DNA Double-Strand Breaks,Potential Targets for HBV Integration

Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis.More and more researches were designed to find the relationship of the two.In this study,we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks(DSBs),one of the most detrimental DNA damage.An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection,then cells were incubated in patients’ serum with high HBV DNA copies and at the same time,DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector.By using nest PCR,the viral DNA was detected at the sites of the break.It appeared that integra-tion occurred between part of HBV x gene and the I-SceI induced breaks.The results suggested that DSBs,as the DNA damages,may serve as potential targets for hepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily.It provided a new site to investi-gate the integration.

Application of Artificially Induced Double-strand Breaks (DSB) and Triplex-forming Oligonucleotides (TFO) in the Improvement of Gene Targeting Efficiency

Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks （DSB） and triplex forming oligonucleotide （TFO） are currently developed methods to improve the targeting efficiency. This paper summarized the basic principles, design ideas and application in gene targeting efficiency improvement of these two methods, analyzed and com- pared their characteristics, and finally proposed prospects for their future development.

Exposure to Long Magnetic Resonance Imaging Thermometry Does Not Cause Significant DNA Double-Strand Breaks on CF-1 Mice

The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbent assay (ELISA) was used to quantify γH2AX, a molecular marker for DSBs, in the blood of mice after a 6-hour exposure to magnetic resonance imaging (MRI). Fourteen CF-1 female mice were separated into 4 experimental groups: Untreated negative control, MRI-treated, MRI-Control, and exposed to ionizing radiation positive control. Untreated negative control was used as a baseline for ELISA to quantify γH2AX. MRI-treated consisted of a 6-hour continuous magnetic resonance imaging (MRI) echo planar imaging (EPI) sequence with a slew rate of 192 mT/m/s constituting a significantly longer imaging time than routine clinical imaging. MRI-control mice were maintained under the same conditions outside the MRI scanner for 6-hours. Mice in the irradiation group served as a positive control of DSBs and were exposed to either 2 Gy, 5 Gy or 10 Gy of ionizing radiation. DSBs in the blood lymphocytes from the treatment groups were analyzed using the γH2AX ELISA and compared. Total protein concentration in lysates was determined for each blood sample and averaged 1 ± 0.35 mg/mL. Irradiated positive controls were used to test radiation dose-dependency of the γH2AX ELISA assay where a linear dependency on radiation exposure was observed (r2 = 0.93) between untreated and irradiated samples. Mean and standard error mean of γH2AX formation were calculated and compared between each treatment group. Repeated measures 1-way ANOVA showed statistically significant differences between the means of irradiated controls and both the MRI-control and MRI-treated groups. There was no statistically significant difference between the MRI-treated samples and the MRI-control groups. Our results show that long MRI exposure at a high slew rate did not cause increased levels of γH2AX when compared to control mice, suggesting that no increase in DSBs was caused by the long MR thermometry imaging session. The novelty of this work contradicts other studies that have suggested MRI may cause DSBs;this work suggests an alternative cause of DNA damage.

Comparison of DNA double-strand breaks induced by ^(16)O^(8+) in deproteinized DNA and intact cells

The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and their DNA in DSBs induced by 75 MeV/u16O8+ beam. Results show that the percentages of DNA released from the plug(PR) in bothkinds of tile samples increase with the dose and approach a similar quasi-threshold of about81%. A simple new equation was presented to calculate the break level of DNA molecules.Within a certain dose, the relationship between the break level and the dose is linear. Theyield of DSBs in deproteinized DNA was 1.11 DSBs/100 Mbp/Gy, while that in intact cells was0.60DSBs/100Mbp/Gy. It is testified that deproteinized DNA is more sensitive to oxygen ionsirradiation than intact cells.

Across two phylogeographic breaks: Quaternary evolutionary history of a mountain aspen (Populus rotundifolia) in the Hengduan Mountains

Biogeographical barriers to gene flow are central to plant phylogeography.In East Asia,plant distribution is greatly influenced by two phylogeographic breaks,the Mekong-Salween Divide and Tanaka-Kaiyong Line,however,few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both.Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia,a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China.Demographic and migration hypotheses were tested using coalescent-based approaches.Limited historical gene flow was observed between the western and eastern groups of P.rotundifolia,but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line,manifesting in clear admixture and high genetic diversity in the central group.Wind-borne pollen and seeds may have facilitated the dispersal of P.rotundifolia following prevalent northwest winds in the spring.We also found that the Hengduan Mountains,where multiple genetic barriers were detected,acted on the whole as a barrier between the western and eastern groups of P.rotundifolia.Ecological niche modeling suggested that P.rotundifolia has undergone range expansion since the last glacial maximum,and demographic reconstruction indicated an earlier population expansion around 600 Ka.The phylogeographic pattern of P.rotundifolia reflects the interplay of biological traits,wind patterns,barriers,niche differentiation,and Quaternary climate history.This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.

Hot spots of DNA double-strand breaks and genomic contacts of human rDNA units are involved in epigenetic regulation

DNA double-strand breaks(DSBs)are involved in many cellular mechanisms,including replication,transcription,and genome rearrangements.The recent observation that hot spots of DSBs in human chromosomes delimit DNA domains that possess coordinately expressed genes suggests a strong relationship between the organization of transcription patterns and hot spots of DSBs.In this study,we performed mapping of hot spots of DSBs in a human 43-kb ribosomal DNA(rDNA)repeated unit.We observed that rDNA units corresponded to the most fragile sites in human chromosomes and that these units possessed at least nine specific regions containing clusters of extremely frequently occurring DSBs,which were located exclusively in non-coding intergenic spacer(IGS)regions.The hot spots of DSBs corresponded to only a specific subset of DNase-hypersensitive sites,and coincided with CTCF,PARP1,and HNRNPA2B1 binding sites,and H3K4me3 marks.Our rDNA-4C data indicate that the regions of IGS containing the hot spots of DSBs often form contacts with specific regions in different chromosomes,including the pericentromeric regions,as well as regions that are characterized by H3K27ac and H3K4me3 marks,CTCF binding sites,ChIA-PET and RIP signals,and high levels of DSBs.The data suggest a strong link between chromosome breakage and several different mechanisms of epigenetic regulation of gene expression.

Effect of prolonging interval time between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes

Background It is desirable to minimize the risk of adverse radiation effects associated with percutaneous coronary intervention.The aim of this study was to determine the impact of prolonging the interval between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes using γ-H2AX immunofluorescence microscopy.Methods Blood samples of eight patients were taken before the first exposure to ionizing radiation,10 minutes,20 minutes,30 minutes,1 hour,and 24 hours after the last exposure to determine the γ-H2AX foci repair kinetics.Fifty-eight patients undergoing percutaneous coronary intervention were randomized to an intermittent radiation exposure group and a continuous radiation exposure group.Blood samples were taken before coronary angiography and 15 minutes after the last exposure.By enumerating γ-H2AX foci,the impact of prolonging the interval on DNA double-strand breaks was investigated.Student t-test was used to compare the difference in DNA double-strand breaks between the two groups.Results An increase in foci was found in all patients received percutaneous coronary intervention.The maximum number of γ-H2AX foci was found 10-20 minutes after the end of the last exposure.There was no statistically significant difference between the two groups in γ-H2AX foci at baseline.On average there were （0.79±0.15） γ-H2AX foci induced by interventional X-rays per lymphocyte in the continuous radiation exposure group and （0.66±0.21） in the intermittent radiation exposure group after exposure （P〈0.05）.Conclusions A significant number of γ-H2AX foci develop following the percutaneous coronary intervention procedures.The number of X-ray-induced DNA double-strand breaks may be decreased by prolonging the interval time between coronary angiography and percutaneous coronary intervention to 30 minutes.

Double-stranded DNA breaks and gene functions in recombination and meiosis

Meiotic prophase I is a long and complex phase. Homologous recombination is an important process that occurs between homologous chromosomes during meiotic prophase I. Formation of chiasmata, which hold homologous chromosomes together until the metaphase I to anaphase I transition, is critical for proper chromosome segregation. Recent studies have suggested that the SPO 11 proteins have conserved functions in a number of organisms in generating sites of double-stranded DNA breaks （DSBs） that are thought to be the starting points of homologous recombination. Processing of these sites of DSBs requires the function of RecA homologs, such as RAD5 1, DMC 1, and others, as suggested by mutant studies; thus the failure to repair these meiotic DSBs results in abnormal chromosomal alternations, leading to disrupted meiosis. Recent discoveries on the functions of these RecA homologs have improved the understanding of the mechanisms underlying meiotic homologous recombination.

Investigation of hydroxyl-terminated polybutadiene propellant breaking characteristics and mechanism impacted by submerged cavitation water jet

A submerged cavitation water jet(SCWJ)is an effective method to recycle solid propellant from obsolete solid engines by the breaking method.Solid propellant's breaking modes and mechanical process under SCWJ impact are unclear.This study aims to understand those impact breaking mechanisms.The hydroxyl-terminated polybutadiene(HTPB)propellant was chosen as the research material,and a self-designed test system was used to conduct impact tests at four different working pressures.The high-speed camera characterized crack propagation,and the DIC method calculated strain change during the impact process.Besides,micro and macro fracture morphologies were characterized by scanning electron microscope(SEM)and computed tomography(CT)scanning.The results reveal that the compressive strain concentration region locates right below the nozzle,and the shear strain region distributes symmetrically with the jet axis,which increases to 4% at first 16th ms,the compressive strain rises to 2% and 6% in the axial and transverse direction,respectively.The two tensile cracks formed first at the compression strain concentrate region,and there generate many shear cracks around the tensile cracks,and those shear cracks that develop and aggregate cause the cracks to become wider and cut through the tensile cracks,forming the tensile-shear cracks and the impact parts eventually fail.The HTPB propellant forms a breaking hole shaped conical after impact 10 s.The mass loss increases by 17 times at maximum,with the working pressure increasing by three times.Meanwhile,the damage value of the breaking hole remaining on the surface increases by 7.8 times while 2.9 times in the depth of the breaking hole.The breaking efficiency is closely affected by working pressures.The failure modes of HTPB impacted by SCWJ are classified as tensile crack-dominated and tensile-shear crack-dominated damage mechanisms.

Volatility spillovers,structural breaks and uncertainty in technology sector markets

This study uses the dynamic conditional correlation to investigate how technology subsector stocks interact with financial assets in the face of economic and financial uncertainty.Our results suggest that structural breaks have diverse effects on financial asset connectedness and that the level of bond linkage increases when the trend breaks.We see a growing co-movement between the technology sector and major financial assets when uncertainty is considered.Overall,our findings indicate that the connectedness response varies depending on the type of uncertainty shock.

Observation of Zero-Energy Modes with Possible Time-Reversal Symmetry Breaking on Step Edge of CaKFe_(4)As_(4)

Topologically nontrivial Fe-based superconductors attract extensive attentions due to their ability of hosting Majorana zero modes(MZMs)which could be used for topological quantum computation.Topological defects such as vortex lines are required to generate MZMs.Here,we observe the robust edge states along the surface steps of CaKFe_(4)As_(4).Remarkably,the tunneling spectra show a sharp zero-bias peak(ZBP)with multiple integerquantized states at the step edge under zero magnetic field.We propose that the increasing hole doping around step edges may drive the local superconductivity into a state with possible spontaneous time-reversal symmetry breaking.Consequently,the ZBP can be interpreted as an MZM in an effective vortex in the superconducting topological surface state by proximity to the center of a tri-junction with different superconducting order parameters.Our results provide new insights into the interplay between topology and unconventional superconductivity,and pave a new path to generate MZMs without magnetic field.

Generating highly active oxide-phosphide heterostructure through interfacial engineering to break the energy scaling relation toward urea-assisted natural seawater electrolysis

Urea-assisted natural seawater electrolysis is an emerging technology that is effective for grid-scale carbon-neutral hydrogen mass production yet challenging.Circumventing scaling relations is an effective strategy to break through the bottleneck of natural seawater splitting.Herein,by DFT calculation,we demonstrated that the interface boundaries between Ni_(2)P and MoO_(2) play an essential role in the selfrelaxation of the Ni-O interfacial bond,effectively modulating a coordination number of intermediates to control independently their adsorption-free energy,thus circumventing the adsorption-energy scaling relation.Following this conceptual model,a well-defined 3D F-doped Ni_(2)P-MoO_(2) heterostructure microrod array was rationally designed via an interfacial engineering strategy toward urea-assisted natural seawater electrolysis.As a result,the F-Ni_(2)P-MoO_(2) exhibits eminently active and durable bifunctional catalysts for both HER and OER in acid,alkaline,and alkaline sea water-based electrolytes.By in-situ analysis,we found that a thin amorphous layer of NiOOH,which is evolved from the Ni_(2)P during anodic reaction,is real catalytic active sites for the OER and UOR processes.Remarkable,such electrode-assembled urea-assisted natural seawater electrolyzer requires low voltages of 1.29 and 1.75 V to drive 10 and600 mA cm^(-2)and demonstrates superior durability by operating continuously for 100 h at 100 mA cm^(-2),beyond commercial Pt/C||RuO_(2) and most previous reports.

Team China’s Groundbreaking Success at Paris Olympics

China’s Olympic delegation at the Paris 2024,with 404 athletes competing in 232 events across 30 sports,clinched 40 gold,27 silver,and 24 bronze medals,marking their best performance at an Olympics held abroad.The success of these athletes across various disciplines demonstrates the country’s efforts to expand its athletic prowess while also marks a new chapter for Chinese sportsmanship on the international stage.

Enhancing textile production:Smartex exhibits groundbreaking solutions

Smartex,a trailblazing leader in textile industry innovation,was proud to announce its return to ITM 2024,showcasing unparalleled advancements in quality control and production efficiency.Building on the success of previous exhibitions at ITM 2022 and ITMA Milan 2023,Smartex emerges stronger than ever,presenting its complete Smartex System tailored to transform textile manufacturing.

Impacts of monsoon break events in the western North Pacific on the cross-equatorial flows over the Maritime Continent

本文利用ERA5逐日再分析资料,探讨了1979-2020年间西北太平洋季风中断事件对海洋性大陆越赤道气流的影响.合成结果表明,西北太平洋季风中断事件会造成高,低空越赤道气流减弱,即高层南风异常,低层北风异常,与此相关的环流异常表现为西北太平洋高层气旋,低层反气旋的斜压结构。特别的是,西北太平洋季风中断对高空越赤道气流的影响更为显著,92%的季风中断事件都导致高空越赤道气流减弱,而只有70%的事件造成低空越赤道气流减弱,这是由于低空越赤道气流同时还受到赤道中东太平洋海温异常的调控.

Numerical Simulation of Dam-Break Flows Using Radial Basis Functions: Application to Urban Flood Inundation

Dam-break flows pose significant threats to urban areas due to their potential for causing rapid and extensive flooding. Traditional numerical methods for simulating these events struggle with complex urban landscapes. This paper presents an alternative approach using Radial Basis Functions to simulate dam-break flows and their impact on urban flood inundation. The proposed method adapts a new strategy based on Particle Swarm Optimization for variable shape parameter selection on meshfree formulation to enhance the numerical stability and convergence of the simulation. The method’s accuracy and efficiency are demonstrated through numerical experiments, including well-known partial and circular dam-break problems and an idealized city with a single building, highlighting its potential as a valuable tool for urban flood risk management.

Auto-pick first breaks with complex raypaths for undulate surface conditions

First-break picking is the key step in seismic data processing for surveying undulate surfaces, and directly infl uences the precision of near-surface modeling and effects of static corrections. The current first-break auto-picking methods may fail when the signalto-noise ratio（SNR） is low for seismic data in the undulate area, and require labor and time intensive manual picking. This study develops an improved super-virtual interferometry（SVI） method that combines multichannel and multidomain quality control（MMQC） techniques to achieve auto-picked first breaks. The improved SVI method extends the SVI application to enhance the SNR for near-surface scattered waves for the first time, which allows for the SVI method to adapt to first breaks with complex raypaths by linear combination of refractions and near-surface scattered waves. Methods of inverse and multidomain interferometry are developed to effectively enhance the virtual records extracted by the SVI method. The deconvolution filter for waveforms is used to increase resolution and reduce false picks, while the MMQC technique is designed to auto-correct false picks and increase the stability of auto-picking first breaks. The robust technique developed in this study enables stable processing of large 3D seismic datasets. Higher quality results are obtained using the approach presented in this paper to actual field data from the mountain areas in western China, when compared to some commonly used commercial software.

Maternal gene Ooep may participate in homologous recombination-mediated DNA double-strand break repair in mouse oocytes

DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks （DSBs） are highly deleterious and can substantially impair genome integrity. Homologous recombination （HR）-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated （ATM） kinase activation and Rad51 recombinase （RAD51） focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.

Non-buckled vitrectomy for retinal detachment with inferior breaks and proliferative vitreoretinophathy

AIM: To investigate the efficacy of non-buckled vitrectomy with classical endotamponade agents in the treatment of primary retinal detachment (RD) complicated by inferior breaks and proliferative vitreoretinophathy (PVR). METHODS: A retrospective, consecutive and case series study of 40 patients with inferior break RD and PVR >= C1 was conducted. All patients underwent a standard 3-port 20-gauge pars plana vitrectomy (PPV) with gas or silicone oil tamponade without supplementary scleral buckling. The vitreous and all proliferative membrane were completely removed, and retinectomy was performed when necessary. The mean follow-up was 12.5 months. The primary and final anatomic success rate, visual acuity and complications were recorded and analyzed. RESULTS: Primary anatomic success rate was achieved in 35 of 40 eyes (87.5%) and the final anatomic success rate was 100%. The most common cause of redetachment was recurrent PVR. The best-corrected visual acuity (BCVA) at final follow-up was improved in 34 eyes (85%), remained stable in 1 eye (2.5%), and worsened in 5 eyes (12.5%). The mean visual acuity at final follow-up was improved significantly (P=0.000). CONCLUSION: This retrospective study provides evidence that vitrectomy without scleral buckling seemed to be an effective treatment for inferior break RD with PVR. With complete removal of vitreous and proliferative membranes and timing of retinectomy, the inferior breaks which complicated with PVR could be dosed successfully without additional sclera! buckling.

Selection of Multifractal Scaling Breaks andSeparation of Geochemical andGeophysical Anomaly

Spatially superimposed multiple processes such as multiplicative cascade processes often generate multifractal measures possessing so-called self-similarity or self-affinity that can be described by power- law type of functions within certain scale ranges The multifractalities can be estimated by applying multifractal modeling to the measures reflecting the characteristics of the physical processes such as the element concentration values analyzed in rock and soil samples and caused by the underlying mineralization processes and the other geological processes. The local and regional geological processes may result in geochemical patterns with distinct multifractalities as wall as variable scaling ranges. Separation of these multifractal measures on the basis of both the distinct multifractalities and the scaling ranges will be significant for both theoretical studies of multifractal modeling and its applications. Multifractal scaling breaks have been observed from various multifractal patterns. This paper introduces a technique for separating multifractal measures on the basis of scaling breaks. It has been demonstrated that the method is effective for decomposing geochemical and geophysical anomalies required for mineral exploration. A dataset containing the element concentration values of potassium and phosphorus in soil samples was employed for demonstrating the application of the method for studying the fertilizer and yield optimization in agriculture