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Yunchen Meng,1 Dan Xu,1 Weinan Zhang,1 Wenshu Meng,2 Xingyu Lan,3 Xiaoxi Wang,3 Mingjuan Li,3 Xiaoyan Zhang,1 Yu Zhao,1 Haodong Yang,1 Rong Zhang,3– 6 Zhiping Zhen1 1College of P.E and Sports, Beijing Normal University, Beijing, People’s Republic of China; 2College of Life Sciences, Beijing Normal University, Beijing, People’s Republic of China; 3Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 4Neuroscience Research Institute, Peking University, Beijing, People’s Republic of China; 5Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, People’s Republic of China; 6Autism Research Center of Peking University Health Science Center, Beijing, People’s Republic of ChinaCorrespondence: Zhiping Zhen; Rong Zhang, Email zzpxt@bnu.edu.cn; zhangrong@bjmu.edu.cnBackground: Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficits and stereotyped behaviors in childhood that lacks satisfactory medical intervention. Early swimming intervention is a noninvasive method combining enriched environment and exercise, which has been proven to improve brain development in young children and to treat neurodevelopmental diseases.Methods: In this study, we tested the autism-like behavior of rats with deletions in exons 11– 21 of the Shank3 gene and evaluated the effect of early swimming intervention (from postnatal day 8 to 60) on the behavior of this animal model of autism. In addition, the transcriptomes of the striatal tissues of wild-type, Shank3 knockout and Shank3 knockout swimming groups rats were analyzed.Results: Shank3 knockout rats exhibit core symptoms of autism, and early swimming improved the social and stereotyped behaviors in this autism rat model. Transcriptomics results revealed that compared to the wild-type group, 291 differentially expressed genes (DEGs) were identified in the striatum of the Shank3 knockout group. Compared to Shank3 knockout group, 534 DEGs were identified in the striatum of Shank3 knockout swimming group. The DEGs annotated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway shows that the impacts of Shank3 deletion were primarily reflected in synaptic structure, development, morphology, receptor function and signaling, and swimming primarily changed the terms related to the synapses in the striatum of Shank3 knockout rats, including the morphology, structure, composition, development and regulation of synapses.Conclusion: Early swimming intervention can ameliorate behavioral abnormalities caused by Shank3 knockout, by a mechanism that may involve the process of striatal synaptic development and should be further investigated.Keywords: Shank3, autism, early swimming, behavior, transcriptome

Janus kinase 2 ( JAK2 ) plays a critical role in myoblast proliferation and fat deposition in animals. Our previous RNA-Seq analyses identified a close association between the JAK2 gene and muscle development. To date, research delving into the relationship between the JAK2 gene and growth traits has been sparse. In this study, we sought to investigate the relationship between novel mutations within the JAK2 gene and goat growth traits. Herein, two novel InDel (Insertion/Deletion) polymorphisms within the JAK2 gene were detected in 548 goats, and only two genotypes were designated as ID (Insertion/Deletion) and DD (Deletion/Deletion). The results indicate that the two InDels, the del19008 locus in intron 2 and del72416 InDel in intron 6, showed significant associations with growth traits ( p < 0.05). Compared to Nubian and Jianzhou Daer goats, the del72416 locus displayed a more pronounced effect in the Fuqing breed group. In the Nubian breed (NB) group, both InDels showed a marked influence on body height (BH). There were strong linkages observed for these two InDels between the Fuqing (FQ) and Jianzhou (JZ) populations. The DD-ID diplotype was associated with inferior growth traits in chest width (ChW) and cannon circumference (CaC) in the FQ goats compared to the other diplotypes. In the NB population, the DD-DD diplotype exhibited a marked negative impact on BH and HuWI (hucklebone width index), in contrast to the other diplotypes. In summary, our findings suggest that the two InDel polymorphisms within the JAK2 gene could serve as valuable molecular markers for enhancing goat growth traits in breeding programs.

The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro . Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on tumor responses and brain injury in immunocompetent mice which can better mimic the tumor-host interactions observed in patients. We also evaluated the role of the hypoxia-inducible factor-1 alpha under radiation as potential target for combating radiation-induced brain injury. Methods : Naïve and Hif-1α +/- heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×10 5 human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. Bioluminescence imaging, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. Results : Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, Hif-1α +/- mice exhibited more severe vascular damage after fractionated radiation of 3×20 Gy. Conclusion : Ultra-high dose fractionated 3×20 Gy radiation has the potential to fully eradicate GBM cells at the cost of only mild brain injury. The Hif-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies., Competing Interests: Competing Interests: Miroslaw Janowski and Piotr Walczak are co-founders and co-owners of IntraART, LLC and Ti-Com, LLC. Other co-authors declare no potential competing interests., (© The author(s).)

Futile recanalization (FR) after endovascular treatment (EVT) remains a significant challenge for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The pathogenesis of FR has not been well elucidated. We prospectively enrolled anterior circulation LVO-AIS patients who achieved successful recanalization after EVT. The jugular venous blood ipsilateral to stroke was collected before and immediately after recanalization. Plasma proteomic analysis based on liquid chromatography-mass spectrometry was performed using data-independent acquisition method. Differentially expressed proteins (DEPs) among patients with or without FR in the whole or propensity score matching (PSM) cohorts were screened according to the absolute value of fold change ≥1.5 and P value <0.05. We identified 104 and 34 DEPs between patients with or without FR in the whole cohort and PSM cohort, respectively. Bioinformatic analysis indicated that the identified proteins were primarily related to specific biological processes including immune response, complement activation, oxidative stress, lipid metabolism, protein ubiquitylation as well as autophagy, suggesting that these may be mechanisms in FR pathogenesis. Collectively, we discovered proteins that may be potential research targets for FR. The combination of proteomic and bioinformatic analysis could provide a better understanding of the pathogenesis of FR in a comprehensive manner., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T. Nguyen reports advisory board with Idorsia.

Background: Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children., Methods: A sample of 151 ASD children's parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses., Results: Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81)., Conclusions: Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies., (© 2024. The Author(s).)

As a hot candidate for marine pollution control, electrocatalytic oxidation strongly depends on the characteristics of anode materials. Even though emerging 2D metal-organic frameworks (2D-MOFs)/graphene oxide (GO) complex has satisfied the conductive and tunable requirements of anode, electrocatalytic efficiency still needs to be improved by maximizing the electron carriers or shuttles. Herein, we capitalized upon crosslinking heteroatoms as pointcut to adjust the electron distribution, mobility, and transfer orientation in 2D-MOFs/GO. As a result, Ni 3 (BHT) 2 /2GO (metal centers: Ni; crosslinking heteroatoms: S), which was much higher than materials with metal centers of Cu or crosslinking heteroatoms of N, achieved superior conductivity and 100% tetracycline hydrochloride removal within 12 min. In Ni 3 (BHT) 2 /2GO, Ni ions and S atoms cooperated as electron shutters rather than isolated active center and granted accelerated electron transfer from 2D-MOFs to GO layers. Furthermore, Ni sites and S crosslinking heteroatoms exhibited superior activity for ⋅O 2 - and ⋅OH generation, whereas 1 O 2 depended more on C and O substrates. All experiments, theory calculations, and application expanding approved the practice feasibility of 2D-MOFs/GO in electrocatalytic oxidation by adjusting crosslinking heteroatoms. All these results provided new perspectives on the micro-molecular regulation for improving electrocatalytic efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen-to-albumin ratio (FAR) could act as an indicator of futile recanalization., Methods: This is a single-center, retrospective analysis of patients with acute anterior circulation large-vessel occlusion and successful thrombectomy between May 2019 and June 2022. FAR was defined as postoperative blood levels of fibrinogen divided by those of albumin, and dichotomized into high and low levels based on the Youden index. Futile recanalization was defined as patients achieving a successful recanalization with a modified Rankin Scale score of 3-6 at 90 days. Multivariable logistic regression was used to assess the association of FAR with futile recanalization., Results: A total of 255 patients were enrolled, amongst which 87 patients (34.1%) had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR (74.7% vs. 53.0%, p = .001). After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile recanalization (adjusted OR 2.40, 95%CI 1.18-4.87, p = .015). This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status., Conclusion: Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The mustache toads Leptobrachium boringii and Leptobrachium liui are two attractive species in Megophryidae, in which adult males have mustache-like keratinized nuptial spines on their upper lip. However, both are under threat due to multiple factors, of which scientific studies are still very limited. In this study, two new complete mitochondrial genomes of L. boringii and L. liui were sequenced, assembled, and annotated based on next-generation sequencing. The mitogenome lengths of L. boringii and L. liui were found to be 17,100 and 17,501 bp, respectively, with both containing 13 protein coding genes, 23 tRNAs, 2 rRNAs, and 1 non-coding control region. Nucleotide diversity analyses indicate that atp8 , atp6 , and nad2 showed higher nucleotide diversity than cox1 , cox3, and cytb . The intraspecific genetic distances among three different populations of L. boringii exceed 4%, and those between two populations of L. liui reach 7%. Phylogenetic relationships support their division into two subfamilies of Megophryidae (Leptobrachiinae and Megophryinae) as well as two species groups within Leptobrachium, corresponding to the number of keratinized nuptial spines (10-48 in the L. boringii species group vs. 2-6 in the L. liui species group). The two new mitogenomes reported in this study provide valuable data for future molecular evolutionary and conservation studies of the genus Leptobrachium and other Megophryidae toads.

Introduction: Maternal immune activation (MIA) is closely related to the onset of autism-like behaviors in offspring, but the mechanism remains unclear. Maternal behaviors can influence offspring's development and behaviors, as indicated in both human and animal studies. We hypothesized that abnormal maternal behaviors in MIA dams might be other factors leading to delayed development and abnormal behaviors in offspring. Methods: To verify our hypothesis, we analyzed poly(I:C)-induced MIA dam's postpartum maternal behavior and serum levels of several hormones related to maternal behavior. Pup's developmental milestones and early social communication were recorded and evaluated in infancy. Other behavioral tests, including three-chamber test, self-grooming test, open field test, novel object recognition test, rotarod test and maximum grip test, were performed in adolescence of pups. Results: Our results showed that MIA dams exhibit abnormal static nursing behavior but normal basic care and dynamic nursing behavior. The serum levels of testosterone and arginine vasopressin in MIA dams were significantly reduced compared with control dams. The developmental milestones, including pinna detachment, incisor eruption and eye opening, were significantly delayed in MIA offspring compared with control offspring, while the weight and early social communication showed no significant differences between the two groups. Behavioral tests performed in adolescence showed that only male MIA offspring display elevated self-grooming behaviors and reduced maximum grip. Discussion: In conclusion, MIA dams display abnormal postpartum static nursing behavior concomitantly with reduced serum levels of testosterone and arginine vasopressin, possibly involving in the pathogenesis of delayed development and elevated self-grooming in male offspring. These findings hint that improving dam's postpartum maternal behavior might be a potential regime to counteract delayed development and elevated self-grooming in male MIA offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lan, Gu, Li, Song, Zhai, Zhang, Zhan, Böckers, Yue, Wang, Yuan, Jin, Xie, Dang, Hong, Guo, Wang and Zhang.)

Mitochondrial genomes (mitogenomes) are valuable resources in molecular and evolutionary studies, such as phylogeny and population genetics. The complete mitogenomes of two crocodile newts, Tylototriton broadoridgus and Tylototriton gaowangjienensis , were sequenced, assembled, and annotated for the first time using next-generation sequencing. The complete mitogenomes of T. broadoridgus and T. gaowangjienensis were 16,265 bp and 16,259 bp in lengths, which both composed of 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and 1 control region. The two mitogenomes had high A + T content with positive AT-skew and negative GC-skew patterns. The ratio of non-synonymous and synonymous substitutions showed that, relatively, the ATP8 gene evolved the fastest and COI evolved the slowest among the 13 PCGs. Phylogenetic trees from BI and ML analyses resulted in identical topologies, where the Tylototriton split into two groups corresponding to two subgenera. Both T. broadoridgus and T. gaowangjienensis sequenced here belonged to the subgenus Yaotriton , and these two species shared a tentative sister group relationship. The two mitogenomes reported in this study provided valuable data for future molecular and evolutionary studies of the genus Tylotoriton and other salamanders.

In recent years, plentiful studies have uncovered the long noncoding RNA's (lncRNA's) momentous functions in osteonecrosis of the femoral head (ONFH), but the specific mechanism has not been fully illustrated. The study was to figure out lncRNA Zinc finger antisense 1 (LncZFAS1)'s biological function and its latent downstream molecular mechanism in glucocorticoid- (GC-) induced ONFH. The results manifested LncZFAS1 and transforming growth factor type III receptor (TGFBR3) were elevated, while microRNA- (miR-) 124-3p was reduced in ONFH tissues and cells. Knockdown LncZFA1 reduced rat femoral cell apoptosis, perfected bone microstructure and bone density, and accelerated osteogenic proteins bone morphogenetic protein- (BMP-) 9, BMP-3, and osteocalcin. In vitro studies manifested knockdown LncZFAS1 prevented GC-induced reduction in osteoblast advancement with facilitating osteoblast calcification capacity, ALP activity, and osteogenic proteins. Elevation of LncZFAS1 further aggravated GC-induced osteoblast injury, but this effect was turned around by enhancement of miR-124-3p or knockdown of TGFBR3. Mechanistically, LncZFAS1 performed as a sponge for miR-124-3p to mediate TGFBR3 expression to motivate GC-induced ONFH. All in all, the results of this study indicate the LncZFAS1/miR-124-3p/TGFBR3 axis is supposed to be a latent therapeutic molecular target for GC-induced ONFH., Competing Interests: The authors declared that they have no conflicts of interest regarding this work., (Copyright © 2022 Xiao Yong Lan et al.)

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Exosomes are a subset of nano-sized extracellular vesicles originating from endosomes. Exosomes mediate cell-to-cell communication with their cargos, which includes mRNAs, miRNAs, lncRNAs, and circRNAs. Exosomal RNAs have cell specificity and reflect the conditions of their donor cells. Notably, their detection in biofluids can be used as a diagnostic marker for various diseases. Exosomal RNAs are ideal biomarkers because their surrounding membranes confer stability and they are detectable in almost all biofluids, which helps to reduce trauma and avoid invasive examinations. However, knowledge of exosomal biomarkers remains scarce. The present review summarizes the biogenesis, secretion, and uptake of exosomes, the current researches exploring exosomal mRNAs, miRNAs, lncRNAs, and circRNAs as potential biomarkers for the diagnosis of human diseases, as well as recent techniques of exosome isolation.

Mitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis., (© 2021. The Author(s).)

SheXiang XinTongNing (XTN), which is composed of six traditional Chinese herbs, is a commercially available Chinese patent medicine that has been widely used as the treatment of coronary heart disease (CHD). Its mechanisms against coronary heart disease, however, remain largely unknown. This study aimed to investigate the pharmacological mechanisms of XTN against CHD via network pharmacology and experimental evaluation. In this study, GO enrichment and KEGG pathway enrichment were firstly performed for acquiring the potentially active constituents of XTN, the candidate targets related to coronary heart disease, the drug-components-targets network as well as the protein-protein interaction network and further predicting the mechanisms of XTN against coronary heart disease. Subsequently, a series of in vitro experiments, specifically MTT assay, flow cytometry and Real-time quantitative polymerase chain reaction analysis, and a succession of in vivo experiments, including Tunel staining and immunohistochemical staining were conducted for further verification. Results showed that Bcl-2, IGF1, CASP3 were the key candidate targets which significantly associated with multiple pathways, namely PI3K-Akt signaling pathway and MAPK signaling pathway. It indicated that the potential mechanism of XTN against CHD may be predominantly associated with cell apoptosis. The in vitro experimental results showed that XTN treatment remarkably decreased the apoptotic rate and Bax/Bcl-2 ratio of H9c2 cells. Histological results confirmed that XTN not only effectively alleviated oxidative damage caused by myocardial ischemia but inhibited cell apoptosis. Given the above, through the combined utilization of virtual screening and experimental verification, the findings suggest that XTN makes a significant contribution in protecting the heart from oxidative stress via regulating apoptosis pathways, which lays the foundations and offers an innovative idea for future research., Competing Interests: Z-QM, G-YC, and J-XL were employed by the company Shandong Hongjitang Pharmaceutical Group Co., Ltd. The remaining authors declare that the research is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jia, Cao, Li, Gan, Li, Lan, Meng, He, Zhang, Wang and Yuan.)

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. It is well recognized that environmental challenges such as smoking, viral infection and alcohol consumption are key factors underlying HNSCC pathogenesis. Other than major clinical interventions (e.g., surgical resection, chemical and radiotherapy) that have been routinely practiced over years, adjuvant anticancer agents from Traditional Herbal Medicine (THM) are proposed, either alone or together with conventional therapies, to be experimentally effective for improving treatment efficacy in different cancers including HNSCCs. At a cellular and molecular basis, THM extracts could modulate different malignant indices via distinct signaling pathways and provide better control in HNSCC malignancy and its clinical complications such as radiotherapy-induced xerostomia/oral mucositis. In this article, we aim to systemically review the impacts of THM in regulating HNSCC tumorous identities and its potential perspective for clinical use.

The balance between charge transport and charge injection is always a key factor in enhancing the performance of quantum-dot light-emitting diodes (QD-LEDs), particularly for the blue QDs due to their large optical band gap and relatively low valence band level compared with their green and red counterparts. High performance blue QD-LEDs have been demonstrated by blending polyethylene glycol (PEG) into solution-processed ZnO nanocrystals as the electron transport layer. PEG can effectively tune the electron mobility of ZnO and simultaneously passivate its surface defect states. As a result, the maximum current efficiency (CE) and external quantum efficiency (EQE) of the blue QD-LEDs increased from 4.33 cd A -1 and 9.98% for pure ZnO to 8.03 cd A -1 and 14.84% for 4% PEG blended into ZnO, respectively. Furthermore, operational lifetime of the device is also significantly improved from 8.95 h to 25.06 h. This result indicates that PEG is a promising material for regulating the charge balance of the blue QD-LEDs., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Microsorum pteropus has been proven to be a potential novel aquatic Cd hyperaccumulator. In this study, Non-invasive Micro-test Technology (NMT) was used to observe the ion fluxes of different M. pteropus tissues under Cd exposure. M. pteropus can hyperaccumulate more than 1000 mg/kg Cd in roots and leaves and approximately 600 mg/kg Cd in stems after seven days of exposure to 500 μM Cd, showing that this plant have a great capacity for Cd enrichment and resistance. The NMT test found H + fluxes increased in all tissues after Cd exposure, with the largest increases being observed in stems, followed by the leaves and roots. Cd 2+ fluxes showed different accumulation levels in different tissues, with low-level Cd exposure leading to influxes into roots and leaves, and high-level Cd exposure resulting in effluxes from roots. No significant influxes or effluxes were observed in leaves under high-level Cd exposure, or in stems under low- and high-levels of Cd exposure. However, transient high-level Cd exposure showed long-term Cd 2+ influxes into roots and short-term Cd 2+ effluxes out of stems and leaves. The roots of M. pteropus had greater regulation mechanisms for Cd enrichment and resistance, with influxes occurring following low-level exposure and effluxes occurring from high-level exposure. When exposed to Cd, M. pteropus stems showed less transportation and absorption. Low-level Cd exposure resulted in individual leaves directly absorbing Cd from hydroponic solutions. Different Cd enrichment and resistance mechanisms were exhibited by different M. pteropus tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis. Here we show that NCAM is dynamically expressed in the developing cortex. NCAM expression in NPCs is highest in the neurogenic period and declines during the gliogenic period. In mice bearing an NPC-specific NCAM deletion, proliferation of NPCs is reduced, and production of cortical neurons is delayed, while formation of cortical glia is advanced. Mechanistically, NCAM enhances actin polymerization in NPCs by interacting with actin-associated protein profilin2. NCAM-dependent regulation of NPCs is blocked by mutations in the profilin2 binding site. Thus, NCAM plays an essential role in NPC proliferation and fate decision during cortical development by regulating profilin2-dependent actin polymerization., (© 2019 Huang et al.)

Copy number variation (CNV) caused by gene rearrangement is an important part of genomic structural variation. We found that the copy number variation region of the Src Homology 2 Domain Containing E ( SHE ) gene correlates with a quantitative trait locus of sheep related to milk fat percentage and bone density. The aim of our study was to detect the copy number variation of the SHE gene in four sheep breeds and to conduct a correlation analysis with economic traits, hoping to provide some reference for sheep breeding. In this study, we examined 750 sheep from four Chinese breeds: Chaka sheep (CKS), Hu sheep (HS), Large Tail Han sheep (LTHS) and Small Tail Han sheep (STHS). We used qPCR to evaluate the copy number of the SHE gene, and then used general linear models to analyze the associations between CNV and economic traits. The results showed that there were more individuals with SHE copy number loss in CKS and HS than in STHS and LTHS individuals. Association analyses showed that gain and normal copy number types were correlated to body length, circumference of cannon bone, heart girth, chest width and high at the cross in CKS, HS and STHS ( p < 0.05), but this association was not observed for LTHS. Chi-square values (χ 2 ) found prominent differences in CNV distribution among the studied breeds. Overall, the CNV of the SHE gene may be an important consideration for sheep molecular breeding.

Microsorum pteropus is a novel potential Cd (cadmium) aquatic hyperaccumulator. In the present study, hydroponic experiments were conducted to assess the accumulation and subcellular distribution of Cd in the root, stem and leaf of M. pteropus. SEM (scanning electron microscopy) - EDX (energy dispersive X-ray fluorescence spectrometer) and TEM (transmission electron microscopy) were used to observe the ultrastructure of different tissues under 500 μM Cd exposure. After exposure to 500 μM Cd for 7 days, the root, stem and leaf of M. pteropus can accumulate to be > 400 mg/kg Cd in dry mass with no significant influence on the growth. In the root and leaf of M. pteropus, the Cd was more likely to store in the cell wall fraction. However, Cd in the stem was mainly stored in both the cell wall fraction and the cytoplasm fraction. Under SEM observation and EDX detection, 1) Cd was found to be sequestrated in the epidermis or chelated in the root cells, 2) no significant deposit spots were observed in the stem, 3) Cd was found in the trichome of the leaf, and the sporangium was not damaged. TEM observations revealed 1) possible Cd precipitations in the root cell and 2) no significant ultrastructure variation in the stem, and 3) the chloroplast retained its structure and was not affected by the Cd. M. pteropus showed great capacity for Cd accumulation without influencing growth. In addition, the ultrastructure of all the tissues was not damaged by the Cd. M. pteropus showed a great potential in phytoremediation in heavy metal polluted water solutions, and may provide new directions for the study of resistance mechanisms of aquatic hyperaccumulators., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11-21 of Shank3 , leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3 -deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3 -depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3 -deficient rats. It is worth to note that Shank3 -deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3 -related neurodevelopmental disorders.

Copy number variation is a large genome variation which usually happens in the noncoding-region, and it may occur at the locus associated with the functional gene to further influence the phenotype. Potassium inwardly-rectifying channel, subfamily J 12 (KCNJ12) gene expressed widely in cardiomyocytes and neurons, plays an important role in tumor therapy and muscle movement regulation. In this study, we detected the distribution of CNVs for KCNJ12 gene in 404 individuals belonging to four Chinese cattle breeds (NY, JX, JA and GF). We also investigated the KCNJ12 gene expression in different tissues of JX cattle. Additionally, we examined the association of two CNV regions (CNV1: 1,600 bp, intron 1; CNV2: 4,800 bp, intergenic) with growth traits. The statistical analyses indicated that the CNV1 is associated with the body length, rump length and weight in JX cattle population (P < 0.05); and there has a significant association with the body length, chest circumference, and body weight in GF cattle (P < 0.05).The CNV2 had a significant effect on the body length and body weight in JX cattle (P < 0.05); the body length, chest circumference, rump length and body weight in GF cattle (P < 0.01 or P < 0.05). The copy numbers of KCNJ12 gene presented the negative correlations with the transcript level of gene in skeletal muscles (P < 0.05). Our results provide evidence that CNV1 and CNV 2 in KCNJ12 are associated with growth traits in two cattle populations and may be used as candidates for marker-assisted selection and breeding management in cattle., (Copyright © 2018. Published by Elsevier B.V.)

Genetic polymorphism has great influences on the improvement of cattle traits. The polymorphism of the same gene family will greatly change the growth traits of cattle, such as the pleomorphic adenoma gene (PLAG) family. Many studies have shown that the PLAG family proteins are the transcription regulators of nuclear protein, which mainly regulates the expression of many important genes in the body. In cattle, single nucleotide polymorphisms (SNPs) within or near the PLAG1 gene is associated with economic traits of height in cattle. Here we investigate a SNPs of bovine PLAG1 in 646 cattle from five breeds. We found three different genotypes by using cleaved amplification polymorphism sequence-tagged sites (CAPs), includes some significant differences in body height, chest circumference and other shapes (P < 0.05), also we found that the TT genotype had no advantage in body shape. These results indicate that the selection of PLAG1 gene could be used to ensure the breeding direction for growth traits of the beef cattle., (Copyright © 2018. Published by Elsevier B.V.)

Copy number variation (CNV) related to complex traits, such as disease and quantitative phenotype, is considered an important and wealthy source of genetic and phenotypic diversity. It suggests that the copy number variation of function gene maybe leads to the phenotypic changes. Kupple like factor 3 (KLF3) gene is a vital transcription factor associated with the growth and development of muscle and adipose tissue. It has been mapped in a CNV region by animal genome re-sequencing. In this study, we detected the distribution diversity of KLF3 gene copy numbers in six Chinese cattle breeds (QC, NY, XN, PN, QDM and JX) and associated the phenotypic traits with it. Then, we analyzed the KLF3 gene transcription expression level in different tissues of Jiaxian (JX) cattle. Furthermore, we detected mRNA expression level of muscle and fat tissues of Jiaxian cattle (JX), Angus × Jiaxian (AJ). The results showed that the copy number in CNV loss was more frequent in QC than others. And we revealed a positive effect of KLF3 CNV on growth traits, such as body mass and heart girth (P < 0.05). In a word, we ascertained the significance between CNVs of KLF3 gene and growth traits in different cattle breeds, and our data indicates that the CNVs of KLF3 gene may as a marker for the future molecular breeding of Chinese beef cattle., (Copyright © 2018 Elsevier B.V. All rights reserved.)

As an important epigenetic modification DNA methylation is catalyzed by DNA methylation transferases (DNMTs) and occurs mainly in CpG islands. DNA methylation plays an important role in regulates gene expression, cell differentiation, genetic imprinting and tumor therapy. Retinoic acid-binding proteins (RAC) is vital for the absorption, transport, metabolism and maintenance of homeostasis of retinoic acid, which in turn regulates the differentiation and proliferation of cells by regulating the transcription of many target genes, therefore, these proteins influence differentiation and proliferation of adipocytes and muscle fibroblasts. Thus, cellular retinoic acid binding protein 2 (CRABP2) may be a candidate gene which affects beef quality, yield and fat deposition. The aim of this study was to evaluate the expression and the methylation pattern on the differentially methylated region (DMR) of the promoter of CRABP2. The DNA methylation pattern was tested by bisulfite sequencing polymerase chain reaction (BSP), the quantitative real-time PCR (qPCR) was used to analysis the expression of CRABP2 gene. The results showed that the DNA methylation level was higher in purebred cattle breed than that in hybrid cattle breeds which was negative correlation with the expression of the gen. These results indicate that the methylation status of the CRABP2 DMR can regulate mRNA expression. What's more, there are different methylation and expression patterns in different breeds and tissues which may influence the phenotype, and the results may be a useful parameter to investigate the function of CRABP2 in muscle and fat developmental in Chinese cattle., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Copy number variations (CNVs) recently have been recognized as another important genetic variability followed single nucleotide polymorphisms (SNPs). The guanylate binding protein 2 (GBP2) gene plays an important role in cell proliferation. This study was performed to determine the presence of GBP2 CNV (relative to Angus cattle) in 466 individuals representing six main cattle breeds from China, identify its relationship with growth, and explore the biological effects of gene expression. There were two CNV regions in the GBP2 gene, for three types, CNV1 loss type (relative to Angus cattle) was more frequent in XN than other breeds, and CNV2 loss type (relative to Angus cattle) was more frequent in XN and CDM than other breeds. Though the GBP2 gene copy number presented no correlation with the transcriptional expression of JX (P > .05), but the transcriptional expression in heart is higher than other tissues, and the copy number in muscles and fat of JX is higher than others breeds. Statistical analysis revealed that the GBP2 gene CNV1 and CNV2 were significantly associated with growth traits (P < .05). In conclusion, this research established the correlations between CNVs of GBP2 gene and growth traits in different cattle breeds, and our results suggested that the CNVs in GBP2 gene may be considered markers for the molecular breeding of Chinese beef cattle., (Copyright © 2018. Published by Elsevier B.V.)

WNT-β-catenin-TCF pathway is involved in carcinogenesis and foetal development. As a member of the WNT gene family, Wnt8A encodes secreted signalling proteins and responds to many biological processes.However, similar research on the effects of genetic variations of Wnt8A gene on growth traits is lacking. Therefore, in this study, polymorphisms of Wnt8A were detected in 396 animals from Chinese Qinchuan cattle using DNA pool sequencing and PCR-RFLP methods. Four novel single-nucleotide polymorphisms (SNPs) of Wnt8A gene were identified, including three mutations in introns (g.T-445C, g.G244C and g.G910A) and one in exon (g.T4922C). Additionally, we examined the associations of four SNPs with growth traits. The results revealed that SNP2 (g.G244C) was significantly associated with shoulder height, hip height, body length, hip width, and body weight (P < 0.05). SNP3 (g.G910A) also displayed notable effects on hip width (P < 0.05). Meanwhile, the haplotype combination CC-GC-GA-CC was strongly associated with heavier, taller and longer animals (P < 0.05). These results show that the Wnt8A gene may be a potential candidate gene, and the SNPs could be used as molecular markers in early marker-assisted selection in beef cattle breeding programmes.

MicroRNAs (miRNAs) are 18-24 nucleotides non-coding RNAs that regulate gene expression by post-transcriptional suppression of mRNA. The Chinese giant salamander (CGS, Andrias davidianus ), which is an endangered species, has become one of the important models of animal evolution; however, no miRNA studies on this species have been conducted. In this study, two small RNA libraries of CGS ovary and testis were constructed using deep sequencing technology. A bioinformatics pipeline was developed to distinguish miRNA sequences from other classes of small RNAs represented in the sequencing data. We found that many miRNAs and other small RNAs such as piRNA and tsRNA were abundant in CGS tissue. A total of 757 and 756 unique miRNAs were annotated as miRNA candidates in the ovary and testis respectively. We identified 145 miRNAs in CGS ovary and 155 miRNAs in CGS testis that were homologous to those in Xenopus laevis ovary and testis respectively. Forty-five miRNAs were more highly expressed in ovary than in testis and 21 miRNAs were more highly expressed in testis than in ovary. The expression profiles of the selected miRNAs (miR-451, miR-10c, miR-101, miR-202, miR-7a and miR-499) had their own different roles in other eight tissues and different development stages of testis and ovary, suggesting that these miRNAs play vital regulatory roles in sexual differentiation, gametogenesis and development in CGS. To our knowledge, this is the first study to reveal miRNA profiles that are related to male and female CGS gonads and provide insights into sex differences in miRNA expression in CGS., (© 2017 Society for Reproduction and Fertility.)

Contamination of raw milk with bacterial pathogens is potentially hazardous to human health. The aim of this study was to evaluate the total bacteria count (TBC) and presence of pathogens in raw milk in Northern China along with the associated herd management practices. A total of 160 raw milk samples were collected from 80 dairy herds in Northern China. All raw milk samples were analyzed for TBC and pathogens by culturing. The results showed that the number of raw milk samples with TBC <2 × 10 6 cfu/mL and <1 × 10 5 cfu/mL was 146 (91.25%) and 70 (43.75%), respectively. A total of 84 (52.50%) raw milk samples were Staphylococcus aureus positive, 72 (45.00%) were Escherichia coli positive, 2 (1.25%) were Salmonella positive, 2 (1.25%) were Listeria monocytogenes positive, and 3 (1.88%) were Campylobacter positive. The prevalence of S. aureus was influenced by season, herd size, milking frequency, disinfection frequency, and use of a Dairy Herd Improvement program. The TBC was influenced by season and milk frequency. The correlation between TBC and prevalence of S. aureus or E. coli is significant. The effect size statistical analysis showed that season and herd (but not Dairy Herd Improvement, herd size, milking frequency, disinfection frequency, and area) were the most important factors affecting TBC in raw milk. In conclusion, the presence of bacteria in raw milk was associated with season and herd management practices, and further comprehensive study will be powerful for effectively characterizing various factors affecting milk microbial quality in bulk tanks in China., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The temporal-spatial distributions of DDT-related contaminants (DDXs), including DDT (dichlorodiphenyltrichloroethane), DDE (dichlorodiphenyldichloroethylene) and DDD (dichlorodiphenyldichloroethane), in the sediments of Lake Chaohu and their influencing factors were studied. p,p-DDE and p,p-DDD were found to be the two dominant components of DDXs in both surface and core sediments. The parent DDT compounds were still detectable in sediment cores after the late 1930s. Historical usage of technical DDT was identified as the primary source of DDXs in sediments, as indicated by DDT/(DDD + DDE) ratios of less than one. The residual levels of DDXs were higher in the surface and core sediments in the western lake area than in other lake areas, which might be due to the combined inflow effects of municipal sewage, industrial wastewater and agricultural runoff. The DDX residues in the sediment cores reached peak values in the late 1970s or early 1980s. There were significant positive relationships between DDX residues in sediment cores with annual DDT production and with fine particulate sizes (<4.5 μm). The relationship between the DDXs and TOC in sediment was complex, as indicated by the significant differences among the surface and core sediments. The algae-derived organic matter significantly influenced the amount of residue, composition and distribution of DDXs in the sediments. The DDD/DDE ratios responded well to the anaerobic conditions in the sediments that were caused by algal blooms after the late 1970s in the western lake area. This suggests that the algae-derived organic matter was an important factor and served as a biomarker of eutrophication and also affected the DDX residues and lifecycle in the lake ecosystem., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

As a member of the POU-domain family, the POU1F1 is a positive regulator for growth hormone, prolactin and thyroid-stimulating hormone b, by binding to target DNA promoters as a dimer in mammals. This study described the polymorphisms at the goat POU1F1-DdeI locus and analyzed the distribution of alleles in 15 indigenous Chinese goat breeds. The PCR-RFLP analysis showed a predominance of the D1D1 genotype and the D1 allele, with average frequencies of 0.550 and 0.790, respectively, irrespective of goat utility type. The D1D2 genotype was the second most frequent, with a mean frequency of 0.371. The distributions of genotypic and allelic frequencies at this locus were found to be significantly different among populations based on a Chi square test (P < 0.001), suggesting that the breed factor significantly affected the molecular genetic character of the POU1F1 gene. The genetic diversity analysis revealed that Chinese indigenous populations had a wide spectrum of genetic diversity at the goat POU1F1-DdeI locus. However, an ANOVA analysis revealed no significant differences in gene homozygosity, gene heterozygosity, effective allele numbers, or polymorphism information content among meat, dairy, and cashmere utility types (P > 0.05). This suggests that the goat utility types had no significant effect on the spectrum of genetic diversity.

MicroRNAs (miRNAs), a class of single stranded, small (~22 nucleotides), non-coding RNAs, play an important role in muscle development. We focused on the role of the miR-30-5p family during bovine muscle development from previous high-throughput sequencing results and analyzed their expression profiles. MHC and MyoG mRNAs expression as well as their proteins were suppressed in differentiated C2C12 cells, suggesting the importance of miR-30-5p in muscle development. MBNL, the candidate target of miR-30-5p, is an alternative splicing regulation factor. MBNL1 and MBNL3 have opposite effects on muscle differentiation. Our results confirmed that miR-30a-5p and miR-30e-5p repress the expression of MBNL1, MBNL2 and MBNL3, whereas miR-30b-5p inhibits MBNL1 and MBNL2 expression. This provides direct evidence that MBNL expression can be flexibly regulated by miR-30-5p. Previous studies showed that MBNL1 promotes exon inclusion of two muscle-related genes (Trim55 and INSR). Through RNA splicing studies, we found that miR-30-5p had an effect on their alternative splicing, which means miR-30-5p via MBNL1 could be integrated into muscle signaling pathways in which INSR or Trim55 are located. In conclusion, miR-30-5p could inhibit muscle cell differentiation and regulate the alternative splicing of Trim55 and INSR by targeting MBNL. These results promote the understanding of the function of miRNAs in muscle development.

Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a member of the patatin like phospholipase domain-containing (PNPLA) family, plays an important role in energy balance, fat metabolism regulation, glucose metabolism and fatty liver disease. Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) is a new method offering fast detection and extreme simplicity at a negligible cost for SNP genotyping. In this paper, we investigated the genetic variations at different ages of 660 Chinese indigenous cattle belonging to three breeds (QC, NY, JX) and applied T-ARMS-PCR and PCR-RFLP methods to genotype four SNPs, SNP1: g.A2980G, SNP2: g.A2996T, SNP3: g.A36718G, SNP4: g.G36850A. The statistical analyses indicated that these 4 SNPs affected growth traits markedly (P<0.05) in QC population, whereas combined haplotypes were not (P>0.05). The qPCR (quantitative PCR) indicated that bovine PNPLA3 gene was exclusively expressed in fat tissues. Besides, the analysis between SNP and mRNA expression revealed that, in SNP1, the expression of AG was much higher than AA and GG (P<0.05), which was in accordance with the results of growth traits association analysis, while the results of SNP4 was not. These results supported high potential that SNPs of bovine PNPLA3 gene might be utilized as genetic markers in marker-assisted selection (MAS) for Chinese cattle breeding programs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Gray horses are born colored, and they then gradually lose their hair pigmentation. Tremendous progress has been made in identifying the genes responsible for graying with age in horses in recent years. Results show that gray coat color in horses is caused by a 4.6-kb duplication in intron 6 of the syntaxin 17 gene (STX17), which constitutes a cis-acting-regulatory mutation. However, little is known about the gray phenotype in native Chinese horses. This study was conducted to explore the frequency distribution of the gray mutation in native Chinese horse breeds. A total of 489 samples from 14 native Chinese horse breeds were genotyped for the STX17 duplication using a simplified conventional PCR-based method. The results show that the gray mutation was present in 12 native Chinese horse breeds, except the Balikun and Guanzhong breeds. The Chakouyi and Hequ breeds had the highest frequency of the gray mutation (P(G) = 0.367 and P(G) = 0.274, respectively). There was no significant geographical difference in the distribution of gray coat color across native Chinese horse breeds. Our results suggest that gray is a common coat color in Chinese horses.

Cell death-inducing DFFA-like effector c (CIDEC, also known as Fsp27) has emerged as an important regulator of metabolism associated with lipodystrophy, diabetes, and hepatic steatosis. It is required for unilocular lipid droplet formation and optimal energy storage. The mechanism between this gene and livestock growth traits, however, has yet to be reported. In this study, we found ten novel single nucleotide polymorphisms (SNPs) in the 5' transcriptional region of CIDEC in Nanyang (NY) cattle, which are located in the recognition sequences (potential cis-acting elements) of 22 transcription factors, and the nine haplotypes represent nine different combinations of polymorphic potential cis-acting elements. The results indicated that individuals with the H8-H8 diplotype had heavier body weights and faster growth rates (P < 0.01) at 18th months than those with H1-H8. We evaluated the transcriptional activities of different haplotypes in vitro, the results were consistent with the association analysis. The H8 haplotype had 1.88-fold (P < 0.001) higher transcriptional activity than the H1 haplotype. We speculate that the haplotypes of the potential cis-acting elements may affect the transcriptional activity of CIDEC, thus affecting the growth traits of cattle. This information may be used in molecular marker-assisted selection of cattle breeding in the future.

Background: The awareness, treatment and prevention of chronic diseases are generally poor among the elderly population of China, whereas the prevention and control of chronic diseases in elderly veteran communities have been ongoing for more than 30 years. Therefore, investigating the awareness status of chronic disabling neurological diseases (CDND) and common chronic diseases (CCD) among elderly veterans may provide references for related programs among the elderly in the general population., Methods: A cross-sectional survey was conducted among veterans ≥60 years old in veteran communities in Beijing. The awareness of preventive strategies against dementia, Alzheimer's disease (AD), Parkinson's disease (PD), sleep disorders, cerebrovascular disease (CVD) and CCD such as hypertension, and the approaches used to access this information, including media, word of mouth (verbal communication among the elderly) and health care professionals, were investigated via face-to-face interviews., Results: The awareness rates for CCD and CVD were approximately 100%, but that for AD was the lowest at <10%. The awareness rates for sleep disorders, PD and dementia, were 51.0-89.4%. Media was the most commonly selected mode of communication by which veterans acquired knowledge about CCD and CVD. Media was used by approximately 80% of veterans. Both health care professionals and word of mouth were used by approximately 50% of veterans. With respect to the source of information about CDND excluding AD, the rates of the use of health care professionals, word of mouth and media were 10.6-28.2%, 56.5-76.5%, and approximately 50%, respectively., Conclusions: The awareness of CDND among elderly veterans was significantly lower than that of CCD. More information about CDND should be disseminated by health care professionals. Appropriate guidance will promote the rapid and extensive dissemination of information about the prevention of CDND by media and word-of-mouth peer education.

The LIM-homeobox gene 3 (LHX3) plays an essential role in pituitary gland and nervous system development. Sequence variants (SVs) in coding and non-coding regions of LHX3 gene have an impact on LHX3 transcription and growth traits in cattle. Previously, we have identified 3 single nucleotide polymorphisms (SNPs: 1-3) in all exons and intron 2 regions of the LHX3 gene in cattle. Here, 7 novel SNPs (SNPs: 4-10) were identified by DNA sequencing and polymerase chain reaction single-stranded conformational polymorphism (PCR-SSCP) methods. In the present study, a total of 10 SNPs were assessed linkage disequilibrium (LD) in 802 cows representing four main cattle breeds from China (Nanyang, Qinchuan, Jiaxian, and Chinese Holstein). The assessment results demonstrated that 17 haplotypes and 18 diplotypes were revealed in these cattle populations. Moreover, association analysis indicated that the genotypes of SNPs 1-6 are associated with the body weight at 6, 12 and 18months of age in Nanyang cattle (P<0.01 or P<0.05), whereas no significant association was found between the 18 diplotypes and growth traits. Our results provide evidence that some SNPs in LHX3 gene may be associated with body weight at certain age, and LHX3 gene may be used as candidate gene for marker-assisted selection (MAS) in beef cattle breeding., (Copyright © 2015. Published by Elsevier B.V.)

DNA methylation is a key epigenetic modification in mammals and plays important roles in muscle development. We sampled longissimus dorsi muscle (LDM) from a well-known elite native breed of Chinese Qinchuan cattle living within the same environment but displaying distinct skeletal muscle at the fetal and adult stages. We generated and provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA for fetal and adult muscle studies. Integration analysis revealed a total of 77 and 1,054 negatively correlated genes with methylation in the promoter and gene body regions, respectively, in both the fetal and adult bovine libraries. Furthermore, we identified expression patterns of high-read genes that exhibit a negative correlation between methylation and expression from nine different tissues at multiple developmental stages of bovine muscle-related tissue or organs. In addition, we validated the MeDIP-Seq results by bisulfite sequencing PCR (BSP) in some of the differentially methylated promoters. Together, these results provide valuable data for future biomedical research and genomic and epigenomic studies of bovine skeletal muscle that may help uncover the molecular basis underlying economically valuable traits in cattle. This comprehensive map also provides a solid basis for exploring the epigenetic mechanisms of muscle growth and development.

The insulin-like growth factor I (IGF-1) gene plays important roles in the growth and body composition of animals. Serum IGF1 concentration has been associated with growth traits in many livestock species. We found a polymorphism of cattle IGF1-TasI locus and analyzed the distribution of alleles in three cattle breeds, including Qinchuan, Nanyang, and Chinese Holstein. PCR-RFLP analysis showed that allele A was the dominant allele. The frequencies of allele A varied from 0.84 to 0.97. Distributions of genotypic and allelic frequencies were significantly different among breeds. Polymorphism of the IGF1 gene was significantly affecting hucklebone width at 6 months in the Nanyang breed and protein and fat yield of the third lactation in Chinese Holstein cattle. Individuals with allele C had a significantly higher performance in production traits.

Hepatocyte nuclear factor-4α (HNF-4α), a member of the hepatocyte nuclear factor family, plays an important role in regulating the expression of genes involved in the development, differentiation and normal function of liver and pancreatic β cells, as well as the maintenance of glucose homeostasis. Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) is a new method offering fast detection and extreme simplicity at a negligible cost for SNP genotyping. In this paper, we characterize the polymorphisms of the bovine HNF-4α gene in three Chinese indigenous cattle breeds (n=660). Six novel SNPs were identified including 1 mutation in the coding region and others in introns. The statistical analyses indicated that 4 SNPs (g.T53729C, g.A53861G, g.A65188C and g.T65444C) affected growth traits markedly (P<0.05) in Qinchuan cattle (2 years after birth). Besides, haplotypes involving these 4 SNP sites in the bovine HNF-4α gene were identified and their effects on growth traits were also analyzed. The results showed that haplotypes 2, 7, 9 and 11 were predominant and accounted for 73.2%, 59.6%, and 67.1% in Qinchuan, Nanyang and Jiaxian cattle breeds, respectively. Hap9 (TAAT) was extremely predominant in all test populations, which suggested that individuals with Hap9 were more adapted to the environment. Furthermore, 4 combined haplotypes were constructed to guarantee the reliability of analysis results in Qinchuan cattle. There were also significant differences in body length (P<0.05). These findings will benefit for the application of DNA marker related to the growth traits on marker-assisted selection (MAS), and improve the performance of beef cattle., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. In this study, we found that the expression of the ZBED6 and IGF2 were upregulated during C2C12 differentiation. The IGF2 expression levels were negatively associated with the methylation status in beef cattle (P < 0.05). A luciferase assay for the IGF2 intron 3 and P3 promoter showed that the mutant-type 439 A-SNP-pGL3 in driving reporter gene transcription is significantly higher than that of the wild-type 439 G-SNP-pGL3 construct (P < 0.05). An over-expression assay revealed that ZBED6 regulate IGF2 expression and promote myoblast differentiation. Furthermore, knockdown of ZBED6 led to IGF2 expression change in vitro. Taken together, these results suggest that ZBED6 inhibits IGF2 activity and expression via a G to A transition disrupts the interaction. Thus, we propose that ZBED6 plays a critical role in myogenic differentiation.

Adipose differentiation-related protein (ADFP) is important for regulation of lipid metabolism and insulin secretion in beta-cells. In this study, we investigated polymorphisms within the caprine ADFP gene and determined its relationship with production traits. As there was no sequence information available for the caprine ADFP gene, we generated DNA sequence data and examined the genomic organisation. The caprine ADFP gene is organised into 7 exons and 6 introns that span approximately 8.7 kbp and is transcribed into mRNA containing 1,353 bp of sequence coding for a protein of 450 amino acids. The protein sequences showed substantial similarity (71-99%) to orthologues from cattle, human and mouse. We identified polymorphisms in the sequences using DNA sequencing, PCR-RFLP and forced PCR-RFLP methods. Seven single nucleotide polymorphisms (SNPs) were identified using samples from 4 different goat populations consisting of 1408 healthy and unrelated individuals. Six haplotypes involving the 7 SNPs from the caprine ADFP gene were identified and their effects on production traits were analysed. Haplotype 6 had the highest haplotype frequency and was highly significantly associated with chest circumference and milk yield in the analysed populations. The results of this study suggest that the ADFP gene is a strong candidate gene affecting production traits and may be used for marker-assisted selection and management in Chinese dairy goat breeding programmes., (Copyright © 2014. Published by Elsevier B.V.)

LIM homeobox transcription factor 4 (LHX4) is a LIM homeodomain transcription factor involved in pituitary gland and nervous system development. The aim of this study was to examine the association of the LHX4 polymorphisms with growth traits in beef cattle breed. A total of 7 single nucleotide polymorphyisms (SNPs) have been identified in the coding region and noncoding region of the bovine LHX4 by sequencing pooled DNA samples (Pool-Seq) and PCR-single strand conformation polymorphism (PCR-SSCP) methods. The linkage disequilibrium was assessed in 871 individuals representing four main cattle breeds from China. The SNPs 2-5 and 7-8 were found to be in complete linkage disequilibrium, respectively. The result of haplotype analysis of 13 SNPs showed that 31 haplotypes were found in four Chinese cattle breeds, and 20 genotypes were only found in Nanyang cattle. The statistical analyses indicated that the SNP1-5, and 6 are associated with the body weight at 18, and 6 months of age in Nanyang cattle population (P<0.05), but no significant associations between their twenty combined genotypes. Our results provide evidence that some polymorphisms in LHX4 are associated with growth traits at certain ages, and may be used as candidates for marker-assisted selection and management in cattle., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The myostatin gene (MSTN) is a genetic determinant of skeletal muscle growth. Single nucleotide polymorphisms (SNP) in MSTN are of importance due to their strong associations with horse racing performances. In this study, we screened the SNPs in MSTN gene in 514 horses from 15 Chinese horse breeds. Six SNPs (g.26T>C, g.156T>C, g.587A>G, g.598C>T, g.1485C>T, g.2115A>G) in MSTN gene were detected by sequencing and genotyped using PCR-RFLP method. The g.587A>G and g.598C>T residing in the 5'UTR region were novel SNPs identified by this study. The g.2115A>G which have previously been associated with racing performances were present in Chinese horse breeds, providing valuable genetic information for evaluating the potential racing performances in Chinese domestic breeds. The six SNPs together defined thirteen haplotypes, demonstrating abundant haplotype diversities in Chinese horses. Most of the haplotypes were shared among different breeds with no haplotype restricted to a specific region or a single horse breed. AMOVA analysis indicated that most of the genetic variance was attributable to differences among individuals without any significant contribution by the four geographical groups. This study will provide fundamental and instrumental genetic information for evaluating the potential racing performances of Chinese horse breeds., (Copyright © 2013 Elsevier B.V. All rights reserved.)

DNA methylation is a key epigenetic modification in mammals and has an essential and important role in muscle development. Insulin-like growth factor 2 (IGF2) is a fetal growth and differentiation factor that plays an important role in muscle growth and in myoblast proliferation and differentiation. The aim of this study was to evaluate the expression of IGF2 and the methylation pattern on the differentially methylated region (DMR) of the last exon of IGF2 in six tissues with two different developmental stages. The DNA methylation pattern was compared using bisulfite sequencing polymerase chain reaction (BSP) and combined bisulfite restriction analysis (COBRA). The quantitative real-time PCR (qPCR) analysis indicated that IGF2 has a broad tissue distribution and the adult bovine group showed significant lower mRNA expression levels than that in the fetal bovine group (P<0.05 or P<0.01). Moreover, the DNA methylation level analysis showed that the adult bovine group exhibited a significantly higher DNA methylation levels than that in the fetal bovine group (P<0.05 or P<0.01). These results indicate that IGF2 expression levels were negatively associated with the methylation status of the IGF2 DMR during the two developmental stages. Our results suggest that the methylation pattern in this DMR may be a useful parameter to investigate as a marker-assisted selection for muscle developmental in beef cattle breeding program and as a model for studies in other species., (© 2013.)

Bone morphogenetic proteins (BMPs) are peptide growth factors belonging to the transforming growth factor-beta (TGF-β) superfamily, and some members of the BMP family support white adipocyte differentiation. In this study, we focused on the BMP7 which singularly promotes the differentiation of brown preadipocytes. Haplotypes involving 5 single nucleotide polymorphism (SNP) sites in the bovine BMP7 gene were identified and their effect on body weight was analyzed. 16 haplotypes and 18 combined haplotypes were revealed and the linkage disequilibrium was assessed in the cattle population with 602 individuals representing three main cattle breeds from China. The results showed that haplotypes 3, 10 and 14 were predominant and accounted for 75.64%, 69.85%, and 83.36% in Nanyang, Qinchuan and Jiaxian cattle breeds, respectively. The statistical analyses indicated that the SNP 1, 4, and 5 are associated with the body weight, body length, and heart girth at 12 and 24 months in Nanyang cattle population (P<0.05), whereas there is no significant association between their 16 haplotypes and 18 combined haplotypes. Our results provide evidence that some SNPs and haplotypes in BMP7 are associated with growth traits, and may be utilized as a genetic marker in marker-assisted selection for beef cattle breeding programs., (Copyright © 2013. Published by Elsevier B.V.)