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ABSTRACT: The transgalactosylase activity of β-galactosidases offers a convenient and promising strategy for conversion of lactose into high-value oligosaccharides, such as galactooligosaccharides (GOS) and human milk oligosaccharides. In this study, we cloned and biochemically characterized a novel C-terminally truncated β-galactosidase (PaBgal2A-D) from Paenibacillus antarcticus with high transglycosylation activity. PaBgal2A-D is a member of glycoside hydrolase family 2. The optimal pH and temperature of PaBgal2A-D were determined to be pH 6.5 and 50°C, respectively. It was relatively stable within pH 5.0–8.0 and up to 50°C. PaBgal2A-D showed high transglycosylation activity for GOS synthesis, and the maximum yield of 50.8% (wt/wt) was obtained in 2 h. Moreover, PaBgal2A-D could synthesize lacto-N-neotetraose (LNnT) using lactose and lacto-N-triose II, with a conversion rate of 16.4%. This study demonstrated that PaBgal2A-D could be a promising tool to prepare GOS and lacto-N-neotetraose.

Abstract River ecosystems face challenges due to environmental degradation and alterations in flow and sediment transport resulting from climate change and other anthropogenic impacts. These changes may substantially affect river morphology, nutrient dynamics, wetland vegetation, aquatic habitats, and river ecological stability. This highlights the urgent need for systematic and quantitative studies on the interactions and feedback between changes in flow, sediment transport, and river ecology. In this study, we reviewed flow and sediment transport changes in major Chinese rivers, along with their resulting ecological impacts. We propose conducting eco‐fluvial dynamic studies, a potential solution that can guide the evaluation and restoration of ecological health impacted by physical processes. These studies can provide major benefits in balancing human and environmental needs in large river systems, which is crucial for the healthy and sustainable development of rivers.

Retinal vascular segmentation holds significant value in medical research, playing an indispensable role in facilitating the screening of various diseases, such as diabetes, hypertension, and glaucoma. However, most current retinal vessel segmentation methods mainly rely on convolutional neural networks, which present limitations when dealing with long-term dependencies and global context connections. These limitations often result in poor segmentation of small blood vessels and low contrast between the ends of fundus blood vessel branches and the background. Addressing these issues is a pressing concern. To tackle these challenges, this paper proposes a new retinal blood vessel segmentation model, namely Dual Swin Transformer Fusion (DS-TransFusion). This model uses a two-scale encoder subnetwork based on a Swin Transformer, which is able to find correspondence and align features from heterogeneous inputs. Given an input image of a retinal blood vessel, the model first splits it into two nonoverlapping blocks of different sizes. These are then fed into the two branches of the encoder to extract coarse-grained and fine-grained features of the retinal blood vessels. At the jump junction, DS-TransFusion introduces the Transformer interactive fusion attention (TIFA) module. The core of this module is to use a multiscale attention (MA) mechanism to facilitate efficient interaction between multiscale features. It integrates features from two branches at different scales, achieves effective feature fusion, enriches cross-view context modeling and semantic dependency, and captures long-term correlations between data from different image views. This, in turn, enhances segmentation performance. In addition, to integrate multiscale representation in the hierarchical backbone, DS-TransFusion introduces an MA module between the encoder and decoder. This module learns the feature dependencies across different scales, collects the global correspondence of multiscale feature representations, and further optimizes the segmentation effect of the model. The results showed that DS-TransFusion performed impressively on public data sets STARE, CHASEDB1, and DRIVE, with accuracies of 96.50%, 97.22%, and 97.80%, and sensitivities of 84.10%, 84.55%, and 83.17%, respectively. Experimental results show that DS-TransFusion can effectively improve the accuracy of retinal blood vessel segmentation and accurately segment small blood vessels. Overall, DS-TransFusion, as a Swin Transformer-based retinal vessel segmentation model, has achieved remarkable results in solving the problems of unclear segmentation of small vessels and global context connection. Experimental results on several public data sets have validated the effectiveness and superiority of this method, suggesting its potential to provide more accurate retinal vascular segmentation results for auxiliary screening of various diseases.

Boron has been considered a promising powdered metal fuel for enhancing composite propellants' energy output due to its high energy density. However, the high ignition temperature and low combustion efficiency limit the application of boron powder due to the high boiling point of the boron oxide layer. Much research is ongoing to overcome these shortcomings, and one potential approach is to introduce a small quantity of metal oxide additives to promote the reaction of boron. This study prepared boron-rich fuels with 10 wt% of eight nano-metal oxide additives by mechanical ball milling. The effect of metal oxides on the thermo-oxidation, ignition, and combustion properties of boron powder was comprehensively studied by the thermogravimetric analysis (TG), the electrically heated filament setup (T-jump), and the laser-induced combustion experiments. TG experiments at 5 K/min found that Bi2O3, MoO3, TiO2, Fe2O3, and CuO can promote thermo-oxidation of boron. Compared to pure boron, Tonset can be reduced from 569 °C to a minimum of 449 °C (B/Bi2O3). Infrared temperature measurement in T-jump tests showed that when heated by an electric heating wire at rates from 1000 K/s to 25000 K/s, the ignition temperatures of B/Bi2O3 are the lowest, even lower than the melting point of boron oxide. Ignition images and SEM for the products further showed that the high heating rate is beneficial to the rapid reaction of boron powder in the single-particle combustion state. Fuels (B/Bi2O3, B/MoO3, and B/CuO) were mixed with the oxidant AP and ignited by laser to study the combustion performance. The results showed that B/CuO/AP has the largest flame area, the highest BO2 characteristic spectral intensity, and the largest burn rate for powder lines. To combine the advantages of CuO and Bi2O3, binary metal oxide (CBO, mass ratio of 3:1) was prepared and the test results showed that CBO can very well improve both ignition and combustion properties of boron. Especially B/CBO/AP has the highest burn rate compared with all fuels containing other additives. It was found that multi-component metal-oxide additive can more synergistically improve the reaction characteristics of boron powder than unary additive. These findings contribute to the development of boron-rich fuels and their application in propellants.

IntroductionSymbiotic microorganisms in insects regulate multiple physiological functions, widely participating in nutrient metabolism, immune regulation, and crucial regulatory roles in development. However, little is known about how microbial factors might respond to the preparation of insect diapause.MethodsThe gut bacterial communities of Loxostege sticticalis larvae induced at different photoperiod of long (LD16:8, nondiapause) and short (LD12:12, prediapause) daylength were compared, by 16S rRNA Illumina MiSeq.ResultsA total number of 42 phylum, 78 classes, 191 orders, 286 families, 495 genera, and 424 species were identified in the intestinal bacterial community of L. sticticalis larvae. Alpha diversity and beta diversity analyses revealed significant differences between nondiapause and prediapause larvae. In non-diapause larvae, the dominant intestinal bacteria were Firmicutes and Proteobacteria. In specific, in 3rd and 4th instar larvae, the main intestinal bacteria were Staphylococcus, while in 5th instar, it was JC017. For the prediapause larvae, the dominant phylum in 3rd instar larvae was Firmicutes, with the dominant genus of Staphylococcus, while in 4th and 5th instar larvae was Bacteroidota, with the dominant genus 4th instar was Staphylococcus, and in 5th instar was JC017. KEGG functional prediction analysis revealed that functional bacterial groups involved in metabolism had the highest abundance values. Specifically, the amino acid metabolism of metabolism-related functional genes in the 3rd instar prediapause larvae was significantly lower than that in the 4th and 5th instar prediapause larvae and the non-diapause treatment. However, the carbohydrate metabolism in 3rd instar prediapause larvae was significantly higher than that in 4th and 5th instar prediapause larvae and non-diapause treatments. The dominant bacterial phylum in the prediapause larvae at different stages of L. sticticalis was varied, and there were significant differences in community diversity and richness.DiscussionThese results suggest a complex interaction between the hosts’ physiological state and its gut microbiota, indicating that bacterial communities may assist insects in adapting to diapause preparation by regulating their metabolic levels. This study lays the foundation for further understanding the physiological mechanisms by which intestinal microorganisms regulate overwintering dormancy in the L. sticticalis.

Sulfur mustard (2,2′-dichloroethylsulfide; SM) is a bifunctional alkylating agent that can easily penetrate skin and cause persistent pain and damage. Effective biological dressings are required to treat wounds caused or poisoned by SM. Though the use of SM is regulated under the Chemical Weapons Convention, it is still a threat during wars and terrorist attacks. Herein, we present a photothermal-enhanced detoxification microneedles array (MNA) encapsulated with ZnIn2S4@UiO-66-NH2 (ZnInS/UIO) catalysts for the treatment of 2-chloroethyl ethyl sulfide (CEES, SM analog)-poisoned wounds under simulated sunlight (SSL) irradiation. Due to the excellent photothermal detoxification capability possessed by ZnInS/UIO, the conversion rate of CEES can be significantly increased under SSL exposure. When encased in a polyvinyl alcohol (PVA) MNA and piercing into the skin, ZnInS/UIO catalysts can be released quickly from MNA for detoxification. After applying the resultant ZnInS/UIO-MNA to the CEES-poisoned wound bed, acceleration of the wound healing process and a reduced inflammatory response can be confirmed. In conclusion, ZnInS/UIO-MNA has encouraging potential as a first-aid dressing for CEES-poisoned wound healing in battlefields and injuries related to acts of terrorism.

Scientific knowledge about the ancestral genome of core eudicot plant kingdom can potentially have profound impacts on both basic and applied research, including evolution, genetics, genomics, ecology, agriculture, forestry, and global climate. To investigate which plant conserves best the core eudicots common ancestor genome, we compared Arcto-Tertiary relict Nyssaceae and 30 other eudicot plant families. The genomes of Davidia involucrata (a known living fossil), Camptotheca acuminata and Nyssa sinensis, one per existent genus of Nyssaceae, were performed comparative genomic analysis. We found that Nyssaceae originated from a single Nyssaceae common tetraploidization event (NCT)– autotetraploidization 28–31 Mya after the core eudicot common hexaploidization (ECH). We identified Nyssaceae orthologous and paralogous genes, determined its chromosomal evolutionary trajectory, and reconstructed the Nyssaceae most recent ancestor genome. D. involucrata genome contained the entire seven paleochromosomes and 17 ECH-generated eudicot common ancestor chromosomes and was the slowest in mutation among the analyzed 42 species of 31 plant families. Combing both its high retention of paleochromosomes and its low mutation rate, D. involucrata provides the best case in conservation of the core eudicot paleogenome.

Abstract The authors study the problem of compressive target detection in a single‐frequency network (SFN)‐based multistatic passive radar system (MS‐PRS) consisting of multiple illuminators of opportunity (IOs) and one receiver. Firstly, a generalised likelihood ratio test (GLRT)‐based SFN‐based compressive subspace detector (SFN‐CSD) is derived by exploiting the sparsity of the target echoes for the case of known noise variance. When the noise variance is unknown, an SFN‐based unknown‐noise (UN) compressive subspace detector is proposed, referred to as the SFN‐UNCSD. Moreover, closed‐form expressions of the probability of false alarm and detection of the proposed detectors are deriived. It is proved that the SNF‐UNCSD has a constant false alarm rate (CFAR) property. Finally, numerical simulations are conducted to verify the theoretical analysis and illustrate the performance of the proposed detector relative to several benchmark detectors.

Background: The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. Methods: A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Results: Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels ( P

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

Abstract Polarization drift in fiber and free-space optical links is a major factor in the dynamic increase of bit error rate in polarization-coded quantum key distribution (QKD) systems. A dynamic polarization compensation method applicable to both links is a challenge. Here we propose a universally applicable real-time polarization compensation method, that the Muller parameters of the optical links are first detected using a polarization detector, and then the optimal parameters of the controller are obtained by gradient descent algorithm. Simulation results indicate advantages over current methods, with fewer waveplates, faster speed, and wider applicability for various optical links. In equivalent experiments of both satellite and fiber optical links, the average polarization extinction ratio of 27.9 dB and 32.2 dB are respectively achieved. The successful implementation of our method will contribute to the real-time polarization design of fiber and free-space QKD systems, while also contributing to the design of laser-based polarization systems.

Abstract Ultra-compact spectrometers are becoming increasingly popular for their promising applications in biomedical analysis, environmental monitoring, and food safety. In this work, we report a single-pixel-photodetector spectrometer with a spectral range from 480 nm to 820 nm, based on the AlGaAs/GaAs p-graded-n junction with a voltage-tunable optical response. To reconstruct the optical spectrum, we propose a tailored method called Neural Spectral Fields (NSF) that leverages the unique wavelength and bias-dependent responsivity matrix. Our spectrometer achieves a high spectral wavelength accuracy of up to 0.30 nm and a spectral resolution of up to 10 nm. Additionally, we demonstrate the high spectral imaging performance of the device. The compatibility of our demonstration with the standard III-V process greatly accelerates the commercialization of miniaturized spectrometers.

Abstract This paper uses the Entropy Weight Method‐Grey Relational Analysis (EWM‐GRA) and Covariance Base Structural Equations Model (CB‐SEM) to study the relationships between driving habits and efficiency. EWM‐GRA ranks 12 indicators in terms of their relevance of lane‐changing and driving efficiency. Based on this, a CB‐SEM‐based framework to describe the relevance between driving habits and lane‐changing is established, focusing on the effects of lane‐changing and car‐following behaviour. To validate the established framework, NGSIM trajectory data is used as measurement variables to describe latent variables. Several hypotheses about the relationships between the latent variables in this framework are proposed, and they are verified using trajectory data. The results show that driving habits have a direct impact on efficiency, and this impact becomes more significant when associated with lane‐change behaviour.

Coptis chinensis Franch., also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value. In our study, by using syntenic analysis combined with phylogenomic analysis of C. chinensis and four other representative genomes from basal and core eudicots, we confirmed that the WGD event in C. chinensis was shared by Aquilegia coerulea and Papaver somniferum L. and quickly occurred after Ranunculales diverged from other eudicots, likely a Ranunculales common tetraploidization (RCT). The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P. somniferum genome is faster than that of the C. chinensis genome by approximately 13.7%, possibly due to Papaveraceaes having an additional special tetraploidization event (PST). After Ks correction, the RCT dated to 115–130 million years ago (MYA), which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately 115.45–130.51 MYA. Moreover, we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes. Notably, the event-related subgenomes in the basal genomes all showed genomic fractionation bias, suggesting a likely allopolyploid nature of the RCT, PST and T-Alpha and T-Beta events in Tetracentron sinense. In addition, we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales, and most of them were related to the RCT and PST events. We constructed a new platform for Early Eudicot Comparative Genomic Research (http://www.cgrpoee.top/index.html) to store more information. In summary, our findings support the WGD of C. chinensis shared by Ranunculales, which is likely an allotetraploidization event. This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

Long-wave infrared (LWIR) spectral imaging plays a critical role in various applications such as gas monitoring, mineral exploration, and fire detection. Recent advancements in computational spectral imaging, powered by advanced algorithms, have enabled the acquisition of high-quality spectral images in real time, such as with the Uncooled Snapshot Infrared Spectrometer (USIRS). However, the USIRS system faces challenges, particularly a low spectral resolution and large amount of data noise, which can degrade the image quality. Deep learning has emerged as a promising solution to these challenges, as it is particularly effective at handling noisy data and has demonstrated significant success in hyperspectral imaging tasks. Nevertheless, the application of deep learning in LWIR imaging is hindered by the severe scarcity of long-wave hyperspectral image data, which limits the training of robust models. Moreover, existing networks that rely on convolutional layers or attention mechanisms struggle to effectively capture both local and global spectral correlations. To address these limitations, we propose the pixel-based Hierarchical Spectral Transformer (HST), a novel deep learning architecture that learns from publicly available single-pixel long-wave infrared spectral databases. The HST is designed to achieve a high spectral resolution for LWIR spectral image reconstruction, enhancing both the local and global contextual understanding of the spectral data. We evaluated the performance of the proposed method on both simulated and real-world LWIR data, demonstrating the robustness and effectiveness of the HST in improving the spectral resolution and mitigating noise, even with limited data.

The stable and high-precision acquisition of attitude data is crucial for sustaining the long-term robustness of laser links to detect gravitational waves in space. We introduce an effective method that utilizes an adaptive weight optimization approach for the fusion of attitude data obtained from charge-coupled device (CCD) spot-positioning-based attitude measurements, differential power sensing (DPS), and differential wavefront sensing (DWS). This approach aims to obtain more robust and lower-noise-level attitude data. A system is designed based on the Michelson interferometer for link simulations; validation experiments are also conducted. The experimental results demonstrate that the fused data exhibit higher robustness. Even in the case of a single sensor failure, valid attitude data can still be obtained. Additionally, the fused data have lower noise levels, with root mean square errors of 9.5%, 37.4%, and 93.4% for the single CCD, DPS, and DWS noise errors, respectively.

Gas cloud imaging with uncooled infrared spectroscopy is influenced by ambient temperature, complicating the quantitative detection of gas concentrations in open environments. To solve the aforementioned challenges, the paper analyzes the main factors influencing detection errors in uncooled infrared spectroscopy gas cloud imaging and proposes a temperature correction method to address them. Firstly, to mitigate the environmental effects on the radiative temperature output of uncooled infrared detectors, a snapshot-based, multi-band infrared temperature compensation algorithm incorporating environmental awareness was developed. This algorithm enables precise infrared radiation prediction across a wide operating temperature range. Validation tests conducted over the full temperature range of 0 °C to 80 °C demonstrated that the prediction error was maintained within ±0.96 °C. Subsequently, temperature compensation techniques were integrated, resulting in the development of a comprehensive uncooled infrared spectroscopy gas cloud imaging detection method. Ultimately, the detection limits for SF6, ethylene, cyclohexane, and ammonia were enhanced by 50%, 33%, 25%, and 67%, respectively.

Human babesiosis is a tick-borne disease caused by Babesia pathogens. The disease, which presents with malaria-like symptoms, can be life-threatening, especially in individuals with weakened immune systems and the elderly. The worldwide prevalence of human babesiosis has been gradually rising, prompting alarm among public health experts. In other pathogens, genetic techniques have proven to be valuable tools for conducting functional studies to understand the importance of specific genes in development and pathogenesis as well as to validate novel cellular targets for drug discovery. Genetic manipulation methods have been established for several non-human Babesia and Theileria species and, more recently, have begun to be developed for human Babesia parasites. We have previously reported the development of a method for genetic manipulation of the human pathogen Babesia duncani. This method is based on positive selection using the hDHFR gene as a selectable marker, whose expression is regulated by the ef-1aB promoter, along with homology regions that facilitate integration into the gene of interest through homologous recombination. Herein, we provide a detailed description of the steps needed to implement this strategy in B. duncani to study gene function. It is anticipated that the implementation of this method will significantly improve our understanding of babesiosis and facilitate the development of novel and more effective therapeutic strategies for the treatment of human babesiosis.

Daily precipitation of different intensities is expected to change differently in response to global warming. Based on station observations and simulations from the latest climate models, we investigated the non-uniform features of changes in daily precipitation frequency, intensity and amount over China. Results show that western China experiences an overall wetting trend across the spectrum of precipitation intensity, while eastern China exhibits negative trends in light-to-moderate precipitation and positive trends in heavy-to-extreme precipitation with respect to precipitation frequency and amount. Changes in precipitation intensity do not show a spatially consistent pattern of intensification in most intensity spectra, but exhibit the most pronounced intensification in heavy-to-extreme precipitation. Interestingly, changes in precipitation frequency dominate changes in the amount of precipitation for each intensity level, particularly for the spatial patterns. Although climate models show limited skills in reproducing the magnitudes of these observed changes, they show skills in simulating the sign of the changes. Also, they reasonably reproduce the observed non-uniform patterns of daily precipitation changes, especially for changes in the contributions from different intensity levels to annual total precipitation on average over the whole country. The evaluation of current climate models in simulating daily precipitation changes as a function of precipitation intensity suggests that improvement in the detection and attribution of precipitation changes in China can be gained by dividing daily precipitation into different categories.

Perfluorooctane sulfonate (PFOS), an officially listed persistent organic pollutant, is a widely distributed perfluoroalkyl substance. Epidemiological studies have shown that PFOS is intimately linked to the occurrence of insulin resistance (IR). However, the detailed mechanism remains obscure. In previous studies, we found that mitochondrial calcium overload was concerned with hepatic IR induced by PFOS. In this study, we found that PFOS exposure noticeably raised lysosomal calcium in L-02 hepatocytes from 0.5 h. In the PFOS-cultured L-02 cells, inhibiting autophagy alleviated lysosomal calcium overload. Inhibition of mitochondrial calcium uptake aggravated the accumulation of lysosomal calcium, while inhibition of lysosomal calcium outflowing reversed PFOS-induced mitochondrial calcium overload and IR. Transient receptor potential mucolipin 1 (TRPML1), the calcium output channel of lysosomes, interacted with voltage-dependent anion channel 1 (VDAC1), the calcium intake channel of mitochondria, in the PFOS-cultured cells. Moreover, we found that ATP synthase F1 subunit beta (ATP5B) interacted with TRPML1 and VDAC1 in the L-02 cells and the liver of mice under PFOS exposure. Inhibiting ATP5B expression or restraining the ATP5B on the plasma membrane reduced the interplay between TRPML1 and VDAC1, reversed the mitochondrial calcium overload and deteriorated the lysosomal calcium accumulation in the PFOS-cultured cells. Our research unveils the molecular regulation of the calcium crosstalk between lysosomes and mitochondria, and explains PFOS-induced IR in the context of activated autophagy.

Background: Oesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression is closely associated with tumour progression and poor prognosis. However, the role and mechanism of CTSL as an oncogene in ESCC remain unclear. Methods: Genome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate the possible relationships between CTSL and ESCC. The correlation between CTSL expression and prognosis was analysed using GEO, TCGA, and GEPIA data. We compared CTSL expression among the cell types using single-cell sequencing. Correlations between CTSL and the tumour microenvironment, immune cell infiltration, tumour mutational load, immunological checkpoints, and treatment sensitivity in patients with ESCC were investigated. Finally, using mouse models and cellular investigations, we assessed the effects of CTSL on the growth, apoptosis, and metastasis of ESCC tumour cells. Results: CTSL was overexpressed in ESCC and correlated with prognosis. We also discovered its close association with cell immunity, especially with tumour-associated macrophages and immune checkpoints in the tumour microenvironment. CTSL may play a key role in ESCC development by affecting M2 macrophage polarisation. CTSL and the M2 macrophage marker genes showed significant positive correlations. Mendelian randomization analysis confirmed a relationship between CTSL and ESCC. Finally, our in vitro and in vivo experiments demonstrated that CTSL promoted the proliferation and migration of ESCC cells, validating our bioinformatic analysis. Conclusion: CTSL emerged as a crucial gene in ESCC that influences patient prognosis and immunity, particularly in association with M2 macrophages. Therefore, targeting or modulating CTSL levels may provide new therapeutic strategies for patients with ESCC.

Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward ‘cause‐and‐effect relationships’. We have developed a ‘dry‐lab‐driven knowledge discovery and wet‐lab validation’ approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11–Sec23a) and the exosomal crosstalk (miR‐487a‐5p) to transfer their ‘polymetastatic competency’ to the oligometastatic (OL) melanoma cells, via synergistic co‐targeting of the tumor‐suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

Abstract Background Anterior cruciate ligament injury is a common knee joint injury. Anterior cruciate ligament reconstruction is a common surgical treatment to treat anterior cruciate ligament injury. It may have certain advantages to retain the ligament stump during the operation, but the results of systematic evaluation on whether to retain the ligament stump are different. The conclusion is still controversial, and the quality needs to be strictly evaluated. Objective To evaluate the methodological quality, risk of bias, reporting quality and evidence quality of the systematic review of remnant preservation in anterior cruciate ligament reconstruction, and to provide reference for clinical work. Methods We systematically searched the system evaluations in 8 electronic databases, the languages were limited to Chinese and English, and the time limit was from the establishment of the database to June 2023. Two reviewers independently screened literature and extracted data. The methodological quality, risk of bias, reporting quality and quality of evidence were evaluated by AMSTAR-2, ROBIS, PRISMA and GRADE tools. Results A total of 14 systematic reviews were included. The evaluation of results showed that the methodological quality of the included systematic reviews was relatively low, of which 5 were low quality and 9 were critically low quality. A small number of systematic reviews were low risk of bias. The system evaluation reports are relatively complete, but the lack of program registration is a common problem. A total of 111 pieces of clinical evidence were extracted from the included 14 systematic reviews. The quality of evidence was generally low, with only 7 pieces of high-quality evidence, 45 pieces of medium-quality evidence, and the rest were low and very low-quality evidence. Among the reasons for relegation, imprecision is the most common, followed by inconsistency and indirectness. The existing evidence shows that patients after anterior cruciate ligament reconstruction with remnant preservation have certain advantages in knee joint function, joint stability and proprioception recovery, which may be a more effective surgical method. However, it may also increase the incidence of postoperative complications and adverse reactions. Conclusion Compared with Standard Technique, Remnant Preservation in Anterior Cruciate Ligament Reconstruction has more advantages in restoring joint function and stability and proprioception. But the potential risks should also be considered by surgeons. At present, the quality of evidence is generally low, and the reliability of the conclusion is insufficient. It still needs to be verified and further in-depth research is needed.

Background: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits “moonlighting” functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. Methods: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. Results: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. Conclusion: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.

Pansharpening refers to the process of fusing multispectral (MS) images with panchromatic (PAN) images to obtain high-resolution multispectral (HRMS) images. However, due to the low correlation and similarity between MS and PAN images, as well as inaccuracies in spatial information injection, HRMS images often suffer from significant spectral and spatial distortions. To address these issues, a pansharpening method based on multimodal texture correction and adaptive edge detail fusion is proposed in this paper. To obtain a texture-corrected (TC) image that is highly correlated and similar to the MS image, the target-adaptive CNN-based pansharpening (A-PNN) method is introduced. By constructing a multimodal texture correction model, intensity, gradient, and A-PNN-based deep plug-and-play correction constraints are established between the TC and source images. Additionally, an adaptive degradation filter algorithm is proposed to ensure the accuracy of these constraints. Since the TC image obtained can effectively replace the PAN image and considering that the MS image contains valuable spatial information, an adaptive edge detail fusion algorithm is also proposed. This algorithm adaptively extracts detailed information from the TC and MS images to apply edge protection. Given the limited spatial information in the MS image, its spatial information is proportionally enhanced before the adaptive fusion. The fused spatial information is then injected into the upsampled multispectral (UPMS) image to produce the final HRMS image. Extensive experimental results demonstrated that compared with other methods, the proposed algorithm achieved superior results in terms of both subjective visual effects and objective evaluation metrics.

Abstract Background Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression. Methods The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed. Results This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability. Conclusion We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells. Video Abstract

Natural pigments obtained from plants, animals, and microbes are not only a potent alternative to synthetic dyes in the food, textile, and cosmetic industries, but they also possess immense pharmacological properties. Carmine acids, carotenoids, flavonoids, indigo, anthocyanin, melanins, and curcumin are such natural pigments that have proven pharmacological properties. Zeaxanthin is one such natural water-soluble antioxidant pigment that belongs to the xanthophyll family and is predominantly accumulated in the retina of the eyes. The potency of zeaxanthin against LPS-induced inflammation in in vitro and in vivo conditions was examined. RAW264.7 cells were treated with zeaxanthin and challenged with LPS. The LPS-induced zeaxanthin-treated cells were subjected to assessments of cytotoxicity and inflammatory markers. For the in vivo study, BALB/c male mice were induced to have acute lung inflammation by LPS. The ALI-induced mice were treated with 25 and 50 mg/kg concentrations of zeaxanthin. BALF was collected from zeaxanthin-treated ALI-induced mice and was sacrificed for the excision of lung tissue. Pulmonary edema was examined in the lung tissues. Immune cell infiltration and protein content were examined in the BALF collected. Oxidative stress induction was analyzed in the lung tissue of ALI-induced mice. The inflammatory markers iNOS, COX-2, and PGE-2 were quantified in the lung tissues of zeaxanthin-treated ALI-induced mice. Zeaxanthin effectively prevented lung edema and immune cell infiltration. Oxidative stress and inflammatory cytokine synthesis induced by LPS in the lungs were significantly decreased with zeaxanthin treatment. Histopathological analysis also confirms our in vitro and in vivo biochemical analyses. Overall, our findings corroborate that zeaxanthin is a potent anti-inflammatory agent that effectively inhibits LPS-induced ALI in both in vitro and in vivo conditions.

RH (Rathu Heenati), an indica rice cultivar from Sri Lanka, is highly resistant to several different biotypes of brown planthopper (Nilaparvata lugens Stål, BPH). In contrast, another indica rice cultivar, TN1 (Taichung Native 1), is highly susceptible to all biotypes of BPH. To reveal the molecular biological mechanism of biotic and abiotic stress mediated by BPH suction in two rice cultivars, RH and TN1, the genome-wide gene expressional profiling of these two rice varieties at 6 h after BPH infestation and needle puncturing was conducted by performing transcriptome analysis. In total, six samples (T6C, T6N, T6B, R6C, R6N, and R6B) were collected after performing different treatments for this expressional analysis. The results provide important information for the further isolation of BPH-resistance genes from RH as well as research on the mechanism of BPH resistance in RH. The transcriptome results revealed that TN1 (a BPH-susceptible rice variety) and RH (a BPH-resistant rice variety) harbor different pathways that respond to the physical injury of acupuncture and BPH infestation. The susceptible variety TN1 is more sensitive to the physical damage caused by acupuncture, whereas in the resistant variety RH, the response to insect damage is more rapid and direct. By comparing the gene changes of various plant hormones between the two varieties under different stresses, it was found that, in addition to the traditional SA and ET pathways related to the feeding induction of piercing-sucking pests, the expression patterns of JAZ-related genes in the JA signaling pathway also changed under two stresses (acupuncture induction and brown planthopper feeding induction), while the IAA hormone pathway-related genes in the susceptible variety TN1 also changed significantly after brown planthopper feeding. Furthermore, the results of this study help us to understand the biological process of rice responses to BPH and provide a promising direction to identify BPH-resistance-related genes in RH.

Abstract Rare precipitation events with return periods of multiple decades to hundreds of years are particularly damaging to natural and societal systems. Projections of such rare, damaging precipitation events in the future climate are, however, subject to large inter‐model variations. We show that a substantial portion of these differences can be ascribed to the projected warming uncertainty, and can be robustly reduced by using the warming observed during recent decades as an observational constraint, implemented either by directly constraining the projections with the observed warming or by conditioning them on constrained warming projections, as verified by extensive model‐based cross‐validation. The temperature constraint reduces >40% of the warming‐induced uncertainty in the projected intensification of future rare daily precipitation events for a climate that is 2°C warmer than preindustrial across most regions. This uncertainty reduction together with validation of the reliability of the projections should permit more confident adaptation planning at regional levels.

Abstract Non-line-of-sight (NLOS) imaging aims at reconstructing targets obscured from the direct line of sight. Existing NLOS imaging algorithms require dense measurements at regular grid points in a large area of the relay surface, which severely hinders their availability to variable relay scenarios in practical applications such as robotic vision, autonomous driving, rescue operations and remote sensing. In this work, we propose a Bayesian framework for NLOS imaging without specific requirements on the spatial pattern of illumination and detection points. By introducing virtual confocal signals, we design a confocal complemented signal-object collaborative regularization (CC-SOCR) algorithm for high-quality reconstructions. Our approach is capable of reconstructing both the albedo and surface normal of the hidden objects with fine details under general relay settings. Moreover, with a regular relay surface, coarse rather than dense measurements are enough for our approach such that the acquisition time can be reduced significantly. As demonstrated in multiple experiments, the proposed framework substantially extends the application range of NLOS imaging.

Chinese mahogany (Toona sinensis) is of considerable medical and economic importance, and its genome has been deciphered. However, the process underlying its polyploidy is unclear, and the chromosomal evolutionary trajectory is poorly understood. Here, by reanalysing the T. sinensis genome, we found evidence of a tetraploidization event (T. sinensis special tetraploidization, TST) that occurred approximately 15–17 million years ago (MYA) after the core eudicot-common hexaploidization (ECH or gamma) event. We characterized the synonymous nucleotide substitution rates (Ks values) of collinear genes and found that T. sinensis genes affected by the TST evolve at a slower rate than Acer yangbiense genes. Furthermore, we identified homologous genes related to polyploidization and speciation and constructed multiple alignments with different reference genomes. Notably, the significant balance of gene retention and loss characterized in the two TST-derived subgenomes suggests an autopolyploid nature of the TST. Moreover, we deduced the chromosomal karyotypes of the two subgenomes and identified 7 chromosomal fusions that have shaped the T. sinensis genome; more information is available on a newly constructed karyotype platform (http://www.cgrpoee.top/Toona_sinensis/index.html). The T. sinensis genome preserves the ancestral chromosome structure of dicotyledons well and could serve as a good reference for understanding genomic changes in other Meliaceae and Sapindales plants. In addition, we verified that tandem duplication and the ECH have promoted the expansion of terpene synthase (TPS) genes; conversely, the TST seems to have inhibited expansion of these genes. This present effort has clarified the polyploidy events of the T. sinensis genome, filled gaps in the history of karyotype evolution, and laid a solid foundation for further genomic studies in the Meliaceae research community and beyond.

The three spacecraft of the space gravitational wave antenna employ heterodyne interferometry to mitigate the effects of Doppler shift. Constrained by laser relative intensity noise (RIN) and the sampling frequency constraints of phase readout circuits, the widespread adoption of fixed offset frequencies effectively regulates the frequency of heterodyne interferometric beat notes within a reasonable frequency domain of [5 MHz, 25 MHz]. In this work, a high-precision fitness genetic algorithm for heterodyne interferometry is utilized to generate the initial offset frequency distribution scheme. To address issues with unreasonable switching times and offset frequency settings in the initial scheme for partial frequency domains, optimization strategies are proposed from three aspects: frequency domain selection extension, switch times control, and numerical low frequency. Results demonstrate that the optimization of frequency domain selection extension narrows the reasonable frequency domain to [5 MHz, 15 MHz] and [7 MHz, 17 MHz]. Optimization of switch times control ensures that switching times of offset frequency distribution scheme generated under the settings of [6 MHz, 17 MHz] and wider frequency domains can be controlled within a reasonable range of 6 to 13 times. Fixed offset frequency settings are generally reduced by 24.3% after low-frequency optimization. This methodology and result can provide a reliable reference for Program Taiji and even related space gravitational wave antenna projects.

Intensification of biofuel production processes could play a critical role in boosting the economic and environmental features of the whole process. A novel bionic flow-induced peristaltic reactor with a high conversion rate is constructed to realize efficient biofuel production from high-concentration high-viscosity fluids. It is experimentally verified through biodiesel production from soybean oil. Experimental results show that the conversion efficiency is up to 89.9% at 10 s in the peristaltic reactor, which is 38.4% higher than that in the rigid tube reactor. Furthermore, a three-dimensional peristaltic model is conducted to understand the mechanism of heat and mass transfer enhancement. The simulation results show that an increase in peristaltic amplitude strengthens the mixing of the bionic peristaltic reactor by 92.5-100.8%. The temperature distribution in the bionic peristaltic reactor is more uniform than in the traditional rigid tube reactor. The results demonstrate that the conversion rate of soybean oil in the bionic flow-induced peristaltic reactor is 528.82% min-1, which is 17-60 times higher than other intensified reactors operating in either continuous or batch modes.

Abstract Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

Abstract Background Deer antler is a traditional Chinese medicine with the function of tonifying kidney and strengthening bone, which is often used to treat orthopedic diseases. Methods Eight-week-old C57BL/6 mice were used as the fixation model of open tibial fracture with intramedullary nail. The mice were treated with deer antler extract (DAE) or PBS by oral gavage once daily. The tibial fracture samples were collected and performed to the tissue analysis, including X-ray, micro-CT, histology, qRT-PCR, immunohistochemistry. MC3T3-E1 cells were used to detect the effect of deer antler extract on ability of cell proliferation and migration by CCK-8 assay and cell scratch test. Results Imaging and micro-CT showed that DAE could promote the healing of tibial fracture in mice, and histological analysis showed that DAE could promote the transformation of cartilage callus to bone callus in fracture area. The results of qRT-PCR and immunohistochemistry showed that DAE could promote intrachondral ossification in fracture zone and the mechanism of promoting fracture healing may be related to the activation of BMP-2/SMAD4 signaling pathway. In the cytological experiment of DAE, it can be found that DAE promoted the proliferation of MC3T3-E1 cells and the migration of MC3T3-E1 cells at a certain concentration, which is also related to the promotion of fracture healing by DAE. Conclusion DAE can promote fracture healing by activating BMP-2/SMAD4 signaling pathway. DAE has the potential to be used in clinic as an important means of promoting fracture healing.

Abstract Background Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. Results The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. Conclusion Our study demonstrates that OL cells can acquire the “metastatic ability” from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody’s back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

The rapid warming of the Tibetan Plateau (TP) in recent decades has led to severe consequences, including the melting of glaciers and snow cover, which further accelerates warming. Accurately projecting the magnitude of future warming is crucial for effective climate change adaptation. However, the projection of future temperature change is model dependent. In this study, we demonstrate a significant correlation between the historical inter-model warming trend and future temperature change, suggesting this relationship could be used to calibrate the best estimate of projections and reduce the uncertainty by observations. For a high emission scenario, the constraint helps to narrow down the uncertainty range of annual and summer temperature change on the western TP by up to 2 °C and 4 °C, respectively, in the end of this century. The most substantial calibrated increase of future change is in winter by up to 2 °C, followed by autumn with an increase by about 1 °C. Discrepancies of historical warming trend among different observation datasets expose the largest impact on the constrained best estimate compared with emergent relationship derived from different climate models and warming trend in different historical periods.

Abstract Background It is recorded in the Chinese Pharmacopoeia that deer antlers can be used to tonify the kidney and strengthen bone. Although numerous studies have demonstrated that deer antler has protective effects on the kidney and bone, its molecular mechanisms remain to be elucidated. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney. Methods Water extract of pilose antler was prepared and then filtered through a 0.45 μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. Rats were treated with deer antler extract (DAE) prepared in advance, and gene regulatory network in the kidney and bone was detected by RNA-Seq technique. Micro-CT was used to detect bone trabecular formation, bone mineral density (BMD) and bone volume fraction (BV/TV). Results The results demonstrate that DAE could jointly heighten renal function by maintaining renal homeostasis, combating renal fibrosis, and reducing renal inflammation by regulating ion transport. Furthermore, DAE can strengthen the bone system by stimulating osteoblast differentiation and regulating bone regeneration and the bone marrow microenvironment. Micro-CT results confirmed that DAE can promote bone trabecular formation and increase BMD and BV/TV. We also identified many genes that can regulate both the kidney and bone simultaneously, which explained the theory of “kidney governing bone” at the molecular level and provided possible strategies for further application of this theory to treat diseases. Conclusions DAE enhances renal function, maintains renal homeostasis, positively regulates skeletal system development, and increases bone mineral density. The underlying mechanism involves improving the expression levels of functional genes involved in renal function and regulation and repair, as well as genes that positively regulate skeletal system development.

Abstract Background Fibulin‐4, namely, EFEMP2, is an essential matricellular protein associated with a variety of malignancies. The aim of this study was to explore the role of fibulin‐4 in the progression of esophageal squamous cell carcinoma (ESCC), as well as its effect on ESCC sensitivity to apatinib treatment. Methods The expression of fibulin‐4 in ESCC tissues and cell lines was detected. Stably transfected ESCC cells were established by transducing lentiviral vectors for silencing or overexpressing the fibulin‐4 gene into ESCC cells, and a subcutaneous xenograft tumor model of ESCC in mice was successfully established. IHC, RT–qPCR and western blotting were used to detect the expression of related genes and proteins. The CCK8 assay, EdU cell proliferation assay, wound healing assay, transwell assay and flow cytometry were used to evaluate the proliferation, invasion, migration and apoptosis of ESCC cells. After mice were sacrificed, the transplanted tumors were resected, and their volumes were measured. Results The expression of fibulin‐4 was significantly increased in both ESCC tissues and cell lines, and the high expression was closely related to the poor clinicopathological features. Downregulation of fibulin‐4 inhibited the proliferation, invasion and migration of ESCC cells in vitro and in vivo. Meanwhile, fibulin‐4 knockdown inhibited autophagy of tumor cells by activating the Akt–mTOR signaling pathway and significantly promoted apatinib‐induced apoptosis of ESCC cells. Conclusion Our study showed that fibulin‐4 is an oncogene that can promote ESCC progression and inhibit apoptosis. Downregulation of fibulin‐4 enhances the sensitivity of ESCC cells to apatinib by inhibiting cellular protective autophagy through activating the Akt–mTOR signaling pathway.

BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information for patients with myocarditis. However, due to the low incidence rate of fulminant myocarditis (FM) and accordingly small sample size, the knowledge about the role of LGE to patients with FM is limited.Methods and resultsA total of 44 adults with viral-FM receiving the Chinese treating regimen were included in this retrospective study. They were divided into the low LGE group and the high LGE group according to the ratio of LGE to left ventricular mass (LGE mass%). CMR exams and LGE were performed after hemodynamic assistance at discharge in all patients with FM. Routine echocardiography parameters and global longitudinal strain (GLS) at discharge and at 2-year follow-up were obtained and then compared. Both left ventricular ejection fraction (LVEF) and GLS showed no significant difference in both groups at discharge, whereas significant differences were observed at 2-year follow-up between two groups. Moreover, there were significant improvements of LVEF and GLS in the low LGE group, but not in the high LGE group during the 2-year period. Furthermore, LGE mass% was negatively correlated with GLS and LVEF.ConclusionsThere were two distinct forms of LGE presentation in patients with FM. Moreover, the cardiac function of patients with low LGE was significantly better than those with high LGE at 2-year follow-up. LGE mass% at discharge provided significant prognosis information about cardiac function of patients with FM.

Objective: The prognostic factors for elderly patients with cervical cancer differ from those of younger patients. Competitive risk events could cause biases in the Cox proportional hazards (PH) model. This study aimed to construct a competitive risk model (CRM) nomogram for patients aged > 65 years with nonmetastatic cervical cancer. Methods: We retrospectively analyzed data extracted from the Surveillance, Epidemiology, and End Results (SEER) database and a total of 1856 patients from 18 cancer registries across the United States diagnosed between 2010 and 2015 were included. Kaplan–Meier analysis and log-rank tests were used to compare intergroup survival. Univariate and multivariate Cox proportional regression analyses were performed to identify independent prognostic factors. The cumulative incidence function (CIF) and Fine and Gray's test were used to determine the impact of competitive risk events on prognosis. The CRM nomogram was internally and externally validated using time-dependent receiver operator characteristic (ROC) curve (time-AUC), Brier scores, Harrell's concordance index (C-index), calibration curve, and decision curve analysis (DCA). Results: Analyses revealed that histology, age, the International Federation of Gynaecologists and Obstetricians (FIGO) stage, number of in situ malignancies, chemotherapy, radiotherapy (RT), and surgery were independent prognostic factors. The CRM nomogram accurately predicted 1-year, 3-year, and 5-year disease-specific survival (DSS). The C-indexes and Brier scores of the CRM nomogram were 0.641 and 0.094, respectively, at the 1-year cut-off in the training set. The time-AUC of the CRM nomogram at the 1-year, 3-year, and 5-year intervals in the training set were 77.6%, 77.3%, and 74.5%, respectively. The calibration curve demonstrated a favorable concordance. DCA suggested that the nomogram had a good net benefit. Therefore, the Cox model underestimated the weight of risk factors compared to CRM. Conclusions: This study presents the CRM nomogram to predict DSS in patients aged > 65 years with nonmetastatic cervical cancer. It can help clinicians implement more accurate personalized diagnostic and treatment modalities for elderly patients with cervical cancer.

Diamond abrasive tools play an important role in high-efficient and precision machining of hard and brittle materials such as engineering ceramics, glass and semiconductors. Due to the great challenge presented by the increase of part manufacturing quality, forming requirements and processing efficiency, the improvement of tool’s structure has become the key way for abrasive tools to overcome this challenge, but it has brought difficulties to tool manufacturing. In recent years, additive manufacturing technology has attracted much attention because of its excellent ability to form complex structures. The use of additive manufacturing technology for fabricating diamond abrasive tools has been considered as a potential means to solve the problem, therefore, it has become a research hotspot. Based on the existing relevant research reports, the work of this paper mainly focuses on stereo lithography apparatus technology (SLA), selective laser sintering technology (SLS) and laser selective melting technology (SLM), summarizes the research progress of existing additive manufacturing technology in the fabrication of diamond abrasive tools, analyzes the different characteristics of each method in its manufacturing process, and puts forward prospects and suggestions for making diamond abrasive tools by using this type of technology.

Abstract Background Gene conversion has an important effect on duplicate genes produced by polyploidization. Poplar (Populus trichocarpa) and willow (Salix brachista) are leading models and excellent green plants in the Salicaceae. Although much attention has been paid to the evolution of duplicated genes in poplar and willow, the role of conversion between duplicates generated from polyploidization remains poorly understood. Results Here, through genomic synteny analyses, we identified duplicate genes generated by the Salicaceae common tetraploidization (SCT) in the poplar and willow genomes. We estimated that at least 0.58% and 0.25% of poplar and willow duplicates were affected by whole-gene conversion after the poplar-willow divergence, with more (5.73% and 2.66%) affected by partial-gene conversion. Moreover, we found that the converted duplicated genes were unevenly distributed on each chromosome in the two genomes, and the well-preserved homoeologous chromosome regions may facilitate the conversion of duplicates. Notably, we found that conversion maintained the similarity of duplicates, likely contributing to the conservation of certain sequences, but is essentially accelerated the rate of evolution and increased species divergence. In addition, we found that converted duplicates tended to have more similar expression patterns than nonconverted duplicates. We found that genes associated with multigene families were preferentially converted. We also found that the genes encoding conserved structural domains associated with specific traits exhibited a high frequency of conversion. Conclusions Extensive conversion between duplicate genes generated from the SCT contributes to the diversification of the family Salicaceae and has had long-lasting effects on those genes with important biological functions.