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Abstract The recent high death tolls caused by large earthquakes are a further indication that earthquakes remain one of the most destructive natural hazards in the world and can seriously threaten the achievement of disaster reduction goals. To effectively reduce the existing seismic risk, the limited available mitigation resources should be allocated to areas with the most severe potential risk. However, identifying localized concentrations of risk requires detailed studies. Here, we propose a strategy to delineate regional high seismic risk zone at a fine resolution and with high confidence. We demonstrate this strategy by using the seismic hazard and loss estimation results for earthquake scenarios with a magnitude of Mw 7.5 for the Jiaocheng fault of the Shanxi Rift System, China. Our analyses reveal that the delineated zone accounts for only ~7% of the regional land area but for ~85% of the total financial loss. We recommend prioritizing seismic risk mitigation measures in such high-risk zones, especially for densely populated cities in seismically active areas, to better meet the disaster risk reduction targets in the Sendai Framework.

Abstract 30 min of moderate-intensity aerobic exercise per day is recommended, but the response and adaptation of endothelial function (EF) to this exercise remains controversial. The purpose of this study was to determine the changes in EF in endurance trained and untrained individuals before and after this exercise and to compare the differences between trained and untrained individuals. Twelve endurance-trained male college athletes (trained group) and 12 untrained male college students (untrained group) performed a 30-min run at an intensity of 60% VO2max. Brachial artery flow-mediated dilation (FMD) was measured before exercise, 30 min and 60 min after exercise, and the following morning. Resting diameter and maximum diameter showed large time effects (p

When seismic waves propagate in layered structures, dispersion phenomena occur. Based on the characteristics of dispersion curves, underground velocity structures can be estimated. Using the surface-wave dispersion curves extracted from seismic records and ambient noise for inversion is an important method to constrain the structures of the near surface and lithosphere. In addition to surface waves, significant progress has been made in the research and application of leaky modes and their dispersion in recent years. Leaky modes can provide constraint information for velocity structure inversion, including P-wave velocity, and can compensate for the shortcomings of surface-wave dispersion inversion, which results in more accurate and comprehensive velocity modeling. However, in comparison to surface waves, the amplitude of leaky waves in seismic records and ambient noise is typically much weaker, which leads to significant challenges for the extraction of leaky modes. Furthermore, the study of leaky modes requires a more intricate theoretical framework and numerical solution techniques, which have historically limited their attention in the scientific community. Over the past decades, the theories of leaky modes have been increasingly improved with the relevant research in seismology, optics, and acoustics, which give rise to effective numerical computation tools. This has laid a solid foundation for the practical application of leaky modes. With the increase of high-quality, high-density observational data and advancements in data processing techniques, geoscientists have successfully extracted leaky mode information from various types of data, including natural and artificial earthquakes, as well as ambient noise. This has led to the development of velocity structure imaging methods based on leaky modes. Currently, this imaging approach has been successfully applied in velocity modeling for earthquakes, ambient noise, and exploration seismology, which indicates promising potential for further utilization. In this review, we begin by introducing the theories and numerical methods of leaky modes. We further elaborate on the significance of leaky modes in velocity modeling from a sensitivity perspective. Subsequently, we review several representative studies to highlight the significant advancements in observation and analyze several proposed inversion techniques. Finally, we delve into the critical issues surrounding the use of leaky modes in seismic imaging.

Abstract The Molucca Sea subduction zone is unique for its active divergent double‐subducted slab located in the north of the Java and Banda subduction zones. The spatial proximity of these subduction zones would cause a complex mantle flow field. To clarify the mantle dynamics, here we present P‐wave tilting‐axis anisotropic tomography obtained by inverting a large number of local and teleseismic travel‐time data recorded at 254 seismic stations in eastern Southeast Asia. Our results suggest that the mantle structure and dynamics of the western Molucca Sea subduction zone may be remotely controlled by the Java and Banda subduction zones. Mantle convection in the big mantle wedge west of the Molucca Sea subduction zone is possibly influenced by east‐west mantle flow associated with compression of the Indo‐Australian slab as well as north‐south mantle flow related to rollback of the Indo‐Australian slab. In contrast, the eastern Molucca Sea subduction zone is virtually unaffected by other subduction zones, probably due to the ongoing slab subduction there.

Objective Fast progression (FP) represents a desperate situation for advanced non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor therapy. We aimed to develop a predictive framework based on machine learning (ML) methods to identify FP in advanced NSCLC patients using blood test biomarkers.Methods and analysis We extracted data of 1546 atezolizumab-treated patients from four multicentre clinical trials. In this study, patients from the OAK trial were taken for model training, whereas patients from the other trials were used for independent validations. The FP prediction model was developed using 21 pretreatment blood test variables in seven ML approaches. Prediction performance was evaluated by the receiver operating characteristic (ROC) curve.Results The prevalence of FP was 7.6% (118 of 1546) in all atezolizumab-treated patients. The most important variables for the prediction model were: C reactive protein, neutrophil count, lactate dehydrogenase and alanine transaminase. The Support Vector Machine (SVM) algorithm applied to these four blood test parameters demonstrated good performance: the area under the ROC curve obtained from the training cohort (OAK), validation cohort 1 (BIRCH) and cohort 2 (merged POPLAR and FIR) were 0.908, 0.666 and 0.776, respectively. In addition, the absolute difference in median survival between the SVM-predicted FP and non-FP groups was significant in both progression-free survival and overall survival (p

Abstract SAR439459 (SAR'459), a “second‐generation” human anti‐transforming growth factor beta (TGFβ) monoclonal antibody, enhances the activity of immune checkpoint inhibitors. In this phase I/Ib study, we evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of SAR'459 ± cemiplimab (intravenous) in patients with advanced solid tumors. Increasing doses of SAR'459 were administered every 2 or 3 weeks (Q2W, Q3W) alone (Part 1A) or with 3 mg/kg cemiplimab Q2W or 350 mg Q3W (Part 1B). In Part 2A (dose expansion), melanoma patients were randomly (1:1) administered 22.5 or 7.5 mg/kg SAR'459. In Part 2B (dose expansion), 22.5 mg/kg SAR'459 and 350 mg cemiplimab Q3W were administered. The primary end points were maximum tolerated dose (MTD) or maximum administered dose (MAD; Part 1), preliminary antitumor activity (Part 2B), and optimal monotherapy dose (Part 2A). Twenty‐eight and 24 patients were treated in Parts 1A and 1B, respectively; MTD was not reached, MAD was 15 (Q2W) and 22.5 mg/kg (Q3W) alone and in combination, respectively. Fourteen and 95 patients, including 14 hepatocellular carcinoma (HCC) patients, were treated in Parts 2A and 2B, respectively. The population PK model yielded satisfactory goodness‐of‐fit plots and adequately described the observed data by a two‐compartment PK model with linear elimination. Objective responses were not observed in Parts 1 and 2A. In Part 2B, objective response rate was 8.4% and 7.1% across tumor types and the HCC cohort, respectively. The most frequent treatment‐emergent adverse effects were hemorrhagic events (43.5%), keratoacanthoma (6.8%), and skin neoplasms (6.2%). Fatal bleeding occurred in 21.4% HCC patients despite the implementation of mitigation measures. SAR'459 monotherapy and combination with cemiplimab appeared relatively safe and tolerable in limited number of patients in dose escalation. However, the study was discontinued due to the unclear efficacy of SAR'459 and bleeding risk, particularly in HCC patients.

The switch defective/sucrose non-fermentable (SWI/SNF) multisubunit complex plays an important role in the regulation of gene expression by remodeling chromatin structure. Three SWI/SNF complexes have been identified in Arabidopsis including BAS, SAS, and MAS. Many subunits of these complexes are involved in controlling plant development and stress response. However, the function of these complexes has hardly been studied in other plant species. In this study, we identified the subunits of the SWI/SNF complex in sorghum and analyzed their evolutionary relationships in six grass species. The grass species conserved all the subunits as in Arabidopsis, but gene duplication occurred diversely in different species. Expression pattern analysis in sorghum (Sorghum bicolor) showed that most of the subunit-encoding genes were expressed constitutively, although the expression level was different. Transactivation assays revealed that SbAN3, SbGIF3, and SbSWI3B possessed transactivation activity, which suggests that they may interact with the pre-initiation complex (PIC) to activate transcription. We chose 12 subunits in sorghum to investigate their interaction relationship by yeast two-hybrid assay. We found that these subunits displayed distinct interaction patterns compared to their homologs in Arabidopsis and rice. This suggests that different SWI/SNF complexes may be formed in sorghum to perform chromatin remodeling functions. Through the integrated analysis of MNase-seq and RNA-seq data, we uncovered a positive relationship between gene expression levels and nucleosome phasing. Furthermore, we found differential global nucleosome enrichments between leaves and roots, as well as in response to PEG treatment, suggesting that dynamics of nucleosome occupancy, which is probably mediated by the SWI/SNF complex, may play important roles in sorghum development and stress response.

Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, occupies a pivotal role in Asian traditional medicine and cuisine. The aerial parts and underground stems of H. cordata exhibit remarkable chemical diversity, particularly in essential oil. Nevertheless, the mechanisms regulating essential oil biosynthesis in H. cordata remain unclear. In this study, we present a quantitative overview of the proteomes across four tissues (flower, stem, leaf, and underground stem) of H. cordata, achieved through the application of the isobaric tag for relative and absolute quantitation (iTRAQ). Our research findings indicate that certain crucial ribosomal proteins and their interactions may significantly impact the production of essential oils in H. cordata. These results offer novel insights into the roles of ribosomal proteins and their associations in essential oil biosynthesis across various organisms of H. cordata.

Abstract Very low‐frequency earthquakes (VLFs) are characterized by longer source duration and smaller stress drop than regular earthquakes of similar magnitude. Recent studies have shown their frequent correlation with low‐frequency earthquakes (LFEs) on shared faults. The underlying source processes governing the occurrence of VLFs and their interaction with LFEs remain elusive. Here, we employ a slip‐weakening model for slow earthquakes. By comparing the source parameters of simulations and observations, it is suggested that VLFs are slow self‐arresting earthquakes that self‐terminate within the nucleation patch. Additionally, we adopt a composite model to reproduce the records of the simultaneous occurrences of a VLF and an LFE in the Nankai area. Our results present the possibility that VLFs, LFEs, and regular earthquakes can be distinguished using a unified dynamic framework.

The physical characteristics of analog ICs are intricate, leading to prolonged design and development cycles. Currently, the automatic optimization of analog integrated circuit size heavily relies on simulations, which unfortunately results in a significant waste of simulation resources during the optimization process. To address this issue, this paper introduces a novel optimization framework named “MODE-CNN”, which integrates Multi-Objective Differential Evolution (MODE) algorithm and Convolutional Neural Network (CNN) surrogate models. The MODE-CNN framework is designed to reduce unnecessary consumption of simulation resources while maintaining high optimization accuracy. Within the MODE-CNN framework, we first enhance the predictive capabilities of the surrogate models using Latin Hypercube Sampling and Quantile Transformation. Subsequently, we employ CNN surrogate models to evaluate circuit performance during the optimization process, effectively screening out promising designs and substantially reducing the number of simulations required. Moreover, we propose an improved fast non-dominated sorting method that further enhances the global optimization performance of the MODE algorithm. Through testing on three circuit design cases and comparing MODE-CNN with existing mainstream methods and expert manual designs, we find that MODE-CNN not only significantly reduces the number of simulations (by up to 63%), but also surpasses traditional methods in optimization outcomes, with performance improvements of up to 95.09% for TC and 58.75% for LS. The experimental results validate the effectiveness and advancement of the MODE-CNN framework in the optimization of analog integrated circuits.

L-band advanced land observing satellite-2 (ALOS-2) images are a good source of radar data with better coherence than C-band images. However, significant ionospheric effects are often associated with L-band interferograms. In addition, the tropospheric delay can also be severe in subtropical coastal environments. In this work, different methods are adopted, adapted, or proposed to evaluate the tropospheric signals in ALOS-2 interferograms in the Shenzhen region. Ionospheric effects are estimated by the split spectrum method. Tropospheric delays are estimated through their height dependence or numerical weather prediction models. In addition to the conventional weighting methods that consider distance, variation, and Gaussian models, a stepwise approach to estimate tropospheric signals from height or to scale numerical weather models is proposed in this study. A combination of spectrometer observation and air mass trajectories is also proposed to assess topography-independent tropospheric signals, specifically the moderate resolution imaging spectroradiometer (MODIS) water vapor fields and the Hybrid Single-Particle Lagrangian Integrated Trajectory model. Meanwhile, possible cloud and wind patterns are observed from interferogram. This work demonstrates the feasibility of stepwise estimation of stratified signals using height information or numerical weather models. It also shows the potential for air mass trajectories to move water vapor fields to mitigate the influence of time difference between SAR and spectrometer acquisition times.

Abstract Background Lung cancer is a malignant tumor with the highest mortality worldwide. Abnormalities in the ubiquitin proteasome system are considered to be contributed to lung cancer progression with deleterious effects. DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor of the E3 ubiquitin ligase CRL4, but its role in lung cancer remains unknown. In this study, we aimed to investigate the regulatory mechanisms of DCAF13 in lung adenocarcinoma (LUAD). Methods So as to investigate the effect of DCAF13 on lung adenocarcinoma cell function using in vivo and in vitro. Mechanistically, we have identified the downstream targets of DCAF13 by using RNA-sequencing, as well as ubiquitination assays, co-immunoprecipitation, immunofluorescence, immunohistochemistry and chromatin immunoprecipitation - qPCR experiments. Results Our findings reveal that DCAF13 is a carcinogenic factor in LUAD, as it is highly expressed and negatively correlated with clinical outcomes in LUAD patients. Through RNA-sequencing, it has been shown that DCAF13 negatively regulates the p53 signaling pathway and inhibits p53 downstream targets including p21, BAX, FAS, and PIDD1. We also demonstrate that DCAF13 can bind to p53 protein, leading to K48-linked ubiquitination and degradation of p53. Functionally, we have shown that DCAF13 knockdown inhibits cell proliferation and migration. Our results highlight the significant role of DCAF13 in promoting LUAD progression by inhibiting p53 protein stabilization and the p53 signaling pathway. Furthermore, our findings suggest that high DCAF13 expression is a poor prognostic indicator in LUAD, and DCAF13 may be a potential therapeutic target for treating with this aggressive cancer. Conclusions The DCAF13 as a novel negative regulator of p53 to promote LUAD progression via facilitating p53 ubiquitination and degradation, suggesting that DCAF13 might be a novel biomarker and therapeutical target for LUAD.

The combination of nano sizes, large pore sizes and green synthesis is recognized as one of the most crucial and challenging problems in constructing metal-organic frameworks (MOFs). Herein, a water-based strategy is proposed for the synthesis of nanoscale hierarchical MOFs (NH-MOFs) with high crystallinity and excellent stability. This approach allows the morphology and porosity of MOFs to be fine tuned, thereby enabling the nanoscale crystal generation and a well-defined hierarchical system. The aqueous solution facilitates rapid nucleation kinetics, and the introduced modulator acts as a deprotonation agent to accelerate the deprotonation of the organic ligand as well as a structure-directing agent (SDA) to guide the formation of hierarchical networks. The as-synthesized NH-MOFs (NH-ZIF-67) were assessed as efficient adsorbents and heterogeneous catalysts to facilitate the diffusion of guest molecules, outperforming the parent microZIF-67. This study focuses on understanding the NH-MOF growth rules, which could allow tailor-designing NH-MOFs for various functions.

Abstract Considering the continuous advances in the synthesis and clinical applications of monoclonal antibodies (mAbs), precision therapies that employ mAbs are essential. In recent years, extensive efforts have been invested in developing novel strategies or technologies for detection of mAbs. Given the availability of advanced biosensing materials, various assemblies of multifunctional materials can be prepared by intelligent design when evaluating targets for mAbs. This article provides an overview of the recent advances and functional applications of biosensing materials for mAb detection. Subsequently, we present the approaches by which mAb receptors are combined with materials to construct stimulus‐responsive analytical platforms that evaluate the contents and activities of mAbs in biological systems, enabling real‐time monitoring and diagnosis that could facilitate administration of mAbs during treatment. Furthermore, the review examines various applications of biosensing for mAb detection and implications in real‐world contexts; it also discusses ongoing challenges and future prospects.

Abstract The 180° curvature of the Banda arc at the eastern end of the Java‐Banda subduction zone reflects complicated geodynamic processes. A detailed investigation of its anisotropic structure would reveal its subduction dynamics, further resolving the controversial issue on how the highly arcuate Banda arc formed. We apply tilting‐axis anisotropic tomography to obtain a high‐resolution 3‐D anisotropic model beneath the Java‐Banda region. Our results show significant differences between Java and Banda in the pattern of anisotropy in both the subducting slab and its surrounding mantle, which reflect two distinctly different deformation modes in the two domains. Our results support the single‐slab subduction model for the Banda region. In addition, trench‐normal and upright fast‐velocity‐planes appear in the deep upper mantle, which may indicate material migrations in the big mantle wedge. Fast‐velocity‐planes in the shallow mantle exhibit a toroidal distribution, reflecting past counter‐clockwise rotation and asthenospheric material extrusion.

Environmental DNA (eDNA) technology has emerged as a valuable tool for monitoring species distribution, assessing aquatic biodiversity and fish biomass. This study aimed to investigate the relationship between eDNA and the biomass of Gnathanodon speciosus (G. speciosus) using quantitative Polymerase Chain Reaction (qPCR) technology. Specific primers were designed for the target species. Water samples were collected from three differently-sized aquariums located at Qingdao Polar Ocean Park between July 2022 and March 2023. The results demonstrated a modest correlation between total biomass and eDNA concentration (Pearson, r = 0.74, p 0.05). This preliminary study lays the groundwork for monitoring and assessing the biomass of G. speciosus. This study also provides valuable insights into quantifying the relationship between environmental DNA and biomass, establishing a crucial theoretical framework for future assessments of open-sea fisheries resources through environmental DNA analysis.

Seismic waves generated by an earthquake can produce dynamic perturbations in the Earth’s gravity field before the direct arrival of P-waves. Observations of these so-called prompt elasto-gravity signals by ground-based gravimeters and broadband seismometers have been reported for some large events, such as the 2011 MW9.1 Tohoku earthquake. Recent studies have introduced prompt gravity strain signals (PGSSs) as a new type of observable seismic gravity perturbation that can be used to measure the spatial gradient of the perturbed gravity field. Theoretically, these types of signals can be recorded by in-development instruments termed gravity strainmeters, although no successful detection has been reported as yet. Herein, we propose an efficient approach for PGSSs based on a multilayered spherical Earth model. We compared the simulated waveforms with analytical solutions obtained from a homogeneous half-space model, which has been used in earlier studies. This comparison indicates that the effect of the Earth’s structural stratification is significant. With the help of the new simulation approach, we also demonstrated how the PGSSs depend on the magnitude of the seismic source. We further conducted synthetic tests estimating earthquake magnitude using gravity strain signals to demonstrate the potential application of this type of signal in earthquake early warning systems. These results provide essential information for future studies on the synthesis and application of earthquake-induced gravity strain signals.

As an important part of urban space, mountains play an extremely important role in the overall landscape and ecology of cities. However, with the continuous development of urbanization and building construction, mountains have been occupied and destroyed in unreasonable ways. Therefore, with the aim of reducing the damage to mountains from construction, this paper explores the design methods to deal with the relationship between buildings and mountainous environments. The historic district of Signal Hill in Qingdao is taken as the research area, since buildings here coexist with the mountainous environment harmoniously. Through the combination of modeling and field research, the slope of the mountain can be divided into three grades: “0–5.8°”, “5.8–11.7°” and “11.7–17.3°”. Therefore, the design characteristics and distribution patterns of 20 design methods that dealt with the mountainous environment in different slope grades can be obtained. Furthermore, by analyzing the design characteristics and distribution patterns, the relationship between the design methods and the slope of mountains can be found, providing more suitable design strategies for buildings located on different slopes of mountains. For other mountain cities worldwide, these rational strategies can provide some helpful design suggestions to better use terrain. It can also reduce the amount of construction volume and damage to the mountainous environment, and further better achieve sustainable development goals.

This paper proposes a novel neural network-based control algorithm with fixed-time performance constraints for manipulator systems in workspaces. The algorithm efficiently controls the manipulator’s trajectory tracking by tuning a preset performance function, thereby optimizing both speed and accuracy within a fixed timeframe. Initially, a tangent-type error transformation, applied through homogeneous embryonic transformation, ensures rapid convergence of tracking errors to a specific region. Subsequently, integrating a predetermined control strategy into the fixed-time stability framework ensures the system’s state reaches a defined boundary within a finite period. Lastly, neural networks are employed to approximate dynamic parameters and adjust the controller, achieving optimal parameter approximation and significantly enhancing trajectory tracking robustness. Simulation analyses and comparisons confirm the controller’s effectiveness and superiority in enhancing both the transient and steady-state performance of the control system.

High fracture strength and fracture toughness are vital requirements for the Al2O3/Al2O3 composites. This advanced structural material is composed of two-dimensional alumina fiber fabrics with porous alumina matrices. However, the Al2O3/Al2O3 composites exhibit low delamination resistance under shear stress. In this study, an as-fabricated Al2O3/Al2O3 composite was densified through a slurry infiltration and sintering (SIS) process. The SIS-cycle-dependent mechanical properties of the Al2O3/Al2O3 composites were investigated. The results showed that the matrix was strengthened, and the fibers were unaffected after SIS process. With increasing SIS cycles, the flexural and interlaminar shear strengths increased, whereas the fracture toughness decreased. The best performance was reached after six SIS cycles, which had a flexural strength of 414.7 ± 41.6 MPa, an interlaminar shear strength of 25.6 ± 3.1 MPa, and a fracture toughness of 11.0 ± 0.3 MPa m1/2. The different changes in fracture strength and fracture toughness with the SIS cycles were attributed to matrix densification and enhanced interfacial bonding. The SIS process has the potential to improve the strength without sacrificing the damage tolerance.

This work reports that the plastic deformation mechanism of lamellar microstructure (LM) in Ti-43.5Al-4Nb-1Mo-0.1B (TNM) alloy transforms from stacking faults (SFs)-dominated process to long-period stacking ordering (LPSO) structures-mediated process with a slight increase in lamellar spacing (LS) (20–36 nm). Multiple LPSO bands significantly enhance the work hardening response and trigger the transformation-induced plasticity (TRIP) effect, causing a four-fold higher ductility than SF-deformed LM at 750°C without compromising yield strength (YS). This phenomenon provides novel insights into the development of high-performance TiAl alloys with extremely nano-LM (LS

Abstract The location and origin of Neoproterozoic‐Cambrian sutures provide keys to understand the formation and evolution of the supercontinent Gondwana. The Larsemann Hills is located near a major Neoproterozoic‐Cambrian suture zone in the Prydz Belt, but has not been examined locally by comprehensive geophysical studies. In this study, we analyzed data collected from a one‐dimensional (1D) joint seismic‐MT array deployed during the 36th Chinese National Antarctic Research Expedition. We found that a sharp Moho discontinuity offset of 6–8 km shows up in the stacked image of teleseismic P‐wave receiver function analysis; coinciding with the abrupt Moho offset, a near‐vertical channel with (a) low resistivity extending to the uppermost mantle depths, and (b) high crustal Poisson's ratio in the crust is identified. These findings provide evidence for the determination of the location and collisional nature of the Prydz belt or a portion of it.

Abstract The core‐mantle boundary (CMB) marks the most dramatic changes in physical properties within the Earth, and plays a critical role in the understanding of the Earth's dynamics. PmKP waves are seismic phases that reflect (m − 1) times under the CMB and are useful for studying the complex CMB structure. We present an automated workflow for detecting PmKP phases using multi‐station records from global seismic stations. We employ a novel sampling method to extract PmKP waveforms into a 2‐D matrix. Two deep neural networks are then utilized for initial phase detections and subsequent slowness validations. Numerous PmKPab (3 ≤ m ≤ 7) and their CMB diffracted signals were identified for deep earthquakes (magnitude >6) occurred from 2000 to 2020, including diffracted P7KPab waves with diffraction lengths of nearly 20°. Our approach significantly improves the efficiency of PmKP phase identification and holds the capability to detect other weak core phases, such as PKiKP.

Abstract Monitoring tumor biomarkers in a non‐invasive manner for tumor diagnosis has attracted increasing attention. Liquid biopsy mainly includes three types of biomarkers: circulating tumor cells, extracellular vesicles, and circulating nucleic acids. These biomarkers released by tumor cells can travel to other parts of the circulation system. The analysis of circulating tumor markers in the circulation enables early tumor diagnosis, progression evolution, and treatment monitoring, which are important for individualized clinical decisions. In this study, we summarize different DNA nanotechnology strategies that can be used to capture, amplify, and measure circulating biomarkers and discuss the current challenges and outlook.

Drought stress is the key factor limiting soybean yield potential. Soybean seed formation involves a coordinated “subtending leaf-podshell-seed” process, but little is known about the assimilation and transport of photoassimilates in subtending leaves, podshells and seeds or their relationships with soybean seed formation under drought stress. To address these research gaps, two-year experiments with two soybean cultivars, Wandou 37 (drought tolerant) and Zhonghuang 13 (drought sensitive), were conducted under three soil water content (SWC) conditions in 2020 and 2021 based on the responses of their yield to drought. We analyzed the photosynthetic assimilation and translocation of photoassimilates in subtending leaves, podshells and seeds by stable isotope labeling. Compared with those under 75% SWC, 60% SWC and 45% SWC significantly decreased the Wandou 37 seed weight by 19.4% and 37.5%, respectively, and that of Zhonghuang 13 by 26.9% and 48.6%, respectively. Compared with those under 75% SWC, drought stress decreased the net photosynthetic rate and the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SuSy), which in turn decreased the photosynthetic capacity of the subtending leaves. The podshells ensure the input of photoassimilates by increasing the SuSy activity, but the weakened source–sink relationship between podshells and seeds under drought stress leads to a decrease in the translocation of assimilates from podshells to seeds. The lack of assimilates under drought stress is an important factor restricting the development of soybean seeds. We conclude that the decrease in seed weight was caused by the decrease in the photosynthetic capacity of the subtending leaves and the decrease in the overall availability of photoassimilates; moreover, by a decrease in the translocation of assimilates from podshells to seeds.

Background To evaluate the procedural pain experienced by neonates in a neonatal intensive care unit (NICU) setting and determine the corresponding pain grades.Methods Two experienced nurses independently used the Neonatal Infant Pain Scale (NIPS) to evaluate the neonatal pain during procedures taking place in the tertiary NICU and two level-two neonatal care units in the Children’s Hospital of Zhejiang University School of Medicine. The mean and distribution of NIPS pain scores and the corresponding pain grades of participants when experiencing clinical painful procedures were analysed.Results A total of 957 neonates exposed to 15 common clinical painful procedures were included in the study. The clinical painful procedures experienced by 957 participants could be divided into three groups: severe pain (NIPS score 5–7: peripheral intravenous cannulation, arterial catheterisation, arterial blood sampling, peripherally inserted central catheter placement and nasopharyngeal suctioning), mild to moderate pain (NIPS score 3–4: finger prick, intramuscular injection, adhesive removal, endotracheal intubation suctioning, heel prick, lumbar puncture and subcutaneous injection) and no pain to mild pain (NIPS score 0–2: gastric tube insertion, enema and intravenous injection).Conclusions The neonatal pain response to clinical procedures in NICU had certain pattern and preintervention drug analgesia could be taken for painful procedures with clustered high NIPS pain scores. Meanwhile, full coverage non-drug pain relief measures could be taken for procedures that are with scattered pain scores, and real-time pain evaluation should be provided to determine whether further drug analgesia is required.

Abstract Various plants, including sorghum (Sorghum bicolor L.), are exposed to waterlogging; however, little is known about the effects of waterlogging at different growth stages on sorghum. A pot experiment was conducted using two sorghum hybrids, Jinuoliang 01 (JN01) and Jinza 31 (JZ31), to investigate the effects of waterlogging at different growth stages on the photosynthesis enzyme activity, chlorophyll content, malondialdehyde (MDA) content, photosynthetic parameters, dry matter accumulation, and grain yield. The experiment was conducted using waterlogging treatments implemented at the five-leaf stage (T1), flowering stage (T2), and filling stage (T3), using standard management (no waterlogging) as a control (CK). The adverse effects of waterlogging on sorghum growth varied with the waterlogging timing, with the maximum impact at T1, followed by T2 and T3. JZ31 was more sensitive to waterlogging compared to JN01. Waterlogged conditions inhibited the photosynthetic enzyme activity and reduced the chlorophyll content and photosynthesis, ultimately lowering the biomass yield and grain yield. The maximum yield loss was observed with the T1 waterlogging treatment; the grain yield of JN01 and JZ31 decreased by 52.01–54.58% and 69.52–71.97%, respectively, compared with CK. Furthermore, the decline in grain yield in T1 was associated with reducing grain number per panicle. These findings indicate that sorghum is sensitive to waterlogging at the five-leaf stage and JZ31 is more sensitive to waterlogging than JN01, which may provide a basis for selecting genotypes and management measures to cope with waterlogging in sorghum.

Abstract Background Stool DNA test has been emerged as an effective noninvasive method for colorectal cancer (CRC) screening, but the real‐world performance of stool DNA test in Chinese population has rarely been reported. Methods A total of 36,527 subjects were recruited in Haining City from January 2021 to December 2021. Participants underwent primary screening by taking both two‐samples fecal immunochemical tests (FITs) and high‐risk factor questionnaire (HRFQ), and those who tested either positive by FITs or evaluated to be high risk by HRFQ were recommended to undertake subsequent stool DNA test and colonoscopy. Results Of 36,527 participants, 34,778 (95%) completed both HRFQ and FITs, 9947 (29%) showed positive results during primary screening, and the colonoscopy compliance rate was 49%. Of primary screening positives, 8733 (88%) completed stool sample collections, and colonoscopy results from 4293 eligible participants were used for analyzing the performance of stool DNA test. The sensitivities for detecting CRC and advanced adenomas (AA) were 100% (95% CI: 60–100%) and 40% (95% CI: 34–46%), and the area under curve (AUC) was 0.961 (95% CI:0.954–0.967) and 0.625 (95% CI: 0.609–0.641), respectively. The specificity of stool DNA test was 84% (95% CI: 82–85%). The false‐positive rate for stool DNA test is about 10% less than that of primary screening. Conclusion Stool DNA test is a cost‐effective and promising alternative strategy for CRC screening in China.

Abstract Objective This study aims to examine the impact of preoperative fibrinogen concentration on the short-term outcomes and hospital length of stay (LOS) of patients undergoing Coronary Artery Bypass Grafting (CABG). Methods Between January 2010 and June 2022, a retrospective analysis comprised 633 patients who sequentially received isolated, primary CABG. These patients were categorized into normal fibrinogen group (fibrinogen

Quercetin (QR) is a natural flavonol compound widely distributed in the plant kingdom with extensive pharmacological effects. To find the potential clinical indications of QR, 156 differentially expressed genes (DEGs) regulated by QR were obtained from the Gene Expression Omnibus database, and new potential pharmacological effects and clinical indications of QR were repurposed by integrating compounds with similar gene perturbation signatures and associated-disease signatures to QR based on the Connectivity Map and Coexpedia platforms. The results suggested QR has mainly potential therapeutic effects on multiple sclerosis (MS), osteoarthritis, type 2 diabetes mellitus, and acute leukemia. Then, MS was selected for subsequent animal experiments as a representative potential indication, and it found that QR significantly delays the onset time of classical MS model animal mice and ameliorates the inflammatory infiltration and demyelination in the central nervous system. Combined with network pharmacology technology, the therapeutic mechanism of QR on MS was further demonstrated to be related to the inhibition of the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-17A, and IL-2) related to TNF-α/TNFR1 signaling pathway. In conclusion, this study expanded the clinical indications of QR and preliminarily confirmed the therapeutic effect and potential mechanism of QR on MS.

Synthetic framework materials are appealing candidates for the fabrication of separation membranes but realizing precise control of aperture distribution and separation threshold remains challenging. Here, the authors show a two-dimensional processible supramolecular framework which can be used in the fabrication of separation membranes by integrating directional organic host-guest motifs and inorganic functional polyanionic clusters.

Therapeutic drug monitoring (TDM) has played an important role in clinical medicine for precise dosing. Currently, chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy. However, some problems still exist in practical applications, such as complicated operation and the influence of endogenous substances. Surface plasmon resonance (SPR) has been applied to detect the concentrations of small molecules, including pesticide residues in crops and antibiotics in milk, which indicates its potential for in vivo drug detection. In this study, a new SPR-based biosensor for detecting chloramphenicol (CAP) in blood samples was developed and validated using methodological verification, including precision, accuracy, matrix effect, and extraction recovery rate, and compared with the classic ultra-performance liquid chromatography-ultraviolet (UPLC-UV) method. The detection range of SPR was 0.1–50 ng/mL and the limit of detection was 0.099 ± 0.023 ng/mL, which was lower than that of UPLC-UV. The intra-day and inter-day accuracies of SPR were 98%–114% and 110%–122%, which met the analysis requirement. The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples; moreover, the SPR biosensor has better sensitivity. Therefore, the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.

Wrist pulse is one kind of biomedical signals, it is affected not only by the heart beatings, but also by the conditions of nerves, organs, muscles, skin, etc. Therefore, wrist pulse signals can reflect a person's physical state and it has been widely used in health status analysis. However, previous works mainly use traditional machine learning methods to analyze wrist pulse signal. Because wrist pulse signal is high-dimensional and complex, it is difficult for traditional machine learning methods to learn effective information from them. This study aims to explore the utilizing of deep learning methods on wrist pulse signal analysis. We propose a novel multi-kernel Convolutional Neural Network for wrist pulse signal classification. Our model can handle multiple kinds of input features and each of them will pass through a convolutional neural network that has three different sizes of convolution kernel to capture multi-scale information in different time steps. We compare our method with traditional machine learning methods on two tasks: Coronary Atherosclerotic Heart Disease Classification and Traditional Chinese Medicine Constitution yin deficiency and yang deficiency Classification. Besides, we also research the influence of different input features and different channels on wrist pulse signal analysis. The results show that our model significantly improves the performance on the two tasks, which proves the deep learning method is more suitable to deal with complex wrist pulse data.

Astragali Radix (AR) is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer (NK) cells. However, owing to the complexity of its composition, the specific active ingredients in AR that act on NK cells are not clear yet. Cell membrane chromatography (CMC) is mainly used to screen the active ingredients in a complex system of herbal medicines. In this study, a new comprehensive two-dimensional (2D) NK-92MI CMC/C18 column/time-of-flight mass spectrometry (TOFMS) system was established to screen for potential NK cell activators. To obtain a higher column efficiency, 3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column. In total, nine components in AR were screened from this system, which could be washed out from the NK-92MI/CMC column after 10 min, and they showed good affinity for NK-92MI/CMC column. Two representative active compounds of AR, isoastragaloside I and astragaloside IV, promoted the killing effect of NK cells on K562 cells in a dose-dependent manner. It can thus suggest that isoastragaloside I and astragaloside IV are the main immunomodulatory components of AR. This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

ABSTRACT: Objectives: This study aimed to evaluate the efficacy and safety of ceftolozane/tazobactam (C/T) plus metronidazole versus meropenem plus placebo for the treatment of complicated intra-abdominal infection (cIAI) in Chinese adult participants. Methods: In this phase III clinical trial (NCT03830333), Chinese adult participants with cIAI were randomized 1:1 to receive C/T plus metronidazole or meropenem plus placebo. The primary objective was to assess C/T plus metronidazole for noninferiority versus meropenem for clinical response rate at the test of cure (TOC; 28 ± 2 days after study start) visit in the clinically evaluable population. Secondary endpoints included clinical and microbiologic responses at the TOC and end-of-treatment (≤24 hours after last dose) visits and adverse event rates. Results: Clinical cure at the TOC visit in the clinically evaluable population was 95.2% and 93.1% for C/T plus metronidazole and meropenem, respectively (between-treatment difference: 2.1% [95% confidence interval: -4.7%, 8.8%]); thus, noninferiority was met. Clinical responses at the TOC and end-of-treatment visits and microbiologic responses at the TOC visit were consistent with the primary efficacy endpoint. Safety was comparable between study treatment groups. Conclusion: In Chinese adult participants with cIAI, C/T plus metronidazole was noninferior to meropenem, with comparable safety.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with KD values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl4-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

Abstract The 2016 Mw 5.9 Menyuan earthquake occurred near the Haiyuan fault system in the northeastern Tibetan plateau. Although some kinematic properties of this event have been investigated, more dynamic properties still need to be clarified. First, we use the empirical Green's function method to obtain this event's apparent source time functions (ASTFs), which present a bell shape with a duration of 3s and corresponding smooth spectra. We then conduct dynamic rupture simulations, which are well constrained by the seismic and geodetic observations, to explore more in‐depth source properties. The results show that the characteristics of ASTFs can be explained by the self‐arresting rupture model, which implies that the rupture propagation of this event may spontaneously terminate before reaching the barriers. This result suggests that the initial conditions when this earthquake nucleated may have controlled the rupture process. Our work contributes to understanding the stopping mechanism of some moderate earthquake ruptures.

Abstract We simulated the rupture dynamics and ground motion of the 1850 Xichang, China, earthquake on the Zemuhe fault, which consists of the Lijinbao segment, the Dajing segment, the Chechejie segment, and the Songxin segment, with the curved grid finite‐difference method, and compared the simulation results with the field observed data and written records inferred data. We focused on the rupture extent of this earthquake and the effects of the maximum principal stress azimuth and nucleation location on the rupture process and the corresponding damage distribution. Numerical simulation results suggest that the regional maximum principal stress orientation that surrounds the Zemuhe fault was approximately N55°W, which is identical with the azimuth from the stress relief experiment in the neighboring area. Our simulations further imply that the nucleation location is under Lanbiluo. The simulation of this preferred nucleation location model suggests that the rupture propagated through the entire Dajing segment and the Chechejie segment, and the rupture gradually arrested at shallow depths after it transferred to the Lijinbao segment and the Songxin segment. Moreover, the simulation suggests that the rupture on the Chechejie segment was initiated at the surface and then mainly propagated downward due to the free surface effect. In addition, the Xichang earthquake may have exhibited a low rupture velocity on the Dajing segment. Furthermore, our simulation results emphasize the importance of the stepover width in the earthquake dynamics.

ObjectivesThis study aimed to construct and validate a predictive risk model (PRM) for nosocomial infections with multi-drug resistant organism (MDRO) in neonatal intensive care units (NICUs), in order to provide a scientific and reliable prediction tool, and to provide reference for clinical prevention and control of MDRO infections in NICUs.MethodsThis multicenter observational study was conducted at NICUs of two tertiary children’s hospitals in Hangzhou, Zhejiang Province. Using cluster sampling, eligible neonates admitted to NICUs of research hospitals from January 2018 to December 2020 (modeling group) or from July 2021 to June 2022 (validation group) were included in this study. Univariate analysis and binary logistic regression analysis were used to construct the PRM. H-L tests, calibration curves, ROC curves and decision curve analysis were used to validate the PRM.ResultsFour hundred and thirty-five and one hundred fourteen neonates were enrolled in the modeling group and validation group, including 89 and 17 neonates infected with MDRO, respectively. Four independent risk factors were obtained and the PRM was constructed, namely: P = 1/ (1+ e−X), X = −4.126 + 1.089× (low birth weight) +1.435× (maternal age ≥ 35 years) +1.498× (use of antibiotics >7 days) + 0.790× (MDRO colonization). A nomogram was drawn to visualize the PRM. Through internal and external validation, the PRM had good fitting degree, calibration, discrimination and certain clinical validity. The prediction accuracy of the PRM was 77.19%.ConclusionPrevention and control strategies for each independent risk factor can be developed in NICUs. Moreover, clinical staff can use the PRM to early identification of neonates at high risk, and do targeted prevention to reduce MDRO infections in NICUs.

As chloride (Cl−) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl− improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl− affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl− participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.

Abstract Nitrogen is an essential core element in walnut seedling growth and development. However, nitrogen starvation and excessive nitrogen stress can cause stunted growth and development of walnut seedlings, and environmental pollution is also of concern. Therefore, it is necessary to study the mechanism of walnut seedling resistance to nitrogen stress. In this study, morphological and physiological observations and transcriptome sequencing of walnut seedlings under nitrogen starvation and excess nitrogen stress were performed. The results showed that walnut seedlings under nitrogen starvation and excess stress could adapt to the changes in the nitrogen environment by changing the coordination of their root morphology and physiological indexes. Based on an analysis of transcriptome data, 4911 differential genes (DEGs) were obtained (2180 were upregulated and 2731 were downregulated) in a comparison of nitrogen starvation and control groups. A total of 9497 DEGs (5091 upregulated and 4406 downregulated) were obtained in the comparison between the nitrogen overdose and control groups. When these DEGs were analysed, the differential genes in both groups were found to be significantly enriched in the plant’s circadian pathway. Therefore, we selected the circadian rhythm as the focus for further analysis. We made some discoveries by analysing the gene co-expression network of nitrogen metabolism, circadian rhythm, and hormone signal transduction. (a) Nitrite nitrogen (NO2 −) or Glu may act as a nitrogen signal to the circadian clock. (b) Nitrogen signalling may be input into the circadian clock by regulating changes in the abundance of the CRY1 gene. (c) After the nitrogen signal enters the circadian clock, the expression of the LHY gene is upregulated, which causes a phase shift in the circadian clock. (d) The RVE protein may send information about the circadian clock’s response to nitrogen stress back to the nitrogen metabolic pathway via the hormone transduction pathway. In conclusion, various metabolic pathways in the roots of walnut seedlings coordinated with one another to resist the ill effects of nitrogen stress on the root cells, and these coordination relationships were regulated by the circadian clock. This study is expected to provide valuable information on the circadian clock regulation of plant resistance to nitrogen stress.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Objective: Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by a variety of genomic variations. Our aim is to identify the molecular basis of OCA in two families and lay the foundation for prenatal diagnosis.Methods: Four types of OCA-causing mutations in the TYR, p, TYRP1, or SLC45A2 genes were screened. Linkage analysis was performed because the mutations found in the p gene violated the laws of classical Mendelian heredity. Primer-walking sequencing combined with microsatellite and single-nucleotide polymorphism analysis was used to ascertain deletion ranges. Bioinformatics methods were used to assess the pathogenicity of the new mutations.Results: Proband 1 was diagnosed as OCA2 with Prader–Willi syndrome (PWS) due to a novel atypical paternal deletion (chromosome 15: 22330347–26089649) and a pathogenic mutation, c.1327G>A (Val443Ile), in the p gene of the maternal chromosome. The prenatal diagnosis results for family 1 indicated the fetus was a heterozygous carrier (c.1327G>A in the p gene) with a normal phenotype. Proband 2 was diagnosed as OCA2 with Angelman syndrome (AS) due to a typical maternal deletion of chromosome 15q11-q13 and a novel mutation, c.1514T>C (Phe505Ser), in the p gene of the paternal chromosome. This novel mutation c.1514T>C (Phe505Ser) in the p gene was predicted as a pathogenic mutation.Conclusion: Our study has shown clear genotype–phenotype correlations in patients affected by distinct deletions of the PWS or AS region and missense mutations in the p gene. Our results have enriched the mutation spectrum of albinism diseases and provided insights for more accurate diagnosis and genetic counseling.

The robust bounded control problem for the permanent magnet linear motors with inequality constraints is studied. Firstly, the dynamical model of the system is built, through the state transformation is used to satisfy the inequality constraint of the position output. Thus, the controller after the state transformation can ensure that the control output of the linear motor stays the desired range. Selecting the appropriate boundary function, and then the upper and lower bounds of the control output can be set according to our control requirements. The control scheme can guarantee uniform boundedness and uniform ultimate boundedness. The results of experiments and simulation show that the proposed algorithm can assure the control output within the desired range regardless of the uncertainty.

Meiotic recombination starts with the programmed formation of double-strand breaks (DSB) in DNA, which are catalyzed by SPO11, a type II topoisomerase that is evolutionarily conserved, and several other accessary proteins. Homologs of MEIOSIS INHIBITOR 4 (MEI4/REC24/PRD2) are proteins that are also essential for the generation of meiotic DSBs in budding yeast, mice and Arabidopsis thaliana. In Arabidopsis, the protein ARABIDOPSIS THALIANA PUTATIVE RECOMBINATION INITIATION DEFECTS 2/MULTIPOLAR SPINDLE 1 (AtPRD2/MPS1) has been shown to have additional roles in spindle assembly, indicating a functional diversification. Here we characterize the role of the rice MEI4/PRD2 homolog in meiosis. The osprd2 mutant was completely male and female sterile. In male meiocytes of osprd2, no γH2AX foci were detected and twenty-four univalents were produced at diakinesis, suggesting that OsPRD2 is essential for DSB generation. OsPRD2 showed a dynamic localization during meiosis. For instance, OsPRD2 foci first appeared as discrete signals across chromosome at leptotene, and then became confined to the centromeres during zygotene, suggesting that they might be involved in assembly of the spindle. However we did not observe any obvious aberrant morphologies in neither the organization of the bipolar spindle nor in the orientation of the kinetochore in the mutant. These findings suggest that in rice PRD2 might not be required for spindle assembly and organization, as it does in Arabidopsis. Taken together our results indicate that plant MEI4/PRD2 homologs do play a conserved role in the formation of meiotic DSBs in DNA, but that their involvement in bipolar spindle assembly is rather species-specific.

Deep seismic sounding (DSS) profiles are one of the most powerful tools for detecting crustal structures, and they have been deployed worldwide. Generally, the analysis of DSS data mainly focuses on body waves, while the surface waves are considered noise. We suggest that the surface waves in DSS data can be used to constrain subsurface structures. In this study, we use a DSS profile in the Piedmont and Atlantic Coastal Plain as an example to present the usage of the DSS surface wave. Multimodal dispersion curves were extracted from the DSS data with the Frequency-Bessel transform method, and were used in Monte Carlo joint inversions with body wave refraction traveltimes to constrain the shallow structures. Through the inversion, a horizontal stratum on the surface was identified in the Piedmont, and a two-layer sedimentary structure was identified in the Atlantic Coastal Plain. Comparisons with existing studies verified the accuracy of the shallow structures obtained in this study, demonstrating that the shallow velocity structure could be well constrained with the additional constraints provided by the multimodal dispersion curves. Thus, we believe that further research on the surface waves recorded in DSS surveys is warranted.

On 10 February 2021, an Mw 7.7 thrust earthquake ruptured the megathrust along the southeast Loyalty Islands within the strong bend in the plate boundary between the Australian plate and the North Fiji basin. The mainshock involved rupture with ∼50 s duration, with pure thrust slip concentrated in an east–west-trending slip patch with up to 4.2 m of slip extending from 10 to 25 km depth. Slip at depths

Purpose: The aim of the study was to investigate microcirculation changes in the macula evaluated by optical coherence tomography angiography (OCTA)in patients receiving anatomical repair after surgery for rhegmatogenous retinal detachment (RRD).Methods: A literature search was conducted in PubMed, EMBASE, Web of Science and the Cochrane Library. Studies including patients with macula-on or macula-off RRD and repaired successfully through primary surgery were selected. Foveal avascular zone (FAZ) area and macular vascular density (VD) in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed using RevMan 5.4 software.Results: Twelve studies including 430 RRD eyes and 430 control eyes were selected. In eyes with macula-on RRD, FAZ area, VD in the foveal SCP and DCP, and VD in the parafoveal SCP and DCP were not altered compared with control eyes, after the retina was reattached. In eyes with macula-off RRD that was repaired successfully through surgery, FAZ area in the DCP (0.13 mm2, 95% CI: 0.02 to 0.25, p = 0.02) remained enlarged compared with control eyes. Meanwhile, VD in the foveal DCP was also significantly reduced (−3.12%, 95% CI: −6.15 to −0.09%, p = 0.04), even though retinal reattachment was achieved by surgery in eyes with macula-off RRD.Conclusion: In patients with macula-off rhegmatogenous retinal detachment, foveal avascular zone area in the deep capillary plexuses was enlarged and vascular density in the foveal deep capillary plexus was reduced, even after the retina was successfully reattached through a primary surgery.

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF.Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF.Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the “Metabolite-Target-Component” interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically.Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.