obtained the placental tissues from 20 pregnant women with PE who delivered in the Yueyang Maternal Child Medicine Health Hospital between 2019 and 2021 to serve as the PE group, and a normal group was composed of 20 healthy pregnant women with normal prenatal examinations. The circPTK2 level was significantly reduced in tissues from the PE group. The expression and localization of circPTK2 were verified using RT-qPCR. CircPTK2 silencing inhibited HTR-8/SVneo growth and migration in vitro. To investigate the underlying mechanism of circPTK2 in PE progression, dual-luciferase reporter assays were conducted. It was found that circPTK2 and WNT7B could bind directly to miR-619, and that circPTK2 affected WNT7B expression by sponging miR-619. To conclude, this study identified the functions and mechanisms of the circPTK2/miR-619/WNT7B axis in PE progression. In this way, circPTK2 has the potential to be used both in diagnostic and therapeutic settings for PE.

Green remediation of cadmium-contaminated soil by cellulose nanocrystals.

Cellulose nanocrystals (CNC) were used as a novel, green eluent to remediate Cd-contaminated soil in this study. The influence of washing conditions on the removal of Cd, including CNC concentration, pH value, liquid/solid (L/S) ratio, contact time and temperature were investigated. The effect of CNC remediation of Cd-contaminated soil on soil health and the possible remediation mechanism were also explored. The results showed that CNC concentration, pH value and contact time had a significant effect on the removal efficiency of Cd. CNC rapidly removed heavy metals in soil within 30 min. When the pH value of the eluent was 9.0, the removal efficiency of Cd could reach 86.3 %. The eluent mainly removed exchangeable and reducible fractions of Cd, which could effectively reduce the bioavailability of heavy metals. CNC washing had no negative effects on seed growth, species abundance and Shannon index. C-O, -COO- groups on CNC played an important role in the reaction between CNC and soil Cd, and other oxygen-containing functional groups on CNC could also assist in adsorption, ion exchange and chemical complexation processes. Therefore, cellulose nanocrystals had the potential to remediate heavy metal-contaminated soils in a green and efficient manner.

Coupled and decoupled legumes and cereals in prehistoric northern and southern China.

Legumes and cereals, which provide different nutrients, are cultivated as coupled crops in most centers of plant domestication worldwide. However, as the only legume domesticated in China, the spatio-temporal distribution of soybeans and its status in the millet- and rice-based agricultural system of the Neolithic and Bronze Ages remains elusive. Here, archaeobotanical evidence of soybeans (n=254), millet (n=462), rice (n=482), and zooarchaeological evidence of fish (n=138) were synthesized to elucidate the phenomenon of coupled or decoupled cereals and legumes in prehistoric China. During the Neolithic and Bronze Ages, soybeans was mostly confined to northern China and rarely found in southern China, serving as a companion to millet. In contrast, fish remains have been widely found in southern China, indicating a continuous reliance on fish as a staple food besides rice. Thus, an antipodal pattern of millet-soybeans and rice-fish agricultural systems may have been established in northern and southern China since the late Yangshao period (6000-5000 cal BP) respectively. These two agricultural systems were not only complementary in terms of diet, but they also exhibited positive interactions and feedback in the coculture system. Consequently, these two systems enabled the sustainable intensification of agriculture and served as the basis for the emergence of complex societies and early states in the Yellow and Yangtze Rivers.

Fast control plane for flexible and scalable optical interconnects.

The growth of data centers (DC) and high-performance computing (HPC) requires higher bandwidth, but traffic usually occurs between a small number of computing nodes, and the location of the communication bottleneck dynamically changes as the application runs. Therefore, the traditional static network that solves the communication bottleneck by providing excessive bandwidth cannot meet the demand of high performance and low cost at the same time. The reconfiguration of optical interconnects greatly improves the flexibility of the network, which can allocate unutilized bandwidth to node pairs with dense communication and improve resource utilization. However, this flexibility relies on a fast control plane to achieve efficient interaction between devices in the network. We made improvements in traffic collection, topology calculation, and optical switch configuration, and built an experimental platform to evaluate our control plane. The flexibility of optical interconnects shows a good acceleration effect when running applications that solve large-scale problems, and the experimental results show that a proper reconfiguration cycle can reduce the completion time of 3-D Fast Fourier Transform application by up to 53%.

Association of prenatal organochlorine pesticide-dichlorodiphenyltrichloroethane exposure with fetal genome-wide DNA methylation.

AIMS: To investigate whether intrauterine organochlorine pesticide (OCP)-dichlorodiphenyltrichloroethane (DDT) exposure could lead to epigenetic alterations by DNA methylation with possible important lifetime health consequences for offspring. MAIN METHODS: We used Illumina Infinium HumanMethylation 450 K BeadChip to explore the pattern of genome-wide DNA methylation containing >485,000 gene sites in cord blood of 24 subjects in a 12 mother-newborn pairs birth cohort. Based on the genome-wide DNA methylation data, we chose one potential gene, BRCA1, to verify the results in another group comprising 126 subjects. KEY FINDINGS: We identified 1,131 significantly different CpG sites which included 690 hypermethylation sites and 441 hypomethylation sites in the DNA methylation level between case and control group. The identified sites were located in 598 unique genes. In subsequent validation studies, we found that the DNA methylation level of the identified CpGs of BRCA1 increased with increased exposure to dichlorodiphenyltrichloroethane (DDT) and the level of gene expression in the identified CpGs of BRCA1 decreased with increased exposure to dichlorodiphenyltrichloroethane (DDT). SIGNIFICANCE: The results indicated that epigenetic processes played a possible role in the development of fetuses affected by maternal OCP-DDT exposure. Early prenatal exposure to DDT may affect fetal BRCA1 gene methylation, and increased exposure leads to a higher DNA methylation level and lower gene expression level.

Epigenome-wide study for the offspring exposed to maternal HBV infection during pregnancy, a pilot study.

BACKGROUND & AIM: Hepatitis B virus (HBV) can be transmitted to infants, and is related to infants' later disease risk. Epigenetic change (such as DNA methylation) may be mechanism underlying the relationship. In this study, we aimed to investigate whether prenatal HBV infection could alter DNA methylation status in newborns. METHOD: We selected 12 neonates with intrauterine HBV infection whose mothers were HBsAg-positive during pregnancy, relative to 12 HBV-free neonates with HBsAg-negative mothers. The pattern of genome-wide DNA methylation in the umbilical cord blood was investigated by Illumina Infinium Human Methylation 450K BeadChip. RESULT: The average level of global methylation in infected neonates exposed to maternal HBV infection was not significantly different from controls. However, after adjusting for multiple comparisons, we found differential significance in the cases group compared to the controls for 663 CpG sites, associated with 534 genes. Among these sites, 53.85% (357/663) had decreased methylation (ΔM < 0) and 46.15% (306/663) had increased methylation (ΔM > 0). The average percentage change (Δß) in methylation ranged from -46% to 36%. Validated by pyrosequencing, we identified 4 significantly differentially methylated CpG sites in the KLHL35 gene and additional CpGs for the CPT1B gene. These genes play a role in the development of hepatocellular and colorectal carcinoma and fatty acid oxidation, suggesting the candidature of these genes in HBV related disease. CONCLUSION: Prenatal HBV exposure, even without malformation or preterm birth, may alter the epigenome profile in newborns. We identified a set of genes with differentially methylated CpG sites presented in the cord blood of HBV-infected newborns with HBsAg-positive mothers, demonstrating that DNA methylation status at birth can be used as a biomarker of prenatal exposure. These DNA methylation differences suggest a possible role for epigenetic processes in neonatal development in response to prenatal HBV exposure.

Circular dichroism effect in a double-layer dolmen array nanostructure.

Chiral plasmonic nanostructures have been studied widely in past years and have various applications in biological sensing, negative refractive indexing, and analytical chemistry. Dolmen is also a commonly used nanostructure in many recent research papers. By placing dolmens in different directions and forming a double-layer dolmen array (DLDA), a new nanostructure with good circular dichroism (CD) effect is designed in this paper. We get up to the maximum of 0.5 of CD effect through numerical simulation. Among three obvious resonance wavelengths of CD effect, magnetic dipole resonance appears in two of them and contributes to the origin of a strong CD effect. In these different coupling modes, the strongest one locating at the largest wavelength is the result of a big magnetic dipolar resonance generated by circulation current in two layers of dolmen together, and the second strongest CD effect is caused by individual magnetic dipolar resonance in the opposite direction located in each layer. At the weakest one, the circulation current disappears and only a regular electric dipolar resonance appears. This simulation result shows that magnetic dipolar resonance of plasmonic nanostructure could create a strong CD effect, and much more effectively in the DLDA we propose. The results can help us in designing novel chiral optical nanostructures and provide applications in the interactions between photons and electrons.

[Relationship Between LEP G2548A Polymorphism and Cholesterol Gallstone].

OBJECTIVES: To determine the associations of single nucleotide polymorphism (SNP) in leptin (LEP) genes and environmental factors with cholesterol gallstone in southeast Han populations. METHODS: A 1:2 matched case-control study was conducted involving 200 patients with cholesterol gallstone. Genotyping of the SNP was examined on the LightCycler480 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Multifactor dimensionality reduction (MDR) analysis was applied to examine the effects of potential gene-environment interactions. RESULTS: Three genotypes of LEP G2548A were obtained by HRM genotyping, including 52 cases of GG wild type, 192 cases of GA mutant heterozygosity and 356 cases of AA mutation homozygous type. The genotype distribution of the SNP locus in the control group was in line with the Hardy-Weinberg genetic balance (P>0.05). The AA genotype carriers of LEP G2548A had significantly higher serum leptin than the GA/GG genotype carriers (H=6.83, P<0.05). The conditional logistic regression revealed that high serum leptin [odds ratio (OR)=5.012, 95% confidence interval (CI): 3.248-7.734], AA genotype of LEP G2548A site (OR=2.292, 95%CI: 1.012-5.193), family history of gallstones (OR=2.984, 95%CI: 1.329-6.700), high SBP (OR=1.927, 95%CI: 1.140-3.255) and smoking (OR=1.717, 95%CI: 1.006-2.928) were predictors of cholesterol gallstone. However, regular drinking of strong tea (OR=0.552, 95%CI: 0.336-0.907) and exercise (OR=0.591, 95%CI: 0.395-0.882) were protecting factors for cholesterol gallstone. The results of MDR analysis indicated that tea drinking, genotype of LEP G2548A site and serum leptin formed the optimal gene-environment interaction model. CONCLUSIONS: Individuals who drink less tea, carry AA genotype and have high serum leptin are more susceptible to cholesterol gallstone.

Carnosic acid slows photoreceptor degeneration in the Pde6b(rd10) mouse model of retinitis pigmentosa.

The photoreceptor cell death associated with the various genetic forms of retinitis pigmentosa (RP) is currently untreatable and leads to partial or complete vision loss. Carnosic acid (CA) upregulates endogenous antioxidant enzymes and has proven neuroprotective in studies of neurodegenerative models affecting the brain. In this study, we examined the potential effect of CA on photoreceptor death in the Pde6b(rd10) mouse model of RP. Our data shows that CA provided morphological and functional preservation of photoreceptors. CA appears to exert its neuroprotective effects through inhibition of oxidative stress and endoplasmic reticulum stress.

Deficiency of CC chemokine ligand 2 and decay-accelerating factor causes retinal degeneration in mice.

CC chemokine ligand 2 (CCL2) recruits macrophages to reduce inflammatory responses. Decay-accelerating factor (DAF) is a membrane regulator of the classical and alternative pathways of complement activation. In view of the link between complement genes and retinal diseases, we evaluated the retinal phenotype of C57BL/6J mice and mice lacking Ccl2 and/or Daf1 at 12 months of age, using scanning laser ophthalmoscopic imaging, electroretinography (ERG), histology, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. In comparison to C57BL/6J mice, mutant mice had an increased number of autofluorescent foci, with the greatest number in the Ccl2(-/-)/Daf1(-/-) retina. ERG amplitudes in Ccl2(-/-)/Daf1(-/-), Ccl2(-/-) and Daf1(-/-) mice were reduced, with the greatest reduction in Ccl2(-/-)/Daf1(-/-) mice. TUNEL-positive cells were not seen in C57BL/6J retina, but were prevalent in the outer and inner nuclear layers of Ccl2(-/-)Daf1(-/-) mice and were present at reduced density in Ccl2(-/-) or Daf1(-/-) mice. Cell loss was most pronounced in the outer and inner nuclear layers of Ccl2(-/-)/Daf1(-/-) mice. The levels of the endoplasmic reticulum chaperone GPR78 and transcription factor ATF4 were significantly increased in the Ccl2(-/-)/Daf1(-/-) retina. In comparison to the C57BL/6J retina, the phosphorylation of NF-κB p65, p38, ERK and JNK was significantly upregulated while SIRT1 was significantly downregulated in the Ccl2(-/-)/Daf1(-/-) retina. Our results suggest that loss of Ccl2 and Daf1 causes retinal neuronal death and degeneration which is related to increased endoplasmic reticulum stress, oxidative stress and inflammation.