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Abstract Research demonstrates the important role of genetic factors in attention-deficit/hyperactivity disorder (ADHD). DNA sequencing of families provides a powerful approach for identifying de novo (spontaneous) variants, leading to the discovery of hundreds of clinically informative risk genes for other childhood neurodevelopmental disorders. This approach has yet to be extensively leveraged in ADHD. We conduct whole-exome DNA sequencing in 152 families, comprising a child with ADHD and both biological parents, and demonstrate a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in ADHD cases compared to unaffected controls. Combining these results with a large independent case-control DNA sequencing cohort (3206 ADHD cases and 5002 controls), we identify lysine demethylase 5B (KDM5B) as a high-confidence risk gene for ADHD and estimate that 1057 genes contribute to ADHD risk. Using our list of genes harboring ultra-rare de novo damaging variants, we show that these genes overlap with previously reported risk genes for other neuropsychiatric conditions and are enriched in several canonical biological pathways, suggesting early neurodevelopmental underpinnings of ADHD. This work provides insight into the biology of ADHD and demonstrates the discovery potential of DNA sequencing in larger parent-child trio cohorts.

Scandium (Sc), which has a high melting point and a low density, is widely used in lighting, alloys, ceramics, catalysts, and other industrial fields. Under a specific geological condition, Sc could be enriched in certain coal. As one of strategic metals hosted in coals, the geochemistry of Sc is a hot topic in coal geology. In order to clarify the geochemical characteristics of Sc in Chinese coals, based on a comprehensive collection of the data of Sc concentrations in Chinese coals and four cases of the Huainan coals of Anhui, the Nantong coals of Chongqing, the Baoding coals of Sichuan, and the Mengtuo coals of Yunnan, the content, temporal and spatial distribution, modes of occurrence, and enrichment mechanism of Sc in Chinese coals were discussed, and the Sc resources hosted in coal measures was assessed as well. Results indicated that the scandium in Chinese coals was at normal level with an average of 4.02 mg/kg, which was slightly higher than that of world hard coal. The concentrations of scandium in certain coals from Guizhou, Chongqing, Anhui, Guangxi, Inner Mongolia, Shanxi, and Yunnan were elevated, and with the maximum Sc concentration of 139 mg/kg. Regarding a coalbed, Sc was preferably enriched in country rocks, e.g., the roof, floor, and parting rocks, relative to coal benches. Most Sc-rich Chinese coals were bituminous and with a coal-forming period of Permian, while the Late Jurassic - Early Cretaceous coals were of a low Sc content. Overall, due to a high mineral matter content in the high-ash and sapropelic coals, its Sc concentrations increased. As a lithophilic element, Sc in coals was dominantly hosted in minerals, especially silicate minerals, e.g., kaolinite, and some authigenic minerals, e.g., xenotime. Sc was also partially bounded to organic matter, especially the humic matter in low rank coals. The genetic types of Sc enrichment in Chinese coals included: ① Mafic source rock type. As a compatible element, Sc was of a higher concentration in mafic rocks than that of intermediate and felsic ones. Correspondingly, the weathering of mafic source rock could lead to a Sc enrichment in certain coal; ② Paralic facies type. Due to the marine transgression, the increasing pH value of peat bogs with a large amount of humic acid facilitated the migration of Sc and its combination with organic matter; ③ Groundwater leaching type. The leaching of Sc-bearing minerals by groundwater resulted into a local Sc enrichment in coal benches of a coalbed; ④ Hydrothermal solution type. Hydrothermal solutions leached and/or transported Sc into a coal via a mineral precipitation; ⑤ Magmatic and metamorphic type. Igneous intrusion led to a rise of coal rank, resulting in a reduce of organic matter bound Sc. Meanwhile, Sc hosted by minerals in coals might be enriched due to the increased ash yields; ⑥ Volcanic ash type. Mafic tuff layers or tonsteins occurred in coal measures could provide the coalbeds with Sc.

Abstract In this paper, in the framework of massive gravity, the holographic entanglement entropy (HEE) and holographic subregion complexity (HSC) are numerically investigated by means of the RT formula and the subregion CV conjucture for holographic superconductor with backreaction. We find that both the HEE and HSC exhibit discontinuity of slope at critical temperature, hence both of them are able to reflect the information of phase transition in the holographic superconducting system. Different from the previous studies, the HEE and HSC as function of strip-width are not always lower in the superconducting phase than ones in the normal phase, in particular the HSC decreases linearly as the subregion increases for positive coupling parameters. We notice that when the coupling parameters $$\alpha $$ α and $$\beta $$ β are taken as positive values, the HSC behaves in the same way as HEE, but when they are negative, the HSC has many different behaviors from HEE. Furthermore, we also observe that the HEE and HSC in the superconducting phase illustrate a tendency to converge to the same value as the temperature approaches zero, regardless of the coupling parameters of model. It is worth mentioning that in the massless gravity limit (the coupling parameters $$\alpha =0$$ α = 0 and $$\beta =0$$ β = 0 ), the results given by us are consistent with the case of holographic superconductor with backreaction from Einstein gravity.

Cross-subject electroencephalogram (EEG) based seizure subtype classification is very important in precise epilepsy diagnostics. Deep learning is a promising solution, due to its ability to automatically extract latent patterns. However, it usually requires a large amount of training data, which may not always be available in clinical practice. This paper proposes Multi-Branch Mutual-Distillation (MBMD) Transformer for cross-subject EEG-based seizure subtype classification, which can be effectively trained from small labeled data. MBMD Transformer replaces all even-numbered encoder blocks of the vanilla Vision Transformer by our designed multi-branch encoder blocks. A mutual-distillation strategy is proposed to transfer knowledge between the raw EEG data and its wavelets of different frequency bands. Experiments on two public EEG datasets demonstrated that our proposed MBMD Transformer outperformed several traditional machine learning and state-of-the-art deep learning approaches. To our knowledge, this is the first work on knowledge distillation for EEG-based seizure subtype classification.

The functions of tumour protein, translationally controlled 1 (TPT1), have been extensively researched in various cell types. Although TPT1 was reported to have accelerating effects on the lipid deposition of mouse hepatocytes, and the activation roles in phosphatidylinositol 3 kinase (PI3K/AKT) pathway, its role in the differentiation of ovine stromal vascular fractions (SVFs) and their underlying mechanisms have not been addressed. Therefore, the objective of this study was to explore whether TPT1 participates in the adipogenic differentiation regulation of ovine SVFs and the underlying mechanisms. The results from this study revealed that TPT1 was abundant in the tail fat of sheep and the protein was located in the nucleus of C3H10T1/2 cell line and ovine SVFs. Moreover, TPT1 expression was up-regulated during the adipogenic differentiation of SVFs. The overexpression of TPT1 dramatically accelerated the adipogenic differentiation of SVFs, accompanied by the up-regulation of adipogenic marker genes, while TPT1 inhibition had opposite effects. TPT1 also had a negative effect on forkhead box O1 (FOXO1). The PI3K/AKT pathway was involved in the promotion of adipogenesis induced by overexpressing TPT1. We concluded that TPT1 promotes the adipogenic differentiation of ovine SVFs through PI3K/AKT-dependent pathway and attenuates the expression of FOXO1 in ovine SVFs.

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 μg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Fat tissue—a vital energy storage organ—is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p–PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

Epilepsy is a pervasive neurological disorder affecting approximately 50 million individuals worldwide. Electroencephalogram (EEG) based seizure subtype classification plays a crucial role in epilepsy diagnosis and treatment. However, automatic seizure subtype classification faces at least two challenges: 1) class imbalance, i.e., certain seizure types are considerably less common than others; and 2) no a priori knowledge integration, so that a large number of labeled EEG samples are needed to train a machine learning model, particularly, deep learning. This paper proposes two novel Mixture of Experts (MoE) models, Seizure-MoE and Mix-MoE, for EEG-based seizure subtype classification. Particularly, Mix-MoE adequately addresses the above two challenges: 1) it introduces a novel imbalanced sampler to address significant class imbalance; and 2) it incorporates a priori knowledge of manual EEG features into the deep neural network to improve the classification performance. Experiments on two public datasets demonstrated that the proposed Seizure-MoE and Mix-MoE outperformed multiple existing approaches in cross-subject EEG-based seizure subtype classification. Our proposed MoE models may also be easily extended to other EEG classification problems with severe class imbalance, e.g., sleep stage classification.

Sheep have historically been bred globally as a vital food source. To explore the transcriptome of adipose tissue and investigate key genes regulating adipose metabolism in sheep, adipose tissue samples were obtained from F1 Dorper × Hu sheep. High-throughput sequencing libraries for second- and third-generation sequencing were constructed using extracted total RNA. Functional annotation of differentially expressed genes and isoforms facilitated the identification of key regulatory genes and isoforms associated with sheep fat metabolism. SMRT-seq generated 919,259 high-accuracy cDNA sequences after filtering. Full-length sequences were corrected using RNA-seq sequences, and 699,680 high-quality full-length non-chimeric (FLNC) reads were obtained. Upon evaluating the ratio of total lengths based on FLNC sequencing, it was determined that 36,909 out of 56,316 multiple-exon isoforms met the criteria for full-length status. This indicates the identification of 330,375 full-length FLNC transcripts among the 370,114 multiple-exon FLNC transcripts. By comparing the reference genomes, 60,276 loci and 111,302 isoforms were identified. In addition, 43,423 new genes and 44,563 new isoforms were identified. The results identified 185 (3198), 394 (3592), and 83 (3286) differentially expressed genes (transcripts) between tail and subcutaneous, tail and visceral, and subcutaneous and visceral adipose tissues, respectively. Functional annotation and pathway analysis revealed the following observations. (1) Among the differentially expressed genes (DEGs) of TF and SF tissues, the downregulation of ACADL, ACSL6, and NC_056060.1.2536 was observed in SF, while FFAR4 exhibited upregulation. (2) Among the DEGs of TF and VF tissues, expressions of ACADL, ACSL6, COL1A1, COL1A2, and SCD were downregulated in VF, with upregulation of FFAR4. (3) Among SF and VF expressions of COL1A1, COL1A2, and NC_056060.1.2536 were downregulated in VF. Specific differentially expressed genes (ACADL, ACSL6, COL1A1, COL1A2, FFAR4, NC_056060.1.2536, and SCD) and transcripts (NC_056066.1.1866.16 and NC_056066.1.1866.22) were identified as relevant to fat metabolism. These results provide a dataset for further verification of the regulatory pathway associated with fat metabolism in sheep.

Intrauterine growth restriction (IUGR) is a common perinatal complication in animal reproduction, with long-lasting negative effects on neonates and postnatal animals, which seriously negatively affects livestock production. In this study, we aimed to identify potential genes associated with the diagnosis of IUGR through bioinformatics analysis. Based on the 73 differentially expressed related genes obtained by differential analysis and weighted gene co-expression network analysis, we used three machine learning algorithms to identify 4 IUGR-related hub genes (IUGR-HGs), namely, ADAM9, CRYL1, NDP52, and SERPINA7, whose ROC curves showed that they are a good diagnostic target for IUGR. Next, we identified two molecular subtypes of IUGR through consensus clustering analysis and constructed a gene scoring system based on the IUGR-HGs. The results showed that the IUGR score was positively correlated with the risk of IUGR. The AUC value of IUGR scoring accuracy was 0.970. Finally, we constructed a new artificial neural network model based on the four IUGR-HGs to diagnose sheep IUGR, and its accuracy reached 0.956. In conclusion, the IUGR-HGs we identified provide new potential molecular markers and models for the diagnosis of IUGR in sheep; they can better diagnose whether sheep have IUGR. The present findings provide new perspectives on the diagnosis of IUGR.

Fat deposition involves the continuous differentiation of adipocytes and lipid accumulation. Studies have shown that microRNA miR-136 and 17β-hydroxysteroid dehydrogenase type 12 (HSD17B12) play important roles in lipid accumulation. However, the regulatory mechanism through which miR-136 targets HSD17B12 during ovine adipogenesis remains unclear. This study aimed to elucidate the role of miR-136 and HSD17B12 in adipogenesis and their relationship in ovine adipose-derived stromal vascular fractions (SVFs). The target relationship between miR-136 and HSD17B12 was predicted and confirmed using bioinformatics and a dual-luciferase reporter assay. The results showed that miR-136 promoted proliferation and inhibited adipogenic differentiation of ovine SVFs. We also found that HSD17B12 inhibited proliferation and promoted adipogenic differentiation of ovine SVFs. Collectively, our results indicate that miR-136 facilitates proliferation and attenuates adipogenic differentiation of ovine SVFs by targeting HSD17B12. These findings provide a theoretical foundation for further elucidation of the regulatory mechanisms of lipid deposition in sheep.

Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children ("primary" stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

Abstract Background Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat‐interactive protein 60‐kDa/ataxia–telangiectasia‐mutated (TIP60/ATM) axis‐mediated DNA damage response (DDR) is vital for maintaining genomic integrity. Methods Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co‐immunoprecipitation, proximity ligation assay and GST pull‐down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. Results We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of γH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non‐homologous end‐joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre‐existing TIP60‐ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre‐assembled TIP60‐ATM complex participates in DDR. Conclusions : We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60‐ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment.

Social media is important for providing text information; however, due to its informal and unstructured nature, traditional named entity recognition (NER) methods face the challenge of achieving high accuracy when dealing with social media data. This paper proposes a new method for social media named entity recognition with data augmentation. First, we pre-train the language model by using a bi-directional encoder representation of the transformer (BERT) to obtain a semantic vector of the word based on the contextual information of the word. Then, we obtain similar entities via data augmentation methods and perform substitution or semantic transformation on these entities. After that, the input into the Bi-LSTM model is trained and then fused and fine-tuned to obtain the best label. In addition, our use of the self-attentive layer captures the essential information of the features and reduces the reliance on external information. Experimental results on the WNUT16, WNUT17, and OntoNotes 5.0 datasets confirm the effectiveness of our proposed model.

Adipose tissue plays a crucial role in energy metabolism. Several studies have shown that circular RNA (circRNA) is involved in the regulation of fat development and lipid metabolism. However, little is known about their involvement in the adipogenic differentiation of ovine stromal vascular fractions (SVFs). Here, based on previous sequencing data and bioinformatics analysis, a novel circINSR was identified in sheep, which acts as a sponge to promote miR-152 in inhibiting the adipogenic differentiation of ovine SVFs. The interactions between circINSR and miR-152 were examined using bioinformatics, luciferase assays, and RNA immunoprecipitation. Of note, we found that circINSR was involved in adipogenic differentiation via the miR-152/mesenchyme homeobox 2 (MEOX2) pathway. MEOX2 inhibited adipogenic differentiation of ovine SVFs and miR-152 inhibited the expression of MEOX2. In other words, circINSR directly isolates miR-152 in the cytoplasm and inhibits its ability to promote adipogenic differentiation of ovine SVFs. In summary, this study revealed the role of circINSR in the adipogenic differentiation of ovine SVFs and its regulatory mechanisms, providing a reference for further interpretation of the development of ovine fat and its regulatory mechanisms.

The QKI genes encode RNA-binding proteins regulating cell proliferation, differentiation, and apoptosis. The Goat QKI has six isoforms, but their roles in myogenesis are unclear. In this study, the six isoforms of the QKI gene were overexpressed in goat myoblast. Immunofluorescence, qPCR and Western blot were used to evaluate the effect of QKI on the differentiation of goat myoblast. An RNA-Seq was performed on the cells with the gain of the function from the major isoforms to screen differentially expressed genes (DEGs). The results show that six isoforms had different degrees of deletion in exons 6 and 7, and caused the appearance of different types of encoded amino acids. The expression levels of the QKI-1 and QKI-5 groups were upregulated in the biceps femoris and latissimus dorsi muscle tissues compared with those of the QKI-4, QKI-7, QKI-3 and QKI-6 groups. After 6 d of myoblast differentiation, QKI-5 and the myogenic differentiators MyoG, MyoD, and MyHC were upregulated. Compared to the negative control group, QKI promoted myotube differentiation and the myoblasts overexpressing QKI-5 formed large, abundant myotubes. In summary, we identified that the overexpression of the QKI gene promotes goat-myoblast differentiation and that QKI-5 is the major isoform, with a key role. The RNA-Seq screened 76 upregulated and 123 downregulated DEGs between the negative control and the QKI-5-overexpressing goat myoblasts after d 6 of differentiation. The GO and KEGG analyses associated the downregulated DEGs with muscle-related biological functions. Only the pathways related to muscle growth and development were enriched. This study provides a theoretical basis for further exploring the regulatory mechanism of QKI in skeletal-muscle development in goats.

Coal-fired thermal power plants that meet the huge energy demand of China largely contribute to carbon emissions, environmental pollution, and human health issues. To investigate the impact of coal-fired power plants on the environment in the most developed region of eastern China, samples of feed coal, limestone, slag, fly ash, and flue gas desulfurization (FGD) gypsum were collected from two coal-fired power plants in Hefei City, Anhui Province, China. The concentrations of trace elements in these samples were determined using inductively coupled plasma mass spectrometry (ICP-MS). The results show that the feed coal was slightly rich in V, Cr, Se, In, Sb, Pb, and Ga compared to common Chinese coal. Most trace elements were concentrated in fly ash, especially in the fine particles. Only Sc, Cr, Rb, and Ba were enriched in slag. The smaller the particle size of the fly ash, the higher the fraction of volatile trace elements. The elemental concentrations of old fly ash, which was precipitated in the well of the flue gas pipeline, did not show noticeable differences from fresh fly ash. In addition, the short-time storage of fly ash did not influence the trace elements. To understand the possibility of recovering rare earth elements from coal combustion by-products, the outlook coefficients (Coutl) of coal combustion by-products for the Wanneng (WN) and Tianyuan (TY) power plants were calculated, and they were found to be promising for rare earth elements plus yttrium (REY) recovery. However, as per the evaluation diagram of cut-off grade and Coutl values, all feed coal and its by-products from these two coal-fired power plants are projected to be ‘unpromising’. Therefore, the coal combustion by-products from the WN and TY coal-fired power plants were not candidates for REY recovery.

Adipose tissues represent an important energy storage organ in animals and are the largest endocrine organ. It plays an important regulatory role in the pathogenesis of insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose development is a complex biological process involving multiple key genes, signaling pathways, and non-coding RNAs, including microRNAs and circular RNAs. In this study, we characterized circITGB1 and named its host gene ITGB1, which is differentially expressed in sheep of different months based on sequencing data. We collated and analyzed the sequencing data to select miRNA-23a with strong binding to ARRB1. We found that miRNA-23a regulates the development and differentiation of sheep adipocytes by targeting ARRB1. As a competing endogenous RNA, circITGB1 overexpression effectively alleviated the inhibitory effect of miR-23a on ARRB1. Conclusively, we provide evidence that circITGB1 regulates the proliferation and differentiation of sheep adipocytes via the miR-23a/ARRB1 pathway. This study provides a scientific basis for further studies on adipose tissue development at the circRNA level.

ABSTRACTHelicobacter pylori (H. pylori) recurrence remains a significant public health concern. The study aimed to assess H. pylori reinfection rate and identify its risk factors in China. This prospective open cohort, observational study was performed at 18 hospitals across 15 provinces in China. Consecutive patients who received the successful initial eradication during 1 January 2012 and 31 December 2018 were eligible for enrolment. H. pylori recurrence was defined as reinfection that occurred at more than the 12-month interval after successful initial eradication. Surveyed risk factors that might be associated with reinfection were preliminarily estimated by log-rank test and further determined by Cox regression model to calculate the hazard ratio (HR) and 95% confidence interval (CI). A total of 5193 subjects enrolled in the study. The follow-up intervals varied from 6 to 84 months with a general follow-up rate of 67.9%. Annual reinfection rate was 1.5% (95% CI: 1.2–1.8) per person-year. H. pylori reinfection was independently associated with the following five risk factors: minority groups (HR = 4.7, 95% CI: 1.6–13.9), the education at lower levels (HR = 1.7, 95% CI: 1.1–2.6), a family history of gastric cancer (HR = 9.9, 95% CI: 6.6–14.7), and the residence located in Western China (HR = 5.5, 95% CI: 2.6–11.5) following by in Central China (HR = 4.9, 95% CI: 3–8.1) (all P

Abstract Background In previous study, we performed next-gene sequencing to investigate the differentially expressed transcripts of bovine follicular granulosa cells (GCs) at dominant follicle (DF) and subordinate follicle (SF) stages during first follicular wave. Present study is designed to further identify the key regulatory proteins and signaling pathways associated with follicular development using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multi-omics data analysis approach. Methods DF and SF from three cattle were collected by daily ultrasonography. The GCs were isolated from each follicle, total proteins were digested by trypsin, and then proteomic analyzed via LC-MS/MS, respectively. Proteins identified were retrieved from Uniprot-COW fasta database, and differentially expressed proteins were used to functional enrichment and KEGG pathway analysis. Proteome data and transcriptome data obtained from previous studies were integrated. Results Total 3409 proteins were identified from 30,321 peptides (FDR ≤0.01) obtained from LC-MS/MS analysis and 259 of them were found to be differentially expressed at different stage of follicular development (fold Change > 2, P

17α-Methyltestosterone (MT) is a synthetic androgen. The objective of this study was to explore the effects of exogenous MT on the growth and gonadal development of female rare minnow Gobiocypris rarus. Female G. rarus groups were exposed to 25–100 ng/L of MT for 7 days. After exposure for 7 days, the total weight and body length were significantly decreased in the 50-ng/L MT groups. The major oocytes in the ovaries of the control group were vitellogenic oocytes (Voc) and cortical alveolus stage oocytes (Coc). In the MT exposure groups, some fish had mature ovaries with a relatively lower proportion of mature oocytes, and the diameter of the perinucleolar oocytes (Poc) was decreased compared with those of the control group. Ovarian VTG, FSH, LH, 11-KT, E2, and T were significantly increased after exposure to 50 ng/L of MT for 7 days. Unigenes (73,449), 24 known mature microRNAs (miRNAs), and 897 novel miRNAs in the gonads of G. rarus were found using high-throughput sequencing. Six mature miRNAs (miR-19, miR-183, miR-203, miR-204, miR-205, and miR-96) as well as six differentially expressed genes (fabp3, mfap4, abca1, foxo3, tgfb1, and zfp36l1) that may be associated with ovarian development and innate immune response were assayed using qPCR. Furthermore, the miR-183 cluster and miR-203 were differentially expressed in MT-exposed ovaries of the different G. rarus groups. This study provides some information about the role of miRNA–mRNA pairs in the regulation of ovarian development and innate immune system, which will facilitate future studies of the miRNA–RNA-associated regulation of teleost reproduction.

The present work deals with two kinds of k-essence dark energy models within the framework of loop quantum cosmology (LQC). The two kinds of k-essence models originates from two forms of Lagrangians, i.e., L1=F(X)V(ϕ) and L2=F(X)−V(ϕ), where F(X) and V(ϕ) stand for the kinetic term and potential of the scalar field ϕ, respectively. Two models are based on different phase variables settings, and the general form of autonomous dynamical system is deduced for each Lagrangian. Then, the dynamical stabilities of the critical points in each model are analysed in different forms of F(X) and V(ϕ). Model I is a 3-dim system with four stable points, and Model II is a 4-dim system but reduced to a 3-dim system using the symmetry analysis, which has five stable points. Moreover, the corresponding cosmological quantities, such as Ωϕ, wϕ and q, are calculated at each critical point. To compare these with the case of the classical Einstein cosmology (EC), the dynamical evolutionary trajectories in the phase space and evolutionary curves of the cosmological quantities are drawn for both EC and LQC cases, which shows that the loop quantum gravity effects diminish in the late-time universe but are significant in the early time. Further, the effects of interaction Q=αHρm on the evolutions of the universe are discussed. With the loop quantum gravity effects, bouncing universe is achieved in both models for different initial values of ϕ0, ϕ˙0, H0, ρ0 and coupling parameter α, which helps to avoid singularities. However, the interaction has little effect on bounce, although it is important to the stability of some critical points.

Abstract Background Characterization of molecular factors regulating ovarian follicular development is critical to understanding its functional mechanism of controlling the estrous cycle, determining oocyte competency, and regulating ovulation. In previous studies, we performed next-gene sequencing to investigate the differentially expressed transcripts of bovine follicular granulosa cells (GCs) at the dominant follicle (DF) and subordinate follicle (SF) stages during the first follicular wave. This study aims to investigate the proteomic characterization of GCs of DF and SF in the bovine estrous cycle. Results In total, 3409 proteins were identified from 30,321 peptides obtained from liquid chromatograph-mass spectrometer analysis. Two hundred fifty-nine of these proteins were found to be expressed differently in DF and SF. Out of 259, a total of 26 proteins were upregulated (fold change≥2) and 233 proteins were downregulated (fold change≤0.5) in DF. Gene Ontology (GO) analysis of proteome data revealed the biological process, cellular component and molecular function of expressed proteins in DF and SF, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed important signaling pathways associated with follicular development such as the PI3K-Akt, estrogen, and insulin signaling pathways. Immunoblotting results of OGN, ROR2, and HSPB1 confirmed the accuracy of the data. Bioinformatics analysis showed that 13 proteins may be linked to follicular development. Conclusions Findings from this study will provide useful information for exploring follicular development and function.

Well Wutan 1 is a wildcat well deployed in the Dazhou–Kaijiang paleo-uplift, eastern Sichuan Basin and its design depth is 7570 m. The Cambrian and Sinian strata are its main exploration targets, and the strata below the Silurian in this well are geologically uncertain with a high risk. A large section of gypsum-salt layer may be encountered in the Cambrian and the longitudinal pressure system is complex. It is predicted that the bottom hole temperature is up to 175 °C, and the bottom hole liquid column pressure exceeds 140 MPa, and there is hydrogen sulfide. As a result, the casing program design is confronted with great challenges. In this paper, the difficulties and risks of drilling engineering were analyzed. Then, a casing program was designed and optimized referring to the successful drilling experience of subsalt ultra-deep wells at home and abroad, combined with the pressure system characteristics of Well Wutan 1 and the creep performance of gypsum-salt layers. Finally, the casing program was applied on site. And the following research results were obtained. First, in order to prevent lost circulation, blowout and differential pressure induced stuck pipe in the open hole section, it is determined that the casing program shall be in the pattern of six-section casing with 5 setting points. Second, no setting point is needed in the Carboniferous pressure depleted reservoir for it is lithologically tight and differential pressure induced stuck pipe and lost circulation are less risky. Third, to better isolate the salt layer, one section of casing is specially designed for the Cambrian gypsum-salt layer and its collapse strength is 160 MPa to prevent collapse by salt creep. Fourth, Well Wutan 1 is drilled successfully to the expected strata and its total depth is 8060 m. In conclusion, the unconventional six-section casing program with 5 setting points to ensure the subsalt drilling safety in the eastern Sichuan Basin is rational. The successful drilling of Well Wutan 1 provides experiences and references for the follow-up exploration of deep-seated gas in the Dazhou–Kaijiang paleo-uplift. Keywords: Ultra-deep well, Complex pressure system, Gypsum-salt layer, Hydrogen sulfide bearing, Casing program, Sichuan basin, Eastern sichuan basin, Dazhou–kaijiang paleo-uplift, Well wutan 1

Abstract Background The level of fat deposition in carcass is a crucial factor influencing meat quality. Guangling Large-Tailed (GLT) and Small-Tailed Han (STH) sheep are important local Chinese fat-tailed breeds that show distinct patterns of fat depots. To gain a better understanding of fat deposition, transcriptome profiles were determined by RNA-sequencing of perirenal, subcutaneous, and tail fat tissues from both the sheep breeds. The common highly expressed genes (co-genes) in all the six tissues, and the genes that were differentially expressed (DE genes) between these two breeds in the corresponding tissues were analyzed. Results Approximately 47 million clean reads were obtained for each sample, and a total of 17,267 genes were annotated. Of the 47 highly expressed co-genes, FABP4, ADIPOQ, FABP5, and CD36 were the four most highly transcribed genes among all the known genes related to adipose deposition. FHC, FHC-pseudogene, and ZC3H10 were also highly expressed genes and could, thus, have roles in fat deposition. A total of 2091, 4233, and 4131 DE genes were identified in the perirenal, subcutaneous, and tail fat tissues between the GLT and STH breeds, respectively. Gene Ontology (GO) analysis showed that some DE genes were associated with adipose metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PPAR signaling pathway and ECM-receptor interaction were specifically enriched. Four genes, namely LOC101102230, PLTP, C1QTNF7, and OLR1 were up-regulated and two genes, SCD and UCP-1, were down-regulated in all the tested tissues of STH. Among the genes involved in ECM–receptor interaction, the genes encoding collagens, laminins, and integrins were quite different depending on the depots or the breeds. In STH, genes such as LAMB3, RELN, TNXB, and ITGA8, were identified to be up regulated and LAMB4 was observed to be down regulated. Conclusions This study unravels the complex transcriptome profiles in sheep fat tissues, highlighting the candidate genes involved in fat deposition. Further studies are needed to investigate the roles of the candidate genes in fat deposition and in determining the meat quality of sheep.

Domestic goats are commonly reared for meat and milk production in several regions of the world. However, the genetic mechanism underlying muscle development and meat quality of goats is limited. Therefore, the aim of this study was to identify known and novel genes regulating muscle development and meat quality of goats using second- and third-generation sequencing technologies. To achieve this, the meat quality and transcriptomes of longissimus dorsi (LD) and biceps femoris (BF) muscle tissues of Lingqiu Greyback goats were examined and compared. Differentially expressed genes (DEGs) and isoforms (DEIs) were functionally annotated. Results showed that 45,574 full-length transcripts covering 18,491 loci were characterized, and 12,566 genes were co-expressed in all samples. Differential expression analysis identified 231 DEGs, including 45 novel genes in the LD and BF muscles of the goats. Additionally, 1173 DEIs were found, in which 642 novel isoforms were identified in this study. Functional annotation and pathway analysis of the DEGs and DEIs revealed that some of them were associated with muscle growth and lipid metabolism. Overall, the findings of this study contribute to the understanding of the transcriptomic diversity underlying meat quality and muscle development of goat.

Magnetic nanoparticles (MNPs) can work as temperature sensors to realize temperature measurement due to the excellent temperature sensitivity of their magnetization. This paper mainly reports on a performance optimization method of MNPs DC thermometry model. Firstly, by exploring the influencing factors of MNPs magnetization temperature sensitivity, it is found that the optimal excitation of the magnetic field to make the temperature sensitivity of MNPs reach their optimal value is, approximately, inversely proportional to the particle size of MNPs. Then, the temperature sensitivity of MNP magnetization is modulated by adding appropriate DC bias magnetic field in the original triangular wave excitation field, to optimize the original DC thermometry model based on MNP magnetization. The simulation results show that the temperature measurement performance of small-size MNPs can be significantly improved. In short, this paper optimizes the temperature measurement performance of the original DC thermometry model based on MNP magnetization and provides a new application idea for temperature measurement of small-size MNPs.

Abstract Background Cocaine- and amphetamine-regulated transcript (CART), discovered initially by via differential display RT-PCR analysis of brains of rats administered cocaine, is expressed mainly in central nervous system or neuronal origin cells, and is involved in a wide range of behaviors, such as regulation of food intake, energy homeostasis, and reproduction. The hens egg-laying rate mainly depends on the developmental status of follicles, expression of CART have not been identified from hen follicles, the regulatory mechanisms of CART biological activities are still unknown. The objective of this study was to characterize the mRNA expression of CART in hen follicular granulosa cells and determine CART peptide localization and regulatory role during follicular development. Methods Small white follicles (1–2 mm in diameter) were treated for RNA isolation; Small white follicles (1–2 mm in diameter) and large white follicles (4–6 mm in diameter) were treated for immunohistochemical localization and large white follicles (4–6 mm in diameter), small yellow follicles (6–8 mm in diameter), large yellow follicles (9–12 mm in diameter), mature follicles (F5, F4, F3, F2, F1, >12 mm in diameter) were treated for RNA isolation and Real time PCR. Results The results showed that full length of the CDS of hen CART was 336 bp encoding a 111 amino acid polypeptide. In the hen ovary, CART peptide was primarily localized to the theca layer, but not all, the oocyte and granulosa layer, with diffused, weaker staining than relative to the theca cell layer. Further, amount of CART mRNA was more (P

The eye relies on the synergistic cooperation of many different ocular components, including the cornea, crystalline lens, photoreceptors, and retinal neurons, to precisely sense visual information. Complications with a single ocular component can degrade vision and sometimes cause blindness. Immediate treatment and long-term monitoring are paramount to alleviate symptoms, restore vision, and cure ocular diseases. However, successful treatment requires understanding ocular pathological mechanisms, precisely detecting and monitoring the diseases. The investigation and diagnosis of ocular diseases require advanced medical tools. In this mini review, we discuss non-invasive photoacoustic (PA) imaging as a potential research tool and medical screening device. In the research setting, PA imaging can provide valuable information on the disease progression. In the clinical setting, PA imaging can potentially aid in disease detection and treatment monitoring.

The sheep industry in China has been rapidly developing in recent years; however, the animals’ nutritional requirements under certain conditions have not been thoroughly defined. The objective of this study was to investigate the energy requirements of both the maintenance and growth of Dorper-Jinzhong crossbred ram lambs. Thirty 1/2 Dorper × 1/2 Jinzhong crossed F1 ram lambs (35 ± 0.5 kg of body weight, BW) were randomly selected and divided into five groups in a randomised design for a comparative slaughter trial. The lambs were offered one type of feed at 100%, 65% and 40% of the ad libitum intake. Another 15 lambs were used for the digestibility trial to estimate the metabolisable energy (ME) values of the diet at various feed intake levels. The net energy for maintenance (NEm) and the ME requirement for maintenance (MEm) were 286.68 kJ/kg0.75 of SBW and 437.80 kJ/kg0.75 of SBW, respectively; the energy efficiency for maintenance (km) was 0.655. The net energy for growth (NEg) values for varying average daily gain (100–350 g) in ram lambs grown from 35 to 50 kg increased from 1.31 to 5.93 MJ/d with an energy efficiency for growth (kg) of 0.457. Our results suggest that the energy requirements of Dorper-Jinzhong crossbred ram lambs are lower than the requirements recommended by the National Research Council (NRC) and Agricultural and Food Research Council (AFRC).

Sterol regulatory element binding proteins (SREBPs) can regulate the lipid homeostasis by regulating its target genes, which are crucial for the cholesterol and fatty acid metabolism. However, the transcriptional regulation role of SREBPs in fat-tailed sheep is unclear. In this study, two Chinese representative breeds of total 80 fat-tailed sheep were employed, serum triglyceride, total cholesterol (TC), non-esterified fatty acid (NEFA), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and mRNA expressions of SREBF1 and SREBF2 in seven different adipose tissues and liver were examined in sheep at the ages of 4, 6, 8, 10, and 12 months, respectively. The subcellular localization and function of SREBP1/2 were predicted through bioinformatics approaches. The results demonstrated that serum TC and NEFA levels among breeds were significantly different, and most serum indices were dynamically altered in an age-dependent manner. The mRNA expression profiling of SREBF1 and SREBF2 are breed-specific with temporal and spatial expressions differences. Further analysis shows that SREBF1/2 transcriptional levels and tail traits are closely related. All investigations simplify that SREBF1/2 play a crucial role in lipid metabolism and deposition during growth and development of the fat-tailed sheep, which also provides a novel insight for revealing the genetic mechanism of different tail type and meat quality.

Magnetic iron oxide nanoparticles are relatively advanced nanomaterials, and are widely used in biology, physics and medicine, especially as contrast agents for magnetic resonance imaging. Characterization of the properties of magnetic nanoparticles plays an important role in the application of magnetic particles. As a contrast agent, the relaxation rate directly affects image enhancement. We characterized a series of monodispersed magnetic nanoparticles using different methods and measured their relaxation rates using a 0.47 T low-field Nuclear Magnetic Resonance instrument. Generally speaking, the properties of magnetic nanoparticles are closely related to their particle sizes; however, neither longitudinal relaxation rate r 1 nor transverse relaxation rate r 2 changes monotonously with the particle size d . Therefore, size can affect the magnetism of magnetic nanoparticles, but it is not the only factor. Then, we defined the relaxation rates r i ′ (i = 1 or 2) using the induced magnetization of magnetic nanoparticles, and found that the correlation relationship between r 1 ′ relaxation rate and r 1 relaxation rate is slightly worse, with a correlation coefficient of R 2 = 0.8939, while the correlation relationship between r 2 ′ relaxation rate and r 2 relaxation rate is very obvious, with a correlation coefficient of R 2 = 0.9983. The main reason is that r 2 relaxation rate is related to the magnetic field inhomogeneity, produced by magnetic nanoparticles; however r 1 relaxation rate is mainly a result of the direct interaction of hydrogen nucleus in water molecules and the metal ions in magnetic nanoparticles to shorten the T 1 relaxation time, so it is not directly related to magnetic field inhomogeneity.

The signal transmission module of a magnetic nanoparticle thermometer (MNPT) was established in this study to analyze the error sources introduced during the signal flow in the hardware system. The underlying error sources that significantly affected the precision of the MNPT were determined through mathematical modeling and simulation. A transfer module path with the minimum error in the hardware system was then proposed through the analysis of the variations of the system error caused by the significant error sources when the signal flew through the signal transmission module. In addition, a system parameter, named the signal-to-AC bias ratio (i.e., the ratio between the signal and AC bias), was identified as a direct determinant of the precision of the measured temperature. The temperature error was below 0.1 K when the signal-to-AC bias ratio was higher than 80 dB, and other system errors were not considered. The temperature error was below 0.1 K in the experiments with a commercial magnetic fluid (Sample SOR-10, Ocean Nanotechnology, Springdale, AR, USA) when the hardware system of the MNPT was designed with the aforementioned method.

For two libraries (PDF1 and ODF1) using Illumina sequencing 44,082,301 and 43,708,132 clean reads were obtained, respectively. After being mapped to the bovine RefSeq database, 15,533 genes were identified to be expressed in both types of follicles (cut-off RPKM > 0.5), of which 719 were highly expressed in bovine follicles (cut-off RPKM > 100). Furthermore, 83 genes were identified as being differentially expressed in ODF1 versus PDF1, where 42 genes were upregulated and 41 genes were downregulated. KEGG pathway analysis revealed two upregulated genes in ODF1 versus PDF1, CYP11A1, and CYP19A1, which are important genes in the steroid hormone biosynthesis pathway. This study represents the first investigation of transcriptome of bovine follicles at predeviation and onset of deviation stages and provides a foundation for future investigation of the regulatory mechanisms involved in follicular development in cattle.

Computer vision as a fast, low-cost, noncontact, and online monitoring technology has been an important tool to inspect product quality, particularly on a large-scale assembly production line. However, the current industrial vision system is far from satisfactory in the intelligent perception of complex grain images, comprising a large number of local homogeneous fragmentations or patches without distinct foreground and background. We attempt to solve this problem based on the statistical modeling of spatial structures of grain images. We present a physical explanation in advance to indicate that the spatial structures of the complex grain images are subject to a representative Weibull distribution according to the theory of sequential fragmentation, which is well known in the continued comminution of ore grinding. To delineate the spatial structure of the grain image, we present a method of multiscale and omnidirectional Gaussian derivative filtering. Then, a product quality classifier based on sparse multikernel-least squares support vector machine is proposed to solve the low-confidence classification problem of imbalanced data distribution. The proposed method is applied on the assembly line of a food-processing enterprise to classify (or identify) automatically the production quality of rice. The experiments on the real application case, compared with the commonly used methods, illustrate the validity of our method.

Computer vision-based rice quality inspection has recently attracted increasing interest in both academic and industrial communities because it is a low-cost tool for fast, non-contact, nondestructive, accurate and objective process monitoring. However, current computer-vision system is far from effective in intelligent perception of complex grainy images, comprised of a large number of local homogeneous particles or fragmentations without obvious foreground and background. We introduce a well known statistical modeling theory of size distribution in comminution processes, sequential fragmentation theory, for the visual analysis of the spatial structure of the complex grainy images. A kind of omnidirectional multi-scale Gaussian derivative filter-based image statistical modeling method is presented to attain omnidirectional structural features of grain images under different observation scales. A modified LS-SVM classifier is subsequently established to automatically identify the processing rice quality. Extensive confirmative and comparative tests indicate the effectiveness and outperformance of the proposed method.

Due to its environmental and resource impacts, the geochemistry of uranium in coal is of both academic and practical significance. In order to give a comprehensive summary about the geochemistry of uranium in coals, the abundance, distribution, and modes of occurrence of uranium in Chinese coals were reviewed in this paper. Although some coals from southwestern and northwestern China are significantly enriched in uranium, the common Chinese coals are of a comparable uranium concentration to the world coals. The roof and floor rocks, and parting of coalbeds, or coal benches that are close to the surrounding rock are favorable hosts for uranium in one coalbed. The uranium concentrations in coals of different ages decrease in this order, e.g., Paleogene and Neogene > Late Permian > Late Triassic > Late Carboniferous and Early Permian > Late Jurassic and Early Cretaceous > Early and Middle Jurassic. Uranium in Chinese coals is mainly associated with organic matter, and is correspondingly enriched in subbituminous coal and lignite.

The topic of online product quality inspection (OPQI) with smart visual sensors is attracting increasing interest in both the academic and industrial communities on account of the natural connection between the visual appearance of products with their underlying qualities. Visual images captured from granulated products (GPs), e.g., cereal products, fabric textiles, are comprised of a large number of independent particles or stochastically stacking locally homogeneous fragments, whose analysis and understanding remains challenging. A method of image statistical modeling-based OPQI for GP quality grading and monitoring by a Weibull distribution(WD) model with a semi-supervised learning classifier is presented. WD-model parameters (WD-MPs) of GP images’ spatial structures, obtained with omnidirectional Gaussian derivative filtering (OGDF), which were demonstrated theoretically to obey a specific WD model of integral form, were extracted as the visual features. Then, a co-training-style semi-supervised classifier algorithm, named COSC-Boosting, was exploited for semi-supervised GP quality grading, by integrating two independent classifiers with complementary nature in the face of scarce labeled samples. Effectiveness of the proposed OPQI method was verified and compared in the field of automated rice quality grading with commonly-used methods and showed superior performance, which lays a foundation for the quality control of GP on assembly lines.

Development of improved procedures for in vitro maturation of oocytes collected from prepubertal goats has applications for in vitro embryo production and accompanying strategies for genetic improvement. The objective of described studies was to determine the effects of oocyte grade, in vitro maturation time, antioxidant supplementation and concentrations of estradiol in the maturation medium on in vitro maturation of oocytes harvested from 1-6 mm follicles present on the ovaries (obtained from an abattoir) of 1-6 month-old prepubertal Boer goats. Rates of progression to metaphase II were greater for grade 1 oocytes (>3 compact layers of cumulus cells and evenly granulated cytoplasm) than grade 2 oocytes (in vitro maturation in the presence of high concentrations of estradiol (10 and 100 mg/mL) on progression to metaphase II was observed, and no effect was observed in response to 1 mg/mL estradiol treatment as compared with control. Results suggest that oocyte selection and beta-mercaptoethanol supplementation can positively influence progression to metaphase II of oocytes harvested from ovaries of prepubertal goats, whereas high concentrations of estradiol are inhibitory to in vitro maturation.