Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution.

The dynamics of the chromatin regulatory landscape during human early embryogenesis remains unknown. Using DNase I hypersensitive site (DHS) sequencing, we report that the chromatin accessibility landscape is gradually established during human early embryogenesis. Interestingly, the DHSs with OCT4 binding motifs are enriched at the timing of zygotic genome activation (ZGA) in humans, but not in mice. Consistently, OCT4 contributes to ZGA in humans, but not in mice. We further find that lower CpG promoters usually establish DHSs at later stages. Similarly, younger genes tend to establish promoter DHSs and are expressed at later embryonic stages, while older genes exhibit these features at earlier stages. Moreover, our data show that human active transposons SVA and HERV-K harbor DHSs and are highly expressed in early embryos, but not in differentiated tissues. In summary, our data provide an evolutionary developmental view for understanding the regulation of gene and transposon expression.

scMethBank: a database for single-cell whole genome DNA methylation maps.

Single-cell bisulfite sequencing methods are widely used to assess epigenomic heterogeneity in cell states. Over the past few years, large amounts of data have been generated and facilitated deeper understanding of the epigenetic regulation of many key biological processes including early embryonic development, cell differentiation and tumor progression. It is an urgent need to build a functional resource platform with the massive amount of data. Here, we present scMethBank, the first open access and comprehensive database dedicated to the collection, integration, analysis and visualization of single-cell DNA methylation data and metadata. Current release of scMethBank includes processed single-cell bisulfite sequencing data and curated metadata of 8328 samples derived from 15 public single-cell datasets, involving two species (human and mouse), 29 cell types and two diseases. In summary, scMethBank aims to assist researchers who are interested in cell heterogeneity to explore and utilize whole genome methylation data at single-cell level by providing browse, search, visualization, download functions and user-friendly online tools. The database is accessible at: https://ngdc.cncb.ac.cn/methbank/scm/.

The effect of quenching and Mn substitution for Ni on the magnetic properties of Mn25+xNi50-xGa25.

Ni-Mn based Heusler alloys have attracted widespread attention due to their novel physical properties. However, the structure of Mn2NiGa is metastable at room temperature, making it difficult to obtain its intrinsic physical properties and limiting its application. In this study, we obtained Mn2NiGa by replacing Ni in the precursor alloy Ni2MnGa with Mn and studied its magnetic properties, structures, and phase transitions with floating composition. In addition, we focused on the compositional segregation characteristics of Mn2NiGa caused by different heat treatment and quenching conditions. It was found that the samples quenched after annealing at 773 K for 48 hours exhibited abnormalities in magnetism, phase transformation, and structure. The further electron probe scanning characterization results reveal that the changes in these physical properties were related to component segregation caused by heat treatment.

Hepatic abscess occurred one year after endoscopic transmural management of an infected, walled-off pancreatic necrosis.

A 46-year-old man underwent endoscopic ultrasound (EUS)-guided transgastric drainage with subsequent direct endoscopic necrosectomy (DEN) for an infected walled-off pancreatic necrosis (WOPN). Following treatment, he improved clinically with resolution of fever and substantial reduction in size of the WOPN. He was discharged with indwelling plastic stents which were to be removed after complete resolution of the WOPN. Follow-up CT and EUS 1 months later showed spontaneous stents dislodgement and a residual pancreatic fluid collection (PFC) measuring 4.0×2.3cm, for which re-intervention was technically demanding due to the small size. As he was asymptomatic, a decision was made to manage him expectantly for spontaneous resolution of the residual PFC. However, against our expectation, 1 year later he presented with recurrent fever to 40.1 °C. An hepatic abscess was identified on CT scan, which also revealed the residual PFC, though it was further reduced in size. After one month of antibiotic treatment, follow-up CT revealed that the hepatic abscess had resolved. Concurrently, complete resolution of residual PFC was also observed. EUS-guided drainage/debridement is a first-line therapy for WOPN. Remnant PFC due to premature stent dislodgement may persist as an insidious source of infection in which dormant pathogens may become reactivated sometime and culminate in a flare-up. Since the venous drainage of the pancreatic region ends up in the portal vein, occurrence of the hepatic abscess in the presence of the residual PFC should be considered as causal rather than coincidental. At least we couldn't help arousing a high suspicion of their cause-and-effect relationship. Therefore, despite its being technically challenging, timely reintervention with measures such as EUS-guided needle puncture and irrigation so as to thoroughly eradicate the residual PFC burden should be advocated to reduce the likelihood of late on-set local or distant infection.

The effect of Cr doping on the magnetic and magnetocaloric properties of Ni45Co5Mn36.5In13.5 Heusler alloys.

Herein, Ni45-xCrxCo5Mn36.5In13.5 (x = 0, 0.2, 0.4, and 0.6 at%) and Ni45Co5Mn36.5-yCryIn13.5 (y = 0.2, 0.4, and 0.6 at%) polycrystalline Heusler alloys are prepared by arc melting and then characterized using X-ray diffraction and a vibrating sample magnetometer. A single L21 austenitic phase is confirmed at room temperature. Meanwhile, we studied the effect of Cr doping on the magnetic properties of Ni45Co5Mn36.5In13.5 alloys. It is observed that, with the incorporation of Cr atoms, both the lattice constant and valence electron concentration of the alloys have changed, resulting in the phase transition temperature, saturation magnetization and magnetic entropy changing significantly. In addition, when Cr is replaced by Mn, the change of phase transition temperature (ΔT) induced by the magnetic field decreases; therefore, in the Ni45Co5Mn36.1Cr0.4In13.5 samples, the magnetic entropy change reaches a maximum value of up to 37.1 J kg-1 K-1 under an external magnetic field of 3T, which is more than 50% higher than that of other Ni-Mn based Heusler alloys reported in the literature.

Fishbone foreign body ingestion in duodenal papilla: a cause of abdominal pain resembling gastric ulcer.

BACKGROUND: Foreign body ingestion is a common clinical problem. The upper esophagus is the most common site of foreign body, accounting for more than 75% of all cases, but cases with a foreign body in the duodenal papilla or common bile duct are rarely reported. CASE PRESENTATION: Herein, we report a rare case that a patient's abdominal pain resembling gastric ulcer was caused by a 3 cm long fishbone inserted into the duodenal papilla. CONCLUSION: Fishbone inserted into the duodenal papilla can cause an abdominal pain resembling gastric ulcer. Endoscopy is useful for the diagnosis and treatment of fishbone ingestion in clinical.

MicroRNA-147b Promotes Proliferation and Invasion of Human Colorectal Cancer by Targeting RAS Oncogene Family (RAP2B).

BACKGROUND: MicroRNAs (miRNAs), a class of small-regulatory RNA molecules, were closely involved in the pathogenesis of a broad-spectrum of colorectal cancer (CRC). But role of miR-147b in CRC still remains unclear. METHODS: Real-time RT-PCR or Western blotting was utilized to detect the expressions of miR-147b and RAP2B in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-147b and 3'UTRs of RAP2B. A series of assays were performed to evaluate the effect of miR-147b on proliferation, migration, and invasion of CRC in vitro and in vivo. RESULTS: We found that the level of miR-147b was significantly lower in CRC tissues than in normal tissues (p = 0.0006). Enforced expression of miR-147b led to suppression of CRC cell proliferation in vitro and tumor growth in vivo. Specifically, miR-147b promoted proliferation by arresting CRC cells in the G1/G0 phase. Mechanically, RAP2B was identified as a direct target gene of miR-147b and RAP2B rescued the suppression of proliferation and invasion reduced by miR-147b in CRC cells. CONCLUSIONS: miR-147b not only plays important roles in the regulation of cell proliferation and tumor growth in CRC, which might be a potential prognostic marker or therapeutic target for CRC.

A giant Brunner's gland hamartoma being treated as a pedunculated polyp: a case report.

BACKGROUND: With the development and application of endoscopic technology, most pedunculated polyps can be absolutely resected with a complete specimen by hot snare polypectomy (HSP). Brunner's gland hamartoma (BGH) is a rare benign small bowel tumor. The majority of BGH measuring about 2 cm in diameter, rarely larger than 5 cm. Most patients are asymptomatic, some may present with gastrointestinal hemorrhage or intestinal obstruction. Symptomatic larger lesions leading to bleeding or obstruction should be excised either endoscopically or surgically. Whether it is safe and effective that removing a BGH measuring about 7 cm by HSP is not known. CASE PRESENTATION: Here, we reported a rare case of a proximal duodenum pedunculated mass measuring about 7 cm which was responsible for the patient's severe anemia. we treated it as a pedunculated polyp. After being pretreated the stalk with an endoloop which was placed around the base of the mass to prevent post-polypectomy bleeding (PPB), the pedunculated BGH was removed by HSP completely. The stalk of the mass was negative. We achieved a curative resection. CONCLUSION: It is a safe and effective for our patient to treat the pedunculated BGH measuring about 7 cm as a pedunculated polyp and remove it by HSP. And future prospective studies in larger cohorts are needed to confirm it.

The relationship between the asymmetric magnetoresistive effect and the magnetocaloric effect in Ni43Co7Mn39-xCrxSn11 Heusler alloys.

The correlation between the magnetocaloric effect and magnetotransport property was investigated in Ni43Co7Mn39-xCrxSn11 Heusler alloys. The asymmetric isothermal-magnetoresistance around the phase transformation temperature was observed, from which a parameter γ, determined as the ratio of the asymmetric magnetoresistance to the temperature coefficient of resistance, is proposed. According to Maxwell's equation, the parameter γ is analyzed to be equivalent to the transformation temperature change induced by a magnetic field in martensitic transformation. This finding is confirmed by experimental results. In addition, the γ values can be used to estimate the magnetic entropy change of the martensitic transformation directly without measuring the comprehensive temperature dependence of magnetization curves.

Ultrafast Bubble-Propelled and Magnetic-Field-Navigated Porous Catalytic Janus Micromotor.

In this study, a bubble-propelled catalytic Janus micromotor is demonstrated. This micromotor is magnetically controllable and is capable of both organics absorption and delivery. The motor is fabricated by a low-cost and eco-friendly physical method free from chemical reactions. Such a micromotor is effectively propelled by bubbles generated from hydrogen peroxide decomposition. Applied with a controlled magnetic field, the motor can travel along designed trajectories. An ultrafast travelling speed of up to 3.3 mm/s (∼320 body length) was reached in 6.3% (wt%) H2O2 solution. Additionally, Rodamine B was chosen as a target organic to proof the collection and transportation performance. The collection and release cycle of target organic is repeated for more than 25 times. This result reveals that the motor is efficient in organic absorption and transportation, indicating that the micromotor is promising in water decontamination and targeted drug delivery.

Topography-specific isotropic tunneling in nanoparticle monolayer with sub-nm scale crevices.

Material used in flexible devices may experience anisotropic strain with identical magnitude, outputting coherent signals that tend to have a serious impact on device reliability. In this work, the surface topography of the nanoparticles (NPs) is proposed to be a parameter to control the performance of strain gauge based on tunneling behavior. In contrast to anisotropic tunneling in a monolayer of spherical NPs, electron tunneling in a monolayer of urchin-like NPs actually exhibits a nearly isotropic response to strain with different loading orientations. Isotropic tunneling of the urchin-like NPs is caused by the interlocked pikes of these urchin-like NPs in a random manner during external mechanical stimulus. Topography-dependent isotropic tunneling in two dimensions reported here opens a new opportunity to create highly reliable electronics with superior performance.

Endoscopic band ligation or endoscopic tissue adhesive injection in the treatment of gastric varices: Which is better?

The combination of endoscopic ultrasound with endoscopic treatment of type 1 gastric variceal hemorrhage may improve the robustness and generalizability of the findings in future studies. Moreover, the esophageal varices should also be included in the evaluation of treatment efficacy in subsequent studies to reach a more convincing conclusion.

Study on Anomalous Hall Effect and Spin-Orbit Torque Effect of TbCo-Based Multilayer Films.

The anomalous Hall effect and spin-orbit torque of TbCo-based multilayer films have been methodically studied in recent years. Many properties of the films can be obtained by the anomalous Hall resistance loops of the samples. We report on the effects of a structure composed of two heavy metals as the buffer layers on the anomalous Hall resistance loops of TbCo-based multilayers at different temperatures. The results showed that the coercivity increases dramatically with decreasing temperature, and the samples without perpendicular magnetic anisotropy at room temperature showed perpendicular magnetic anisotropy at low temperatures. We quantified the spin-orbit torque efficiency and Dzyaloshinskii-Moriya interaction effective field size of the films W/Pt/TbCo/Pt at room temperature by measuring the loop shift of anomalous Hall resistance. The results showed that the study of anomalous Hall resistance loops plays an important role in the study of spintronics, which can not only show the basic properties of the sample, but can also obtain other information about the sample through the shift of the loops.

Allelic reprogramming of chromatin states in human early embryos.

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here, we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse embryos. The allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early embryos. Collectively, allele-specific epigenomic reprogramming is different in humans and mice.

DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-κB pathway.

PURPOSE: Breast cancer is one of the most common tumors with high malignancy and metastatic rate. DNAJA1 is closely related to tumor progress in several tumors. However, the role and mechanisms of DNAJA1 in the metastasis and proliferation of breast cancer are unknown. METHODS: Immunohistochemistry and western blot were used to detect the protein expression genes. In vivo and vitro experiments were performed to evaluate the proliferation, invasive and metastatic abilities of breast cancer cells. RESULTS: DNAJA1 was high expressed in 234 cases of breast cancer tissues and associated with metastasis, p53 expression and poor survival for patients. Knock down of DNAJA1 decreased the number of plate clone formation and the OD value of CCK8 assays in breast cancer cells. Depletion of DNAJA1 also in decreased the invasive abilities of breast cancer cells. In vivo, knock down DNAJA1 decreased the growth of subcutaneous tumor and lung metastatic nodes. Mechanically, DNAJA1 could bind with P53-R175H and reduced its degradation. Up regulation of DNAJA1 in mutant P53-R175H breast cancer cell promoted the nuclear translocation of p65, activated NF-κB pathway and enhanced the transcription of its downstream genes such as MMP9, CXCL10 et al. Blockade of NF-κB pathway effectively rescued the effects of DNAJA1 on proliferation and metastasis in breast cancer. CONCLUSION: Our study reveals that DNAJA1 is up regulated in breast cancer and promotes breast cancer cells proliferation and metastasis via P53-R175H/NF-κB pathway. It might be a potential prognosis marker for the breast cancer patients.

Modulating the electronic structures of cobalt-organic frameworks for efficient electrocatalytic oxygen evolution.

The oxygen evolution reaction (OER) is a key process in various energy storage/generation technologies. Tuning the electronic structures of catalysts is an effective approach to improve the catalyst's activity. In this work, we synthesized Ce-doped cobalt-organic frameworks with benzene-1, 4-dicarboxylic acid (BDC) as the ligand as efficient OER electrocatalysts (denoted as Co3Ce1 BDC) with excellent stability and improved catalytic performance. The introduced Ce in Co3Ce1 BDC changes the surface configuration and tunes electronic structures of the active Co site, leading to enhanced interaction between intermediates and catalysts. Besides, the specific surface area, reaction kinetics, charge transfer efficiency, and turnover frequency are also improved in the presence of Ce. As a result, the Co3Ce1 BDC demonstrated excellent performance with a low overpotential of 285 mV at a current of 10 mA·cm-2, a preferable Tafel slope of 56.1 mV·dec-1, and an excellent durability in 1 M KOH, indicating the potential for practical applications in water splitting and other energy storage technologies wherein the OER plays a critical role. Comprehensive theoretical calculations and modeling further identified the key role of Ce in modulating the electronic structure and OER activity of cobalt-organic frameworks. Most importantly, this work provides a new strategy to the development of efficient cobalt-organic framework catalysts in OER-related applications.

Reprogramming of ovarian aging epigenome by resveratrol.

Resveratrol is an antiaging, antioxidant, and anti-inflammatory natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects for improving aging ovarian function. However, the mechanisms underlying prolonged reproductive longevity remain elusive. We found that resveratrol ameliorates ovarian aging transcriptome, some of which are associated with specific changes in methylome. In addition to known aging transcriptome of oocytes and granulosa cells such as decline in oxidoreductase activity, metabolism and mitochondria function, and elevated DNA damage and apoptosis, actin cytoskeleton are notably downregulated with age, and these defects are mostly rescued by resveratrol. Moreover, the aging-associated hypermethylation of actin cytoskeleton is decreased by resveratrol. In contrast, deletion of Tet2, involved in DNA demethylation, abrogates resveratrol-reprogrammed ovarian aging transcriptome. Consistently, Tet2 deficiency results in additional altered pathways as shown by increased mTOR and Wnt signaling, as well as reduced DNA repair and actin cytoskeleton with mouse age. Moreover, genes associated with oxidoreductase activity and oxidation-reduction process were hypermethylated in Tet2-deficient oocytes from middle-age mice treated with resveratrol, indicating that loss of Tet2 abolishes the antioxidant effect of resveratrol. Taking together, our finding provides a comprehensive landscape of transcriptome and epigenetic changes associated with ovarian aging that can be reprogrammed by resveratrol administration, and suggests that aberrantly increased DNA methylation by Tet2 deficiency promotes additional aging epigenome that cannot be effectively restored to younger state by resveratrol.

Human zygotic genome activation is initiated from paternal genome.

Although parental genomes undergo extensive epigenetic reprogramming to be equalized after fertilization, whether they play different roles in human zygotic genome activation (ZGA) remains unknown. Here, we mapped parental transcriptomes by using human parthenogenetic (PG) and androgenetic (AG) embryos during ZGA. Our data show that human ZGA is launched at the 8-cell stage in AG and bi-parental embryos, but at the morula stage in PG embryos. In contrast, mouse ZGA occurs at the same stage in PG and AG embryos. Mechanistically, primate-specific ZNF675 with AG-specific expression plays a role in human ZGA initiated from paternal genome at the 8-cell stage. AG-specifically expressed LSM1 is also critical for human maternal RNA degradation (MRD) and ZGA. The allelic expressions of ZNF675 and LSM1 are associated with their allelically epigenetic states. Notably, the paternally specific expressions of ZNF675 and LSM1 are also observed in diploid embryos. Collectively, human ZGA is initiated from paternal genome.

DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p.

Liver cancer is one of the most common and aggressive malignancies worldwide with poor prognosis. Studies on pathogenesis of liver cancer are urgently demanded to develop better treatment strategy. Here, we found that overexpression of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1) increased cell proliferation, invasion, and angiogenesis in Huh 7 and HepG2 cells, while depletion of DNAJA1 in MHCC-97H and HCC-M3 showed opposite effects. In vivo functional assays indicated that DNAJA1 promoted tumor growth and pulmonary metastasis in mice. Mechanistically, as a direct target of miR-205-5p, DNAJA1 promoted proliferation and metastasis of liver cancer cells by stabilizing eukaryotic elongation factor 1A1 (EF1A1). Moreover, DNAJA was markedly upregulated in liver cancer tissues (P < 0.05) and was significantly associated with poor prognosis. And its expression was correlated with differentiation (P < 0.001), dissemination (P < 0.001), and serum AFP (P = 0.029). The mRNA levels of miR-205-5p and DNAJA1 were negatively correlated in liver cancer. In conclusion, our study reveals that DNAJA1 acts as an oncogene in liver cancer via miR-205-5p/EF1A1 axis and might be a potential biomarker to predict the prognosis for liver cancer patients.

Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human.

Epigenetic information regulates gene expression and development. However, our understanding of the evolution of epigenetic regulation on brain development in primates is limited. Here, we compared chromatin accessibility landscapes and transcriptomes during fetal prefrontal cortex (PFC) development between rhesus macaques and humans. A total of 304,761 divergent DNase I-hypersensitive sites (DHSs) are identified between rhesus macaques and humans, although many of these sites share conserved DNA sequences. Interestingly, most of the cis-elements linked to orthologous genes with dynamic expression are divergent DHSs. Orthologous genes expressed at earlier stages tend to have conserved cis-elements, whereas orthologous genes specifically expressed at later stages seldom have conserved cis-elements. These genes are enriched in synapse organization, learning and memory. Notably, DHSs in the PFC at early stages are linked to human educational attainment and cognitive performance. Collectively, the comparison of the chromatin epigenetic landscape between rhesus macaques and humans suggests a potential role for regulatory elements in the evolution of differences in cognitive ability between non-human primates and humans.