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Abstract Oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane is a therapeutic target in many diseases. Neural stem cells (NSCs) show progress in improving mitochondrial dysfunction in the central nervous system (CNS). However, translating neural stem cell-based therapies to the clinic is challenged by uncontrollable biological variability or heterogeneity, hindering uniform clinical safety and efficacy evaluations. We propose a systematic top-down design based on membrane self-assembly to develop neural stem cell-derived oxidative phosphorylating artificial organelles (SAOs) for targeting the central nervous system as an alternative to NSCs. We construct human conditionally immortal clone neural stem cells (iNSCs) as parent cells and use a streamlined closed operation system to prepare neural stem cell-derived highly homogenous oxidative phosphorylating artificial organelles. These artificial organelles act as biomimetic organelles to mimic respiration chain function and perform oxidative phosphorylation, thus improving ATP synthesis deficiency and rectifying excessive mitochondrial reactive oxygen species production. Conclusively, we provide a framework for a generalizable manufacturing procedure that opens promising prospects for disease treatment.

Abstract Background Although early hemivertebra (HV) resection and short fusion (within 4 segments) have been successful in treating congenital HV, there is limited research comparing the outcomes of the shortest-segment fusion (2 segments) versus 3 or 4 segments, particularly in young children. To evaluate the efficacy of posterior hemivertebrectomy combined with two or more segments fusion in children under the age of 10 years with a solitary simple lower thoracic or lumbar HV (T8-L5). Methods This retrospective study included patients under the age of 10 with lower thoracic or lumbar solitary simple HV who underwent hemivertebra resection (HVR) and transpedicular short fusion and were divided into HV ± 1 group (2 segment fusion) and HV ± 2 group (3 or 4-segment fusion). The study recorded preoperative, postoperative (1 week), and the latest follow-up radiographic parameters and complications. The results of the coronal and sagittal planes were analyzed, and the main curve, segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift were compared. Results The study included 35 patients (15 in the HV ± 1 group and 20 in the HV ± 2 group) with a mean age of 5.26 ± 2.31 years and a mean follow-up of 22.54 months (12–68). The mean preoperative Cobb angle was 32.66° ± 7.339° (HV ± 1) and 29.31°±6.642° (HV ± 2). The final Cobb angle was 10.99°± 7.837° (HV ± 1) and 8.22° ± 4.295° (HV ± 2). The main curve corrected by 72% (HV ± 1), 75% (HV ± 2) postoperatively and 67% (HV ± 1), 72% (HV ± 2) at the final follow-up (P > 0.05). There were no significant differences in the correction of the segmental scoliosis curve, compensatory scoliosis curve, segmental kyphosis curve, and trunk shift between the HV ± 1 and HV ± 2 groups (P > 0.05). The unplanned reoperation rate for HV in the thoracolumbar region (T11-L2) is significantly higher (P = 0.038). Conclusion In the context of solitary simple lower thoracic or lumbar HV (T8-L5), HV ± 1 segment fusion suffices and yields comparable correction outcomes in the midterm period when compared to HV ± 2. The reoperation rate exhibited a statistically significant increase in the thoracolumbar region.

BackgroundScoliosis is a spinal deformity in which one or more spinal segments bend to the side or show vertebral rotation. Some artificial intelligence (AI) apps have already been developed for measuring the Cobb angle in patients with scoliosis. These apps still require doctors to perform certain measurements, which can lead to interobserver variability. The AI app (cobbAngle pro) in this study will eliminate the need for doctor measurements, achieving complete automation. ObjectiveWe aimed to evaluate the reliability and accuracy of our new AI app that is based on deep learning to automatically measure the Cobb angle in patients with scoliosis. MethodsA retrospective analysis was conducted on the clinical data of children with scoliosis who were treated at the Pediatric Orthopedics Department of the Children’s Hospital affiliated with Fudan University from July 2019 to July 2022. Three measurers used the Picture Archiving and Communication System (PACS) to measure the coronal main curve Cobb angle in 802 full-length anteroposterior and lateral spine X-rays of 601 children with scoliosis, and recorded the results of each measurement. After an interval of 2 weeks, the mobile AI app was used to remeasure the Cobb angle once. The Cobb angle measurements from the PACS were used as the reference standard, and the accuracy of the Cobb angle measurements by the app was analyzed through the Bland-Altman test. The intraclass correlation coefficient (ICC) was used to compare the repeatability within measurers and the consistency between measurers. ResultsAmong 601 children with scoliosis, 89 were male and 512 were female (age range: 10-17 years), and 802 full-length spinal X-rays were analyzed. Two functionalities of the app (photography and photo upload) were compared with the PACS for measuring the Cobb angle. The consistency was found to be excellent. The average absolute errors of the Cobb angle measured by the photography and upload methods were 2.00 and 2.08, respectively. Using a clinical allowance maximum error of 5°, the 95% limits of agreement (LoAs) for Cobb angle measurements by the photography and upload methods were –4.7° to 4.9° and –4.9° to 4.9°, respectively. For the photography and upload methods, the 95% LoAs for measuring Cobb angles were –4.3° to 4.6° and –4.4° to 4.7°, respectively, in mild scoliosis patients; –4.9° to 5.2° and –5.1° to 5.1°, respectively, in moderate scoliosis patients; and –5.2° to 5.0° and –6.0° to 4.8°, respectively, in severe scoliosis patients. The Cobb angle measured by the 3 observers twice before and after using the photography method had good repeatability (P

The increasing integration of renewable energy sources such as wind and solar into the distribution grid introduces new complexities and instabilities to traditional electrical grids. This study tackles these challenges by optimizing the configurations of Modular Mobile Battery Energy Storage (MMBES) in urban distribution grids, particularly focusing on capacity-limited areas. Our method investigates five core attributes of energy storage configurations and develops a model capable of adapting to the uncertainties presented by extreme scenarios. This approach not only enhances the adaptability of energy storage systems but also equips decision-makers with proactive and flexible tools for decision-making in complex environments. Empirical evidence from the study shows that modular mobile energy storage significantly improves distribution grid performance by effectively managing the challenges posed by renewable integration. Furthermore, the research confirms that optimizing decision-makers’ cognitive parameters to align with subjective preferences ensures economic viability and enhances grid resilience. This study offers a new perspective and methodology for configuring energy storage, contributing to more flexible and reliable grid operations amidst widespread renewable integration.

The recent rapid development of low Earth orbit (LEO) constellation-based navigation techniques has enhanced the ability of position, navigation, and timing (PNT) services in deep attenuation and interference environments. However, existing navigation modulations face the challenges of high acquisition complexity and do not improve measurement precision at the same signal strength. We propose a pulsed orthogonal time frequency space (Pulse-OTFS) signal, which naturally converts continuous signals into pulses through a special delay-Doppler domain pseudorandom noise (PRN) code sequence arrangement. The performance evaluation indicates that the proposed signal reduces at least 89.4% of the acquisition complexity. The delay measurement accuracy is about 8 dB better than that of the traditional binary phase shift keying (BPSK) signals with the same bandwidth. It also provides superior compatibility and anti-multipath performance. The advantages of fast acquisition and high-precision measurement are verified by processing the real signal in the developed software receiver. As Pulse-OTFS occupies only one time slot of a signal period, it can be easily integrated with OTFS-modulated communication signals and used as a navigation signal from broadband LEO satellites as an effective complement to the global navigation satellite system (GNSS).

Abstract The Earth’s interior and surficial systems underwent dramatic changes during the Paleoproterozoic, but the interaction between them remains poorly understood. Rocks deposited in orogenic foreland basins retain a record of the near surface to deep crustal processes that operate during subduction to collision and provide information on the interaction between plate tectonics and surface responses through time. Here, we document the depositional-to-deformational life cycle of a Paleoproterozoic foreland succession from the North China Craton. The succession was deposited in a foreland basin following ca. 2.50–2.47 Ga Altaid-style arc–microcontinent collision, and then converted to a fold-and-thrust belt at ca. 2.0–1.8 Ga due to Himalayan-style continent–continent collision. These two periods correspond to the assembly of supercratons in the late Archean and of the Paleoproterozoic supercontinent Columbia, respectively, which suggests that similar basins may have been common at the periphery of other cratons. The multiple stages of orogenesis and accompanying tectonic denudation and silicate weathering, as recorded by orogenic foreland basins, likely contributed to substantial changes in the hydrosphere, atmosphere, and biosphere known to have occurred during the Paleoproterozoic.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

Background:. NAFLD is highly prevalent with limited treatment options. Bile acids (BAs) increase in the systemic circulation and liver during NAFLD progression. Changes in plasma membrane localization and zonal distribution of BA transporters can influence transport function and BA homeostasis. However, a thorough characterization of how NAFLD influences these factors is currently lacking. This study aimed to evaluate the impact of NAFLD and the accompanying histologic features on the functional capacity of key hepatocyte BA transporters across zonal regions in human liver biopsies. Methods:. A novel machine learning image classification approach was used to quantify relative zonal abundance and plasma membrane localization of BA transporters (bile salt export pump [BSEP], sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptides [OATP] 1B1 and OATP1B3) in non-diseased (n = 10), NAFL (n = 9), and NASH (n = 11) liver biopsies. Based on these data, membrane-localized zonal abundance (MZA) measures were developed to estimate transporter functional capacity. Results:. NAFLD diagnosis and histologic scoring were associated with changes in transporter membrane localization and zonation. Increased periportal BSEPMZA (mean proportional difference compared to non-diseased liver of 0.090) and decreased pericentral BSEPMZA (−0.065) were observed with NASH and also in biopsies with higher histologic scores. Compared to Non-diseased Liver, periportal OATP1B3MZA was increased in NAFL (0.041) and NASH (0.047). Grade 2 steatosis (mean proportional difference of 0.043 when compared to grade 0) and grade 1 lobular inflammation (0.043) were associated with increased periportal OATP1B3MZA. Conclusions:. These findings provide novel mechanistic insight into specific transporter alterations that impact BA homeostasis in NAFLD. Changes in BSEPMZA likely contribute to altered BA disposition and pericentral microcholestasis previously reported in some patients with NAFLD. BSEPMZA assessment could inform future development and optimization of NASH-related pharmacotherapies.

This study reports coexisting Neoarchean divergent and convergent plate boundary rock assemblages, providing new evidence for the operation of plate tectonics 2.55–2.51 billion years ago; and also suggests the subduction zone was warm then.

Previous breakthroughs in biosensor diagnostics stem from engineering and nanocomposites. Accurately detecting low-abundance compounds such as methotrexate in complex biospecimens (e.g. serum) is an important clinical challenge. To address this issue, a MWCNTs-doped MXene-based multi-spiral-channel field-effect transistor (MMSFETs) biosensor was constructed for ultrasensitive quantification of methotrexate. Our integrated biosensor exhibited following merits: a) The synergetic performance of MXene and MWCNTs for enhanced transconductance (0.63 mS) and detection capability (methotrexate, linear range of 0.001–100 μM and LOD down to 0.352 nM); b) Favorable selectivity, stability (one month), reproducibility (RSD = 0.99%, n = 7) for biosensing of methotrexate; c) Acceptable clinical performances on comparisons of MMFETs against commercial Abbott automatic immunoluminescence instrument (ARCHITECT I1000): favorable linearity and correlation coefficient (YMMSFETs = 1.4305 × Xtargeted concentration + 4.3791 with R2 = 0.949), significant p value (7.68E-12

Statistical analysis and clustering of discontinuities existing in rock mass are the basis of rock mass engineering stability analysis. Considering that the mechanical and hydraulic properties of discontinuities are affected by many factors such as occurrence, trace length, aperture, roughness, and filling state, a multi-parameter dominant grouping method of rock mass discontinuities based on principal component analysis is proposed. Firstly, the principal component analysis method is used to select the criterion of the dominant grouping and calculate the weight value of its participation in similarity measurement. Secondly, the global optimal initial clustering center of the fuzzy C-means clustering algorithm is searched using the annealing genetic algorithm. Lastly, the objective function is established by minimizing the weighted sum of the distance between the discontinuities to be grouped and the clustering center, achieving the dominant grouping of multi-parameter rock mass discontinuity. Two hundred artificial discontinuities are divided into dominant groups using the multi-parameter method and the results are compared with other methods. The results show that this method has higher grouping accuracy. The method is applied to the multi-parameter dominant grouping of the measured discontinuities of Huayang Tunnel of Chongqing Third Ring Expressway. The grouping results are reasonable and reliable, which further verifies that the proposed method has a significant engineering application value.

Abstract Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. We discovered that culturing HuH-7 human hepatoma cells with dexamethasone (DEX) and 0.5% dimethyl sulfoxide (DMSO) for two weeks, with Matrigel overlay after one week, resulted in a shorter and improved differentiation process. These culture conditions increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and the bile salt export pump (BSEP), respectively, in two-week cultures of HuH-7 cells. This in vitro model was further characterized for expression and function of bile acid-metabolizing enzymes, transporters, and cellular bile acids. Differentiated HuH-7 cells displayed a marked shift in bile acid composition and induction of cytochrome P450 (CYP) 7A1, CYP8B1, CYP3A4, and bile acid-CoA: amino acid N-acyltransferase (BAAT) mRNAs compared to control. Inhibition of taurocholate uptake and excretion after a 24-h treatment with prototypical cholestatic drugs suggests that differentiated HuH-7 cells are a suitable model to examine cholestatic hepatotoxicity.

Currently voltage control and network loss caused by the integration of high-penetration of distributed generations are usually tackled out by means of reactive power compensation. However, there are fewer control methods that take into account distributed generations and energy storage systems. Based on the cooperation control of distributed generations and energy storage systems, this paper establishes a multi-objective optimal control model of the distribution network with the goals of minimizing voltage deviation, minimizing network power loss and maximizing the consumption of distributed generation. Combining harmony search algorithm and particle swarm optimization algorithm effectively, a harmony search-particle swarm optimal algorithm(HSA-PSO) is proposed to solve the established model. The simulation example verifies the effectiveness of the optimization control method.

Since Chinese government work report in 2010 put forward the content of strengthening the construction of smart grids, the construction of smart grids has become one of the important contents of the national development strategy. In the in-depth study of smart grids, the issue of security defense systems and disaster prevention frameworks has always been Research hotspots by scholars at home and abroad, but most of my country’s existing security defenses are aimed at large-scale interconnected systems such as transmission grids, and there is a lack of research on disaster prevention of distribution networks. Therefore, in this research context, this article starts from the perspective of multi-source information fusion, takes into account the uncertainty of distribution network information and other factors, constructs a distribution network disaster response resilience index system and a distribution network resilience assessment model, and uses accidents at the same time. The scenario optimization method improves the disaster warning capability of the distribution network, and provides a scientific basis for the distribution network to take active defense measures. Then, a coordinated defense evolution strategy for the distribution network considering the optimization of accident scenarios was established. This strategy takes limited resources as the constraint, takes the minimum load loss as the objective function, and considers the economics of strategy conversion. Power supply equipment output, load transfer, and switching linkage mechanism between the three load is established, forming islands of security, and network transfer, emergency coordination of the three islands of the distribution network evolution strategy of active defense. This strategy looks for a directional evolution path from real-time accident scenarios to defense strategies from both horizontal and vertical perspectives, and realizes the coordinated control of the distribution network’s active defense strategy locally and globally. Finally, this paper takes the ice disaster climate as an example for simulation verification to prove the comprehensiveness of the risk assessment model and the rationality of the security defense method, and prove that the defense strategy can meet the online adaptive evolution requirements of the active defense of the distribution network, while taking into account The local autonomy and global optimal coordinated control of the active defense of the distribution network make up for the shortcomings of the current active defense strategy and are of great significance to further improve the security defense level of the active distribution network.

Giant Axonal Neuropathy (GAN) is a pediatric neurodegenerative disease caused by loss-of-function mutations in the E3 ubiquitin ligase adaptor gigaxonin, which is encoded by the KLHL16 gene. Gigaxonin regulates the degradation of multiple intermediate filament (IF) proteins, including neurofilaments, GFAP, and vimentin, which aggregate in GAN patient cells. Understanding how IFs and their aggregates are processed under stress can reveal new GAN disease mechanisms and potential targets for therapy. Here we tested the hypothesis that hypotonic stress-induced vimentin proteolysis is impaired in GAN. In both GAN and control fibroblasts exposed to hypotonic stress, we observed time-dependent vimentin cleavage that resulted in two prominent ∼40–45 kDa fragments. However, vimentin proteolysis occurred more rapidly and extensively in GAN cells compared to unaffected controls as both fragments were generated earlier and at 4-6-fold higher levels. To test enzymatic involvement, we determined the expression levels and localization of the calcium-sensitive calpain proteases-1 and -2 and their endogenous inhibitor calpastatin. While the latter was not affected, the expression of both calpains was 2-fold higher in GAN cells compared to control cells. Moreover, pharmacologic inhibition of calpains with MDL-28170 or MG-132 attenuated vimentin cleavage. Imaging analysis revealed striking colocalization between large perinuclear vimentin aggregates and calpain-2 in GAN fibroblasts. This colocalization was dramatically altered by hypotonic stress, where selective breakdown of filaments over aggregates occurred rapidly in GAN cells and coincided with calpain-2 cytoplasmic redistribution. Finally, mass spectrometry-based proteomics revealed that phosphorylation at Ser-412, located at the junction between the central “rod” domain and C-terminal “tail” domain on vimentin, is involved in this stress response. Over-expression studies using phospho-deficient and phospho-mimic mutants revealed that Ser-412 is important for filament organization, solubility dynamics, and vimentin cleavage upon hypotonic stress exposure. Collectively, our work reveals that osmotic stress induces calpain- and proteasome-mediated vimentin degradation and IF network breakdown. These effects are significantly augmented in the presence of disease-causing KLHL16 mutations that alter intermediate filament organization. While the specific roles of calpain-generated vimentin IF fragments in GAN cells remain to be defined, this proteolytic pathway is translationally-relevant to GAN because maintaining osmotic homeostasis is critical for nervous system function.

The commercialization of hybrid rice has greatly contributed to the increase in rice yield, with the improvement of its seed production capacity having played an important role. The stigma exsertion rate (SER) is a key factor for improving the outcrossing of the sterile line and the hybrid rice seed production. We used the Zhenshan 97B × IRAT109 recombinant inbred population comprising 163 lines and a natural population of 138 accessions to decipher the genetic foundation of SER over 2 years in three environments. Additionally, we detected eight QTLs for SER on chromosomes 1, 2, and 8 via linkage mapping. We also identified seven and 19 significant associations for SER using genome-wide association study in 2016 and 2017, respectively. Interestingly, we located two lead SNPs (sf0803343504 and sf083344610) on chromosome 8 in the qTSE8 QTL region that were significantly associated with total SER. After transcriptomic analysis, quantitative real-time PCR, and haplotype analysis, we found 13 genes within this reliable region as important candidate genes. Our study results will be beneficial to molecular marker-assisted selection of rice lines with high outcrossing rate, thereby improving the efficiency of hybrid seed production.

Background & Aims: Metabolic imbalance and inflammation are common features of chronic liver diseases. Molecular factors controlling these mechanisms represent potential therapeutic targets. CD73 is the major enzyme that dephosphorylates extracellular adenosine monophosphate (AMP) to form the anti-inflammatory adenosine. CD73 is expressed on pericentral hepatocytes, which are important for long-term liver homeostasis. We aimed to determine if CD73 has nonredundant hepatoprotective functions. Methods: Liver-specific CD73 knockout (CD73-LKO) mice were generated by targeting the Nt5e gene in hepatocytes. The CD73-LKO mice and hepatocytes were characterized using multiple approaches. Results: Deletion of hepatocyte Nt5e resulted in an approximately 70% reduction in total liver CD73 protein (P < .0001). Male and female CD73-LKO mice developed normally during the first 21 weeks without significant liver phenotypes. Between 21 and 42 weeks, the CD73-LKO mice developed spontaneous-onset liver disease, with significant severity in male mice. Middle-aged male CD73-LKO mice showed hepatocyte swelling and ballooning (P < .05), inflammation (P < .01), and variable steatosis. Female CD73-LKO mice had lower serum albumin levels (P < .05) and increased inflammatory genes (P < .01), but did not show the spectrum of histopathologic changes in male mice, potentially owing to compensatory induction of adenosine receptors. Serum analysis and proteomic profiling of hepatocytes from male CD73-LKO mice showed significant metabolic imbalance, with increased blood urea nitrogen (P < .0001) and impairments in major metabolic pathways, including oxidative phosphorylation and AMP-activated protein kinase (AMPK) signaling. There was significant hypophosphorylation of AMPK substrates in CD73-LKO livers (P < .0001), while in isolated hepatocytes treated with AMP, soluble CD73 induced AMPK activation (P < .001). Conclusions: Hepatocyte CD73 supports long-term metabolic liver homeostasis through AMPK in a sex-dependent manner. These findings have implications for human liver diseases marked by CD73 dysregulation.

Drill core lithology is an important indicator reflecting the geological conditions of the drilling area. Traditional lithology identification usually relies on manual visual inspection, which is time-consuming and professionally demanding. In recent years, the rapid development of convolutional neural networks has provided an innovative way for the automatic prediction of drill core images. In this work, a core dataset containing a total of 10 common lithology categories in underground engineering was constructed. ResNeSt-50 we adopted uses a strategy of combining channel-wise attention and multi-path network to achieve cross-channel feature correlations, which significantly improves the model accuracy without high model complexity. Transfer learning was used to initialize the model parameters, to extract the feature of core images more efficiently. The model achieved superior performance on testing images compared with other discussed CNN models, the average value of its Precision, Recall, F1-score for each category of lithology is 99.62%, 99.62%, and 99.59%, respectively, and the prediction accuracy is 99.60%. The test results show that the proposed method is optimal and effective for automatic lithology classification of borehole cores.

Heterosis is the phenomenon in which some hybrid traits are superior to those of their parents. Most studies have analyzed the heterosis of agronomic traits of crops; however, heterosis of the panicles can improve yield and is important for crop breeding. Therefore, a systematic study of panicle heterosis is needed, especially during the reproductive stage. RNA sequencing (RNA Seq) and transcriptome analysis are suitable for further study of heterosis. Using the Illumina Nova Seq platform, the transcriptome of ZhongZheYou 10 (ZZY10), an elite rice hybrid, the maintainer line ZhongZhe B (ZZB), and the restorer line Z7-10 were analyzed at the heading date in Hangzhou, 2022. 581 million high-quality short reads were obtained by sequencing and were aligned against the Nipponbare reference genome. A total of 9000 differential expression genes were found between the hybrids and their parents (DGHP). Of the DGHP, 60.71% were up-regulated and 39.29% were down-regulated in the hybrid. Comparative transcriptome analysis revealed that 5235 and 3765 DGHP were between ZZY10 and ZhongZhe B and between ZZY10 and Z7-10, respectively. This result is consistent with the transcriptome profile of ZZY10 and was similar to Z7-10. The expression patterns of DGHP mainly exhibited over-dominance, under-dominance, and additivity. Among the DGHP-involved GO terms, pathways such as photosynthesis, DNA integration, cell wall modification, thylakoid, and photosystem were significant. 21 DGHP, which were involved in photosynthesis, and 17 random DGHP were selected for qRT-PCR validation. The up-regulated PsbQ and down-regulated subunits of PSI and PSII and photosynthetic electron transport in the photosynthesis pathway were observed in our study. Extensive transcriptome data were obtained by RNA-Seq, providing a comprehensive overview of panicle transcriptomes at the heading stage in a heterotic hybrid.

It is hard to grasp the deformation law of the surrounding rock and the force characteristics of the support structure during the construction of ultra-small clearance tunnels in upper soil and lower rock composite strata. Based on the ultra-small clearance tunnel in Li Shuping, Tongxin Expressway, Guizhou, this paper adopted a combination of numerical simulation and field monitoring to analyze the influence of different burial depths and soil-rock interface positions on the deformation of the surrounding rock and the internal forces of the support structure of the ultra-small clearance tunnel. The conclusions are: (1) the monitoring data show that the stress in the steel frame of the leading tunnel increases first by the influence of proximity construction, and then decreases and reaches a stable value after the secondary lining is applied, and the stress at the arch waist of the soft soil layer furtherest from the side of the middle rock column is greater than that in the rock layer on the side of the middle rock column; (2) the position of the soil-rock interface has a significant influence on the initial support force of the first tunnel, and the bending moment of the structure increases with the downward movement of the soil-rock interface and the increase in the burial depth; (3) the influence of the soil-rock interface position on the initial support moment of the first tunnel is greater than the influence of proximity construction, a point to which attention should be paid during construction; and (4) when the soil-rock interface is located below the foot of the arch, the deformation of the surrounding rock of the following tunnel will be larger than that of the first tunnel. The results can provide a reference for the design and construction of ultra-small clearance tunnels in upper soil and lower rock composite soft strata and soil strata.

CD73, a cell‐surface N‐linked glycoprotein that produces extracellular adenosine, is a novel target for cancer immunotherapy. Although anti‐CD73 antibodies have entered clinical development, CD73 has both protumor and antitumor functions, depending on the target cell and tumor type. The aim of this study was to characterize CD73 regulation in human hepatocellular carcinoma (HCC). We examined CD73 expression, localization, and activity using molecular, biochemical, and cellular analyses on primary HCC surgical specimens, coupled with mechanistic studies in HCC cells. We analyzed CD73 glycan signatures and global alterations in transcripts encoding other N‐linked glycoproteins by using mass spectrometry glycomics and RNA sequencing (RNAseq), respectively. CD73 was expressed on tumor hepatocytes where it exhibited abnormal N‐linked glycosylation, independent of HCC etiology, tumor stage, or fibrosis presence. Aberrant glycosylation of tumor‐associated CD73 resulted in a 3‐fold decrease in 5′‐nucleotidase activity (P

Typical visual simultaneous localization and mapping (SLAM) systems rely on front-end odometry for feature extraction and matching to establish the relations between adjacent images. In a low-light environment, the image obtained by a camera is dim and shows scarce information, hindering the extraction of sufficient stable feature points, consequently undermining visual SLAM. Most existing methods focus on low-light enhancement of a single image, neglecting the strong temporal correlation across images in visual SLAM. We propose a method that leverages the temporal information of an input image sequence to enhance the low-light image and employed the enhanced result to improve the feature extraction and matching quality of visual SLAM. Our method trains a three-dimensional convolutional neural network to estimate pixelwise grayscale transformation curves to obtain a low-light enhancement image. Then, the grayscale transformation curves are iteratively applied to obtain the final enhanced result. The training process of the network does not require any paired reference images. We also introduced a spatial consistency loss for the enhanced image to retain the content and texture of the original image. We further integrated our method into VINS-Mono and compared with similar low-light image enhancement methods on the TUM-VI public dataset. The proposed method provides a lower positioning error. The positioning root-mean-squared error of our method is 19.83% lower than that of Zero-DCE++ in low-light environments. Moreover, the proposed network achieves real-time operation, being suitable for integration into a SLAM system.

Sheath blight disease (ShB) is considered to be the second most important disease affecting rice, and the genetic mechanism of ShB resistance in rice is great complicated. Uncovering genetic mechanism of ShB resistance and strong resistant varieties in rice are the premise for ShB resistance improvement. A rice ShB genome-wide association study (GWAS) was performed using approximately five million SNPs within Ting’s core collection. “Early pradifice”, one typical japonica, was determined to be the most resistant variety in both 2016 and 2017. A total of 34 and four significant (p ≤ 1.93 × 10−8) SNPs were observed in 2016 and 2017, respectively. Moreover, 23 of 34 and two of four gene-based SNPs not reported in previous studies in 2016 and 2017, respectively, were identified as significantly associated with rice ShB resistance. Furthermore, we performed GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses for the genes located at a region within 10 kb of the significant SNPs. Both in 2016 and 2017, we observed that genes were uniquely enriched in the regulation of transcription and RNA processing in the category of “biological process”, plasma membrane, nucleus, integral component of membrane and cell wall in the category of “cellular component”, and ATP binding in the category of “molecular function”. The results of the present study may establish a foundation for further research investigating these elite genes and utilizing the resistant varieties in Ting’s core collection to improve rice ShB resistance.

Herein, the target compound of S-benzyl-O,O'-bis(2-naphthyl)dithiophosphate (SBOB) as corrosion inhibitor with ultra-long lifespan was successfully synthesized and characterized by elemental analysis, single crystal X-ray diffraction and spectroscopy involving FT-IR, 1H, 13C and 31P NMR. Meanwhile, the inhibition performance and mechanism of SBOB for mild steel (MS) in HCl medium were combined to investigate by weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy, scanning electron microscopy and quantum chemical calculation. The potentiodynamic polarization results indicate that SBOB is a mixed-type inhibitor. All experimental results are in good agreement and reveal that the corrosion inhibition increases with the concentration of SBOB. Weight loss results indicate that the inhibition efficiency decreases with HCl concentration and temperature increasing, but the corrosion inhibition performance of SBOB keeps almost unchanged after ultra-long storage time due to the formation of inhibitor film by the physisorption and chemisorption of SBOB on MS surface. Keywords: O,O'-diaryldithiophosphates, Synthesis, Crystal structure, Corrosion inhibition, Ultra-long lifespan

Most visual–inertial navigation systems (VINSs) suffer from moving objects and achieve poor positioning accuracy in dynamic environments. Therefore, to improve the positioning accuracy of VINS in dynamic environments, a monocular visual–inertial navigation system, VINS-dimc, is proposed. This system integrates various constraints on the elimination of dynamic feature points, which helps to improve the positioning accuracy of VINSs in dynamic environments. First, the motion model, computed from the inertial measurement unit (IMU) data, is subjected to epipolar constraint and flow vector bound (FVB) constraint to eliminate feature matching that deviates significantly from the motion model. This algorithm then combines multiple feature point matching constraints that avoid the lack of single constraints and make the system more robust and universal. Finally, VINS-dimc was proposed, which can adapt to a dynamic environment. Experiments show that the proposed algorithm could accurately eliminate the dynamic feature points on moving objects while preserving the static feature points. It is a great help for the positioning accuracy and robustness of VINSs, whether they are from self-collected data or public datasets.

Simultaneous localization and mapping (SLAM) systems have been generally limited to static environments. Moving objects considerably reduce the location accuracy of SLAM systems, rendering them unsuitable for several applications. Using a combined vision camera and inertial measurement unit (IMU) to separate moving and static objects in dynamic scenes, we improve the location accuracy and adaptability of SLAM systems in these scenes. We develop a moving object-matched feature points elimination algorithm that uses IMU data to eliminate matches on moving objects but retains them on stationary objects. Moreover, we develop a second algorithm to validate the IMU data to avoid erroneous data from influencing image feature points matching. We test the new algorithms with public datasets and in a real-world experiment. In terms of the root mean square error of the location absolute pose error, the proposed method exhibited higher positioning accuracy for the public datasets than the traditional algorithms. Compared with the closed-loop errors obtained by OKVIS-mono and VINS-mono, those obtained in the practical experiment were lower by 50.17% and 56.91%, respectively. Thus, the proposed method eliminates the matching points on moving objects effectively and achieves feature point matching results that are realistic.

Human neural stem cell–derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell–derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell–derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell–derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell–derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell–derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell–derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell–derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell–derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell–derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

Using the Mn-Nb-B low carbon bainite high strength steel with the reducing production technology as the research target, the deformation behavior and phase transformation behavior were studied by the thermal simulation testing machine. Combining with the characteristics of the medium and heavy plate production line, the controlled rolling and controlled cooling technology based on ultra-fast cooling were designed to produce low cost high strength construction machinery steel with superior comprehensive mechanical properties. The strengthening mechanisms such as grain refinement strengthening, precipitation strengthening are effective to produce the Mn-Nb-B low carbon bainite high strength steel. The yield strength and tensile strength of the product reach to 678MPa and 756 MPa respectively, the elongation A50 is 33% and the impact energy at -20℃ is 261J. The microstructure of the steel is composed of granular bainite, acicular ferrite and lath bainite. A large number of fine, point, granular M/A constituents and dislocation structures dispersively distributed inside the matrix, and also tiny and dispersed (Nb,Ti) (C,N) precipitates are observed by transmission electron microscopy.

Positioning information has become one of the most important information for processing and displaying on smart mobile devices. In this paper, we propose a visual positioning method using RGB-D image on smart mobile devices. Firstly, the pose of each image in the training set is calculated through feature extraction and description, image registration, and pose map optimization. Then, in the image retrieval stage, the training set and the query set are clustered to generate the vector of local aggregated descriptors (VLAD) description vector. In order to overcome the problem that the description vector loses the image color information and improve the retrieval accuracy under different lighting conditions, the opponent color information and depth information are added to the description vector for retrieval. Finally, using the point cloud corresponding to the retrieval result image and its pose, the pose of the retrieved image is calculated by perspective-n-point (PnP) method. The results of indoor scene positioning under different illumination conditions show that the proposed method not only improves the positioning accuracy compared with the original VLAD and ORB-SLAM2, but also has high computational efficiency.

The surface tension and viscosity values of N-methyldiethanolamine (MDEA) aqueous solutions promoted by tetramethylammonium arginate ([N1111][Arg]) were measured and modeled. The experimental temperatures were 303.2 to 323.2 K. The mass fractions of MDEA (wMDEA) and [N1111][Arg] (w[N1111][Arg]) were 0.300 to 0.500 and 0.025 to 0.075, respectively. The measured surface tension and viscosity values were satisfactorily fitted to thermodynamic models. With the aid of experimentally viscosity data, the activation energy (Ea) and H2S diffusion coefficient (DH2S) of MDEA-[N1111][Arg] aqueous solution were deduced. The surface entropy and surface enthalpy of the solutions were calculated using the fitted model of the surface tension. The quantitative relationship between the calculated values (surface tension, surface entropy, surface enthalpy, viscosity, activation energy, and H2S diffusion coefficient) and the operation conditions (mass fraction and temperature) was demonstrated.

Aims: Osteosarcoma (OS) is an aggressive bone malignancy with poor prognosis. Many OS cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). In our previous study, we found that the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients than in healthy subjects. Our aim was to investigate the effects of CYC1 silencing on TRAIL-induced apoptosis in human OS in vitro and in vivo along with the underlying mechanisms. Methods: First, we determined the expression of CYC1 in human OS tumors and cell lines versus normal adjacent tissues and cell line. We then studied the effects of CYC1 silencing alone or in combination with TRAIL on OS cell growth and apoptosis in vitro and OS tumorigenesis in vivo. Results: We found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1 silencing by shRNA transfection inhibits proliferation, slightly induces apoptosis in human OS cells in vitro, and suppresses human OS tumor growth in a mouse xenograft model in vivo. Additionally, CYC1 silencing sensitizes OS to TRAIL-induced apoptosis in vitro and in vivo. Our results also showed that CYC1 silencing significantly reduces complex III activity and potentiates TRAIL-induced cytochrome c release and caspase-9 activation in OS cells, suggesting that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway. Conclusion: Taken together, our results provide evidence that CYC1 plays an important role in OS tumorigenesis, and modulation of CYC1 may be an effective strategy to potentiate OS to apoptotic induction by TRAIL.

The purpose of this study was to compare and evaluate the event of VTE (Venous Thromboembolism Event) after total artificial joint replacement between two groups diagnosed with either musculoskeletal tumors or osteoarthritis (OA) of the knee. From 2004 to 2014, a total of 1,402 patients (308 in tumor group, 1,094 in OA group) were involved in this study. The rate of asymptomatic DVT (Deep vein thrombosis) was significantly higher in tumor group when compared with OA group. Though both the incidence of symptomatic DVT and PE (Pulmonary embolism) were slightly higher in tumor group, no significant difference was detected. Tumor patients suffered an almost equal risk of VTE compared with OA patients except a higher rate of asymptomatic DVT after total artificial joint replacement. For patients with tumor, no significant association was observed between any potential risk factor and DVT.

Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

The purpose of this study was to compare clinical outcomes of patients with full-thickness small to large sized tears undergoing all-arthroscopic versus mini-open rotator cuff repair.A literature search for electronic databases and references for eligible studies was conducted through Medline, Embase and Cochrane library between 1969 and 2013.A total of 12 comparative studies (n = 770 patients) were included. Pooled results showed: there were no differences in function outcome, pain scores, retear rate or the incidence of adhesive capsulitis between all arthroscopic and mini-open repair groups.There were no differences in outcomes between the arthroscopic and mini-open rotator cuff repair techniques, they should be considered alternative treatment options.Level IV, Meta analysis.

Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation.

BACKGROUND: Displaced fracture of the femoral neck has been a common clinical problem, especially in aged patients. However, the optimal treatment choice remains controversial. The purpose of this study is to conduct a systematic review of randomized clinical trials assessing the results of hemiarthroplasty and total hip replacement in patients undergoing either alternative using meta-analysis. METHODS: A literature search for randomized clinical trials was conducted through Medline, Embase and Cochrane library between 1969 and 2013 with no restrictions. Additional relevant articles were referred as source of information by way of manual searches on major orthopedic journals. Upon the search, two authors independently evaluated study quality and relevant data was extracted. RESULTS: A total of 8 studies with 983 patients were included in this meta-analysis. After pooling the available data, a significant dominance of Harris hip score was found for total hip replacement compared with hemiarthroplasty (SMD: -7.11, 95%:-10.70,-3.53) one year postoperatively and the advantage kept over (SMD: -6.91, 95%:-12.98, -0.85) two years after surgery. A trend toward a higher dislocation rate was found in total hip replacement group (RR: 0.46, 95%: 0.21, 1.02), of which the difference was considered insignificant. The risk of revision in group hemiarthroplasty appeared to be more than two folds higher than that after total hip replacement (RR: 4.14, 95%CI: 2.09, 8.19). CONCLUSION: Even though there is a higher rate of dislocation after total hip replacement, this disadvantage could be accounted for, on the basis of a better functional score and the lower revision rate. However, from the results, it stands to reason that total hip replacement should be strongly suggested in elderly active patients with femoral neck fracture.

Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.

Abstract Background Soft tissue injury imposes major public health burdens worldwide. The positive effect of China's Tibetan medicine and the Lamiophlomis rotata-based herbal Pain Relieving Plaster (PRP) on healing closed soft tissue injury (CSTI) has been reported. The herbs contained in Plaster are also referred as 'blood-activating and stasis-dispelling' in herbal medicine. The formula of the plaster contains four China's Tibetan medical herbs, including Lamiophlomis rotata, Oxytropis falcate Bunge, Curcuma longa Linn, and Myricaria bracteata. Two of these herbs (Lamiophlomis rotate; Curcuma longa Linn) are commonly used in different formulae of Chinese medicine. The objective of this study is to use an interdisciplinary approach to test the hypothesis that the formula and its components influence the process of CSTI. Methods In vivo models have been established in 30 rabbit ear pinnae and studied for: (1) blood flow velocity (BFV) which was affected by pressure of 21.2 kg/cm2 for 30 second over the local rabbit ear tissue; (2) edema formation of the closed soft tissue injury; (3) in vivo local temperature change. Results The results of in vivo studies indicated that CSTI significantly increased the velocity of blood flow and increased edema formation within the control group. The PRP extracts for 5 hours significantly slowed down the BFV of CSTI in rabbit ears, markedly decreased the elevated edema level from the 3rd to the 5th day. Conclusion The ingredients contained in the formula have positive effects in healing CSTI and further study is worth exploring.