Progression of the pluripotent epiblast depends upon the NMD factor UPF2.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that degrades RNAs harboring in-frame stop codons in specific contexts. Loss of NMD factors leads to embryonic lethality in organisms spanning the phylogenetic scale, but the mechanism remains unknown. Here, we report that the core NMD factor, UPF2, is required for expansion of epiblast cells within the inner cell mass of mice in vivo. We identify NMD target mRNAs in mouse blastocysts - both canonical and alternatively processed mRNAs - including those encoding cell cycle arrest and apoptosis factors, raising the possibility that NMD is essential for embryonic cell proliferation and survival. In support, the inner cell mass of Upf2-null blastocysts rapidly regresses with outgrowth and is incompetent for embryonic stem cell derivation in vitro. In addition, we uncovered concordant temporal- and lineage-specific regulation of NMD factors and mRNA targets, indicative of a shift in NMD magnitude during peri-implantation development. Together, our results reveal developmental and molecular functions of the NMD pathway in the early embryo.

Mitochondrial genome undergoes de novo DNA methylation that protects mtDNA against oxidative damage during the peri-implantation window.

Mitochondrial remodeling during the peri-implantation stage is the hallmark event essential for normal embryogenesis. Among the changes, enhanced oxidative phosphorylation is critical for supporting high energy demands of postimplantation embryos, but increases mitochondrial oxidative stress, which in turn threatens mitochondrial DNA (mtDNA) stability. However, how mitochondria protect their own histone-lacking mtDNA, during this stage remains unclear. Concurrently, the mitochondrial genome gain DNA methylation by this stage. Its spatiotemporal coincidence with enhanced mitochondrial stress led us to ask if mtDNA methylation has a role in maintaining mitochondrial genome stability. Herein, we report that mitochondrial genome undergoes de novo mtDNA methylation that can protect mtDNA against enhanced oxidative damage during the peri-implantation window. Mitochondrial genome gains extensive mtDNA methylation during transition from blastocysts to postimplantation embryos, thus establishing relatively hypermethylated mtDNA from hypomethylated state in blastocysts. Mechanistic study revealed that DNA methyltransferase 3A (DNMT3A) and DNMT3B enter mitochondria during this process and bind to mtDNA, via their unique mitochondrial targeting sequences. Importantly, loss- and gain-of-function analyses indicated that DNMT3A and DNMT3B are responsible for catalyzing de novo mtDNA methylation, in a synergistic manner. Finally, we proved, in vivo and in vitro, that increased mtDNA methylation functions to protect mitochondrial genome against mtDNA damage induced by increased mitochondrial oxidative stress. Together, we reveal mtDNA methylation dynamics and its underlying mechanism during the critical developmental window. We also provide the functional link between mitochondrial epigenetic remodeling and metabolic changes, which reveals a role for nuclear-mitochondrial crosstalk in establishing mitoepigenetics and maintaining mitochondrial homeostasis.

Regulation of both transcription and RNA turnover contribute to germline specification.

The nuanced mechanisms driving primordial germ cells (PGC) specification remain incompletely understood since genome-wide transcriptional regulation in developing PGCs has previously only been defined indirectly. Here, using SLAMseq analysis, we determined genome-wide transcription rates during the differentiation of embryonic stem cells (ESCs) to form epiblast-like (EpiLC) cells and ultimately PGC-like cells (PGCLCs). This revealed thousands of genes undergoing bursts of transcriptional induction and rapid shut-off not detectable by RNAseq analysis. Our SLAMseq datasets also allowed us to infer RNA turnover rates, which revealed thousands of mRNAs stabilized and destabilized during PGCLC specification. mRNAs tend to be unstable in ESCs and then are progressively stabilized as they differentiate. For some classes of genes, mRNA turnover regulation collaborates with transcriptional regulation, but these processes oppose each other in a surprisingly high frequency of genes. To test whether regulated mRNA turnover has a physiological role in PGC development, we examined three genes that we found were regulated by RNA turnover: Sox2, Klf2 and Ccne1. Circumvention of their regulated RNA turnover severely impaired the ESC-to-EpiLC and EpiLC-to-PGCLC transitions. Our study demonstrates the functional importance of regulated RNA stability in germline development and provides a roadmap of transcriptional and post-transcriptional regulation during germline specification.

SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.

The Rhox gene cluster suppresses germline LINE1 transposition.

Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (LINE1). Here, we report that LINE1 transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster. LINE1 transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member-RHOX10-suppresses LINE1 transposition during fetal development in vivo when the germline would otherwise be susceptible to LINE1 activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing Piwil2, which encodes a key component in the Piwi-interacting RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress LINE1 is conserved in humans but is lost in RHOXF2 mutants from several infertile human patients, raising the possibility that loss of RHOXF2 causes human infertility by allowing uncontrolled LINE1 expression in the germline. Together, our results support a model in which the Rhox gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the Rhox gene cluster to suppress TEs in different biological contexts.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Variable Temporal Length Training for Action Recognition CNNs.

Most current deep learning models are suboptimal in terms of the flexibility of their input shape. Usually, computer vision models only work on one fixed shape used during training, otherwise their performance degrades significantly. For video-related tasks, the length of each video (i.e., number of video frames) can vary widely; therefore, sampling of video frames is employed to ensure that every video has the same temporal length. This training method brings about drawbacks in both the training and testing phases. For instance, a universal temporal length can damage the features in longer videos, preventing the model from flexibly adapting to variable lengths for the purposes of on-demand inference. To address this, we propose a simple yet effective training paradigm for 3D convolutional neural networks (3D-CNN) which enables them to process videos with inputs having variable temporal length, i.e., variable length training (VLT). Compared with the standard video training paradigm, our method introduces three extra operations during training: sampling twice, temporal packing, and subvideo-independent 3D convolution. These operations are efficient and can be integrated into any 3D-CNN. In addition, we introduce a consistency loss to regularize the representation space. After training, the model can successfully process video with varying temporal length without any modification in the inference phase. Our experiments on various popular action recognition datasets demonstrate the superior performance of the proposed method compared to conventional training paradigm and other state-of-the-art training paradigms.

Single-cell RNAseq analysis of testicular germ and somatic cell development during the perinatal period.

Pro-spermatogonia (SG) serve as the gateway to spermatogenesis. Using single-cell RNA sequencing (RNAseq), we studied the development of ProSG, their SG descendants and testicular somatic cells during the perinatal period in mice. We identified both gene and protein markers for three temporally distinct ProSG cell subsets, including a migratory cell population with a transcriptome distinct from the previously defined T1- and T2-ProSG stages. This intermediate (I)-ProSG subset translocates from the center of seminiferous tubules to the spermatogonial stem cell (SSC) 'niche' in its periphery soon after birth. We identified three undifferentiated SG subsets at postnatal day 7, each of which expresses distinct genes, including transcription factor and signaling genes. Two of these subsets have the characteristics of newly emergent SSCs. We also molecularly defined the development of Sertoli, Leydig and peritubular myoid cells during the perinatal period, allowing us to identify candidate signaling pathways acting between somatic and germ cells in a stage-specific manner during the perinatal period. Our study provides a rich resource for those investigating testicular germ and somatic cell developmental during the perinatal period.

Transcriptome profiling reveals signaling conditions dictating human spermatogonia fate in vitro.

Spermatogonial stem cells (SSCs) are essential for the generation of sperm and have potential therapeutic value for treating male infertility, which afflicts >100 million men world-wide. While much has been learned about rodent SSCs, human SSCs remain poorly understood. Here, we molecularly characterize human SSCs and define conditions favoring their culture. To achieve this, we first identified a cell-surface protein, PLPPR3, that allowed purification of human primitive undifferentiated spermatogonia (uSPG) highly enriched for SSCs. Comparative RNA-sequencing analysis of these enriched SSCs with differentiating SPG (KIT+ cells) revealed the full complement of genes that shift expression during this developmental transition, including genes encoding key components in the TGF-ß, GDNF, AKT, and JAK-STAT signaling pathways. We examined the effect of manipulating these signaling pathways on cultured human SPG using both conventional approaches and single-cell RNA-sequencing analysis. This revealed that GDNF and BMP8B broadly support human SPG culture, while activin A selectively supports more advanced human SPG. One condition-AKT pathway inhibition-had the unique ability to selectively support the culture of primitive human uSPG. This raises the possibility that supplementation with an AKT inhibitor could be used to culture human SSCs in vitro for therapeutic applications.

Ambient particulate matter and in-hospital case fatality of acute myocardial infarction: A multi-province cross-sectional study in China.

The acute myocardial infarction (AMI) outcomes have been extensively linked with ambient particulate matter (PM). However, whether a smaller particle has greater impact and the consequent attributable burden associated with PM of different sizes remain unclear. We conducted a multi-province cross-sectional study among AMI patients using the inpatient discharge datasets from four Chinese provinces (Shanxi, Sichuan, Guangxi, and Guangdong) from 2014 to 2019. Ambient PM exposure for each patient was assessed using the ChinaHighAirPollutants dataset. We employed the mixed-effects logistic regression models to evaluate the association of PM of different sizes (PM1, PM2.5, PM10) on in-hospital case fatality. The potential reducible fractions in in-hospital case fatality were estimated through counterfactual analyses. Of 177,749 participants, 125,501 (70.6 %) were male and the in-hospital case fatality rate was 4.9%. For short-term (7-day average) exposure, the odds ratios (ORs) for PM1, PM2.5, and PM10 (per 10 µg/m3) were 1.052 (95 % confidence interval [CI], 1.032-1.071), 1.026 (95 % CI, 1.014-1.037), and 1.016 (95% CI, 1.008-1.024), respectively. The estimated ORs for long-term exposure (annual average) were 1.303 (95 % CI, 1.252-1.356) for PM1, 1.209 (95 % CI, 1.178-1.241) for PM2.5, 1.157 (95 % CI, 1.134-1.181) for PM10. Short-term exposure to PM1 showed the highest potential reducible fraction (8.5 %, 95 % CI, 5.0-11.7 %), followed by PM2.5 and PM10, while the greatest potential reducible fraction of long-term exposure was observed in PM10 (30.9 %, 95 % CI, 27.2-34.4%), followed by PM2.5 and PM1. In summary, PM with smaller size had a more pronounced impact on in-hospital AMI case fatality, with PM1 exhibiting greater effects than PM2.5 and PM10. Substantial health benefits for AMI patients could be achieved by mitigating ambient PM exposure.

Estimation of the distribution patterns of heavy metal in soil from airborne hyperspectral imagery based on spectral absorption characteristics.

Though soil is widely known as one of the most valuable resources for the world, its quality is going to be lower because of unsustainable economic development and social progress. Therefore, it is important for us to monitor and evaluate the quality of soil, especially its heavy metal contents which is too scarce to identify in soil spectra easily but poisonous enough to affect human health in a long run. Most of the existing estimation methods have based the characteristic bands on statistical analysis to a large extent, which is hard to accurately explain the retrieval mechanism. In this paper, the absorption characteristics of heavy metal are studied based on the soil spectra, and the distribution pattern is mapped in a large-scale continuous space, for environmental monitoring and further decision support. Taking Yitong County, China as the study area. After spectra continuum removal, the heavy metal contents were estimated by 11 features including the absorption depth, absorption area, and band ratio around 2200 nm, which showed the best performance. For arsenic (As), the best model yields Rp2 value of 0.8474, and the RMSEP value is 36.1542 (mg/kg). It is concluded that As is adsorbed by organic matter, clay minerals, and iron/manganese oxides in soil, and the adsorption of As by first two components is greater than that of the last. For airborne spectra after continuum removal, combining the spectral absorption characteristic parameters and the highly correlated bands is more accurate than using the spectral absorption characteristic parameters or bands alone. AdaBoost is presented for the heavy metal estimation, and the fitting ability of the method is found to be stronger than that of the traditional classical methods, with the Rp2 values of 0.6242 and the RMSEP value of 43.6481 (mg/kg). In summary, these results will provide a prospective basis for the rapid estimation of soil heavy metals, the risk assessment of soil heavy metals and soil environmental monitoring in a large scale.

A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position in the Fragile-X region of the X chromosome in placental mammals. Surprisingly, the miRNAs encoded by this cluster (Fx-mir) have a predilection for targeting the immediately adjacent gene, Fmr1, an unexpected finding given that miRNAs usually act in trans, not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP, the protein product of Fmr1, is downregulated when Fx-mir miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx-mir family members act cooperatively to regulate the translation of batteries of mRNAs in a developmentally regulated manner in SCs.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

[Development Status of Irreversible Electric Perforated Tumor Ablation Device].

This study firstly introduced the mechanism, benefits and applications of irreversible electroporation(IRE) for tumor ablation. In addition, this study also introduced the most advanced IRE systems cleared by FDA or CFDA and IRE research equipment. The clinically licensed IRE systems include the Nanoknife 3.0 of Angiodynamics, the DophiTM N3000's steep pulse therapy system of Sanoway, and compound steep pulse therapy equipment of Reeves Technology IRE research equipment include the BTX and Bio-Rad electroporation devices.

Genomic characterization of a novel recombinant porcine astrovirus isolated in northeastern China.

Porcine astroviruses (PAstVs), are widely distributed viruses that are highly prevalent in swine herds. In this study, a novel type 4 porcine astrovirus strain (designated as PAstV4/Tianjin/2018) was identified in a fecal sample from a diarrheal piglet in Tianjin, China and its complete genomic sequence was determined by RT-PCR. Sequence analysis showed that this strain had a capsid protein with a highly variable C-terminal domain, a typical ribosomal frameshifting signal, and a conserved subgenomic promoter sequence. Recombination analysis indicated that PAstV4/Tianjin/2018 was a novel recombinant strain, and a recombination breakpoint was identified at nt position 4220 of the genome. The novel recombinant porcine astrovirus identified in China will be useful for understanding the origin, genetic diversity, and evolution of enteric viruses.

Changes in area and number of nature reserves in China.

Nature reserves (NR) are the cornerstone of biodiversity conservation. Over the past 60 years, the rapid expansion of NRs in China, one of the world's megadiverse countries, has played a critical role in slowing biodiversity loss. We examined the changes in the number and area of China's NRs from 1956 to 2014 and analyzed the effect of economic development on the expansion of China's NRs from 2005 to 2014 with linear models. Despite a continuing increase in the number of NRs, the total area of China's NRs decreased by 3% from 2007 to 2014. This loss resulted from downsizing and degazettement of existing NRs and a slowdown in the establishment of new ones. Nature reserves in regions with rapid economic development exhibited a greater decrease in area, suggesting that downsizing and degazettement of NRs are closely related to the intensifying competition between economic growth and conservation. For example, boundary adjustments to national NRs, the most strictly protected NRs, along the coast of China's Yellow Sea, a global biodiversity hotspot with a fast-growing economy, resulted in the loss of one-third of the total area. One of the most important ecosystems in these NRs, tidal wetlands, decreased by 27.8% because of boundary adjustments and by 25.2% because of land reclamation. Our results suggest conservation achievement, in terms of both area and quality, are declining at least in some regions in the Chinese NR estate. Although the designation of protected areas that are primarily managed for sustainable use has increased rapidly in recent years in China, we propose that NRs with biodiversity conservation as their main function should not be replaced or weakened.

Cambios en la Superficie y el Número de Reservas Naturales en China Resumen Las reservas naturales (RN) son la piedra angular de la conservación de la biodiversidad. Durante los últimos 60 años, la rápida expansión de las RN en China, uno de los países megadiversos, ha jugado un papel crítico en la reducción de la pérdida de biodiversidad. Examinamos los cambios en el número y superficie de las RN en China de 1956 a 2014 y analizamos el efecto del desarrollo económico en la expansión de las RN en China de 2005 a 2014 mediante modelos lineales. A pesar del incremento continuo en el número de RN, la superficie total de RN en China decreció en 3% de 2007 a 2014. Esta pérdida resultó de la reducción y cambio de registro de RN existentes y una desaceleración en el establecimiento de RN nuevas. Las reservas naturales en regiones con desarrollo económico rápido presentaron una mayor disminución en la superficie, lo que sugiere que la reducción y cambio de registro de RN están relacionados cercanamente con la intensificación de la competencia entre crecimiento económico y conservación. Por ejemplo, ajustes en los límites de RN nacionales, las RN más estrictamente protegidas, a lo largo de la costa del Mar Amarillo, un sitio de importancia para la biodiversidad global con una economía en rápido crecimiento, resultó en la pérdida de un tercio de la superficie total. Uno de los ecosistemas más importantes en estas RN, humedales mareales, decreció en 27.8% debido a ajustes en los límites y en 25.2% debido a la reclamación de tierras. Nuestros resultados sugieren que los logros de conservación, en términos tanto de área como de calidad, están declinando en las RN de China. Aunque la designación de áreas protegidas administradas primariamente para un uso sustentable ha incrementado rápidamente en años recientes en China, proponemos que las RN cuya principal función es la conservación de la biodiversidad no deben ser reemplazadas o debilitadas.

Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization.

Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications.

Random forest-based estimation of heavy metal concentration in agricultural soils with hyperspectral sensor data.

Heavy metals in the agricultural soils of reclaimed mining areas can contaminate food and endanger human health. The objective of this study is to effectively estimate the concentrations of heavy metals, such as zinc, chromium, arsenic, and lead, using hyperspectral sensor data and the random forest (RF) algorithm in the study area of Xuzhou, China. The RF's built-in feature selection ability and modeling expressive ability in heavy metal estimation of soil were explored. After the preprocessing of the spectrum obtained by an ASD (analytical spectral device) field spectrometer, the random forest algorithm was carried out to establish the estimation model based on the correlation-selected features and the full-spectrum features respectively. Results of all the different processes were compared with classical approaches, such as partial least squares (PLS) regression and support vector machine (SVM). In all the experimental results, from the perspective of models, the best estimation model for Zn (R2 = 0.9061; RMSE = 6.5008) is based on the full-spectrum data of continuum removal (CR) pretreatment, and the best models for Cr (R2 = 0.9110; RMSE = 4.5683), As (R2 = 0.9912; RMSE = 0.5327), and Pb (R2 = 0.9756; RMSE = 1.1694) are all derived from the correlation-selected features. And these best models of these heavy metals are all established by the RF method. The experiments in this paper show that random forests can make full use of the input spectral data in the estimation of four kinds of heavy metals, and the obtained models are superior to those established by traditional methods.

High-resolution profiles of gene expression and DNA methylation highlight mitochondrial modifications during early embryonic development.

Well-organized mitochondrial functions and dynamics are critical for early embryonic development and are operated via a large number of mitochondria-related genes (MtGs) encoded by both the nuclear and the mitochondrial genome. However, the mechanisms underlying mitochondrial modifications during the critical window between blastocyst implantation and postimplantation organogenesis are poorly understood. Herein, we performed high-resolution dynamic profiling of MtGs to acquire a more detailed understanding of mitochondrial modifications during early development. Our data suggest that the resumption of mitochondrial mass growth is not only facilitated by increased mitochondrial biogenesis and mitochondrial DNA (mtDNA) replication, but also by the appropriate balance between mitochondrial fission and fusion. In addition, increased levels of reactive oxygen species (ROS) resulting from enhanced mitochondrial functions may be the critical inducer for activating the glutathione (GSH)-based stress response system in early embryos. The appropriate balance between the mitochondrial stress response and apoptosis appears to be significant for cell differentiation and early organogenesis. Furthermore, we found that most MtGs undergo de novo promoter methylation, which may have functional consequences on mitochondrial functions and dynamics during early development. We also report that mtDNA methylation can be observed as early as soon after implantation. DNMT1, the predominant enzyme for maintaining DNA methylation, localized to the mitochondria and bound to mtDNA by the implantation stage. Our study provides a new insight into the involvement of mitochondria in early mammalian embryogenesis. We also propose that the epigenetic modifications during early development are significant for modulating mitochondrial functions and dynamics.