The human pre-replication complex is an open complex.

In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome maintenance (MCM) 2-7 double hexamer (DH) to melt origin DNA strands. However, the mechanism for this initial melting is unknown. Here, we report a 2.59-Å cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as the pre-replication complex. In this structure, the hMCM-DH with a constricted central channel untwists and stretches the DNA strands such that almost a half turn of the bound duplex DNA is distorted with 1 base pair completely separated, generating an initial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibits DH formation and replication initiation. Mapping of hMCM-DH footprints indicates that IOSs are distributed across the genome in large clusters aligning well with initiation zones designed for stochastic origin firing. This work unravels an intrinsic mechanism that couples DH formation with initial DNA melting to license replication initiation in human cells.

Genome-wide mapping of human DNA replication by optical replication mapping supports a stochastic model of eukaryotic replication.

The heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual initiation sites make mapping the location and timing of replication initiation in human cells difficult. To address this challenge, we have developed optical replication mapping (ORM), a high-throughput single-molecule approach, and used it to map early-initiation events in human cells. The single-molecule nature of our data and a total of >2,500-fold coverage of the human genome on 27 million fibers averaging ∼300 kb in length allow us to identify initiation sites and their firing probability with high confidence. We find that the distribution of human replication initiation is consistent with inefficient, stochastic activation of heterogeneously distributed potential initiation complexes enriched in accessible chromatin. These observations are consistent with stochastic models of initiation-timing regulation and suggest that stochastic regulation of replication kinetics is a fundamental feature of eukaryotic replication, conserved from yeast to humans.

Cohesin-mediated loop anchors confine the locations of human replication origins.

DNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability1,2. At present, it is unknown how the locations of replication origins are determined in the human genome. Here we dissect the role of topologically associating domains (TADs)3-6, subTADs7 and loops8 in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase.

Pulsed rise and growth of the Tibetan Plateau to its northern margin since ca. 30 Ma.

The onset of mountain building along margins of the Tibetan Plateau provides a key constraint on the processes by which the high topography in Eurasia formed. Although progressive expansion of thickened crust underpins most models, several studies suggest that the northern extent of the plateau was established early, soon after the collision between India and Eurasia at ca. 50 Ma. This inference relies heavily on the age and provenance of Cenozoic sediments preserved in the Qaidam basin. Here, we present evidence in the northern plateau for a considerably younger inception and evolution of the Qaidam basin, based on magnetostratigraphies combined with detrital apatite fission-track ages that date the basin fills to be from ca. 30 to 4.8 Ma. Detrital zircon-provenance analyses coupled with paleocurrents reveal that two-stage growth of the Qilian Shan in the northeastern margin of the Tibetan Plateau began at ca. 30 and at 10 Ma, respectively. Evidence for ca. 30 and 10 to 15 Ma widespread synchronous deformation throughout the Tibetan Plateau and its margins suggests that these two stages of outward growth may have resulted from the removal of mantle lithosphere beneath different portions of the Tibetan Plateau.

Synthesis of flowerlike vanadium diselenide microspheres for efficient electromagnetic wave absorption.

The revelation of MoS2as an efficient electromagnetic wave (EMW) absorbing material has ratcheted up people's attention to other transition metal dichalcogenides (TMDs). To date, extensive studies have been conducted on the semiconducting VIB-Group TMDs while research into metallic VB-Group TMDs has been relatively rare. In this work, we successfully fabricated VB-Group VSe2microspheres through a facile one-step hydrothermal method and used them as EMW absorbers. The flowerlike VSe2microspheres based on VSe2nanosheets exhibited a minimum reflection loss of 46.58 dB with an effective absorption bandwidth of 4.86 GHz. The influence of material morphology, microstructure, and dielectric properties on the EMW absorption performance was systematically investigated. The hierarchically layered structure promoted dielectric loss and EMW absorption by means of multiple reflection, interfacial polarization and related relaxation, and enhanced attenuation ability. This work not only demonstrates that VSe2is potentially a high-efficiency single component EMW absorber, but also provides fresh insights into exploration on the EMW loss mechanisms of the metallic TMD-based absorbing materials.

Synthetic Cell Armor Made of DNA Origami.

The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing the membrane stiffness and lowering the lipid fluidity. The nanoshell also serves as armor to protect cells and improve their viability against mechanical stress from osmotic imbalance, centrifugal forces, and fluid shear stress. Moreover, it enables mediated cell-cell interactions for effective and robust multicellular assembly. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy but also as a platform for cell and cell membrane manipulation.

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction.

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

Light availability and plant shade tolerance modify plant-microbial interactions and feedbacks in subtropical trees.

Plant-soil feedbacks (PSFs) are an important mechanism of species coexistence in forest communities. However, evidence remains limited for how light availability regulates PSFs in species with different shade tolerance via changes in plant-microbial interactions. Here we tested in a glasshouse experiment how PSFs changed as a function of light availability and tree shade tolerance. Soil bacterial and fungal communities were profiled using the 16S rRNA and ITS2 gene sequencing, respectively. Under low light, individual PSFs were positively related to shade tolerance, while the least shade-tolerant species produced the most positive PSFs under high light. Pairwise PSFs between species with contrasting shade tolerance were strongly positive under high light but negative under low light, thereby promoting the dominance of less shade-tolerant species in forest gaps and species coexistence under closed canopy, respectively. Under high light, PSFs were related to soil microbial composition and diversity, with the relative abundance of arbuscular mycorrhizal fungi being the primary driver of PSFs. Under low light, none of soil microbial properties were significantly related to PSFs. These findings indicate PSFs and plant shade tolerance interact to promote species coexistence and improve our understanding of how soil microbes contribute to variation in PSFs.

Speech signal enhancement based on deep learning in distributed acoustic sensing.

The fidelity of a speech signal deteriorates severely in a distributed acoustic sensing (DAS) system due to the influence of the random noise. In order to improve the measurement accuracy, we have theoretically and experimentally compared and analyzed the performance of the speech signal with and without a recognition and reconstruction method-based deep learning technique. A complex convolution recurrent network (CCRN) algorithm based on complex spectral mapping is constructed to enhance the information identification of speech signals. Experimental results show that the random noise can be suppressed and the recognition capability of speech information can be strengthened by the proposed method. The random noise intensity of a speech signal collected by the DAS system is attenuated by approximately 20 dB and the average scale-invariant signal-to-distortion ratio (SI-SDR) is improved by 51.97 dB. Compared with other speech signal enhancement methods, the higher SI-SDR can be demonstrated by using the proposed method. It has been effective to accomplish high-fidelity and high-quality speech signal enhancement in the DAS system, which is a significant step toward a high-performance DAS system for practical applications.

Inversion method for soil moisture content based on a distributed fiber optic acoustic sensing system.

The traditional measurement method can't achieve real-time monitoring of soil moisture content (SMC) within a two-dimensional area. To solve the above problems, we propose a rapid SMC monitoring method for two-dimensional area based on distributed acoustic sensing (DAS). DAS demodulates the backward Rayleigh scattering signal containing seismic wave sound velocity information from the active seismic source. The folding ruler approximation is employed to calculate the sound velocity of the soil, which is then inverted to determine the soil moisture content. The experiment measured the soil within a two-dimensional area formed by the seismic source and the acoustic sensing optical cable. The sensing optical cable and the active seismic source are organized into a two-dimensional area and the measurement range is 3 × 10 m with 33 points. The SMC ranges from 15% to 40%. The experiment shows that the absolute error between the measured values obtained by DAS and the water cut meter is 7%. This experiment verifies the feasibility of using the Rayleigh scattering properties to invert SMC and provides a new method for real-time monitoring of SMC in a large area.

Investigation of anti-aging and anti-infection properties of Jingfang Granules using the Caenorhabditis elegans model.

Jingfang Granule (JFG), a traditional Chinese medicine, is frequently employed in clinical settings for the treatment of infectious diseases. Nevertheless, the anti-aging and anti-infection effects of JFG remain uncertain. In the present study, these effects were evaluated using the Caenorhabditis elegans (C. elegans) N2 as a model organism. The results demonstrated that JFG significantly increased the median lifespan of C. elegans by 31.2% at a dosage of 10 mg/mL, without any discernible adverse effects, such as alterations in the pharyngeal pumping rate or nematode motility. Moreover, JFG notably increased oviposition by 11.3%. Subsequent investigations revealed that JFG enhanced oxidative stress resistance in C. elegans by reducing reactive oxygen species levels and significantly improved survival rates in nematodes infected with Pseudomonas aeruginosa ATCC 9027. These findings suggest that JFG delays reproductive senescence in C. elegans and protects them from oxidative stress, thereby extending their lifespan. Additionally, JFG improves the survival of P. aeruginosa-infected nematodes. Consequently, JFG has potential as a candidate for the development of anti-aging and anti-infection functional medicines.

Effects of tree sex, maturity, local abiotic, and biotic neighborhoods on the growth of a subtropical dioecious tree species Diospyros morrisiana.

PREMISE: Understanding the drivers of the growth in long-lived woody trees is the key to predicting their responses to and maintaining their populations under global change. However, the role of tree sex and differential investment to reproduction are often not considered in models of individual tree growth, despite many gymnosperm and angiosperm species having separate male and female sexes. Thus, better models of tree growth should include tree sex and life stage along with the abiotic and biotic neighborhoods. METHODS: We used a sex-specific molecular marker to determine the sex of 2188 individual trees >1 cm DBH of the dioecious tree species Diospyros morrisiana in a 50-ha subtropical forest plot in China. We used long-term census data from about 300,000 trees, together with 625 soil samples and 2352 hemispherical photographs to characterize the spatially explicit biotic and abiotic neighborhoods. RESULTS: We found a male-biased effective sex ratio and a female-biased overall population sex ratio of D. morrisiana. No sex spatial segregation was detected for the overall population, mature, or immature trees. Immature trees grew faster than mature trees and females grew slower than males. Further, conspecific neighbors significantly decreased tree growth, while the abiotic neighborhood showed no significant effect. CONCLUSIONS: Our findings suggest that variation in resource allocation patterns within and across individual trees of different sexes and life-history stages should be more widely accounted for in models of tree growth. In addition, our study highlights the importance of sex-specific molecular markers for studying populations of long-lived dioecious tree species.

Facile, Direct, De Novo Synthesis of an Alkyl Phosphoric Acid-Decorated Covalent Organic Framework.

The development and understanding of proton conductors based on phosphoric acid are critical for the field of chemistry, biology, and energy. Covalent organic frameworks (COFs), featuring highly crystalline structures and controllable pore sizes, are suitable for constructing phosphoric acid-based proton conductors. However, because of tedious and intricate synthesis, how to develop COFs based on phosphoric acid remains a substantial challenge. Herein, a side-chain decorated strategy is contributed to construct a phosphoric acid-functionalized, imine-linked COF by de novo synthesis. The phosphoric acid side chains with vigorous motion integrating with 1D nanochannels endow the resulting COF with intrinsic proton conductivity. This work expectantly provides a competitive alternative for producing phosphoric acid-functionalized COFs with high intrinsic proton conductivity.

Noninvasive carbon dioxide monitoring in pediatric patients undergoing laparoscopic surgery: transcutaneous vs. end-tidal techniques.

PURPOSE: The present study aimed to investigate the correlation between transcutaneous carbon dioxide partial pressure (PtcCO2) and arterial carbon dioxide pressure (PaCO2) and the accuracy of PtcCO2 in predicting PaCO2 during laparoscopic surgery in pediatric patients. METHODS: Children aged 2-8 years with American Society of Anesthesiologists (ASA) class I or II who underwent laparoscopic surgery under general anesthesia were selected. After anesthesia induction and tracheal intubation, PtcCO2 was monitored, and radial arterial catheterization was performed for continuous pressure measurement. PaCO2, PtcCO2, and end-tidal carbon dioxide partial pressure (PetCO2) were measured before pneumoperitoneum, and 30, 60, and 90 min after pneumoperitoneum, respectively. The correlation and agreement between PtcCO2 and PaCO2, PetCO2, and PaCO2 were evaluated. RESULTS: A total of 32 patients were eventually enrolled in this study, resulting in 128 datasets. The linear regression equations were: PtcCO2 = 7.89 + 0.82 × PaCO2 (r2 = 0.70, P < 0.01); PetCO2 = 9.87 + 0.64 × PaCO2 (r2 = 0.69, P < 0.01). The 95% limits of agreement (LOA) of PtcCO2 - PaCO2 average was 0.66 ± 4.92 mmHg, and the 95% LOA of PetCO2 - PaCO2 average was -4.4 ± 4.86 mmHg. A difference of ≤ 5 mmHg was noted between PtcCO2 and PaCO2 in 122/128 samples and between PetCO2 and PaCO2 in 81/128 samples (P < 0.01). CONCLUSION: In pediatric laparoscopic surgery, a close correlation was established between PtcCO2 and PaCO2. Compared to PetCO2, PtcCO2 can estimate PaCO2 accurately and could be used as an auxiliary monitoring indicator to optimize anesthesia management for laparoscopic surgery in children; however, it is not a substitute for PetCO2. REGISTRATION NUMBER OF CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2100043636.

Coupling electrokinetic remediation with flushing using green tea synthesized nano zero-valent iron/nickel to remediate Cr (VI).

This study focuses on a flushing-electrokinetic remediation technology of hexavalent chromium from the chromium slag dump site. A suspension of nanoscale zero-valent iron/nickel fabricated from green tea (GT-nZVI/Ni), was employed as an eluent to degrade Cr (VI) and enhance the remediation effectiveness of a single EK. The removal efficiency of Cr (VI) was compared under different voltages, electrode spacings and pH values of the anolyte. The results demonstrated that the combined flushing and EK achieved a removal rate of Cr (VI) in the soil throughout all the experiments ranging from 83.08 to 96.97% after 120 h. The optimal result was obtained when the voltage was 28 V, the pH value of anolyte was 3 and the electrode spacing was 15 cm. The removal of Cr (VI) reached 91.49% and the energy consumption was 0.32606 kW·h·g-1. The underlying mechanisms responsible for the removal of Cr (VI) by GT-nZVI/Ni flushing-EK primarily involved electromigration, reduction and adsorption co-precipitation processes. The fractionation analysis of Cr (VI) concentration in the soil after remediation showed that the presence of GT-nZVI/Ni facilitated the conversion of Cr (VI) into oxidizable and residual states with low mobility and toxicity. The results of toxicity characteristic leaching procedure (TCLP) indicated that the leaching concentration of Cr (VI) was below 1 mg·L-1, complying with the standards set by the Environmental Protection Agency. Additionally, the phytotoxicity testing revealed that the germination index (GI) of the remediated soil reached 54.75%, indicating no potential harm to plants.

Hypercrosslinked Polymer Gels as a Synthetic Hybridization Platform for Designing Versatile Molecular Separators.

Hypercrosslinked polymers (HCPs), amorphous microporous three-dimensional networks based on covalent linkage of organic building blocks, are a promising class of materials due to their high surface area and easy functionalization; however, this type of material lacks processability due to its network rigidity based on covalent crosslinking. Indeed, the development of strategies to improve its solution processability for broader applications remains challenging. Although HCPs have similar three-dimensionally crosslinked networks to polymer gels, HCPs usually do not form gels but insoluble powders. Herein, we report the synthesis of HCP gels from a thermally induced polymerization of a tetrahedral monomer, which undergoes consecutive solubilization, covalent bond formation, colloidal formation, followed by their aggregation and percolation to yield a hierarchically porous network. The resulting gels feature concentration-dependent hierarchical porosities and mechanical stiffness. Furthermore, these HCP gels can be used as a platform to achieve molecular-level hybridization with a two-dimensional polymer during the HCP gel formation. This method provides functional gels and corresponding aerogels with the enhancement of porosities and mechanical stiffness. Used in column- and membrane-based molecular separation systems, the hybrid gels exhibited a separation of water contaminants with the efficiency of 97.9 and 98.6% for methylene blue and KMnO4, respectively. This result demonstrated the potentials of the HCP gels and their hybrid derivatives in separation systems requiring macroscopic scaffolds with hierarchical porosity.

Multi-Component Synthesis of a Buta-1,3-diene-Linked Covalent Organic Framework.

We report a multi-component synthetic strategy on a two-dimensional crystalline covalent organic framework (COF) by connecting acetonitrile with aromatic aldehyde and acetaldehyde moieties to form an unprecedented cyano-substituted buta-1,3-diene linkage. Different from most of the COFs that were crystallized from the condensations from two components, the presented COF is generated from two competitive and reversible reactions among three moieties. The buta-1,3-diene COF exhibits remarkable photoactivity with a low exciton binding energy of 44.4 ± 1.5 meV for promoted charge separation, which enables the buta-1,3-diene-linked COF as an efficient photocatalyst for various aerobic oxidation reactions under visible light. Our multi-component synthesis strategy may provide new sights for synthesizing COFs with structural diversity and functional variability that are hard to achieve by traditional COF synthesis.

In Situ Anodic Oxidation Tuning of NiFeV Diselenide to the Core-Shell Heterojunction for Boosting Oxygen Evolution.

Developing non-noble metal-based core-shell heterojunction electrocatalysts with high catalytic activity and long-lasting stability is crucial for the oxygen evolution reaction (OER). Here, we prepared novel core-shell Fe,V-NiSe2@NiFe(OH)x heterostructured nanoparticles on hydrophilic-treated carbon paper with high electronic transport and large surface area for accelerating the oxygen evolution rate via high-temperature selenization and electrochemical anodic oxidation procedures. Performance testing shows that Fe,V-NiSe2@NiFe(OH)x possesses the highest performance for OER compared to as-prepared diselenide core-derived heterojunctions, which only require an overpotential of 243 mV at 10 mA cm-2 and a low Tafel slope of 91.6 mV decade-1 under basic conditions. Furthermore, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) confirm the morphology and elementary stabilities of Fe,V-NiSe2@NiFe(OH)x after long-term chronopotentiometric testing. These advantages are largely because of the strong synergistic effect between the Fe,V-NiSe2 core with high conductivity and the amorphous NiFe(OH)x shell with enriched defects and vacancies. This study also presents a general approach to designing and synthesizing more active core-shell heterojunction electrocatalysts for OER.

Accessing and Assessing the Cell-Surface Glycocalyx Using DNA Origami.

The cell-surface glycocalyx serves as a physiological barrier regulating cellular accessibility to macromolecules and other cells. Conventional glycocalyx characterization has largely been morphological rather than functional. Here, we demonstrated direct glycocalyx anchoring of DNA origami nanotiles and performed a comprehensive comparison with traditional origami targeting to the phospholipid bilayer (PLB) using cholesterol. While DNA nanotiles effectively accessed single-stranded DNA initiators anchored on the glycocalyx, their accessibility to the underlying PLB was only permitted by extended nanotile-to-initiator spacing or by enzymatic glycocalyx degradation using trypsin or pathogenic neuraminidase. Thus, the DNA nanotiles, being expelled by the physiologic glycocalyx, provide an effective functional measure of the glycocalyx barrier integrity and faithfully predict cell-to-cell accessibility during DNA-guided multicellular assembly. Lastly, the glycocalyx-anchoring mechanism enabled enhanced cell-surface stability and cellular uptake of nanotiles compared to PLB anchoring. This research lays the foundation for future development of DNA nanodevices to access the cell surface.

Integrated microenvironment-associated genomic profiles identify LRRC15 mediating recurrent glioblastoma-associated macrophages infiltration.

Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles-based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages-based immunosuppressive effects could be promising for rGBM treatments.