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Abstract Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 μm) and broad modulus adjusting capability (15.8–345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.

Abstract Autonomous vehicles navigating urban roads require technology that combines low latency with high computing power. The limited resources of the vehicle itself compel it to offload task requirements to edge server (ES) for processing assistance. However, as the number of vehicles continues to increase, how edge servers reasonably allocate limited resources to autonomous vehicles becomes critical to the success of urban intelligent transportation services. This paper establishes an urban road scenario with multiple autonomous vehicles and an edge computing server and considers two main driving behaviour transition resource requests, namely car‐following behaviour requests and lane‐changing behaviour requests. Simultaneously, acknowledging that vehicles may encounter unforeseen traffic hazards when switching driving behaviours, a safety redundancy setting strategy is employed to allocate additional resources to the vehicle to ensure safety and model the vehicle resource allocation problem in the autonomous driving system. Double‐deep Q‐network (DDQN) is then used to solve this model and maximize the total system utility by comprehensively considering resource costs, system revenue, and autonomous vehicle safety. Finally, results from the simulation experiment indicate that the proposed dynamic resource allocation scheme, based on deep reinforcement learning for autonomous vehicles under edge computing, not only greatly improves the system's benefits and reduces processing delays compared to traditional greedy algorithms and value iteration, but also effectively ensures security.

Abstract Objective Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. Methods This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. Results and conclusions The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

In order to develop functional rice flour products with anti-digestive and antioxidant activities, the effects of adding Wuyi rock tea (WRT) on the quality, in vitro digestive characteristics and antioxidant activity of rice noodles were studied. The texture and sensory quality of rice noodles were determined by texture analyzer and sensory evaluation method, respectively. The flavor components were characterized by GC-MS, and the antioxidant activity was assessed by FRAP, DPPH and ABTS+ assays. The digestive characteristics of rice noodles were detected by the in vitro simulated digestion method. The results showed that compared to the control rice noodles, the breaking rate of rice noodles added with 2.9%~7.0%. WRT was not significantly changed (P>0.05), while the breaking rate of rice noodles added with 8.3% WRT was significantly increased (P

Abstract The IPv6 extension header mechanism, a new feature of the IPv6 protocol, enhances flexibility and scalability but introduces numerous security threats like firewall evasion and covert channels. Existing threat detection methods face limitations in detection types, universality, and speed. Hence, an adaptive detection model for IPv6 extension header threats (ADM-DDA6) is proposed. Firstly, standard rule sets are designed for common IPv6 extension headers, successfully detecting 70 types of threats from THC-IPv6 and ExtHdr tools using only 20 rules. Secondly, by parsing IPv6 extension headers, matching rules, establishing transition relationships, and deciding packet threat status based on final states (Normal or Abnormal), complex threats like header disorder and header repetition can be detected. Finally, an adaptive rule matching method is introduced, which dynamically selects rule sets based on IPv6 extension header types, effectively reducing rule matching time. Experimental results show that under different threat magnitudes, ADM-DDA6 is 32% faster than Suricata v6.0.12 and 21.2% faster than Snort v3.1.61.0 in detection speed. Additionally, as the number of threats increases, on commodity hardware, ADM-DDA6 incurs only a 0.7% increase in CPU overhead with no significant memory consumption increase, maintains maximum throughput, and exhibits minor performance changes under low and moderate network load conditions.

Abstract Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

BackgroundGlaucoma, a leading cause of global blindness, is characterized by optic nerve damage and visual field loss. Previous studies have suggested a potential association between glaucoma and anxiety disorders. However, the causal relationship between these two conditions remains unclear.MethodsIn this study, we conducted a Mendelian Randomization analysis to investigate the causal relationship between glaucoma and anxiety disorders. We sourced Genome-Wide Association Study (GWAS) datasets for glaucoma and anxiety with the largest sample sizes from the Integrative Epidemiology Unit OpenGWAS (IEU OpenGWAS) project website. Instrumental variables were selected based on specific criteria, and statistical analyses were performed using the R programming language.ResultsAfter filtering and merging the datasets, a total of 60 Single Nucleotide Polymorphisms (SNPs) were obtained for analysis. Regression models were applied to assess the causal relationship between glaucoma and anxiety disorders. The results from all four methods indicated that glaucoma does not cause anxiety disorders (p > 0.05).ConclusionThrough rigorous Mendelian Randomization analysis, our findings indicate that glaucoma is not a causative factor for anxiety, with minimal influence from confounding factors in this study. These findings enhance our understanding of the relationship between glaucoma and anxiety.

Light-flavor Baijiu (LFB) fermentation is a representative spontaneous mixed-culture solid-state fermentation process in which sorghum is used as the raw material. Raw materials and microorganisms are crucial to the flavor formation and quality of LFB. However, the microbial and physicochemical dynamics of different sorghum varieties during LFB fermentation, as well as their impact on flavor compounds are still largely unknown. Herein, PacBio single-molecule real-time (SMRT) sequencing and headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC–MS) were applied to investigate microbial community succession and volatile flavor formation in glutinous/non-glutinous sorghum-based fermented grains during LFB fermentation. Fermented grains made of glutinous sorghum Liangnuo No. 1 (GLN) had higher bacterial α-diversity and lower fungal α-diversity than those with fermented grains prepared with non-glutinous red sorghum (NRS) (p

Abstract Purpose The aim of this study was to assess the potential application of a radiomics features‐based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high‐risk non‐metastatic prostate cancer (PCa). Methods Clinicopathologic information was retrospectively collected from 162 patients with high‐risk non‐metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. Results Sixty‐three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754–0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739–0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839–0.954). The Hosmer–Lemeshow goodness‐of‐fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan–Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. Conclusion The radiomics–clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high‐risk non‐metastatic PCa.

“Green-covering and red-heart” Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the “green-covering” formed on the surface of Guanyin Tuqu (SQ) and the “red-heart” in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of “green-covering and red-heart” characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of “green” outside and “red” inside. This study provides fundamental information support for optimizing the production process of GRTQ.

BackgroundPreterm birth has been associated with an increased risk of myopia, but the causal relationship between these two factors remains unclear. Traditional epidemiological studies are limited by confounding factors and reverse causality. Mendelian randomization (MR) analysis, utilizing genetic variants as instrumental variables, provides a robust approach to investigate causal relationships. In this study, we aimed to explore the potential causal link between preterm birth and myopia risk using a two-sample MR analysis strategy.MethodsWe conducted a Mendelian randomization study to investigate the causal relationship between preterm birth and myopia risk. Genetic variants (single nucleotide polymorphisms, SNPs) were used as instrumental variables, and summary data from genome-wide association studies (GWAS) were utilized. Four regression models, including MR-Egger regression, weighted median regression, inverse variance weighted regression, and Weighted mode regression, were employed to validate the causal relationship. Sensitivity analysis was performed using the leave-one-out method. At the same time, the funnel diagram and MR-Egger test were used to judge the stability of the research results.ResultsThe MR analysis revealed a significant causal effect of preterm birth on myopia risk. Both the inverse variance weighted regression and weighted median regression models showed a p-value less than 0.05, indicating a robust association. The risk of myopia increased by approximately 30% for everyone standard deviation increase in preterm birth. Sensitivity analysis, funnel plot and MR-Egger test all confirm the stability of the research results.ConclusionOur findings provide evidence supporting a causal relationship between preterm birth and myopia risk. Preterm infants are at a higher risk of developing myopia, and this association is not likely to be influenced by confounding factors or reverse causality. The SNP loci rs6699397, rs10871582, and rs2570497 should be closely monitored as they may lead to abnormal concentrations of intraocular cytokines, particularly vascular endothelial growth factor, potentially elucidating one of the pathogenic mechanisms contributing to the higher incidence of myopia in preterm infants. However the complex interconnections involved extend beyond these factors alone.

Matrine (MT) and Oxymatrine (OMT) are two natural alkaloids derived from plants. These bioactive compounds are notable for their diverse pharmacological effects and have been extensively studied and recognized in the treatment of cardiovascular diseases in recent years. The cardioprotective effects of MT and OMT involve multiple aspects, primarily including antioxidative stress, anti-inflammatory actions, anti-atherosclerosis, restoration of vascular function, and inhibition of cardiac remodeling and failure. Clinical pharmacology research has identified numerous novel molecular mechanisms of OMT and MT, such as JAK/STAT, Nrf2/HO-1, PI3 K/AKT, TGF-β1/Smad, and Notch pathways, providing new evidence supporting their promising therapeutic potential against cardiovascular diseases. Thus, this review aims to investigate the potential applications of MT and OMT in treating cardiovascular diseases, encompassing their mechanisms, efficacy, and safety, confirming their promise as lead compounds in anti-cardiovascular disease drug development.

Rutting is a prevalent issue in the Gussasphalt (GA) mixture layer of steel bridge deck pavements. This study aims to investigate the correlation between the rheology of GA mastic and the high-temperature performance of the GA mixture. To achieve this objective, GA mastic underwent temperature and frequency sweep tests, along with multiple stress creep and recovery tests employing a dynamic shear rheometer. Additionally, indentation tests, uniaxial penetration tests, and Lueer fluidity tests were conducted on the GA mixture. The Grey Relational Analysis method was employed to evaluate the relationship between asphalt mastic rheology and the high-temperature deformation resistance of the GA mixture. The findings reveal that the addition of mineral filler enhances the deformation resistance of both GA mastic and the mixture. The percent difference in non-recoverable creep compliance (Jnr-diff) was minimized when the weight ratio of filler to asphalt binder (F/B) was 2.5. Furthermore, increasing the F/B ratio from 2.0 to 3.5 resulted in a more than twofold increase in the GA mixture’s shear strength. Asphalt type emerged as a significant factor affecting the indentation parameter of the GA mixture, with an F-value reaching 8.82 based on ANOVA analysis. The rheological properties of GA mastic exhibited a significant correlation with the high-temperature performance of the mixture. The highest Grey Relational Grade of 0.87 was observed between the non-recoverable creep compliance at a 3.2 kPa stress level (Jnr3.2) and indentation. In future research, greater emphasis can be placed on exploring the micromechanical properties of the GA mastic-aggregate interface.

Abstract Childhood obesity not only has a negative impact on a child's health but is also a significant risk factor for adult obesity and related metabolic disorders, making it a major global public health concern. Recent studies have revealed the crucial role of gut microbiota in the occurrence and development of obesity, in addition to genetic and lifestyle factors. In this study, we recruited 19 normal-weight children and 47 children with varying degrees of obesity. A questionnaire survey was conducted to inquire about the family background, lifestyle habits and dietary composition of the 66 children. Findings indicate that fathers of obese children tend to be obese themselves, while children with highly educated mothers are more likely to maintain a normal weight. Furthermore, overweight children tend to spend more time on electronic devices and less time on physical activities compared to their normal-weight counterparts. Obese children exhibit significant differences in breakfast and dinner dietary composition when compared to children with normal weight. Additionally, the gut microbiota of these 66 children was analyzed using 16S rRNA sequencing. Analysis of gut microbiota composition showed similar compositions among children with varying degrees of obesity, but significant differences were observed in comparison to normal-weight children. Obese children exhibited a reduced proportion of Bacteroidota and an increased proportion of Firmicutes, resulting in an elevated Firmicutes/Bacteroidota ratio. Moreover, Actinobacteriota were found to be increased in the gut microbiota of children with varying degrees of obesity. PICRUSt analysis indicated significant metabolic differences in the microbiota functions between obese and normal-weight children, suggesting the composition of gut microbiota could be a crucial factor contributing to obesity. These findings provide valuable insights for the treatment of childhood obesity.

Abstract Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.

With the increasing amount of space debris in near-earth space, the surveillance of space has become more crucial to prevent potential space collisions. In an optical surveillance system, a multitude of debris with varying sizes, speeds, and intensities exists within images, which brings great difficulties for the extraction of targets. Current methodologies mainly emphasize local saliency enhancement and source extraction based on global statistical attributes, yet often overlook the distribution similarity of individuals and how to map them in a standardized space. To address this limitation, this article introduces an innovative transformation from the grayscale space to the correlation space. Initially, a fourfold-structure model is designed to measure the local correlation for each element in the grayscale space. Subsequently, the standardized correlation space is constructed by correlation measurement. Then, combining an adaptive threshold choosing method based on statistics and a threshold limitation strategy based on correlation, the individuals can be separated from the feature space. Finally, a deblending method is applied to disentangle merged individuals based on the local gradient correlation. Thoroughly assessed using ten subimage sequences featuring targets with typical traits against complex backgrounds, the results confirm its superior extraction capabilities and effectiveness when compared to ten common baseline methods, which achieves an average 90.9% true positive rate in just 2.8 ms. Furthermore, the extraction outcomes serve as a basis for detecting true target trajectories in continuous sequences. This integration holds significant implications for practical applications in space surveillance engineering.

A digital controlled unipolar hysteresis current control strategy applied to the single-phase grid-connected inverter is studied in the paper. In view of the problem of current zero-crossing distortion in the traditional unipolar hysteresis current control based on finite state machines (FSM), a new unipolar hysteresis current control strategy based on current decoupling is proposed. By introducing a virtual zero-sequence current, the single-phase full-bridge inverter is decoupled into two independent half-bridge inverter units, which are controlled by two bipolar hysteresis current control loops under the constraints of a finite state machine. Therefore, the operation rules of the FSM ensure the frequency doubling output of the unipolar modulation, and the virtual two-phase decoupled current eliminates the zero-crossing distortion problem of inverter output current. Finally, the effectiveness and feasibility of the proposed method were verified by building a 1kW single-phase full-bridge grid-connected inverter in the laboratory.

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p

Summary: The swift advancement of the solid oxide fuel cell (SOFC) sector necessitates a harmony between electrode performance and commercialization cost. The economic value of elements is frequently linked to their abundance in the Earth’s crust. Here, we develop abundant rare-earth iron perovskite electrodes of Ln0.6Sr0.4FeO3-δ (Ln = La, Pr, and Nd) with high abundant rare-earth metals and preferred iron metal for SOFCs. All three symmetric electrode materials display a cubic perovskite phase and excellent chemical compatibility with Gd0.2Ce0.8O2-δ electrolyte. All three electrodes possess exceptional surface oxygen exchange ability. At 800°C, single cells with La0.6Sr0.4FeO3-δ, Pr0.6Sr0.4FeO3-δ, and Nd0.6Sr0.4FeO3-δ symmetric electrodes attained excellent open circuit voltages of 1.108, 1.101, and 1.097 V, respectively, as well as peak powers of 213.52, 281.12, and 254.58 mW cm−2. The results suggest that overall performance of abundant rare-earth iron perovskite electrodes has a favorable impact on the extensive expansion of SOFCs, presenting significant potential for practical applications.

IntroductionTreatments that currently exist in the strategic national stockpile for acute radiation syndrome (ARS) focus on the hematopoietic subsyndrome, with no treatments on gastrointestinal (GI)-ARS. While the gut microbiota helps maintain host homeostasis by mediating GI epithelial and mucosal integrity, radiation exposure can alter gut commensal microbiota which may leave the host susceptible to opportunistic pathogens and serious sequelae such as sepsis. To mitigate the effects of hematopoietic ARS irradiation, currently approved treatments exist in the form of colony stimulating factors and antibiotics: however, there are few studies examining how these therapeutics affect GI-ARS and the gut microbiota. The aim of our study was to examine the longitudinal effects of Neulasta and/or ciprofloxacin treatment on the gut microbiota after exposure to 9.5 Gy 60Co gamma-radiation in mice.MethodsThe gut microbiota of vehicle and drug-treated mice exposed to sham or gamma-radiation was characterized by shotgun sequencing with alpha diversity, beta diversity, and taxonomy analyzed on days 2, 4, 9, and 15 post-irradiation.ResultsNo significant alpha diversity differences were observed following radiation, while beta diversity shifts and taxonomic profiles revealed significant alterations in Akkermansia, Bacteroides, and Lactobacillus. Ciprofloxacin generally led to lower Shannon diversity and Bacteroides prevalence with increases in Akkermansia and Lactobacillus compared to vehicle treated and irradiated mice. While Neulasta increased Shannon diversity and by day 9 had more similar taxonomic profiles to sham than ciprofloxacin-or vehicle-treated irradiated animals. Combined therapy of Neulasta and ciprofloxacin induced a decrease in Shannon diversity and resulted in unique taxonomic profiles early post-irradiation, returning closer to vehicle-treated levels over time, but persistent increases in Akkermansia and Bacteroides compared to Neulasta alone.DiscussionThis study provides a framework for the identification of microbial elements that may influence radiosensitivity, biodosimetry and the efficacy of potential therapeutics. Moreover, increased survival from H-ARS using these therapeutics may affect the symptoms and appearance of what may have been subclinical GI-ARS.

AbstractBacillus coagulans LYBC06 strain with lactate-producing capacity was isolated from mucosal tissue of the digestive tract of a fattening pig. The resequencing of the LYBC06 strain revealed that the overall genome was less variable, with a genome-wide heterozygous ratio of 0.042 %, total SNP locus variants 0.4273% of the entire genome, total InDel mutations 0.0182%, total increased and decreased CNV copies 0.0031% and total SV annotated variants 0.0083% of the entire genome. The mutated genes were mainly involved in the growth of the strain, regulation of energy metabolism, and production of proteases and lactate. The whole genome of LYBC06 strain was sequenced with the length of 3385106 bp, GC content of 46.86% and 4092 coding genes (85.96% of coding). Functional annotation of the proteins encoding genes showed that the growth process of LYBC06 strain involved several metabolic pathway transformation processes of various substances, and many encoding genes were involved in the resistance to macrolides, polypeptides and tetracyclines. The basic characteristics of the genome of LYBC06 strain were relatively similar to those of other Bacillus coagulans, and the collinearity between several Bacillus coagulans strains was relatively good. Bacterial growth, gene expression of lactate dehydrogenase and lactate production in LYBC06 strain were largely synchronized, and the maximum amount of lactate could be produced up to 92 g/L at 16 h culture during the logarithmic growth phase, in which the LdhL1 gene played an important role in the production of lactate in LYBC06 strain.

Abstract Objective To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC). Methods Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality‐of‐life scores and postoperative clinical parameters. Results Spearman correlation analysis showed that postoperative BMI, late complications and catheter‐free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter‐free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p

Abstract Due to the advantages of rapid deployment, flexible response and strong invulnerability, unmanned aerial vehicle (UAV) swarm has been widely applied in collaborative warfare and emergency communication. However, UAV swarm in complex environments is prone to chaotic collapse due to obstructions. A UAV swarm obstacle avoidance system model for multi-narrow type obstacles is established. Due to the fact that only one UAV is allowed to pass through each small hole at any given moment, addressing the issue of congestion caused by swarming effects becomes crucial in addition to managing the competitive allocation of multiple UAVs to multiple holes. Aiming at this problem, a dual-game real-time obstacle avoidance scheme is proposed for UAV swarm with multi-narrow type obstacle scenarios, which divides the flight process of the UAV swarm into two stages: maintaining the flight state of the UAV swarm unchanged when no obstacles are encountered, and implementing matching separation and motion state switching by means of dual-game strategy when facing multi-narrow type obstacles, ultimately achieving orderly passage after multiple rounds of games. For the proposed scheme, a dual-game based Flocking (DGF) obstacle avoidance algorithm is proposed. Specifically, the motion state of each UAV obtained from the game is parameterized and integrated with the Flocking algorithm to calculate the motion control input for each UAV. The solution is iteratively obtained until the UAV swarm completes the obstacle avoidance. Simulation results demonstrate that the proposed DGF algorithm not only enables smooth obstacle avoidance for the UAV swarm in multi-narrow type obstacle scenarios, but also effectively resolves the internal chaos problem in the UAV swarm, thereby preventing rigid collisions.

Abstract Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient’s renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma.

Defect-engineering accelerates the conduction of lithium ions in the cathode materials of lithium-ion batteries. However, the effects of defect-engineering on ion conduction and its mechanisms in humid environments remain unclear in the academic discourse. Here, we report on the effect of vacancy defects on the electronic properties of and Li-ion diffusion in a LiFePO4 material in humid environments. The research findings indicate that vacancy defects reduce the lattice constant and unit cell volume of LiFePO4. Additionally, the water molecules occupy the Li-ion vacancies, leading to an increase in the lattice constant of LiFePO4. The computational results of the electronic properties show that the introduction of water molecules induces a transition in LiFePO4 from a semiconductor to a metallic behavior, with a transfer of 0.38 e of charge from the water molecules to LiFePO4. Additionally, the migration barrier for Li ions in the H2O + LiFePO4 system is found to be 0.50 eV, representing an 11.1% increase compared to the pristine LiFePO4 migration barrier. Our findings suggest that water molecules impede the migration of Li ions and provide important insights into the effect of defect-engineering on electronic properties and ion conduction under humid conditions.

Introduction: Due to the cardiotoxicity of pirarubicin (THP), it is necessary to investigate new compounds for the treatment of THP-induced cardiotoxicity. Isoquercitrin (IQC) is a natural flavonoid with anti-oxidant and anti-apoptosis properties. Thus, the present study aimed to investigate the influence of IQC on preventing the THP-induced cardiotoxicity in vivo and in vitro.Methods: The optimal concentration and time required for IQC to prevent THP-induced cardiomyocyte damage were determined by an MTT assay. The protective effect was further verified in H9c2 and HCM cells using dichlorodihydrofluorescein diacetate fluorescent probes, MitoTracker Red probe, enzyme-linked immunosorbent assay, JC-1 probe, and real time-quantitative polymerase chain reaction (RT-qPCR). Rats were administered THP to establish cardiotoxicity. An electrocardiogram (ECG) was performed, and cardiac hemodynamics, myocardial enzymes, oxidative stress indicators, and hematoxylin-eosin staining were studied. Voltage-dependent anion channel 1 (VDAC1), adenine nucleotide translocase 1 (ANT1), and cyclophilin D (CYPD) were detected by qRT-PCR, and the Phlpp1/AKT/Bcl-2 axis proteins were detected by western blot, confirming that IQC markedly increased cell viability and superoxide dismutase (SOD) levels, diminished the levels of ROS and MDA, and elevated mitochondrial function and apoptosis in vivo and in vitro.Results: Results showed that IQC reduced THP-induced myocardial histopathological injury, electrocardiogram (ECG) abnormalities, and cardiac dysfunction in vivo. IQC also decreased serum levels of MDA, BNP, CK-MB, c-TnT, and LDH, while increasing levels of SOD and GSH. We also found that IQC significantly reduced VDAC1, ANT1, and CYPD mRNA expression. In addition, IQC controlled apoptosis by modulating Phlpp1/AKT/Bcl-2 signaling pathways. IQC markedly increased H9c2 and HCM cell viability and SOD levels, diminished the levels of ROS and MDA, and elevated mitochondrial function in H9c2 and HCM cells to defend against THP-induced cardiomyocyte apoptosis in vitro. The AKT inhibitor IMQ demonstrated that IQC lacked antioxidant and anti-apoptotic properties. Moreover, our data showed that IQC regulates Phlpp1 expression, thereby influencing the expression levels of p-AKT, cytochrome c, caspase-3, caspase-9, Bcl-2, and Bax.Discussion: In conclusion, our results indicate that IQC protects the changes in mitochondrial membrane permeability in cardiomyocytes by regulating the Phlpp1/AKT/Bcl-2 signaling pathway, inhibits the release of cytc from the mitochondrial inner membrane to the cytoplasm, forms apoptotic bodies, induces cell apoptosis, and reduces THP induced cardiotoxicity.

Due to the randomness of hard and brittle material damage evolution, assessing damage and interpreting mechanisms is challenging. This study focuses on analyzing material damage mechanisms by employing extensive multi-source heterogeneous data to extract quantitative information. A machine vision-based method for detecting and assessing defects in ceramics was proposed, achieving 98 % accuracy. Leveraging this method in scratching experiments, the progression of damage and micro-failure mechanisms in Si3N4 was investigated through the analysis of defect area distribution, force and acoustical signals. Results revealed that the distribution of defect areas conforms to a three-parameter Weibull distribution. At scratch depths of 0.01, 0.02 mm, approximately 90 % of damage accumulated within 1e2–1e4 μm2; conversely, 0.03–0.06 mm led to a decrease to 30 – 40 %. Extensive crack propagation occurs within 0.02–0.03 mm, resulting in the intersecting formation of spalling blocks. Damage evolution occurs in three stages: shallow and small cracks with scattered spalling blocks in the first stage, deep and long cracks with continuous and irregularly shaped spalling blocks in the second stage, and nearly no cracks with continuous and regularly shaped blocks in the third stage. This study not only proposes an efficient method to detect and evaluate ceramic defects, but also deeply understands the evolution process of material damage mechanism. Considering defect distribution and statistical trends, this research not only provide guidance for the optimization of machining parameters, especially in the scene of specific precision and high removal rate. At the same time, the damage evolution and failure mechanism of Si3N4 provide useful experimental basis and data support for deepening the understanding of material behavior during ultra-precision grinding.

Abstract A potential probiotic strain BXM2 was isolated from naturally fermented honey passion fruit beverage, and identified as Lactiplantibacillus plantarum using 16S rDNA sequence analysis, rpoA gene sequence analysis combined with API bacterial identification method. BXM2 was evaluated for its probiotic and technological properties, such as growth efficiency, gastrointestinal tolerance, antibacterial activity and antibiotic resistance. The results showed that the optimum growth efficiency of BXM2 was achieved under the fermentation temperature ranged from 30°C to 37°C. The initial content of BXM2 (8.50 log CFU/mL) was decreased to 7.53 log CFU/mL after 3 h treatment in simulated gastric fluid (pH = 3.0) and 8.12 log CFU/mL after 6 h treatment in simulated intestinal fluid (pH = 8.0) (p

Abstract Background Recent studies have shown that gut microbiome plays important roles in response to radiation exposure. IL-18, an inflammatory cytokine, is highly elevated in mice, mini-pigs and nonhuman primates after radiation exposure. Blocking IL-18 using its endogenous binding protein (IL-18BP) increases mice survival after radiation exposure by decreasing bone marrow interferon-gamma levels. Methods To further characterize the roles of IL-18 in response to radiation, both wild type and IL-18 knockout (IL-18 KO) mice were exposed to 9.0 Gy total body irradiation (TBI). The 30-day survival result demonstrated that IL-18 KO mice were significantly more resistant to radiation compared to the wild type mice (p

The shadow mode-based regular sampling methods are usually used in the digital control of power inverters, which introduce a control delay of one and a half sampling periods. The control delay affects the closed loop bandwidth and the stability of dc–ac inverters. Recently, regular sampling methods based on the immediate mode is emerging and helpful for reducing the digital control delay. When employing the immediate mode, the induced vertical crossings may arouse the duty-cycle loss and dead-band effect during the modulation process, which deteriorate the normal operation of the inverters. Although the duty-cycle loss can be avoided by forcing the PWM signal to flip at the occurrence of vertical crossings, the introduced dead bands still exist. Thus, this paper investigates the phenomenon of vertical crossings and proposes a control algorithm composed of predicting the occurrence of vertical crossings and compensating the dead-band effect for regular sampling methods based on the immediate mode. Finally, experimental results on a single-phase dc–ac inverter prototype are provided to compare the efficacy of different approaches.

With the high flexibility and low cost of the deployment of UAVs, the application of UAV-assisted data collection has become widespread in the Internet of Things (IoT) systems. Meanwhile, the age of information (AoI) has been adopted as a key metric to evaluate the quality of the collected data. Most of the literature generally focuses on minimizing the age of all information. However, minimizing the overall AoI may lead to high costs and massive energy consumption. In addition, not all types of data need to be updated highly frequently. In this paper, we consider both the diversity of different tasks in terms of the data update period and the AoI of the collected sensing information. An efficient data collection method is proposed to maximize the system utility while ensuring the freshness of the collected information relative to their respective update periods. This problem is NP-hard. With the decomposition, we optimize the upload strategy of sensor nodes at each time slot, as well as the hovering positions and flight speeds of UAVs. Simulation results show that our method ensures the relative freshness of all information and reduces the time-averaged AoI by 96.5%, 44%, 90.4%, and 26% when the number of UAVs is 1 compared to the corresponding EMA, AOA, DROA, and DRL-eFresh, respectively.

ABSTRACTThe psychological factors of senior executives have an important impact on the firm’s financial policies. In this paper, we investigate the association between CEO risk-taking entrepreneurial spirit and firm cash holdings, and find that firms with higher CEO risk-taking entrepreneurial spirit have less cash holdings. Further, we find that financing constraints can mitigate the negative association between CEO risk-taking entrepreneurial spirit and firm cash holdings, whereas financing needs enhances the association between them. Mechanism test illustrates that CEO risk-taking entrepreneurial spirit affects firm cash holdings through corporate investment. Finally, the results reveal that CEO risk-taking entrepreneurial spirit not only promotes the value of cash holdings, but also is significantly positively associated with both accounting performance and market performance. Our findings shed lights on the impact of executive psychological factors on financial decisions and have important implications for cash-holding decisions of listed firms.

Abstract Although the ‘one ticket transfer’ mode brings convenience to passengers, it also poses challenges to the passenger flow assignment. The current widely used multi‐path probability assignment model based on traffic cost realizes the passenger flow distribution from the macro‐perspective but lacks the consideration of passenger attributes and the time‐varying characteristics of passenger travel time. Here, a novel spatiotemporal path inference model is proposed for Urban Rail Transit (URT) passengers based on the travel time data and train operation information. In this study, the impact of passengers detained at the platform on passenger travel itinerary is considered by characterizing the passenger detention rate. The proposed method realizes the reverse inference of passenger path from the micro‐perspective, and can accurately describe the specific travel process of each passenger. Moreover, the real‐world data of Shenzhen Metro in China is taken to verify the rationality of the proposed model. The results show that the model is in good agreement with the existing clearance model and can accurately infer the passenger travel itinerary from the micro‐perspective. The proposed method provides a more refined solution for the spatial‐temporal assignment of URT passenger flow.

We developed a simple method of in-situ synthesize carbon nanotubes (CNTs) on Ti–6Al–4V (TC4) alloy powder to fabricate CNTs/TC4 compound powders through plasma-enhanced chemical vapor deposition (PECVD). By this approach, CNTs on TC4 alloy powder exhibit better uniform dispersion and morphology compared with the traditional CVD methods. In order to reveal the growth behavior of CNTs during the PECVD process, XRD, SEM, TEM, and Raman spectroscopy were used to analyze the morphology and graphitization of CNTs at different synthesis conditions. The plasma is benefit to the pyrolysis of CH4, but overmuch plasma bombardment also reduces the yield and quality of CNTs. The number of CNTs can be significantly improved with appropriately increasing the temperature and time, but excessive temperature, time and carbon concentration can increase the number of impurities such as amorphous carbon. Significantly, the growth mechanism of CNTs synthesized in TC4 powders is following tip-growth mode in PECVD process. Additionally, the quantity and quality were satisfactory at 600 °C for 30 min with 50 W plasma power. This study about PECVD process lays a foundation for improving the comprehensive properties of CNTs/TC4 composites in the future.

IntroductionBrain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20–40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP.MethodsB6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3).ResultsCIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased.DiscussionCIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

IntroductionPrevious studies have shown disrupted effective connectivity in the large-scale brain networks of individuals with major depressive disorder (MDD). However, it is unclear whether these changes differ between first-episode drug-naive MDD (FEDN-MDD) and recurrent MDD (R-MDD).MethodsThis study utilized resting-state fMRI data from 17 sites in the Chinese REST-meta-MDD project, consisting of 839 patients with MDD and 788 normal controls (NCs). All data was preprocessed using a standardized protocol. Then, we performed a granger causality analysis to calculate the effectivity connectivity (EC) within and between brain networks for each participant, and compared the differences between the groups.ResultsOur findings revealed that R-MDD exhibited increased EC in the fronto-parietal network (FPN) and decreased EC in the cerebellum network, while FEDN-MDD demonstrated increased EC from the sensorimotor network (SMN) to the FPN compared with the NCs. Importantly, the two MDD subgroups displayed significant differences in EC within the FPN and between the SMN and visual network. Moreover, the EC from the cingulo-opercular network to the SMN showed a significant negative correlation with the Hamilton Rating Scale for Depression (HAMD) score in the FEDN-MDD group.ConclusionThese findings suggest that first-episode and recurrent MDD have distinct effects on the effective connectivity in large-scale brain networks, which could be potential neural mechanisms underlying their different clinical manifestations.

With global warming and an increase in extreme weather, reducing carbon emissions in response to climate change has become a global consensus. Compared with traditional fuel vehicles, hybrid vehicles have the benefits of energy savings, low grid-load, and low emissions. The hybrid vehicles use the internal combustion engine and lithium-ion batteries as the hybrid power source to achieve the best match between the engine and the motor. However, the current commercial hybrid vehicle still has such defects as high dependence on fossil fuels, high carbon emissions, poor safety, etc. As such, it is necessary to explore and develop the next generation low-carbon hybrid vehicles. Herein, we propose a new-type hybrid of ammonia fuel cell and internal combustion engine with high-energy conversion efficiency and low-carbon emissions. Considering the advantages of low-carbon emissions, high mileage, fast refueling, low-cost, high-energy conversion efficiency, and high safety, a green low-carbon concept of the ammonia fuel cell-internal combustion engine hybrid vehicle (AFC-ICE HV) is proposed. This will help improve the scale and efficiency of China's green energy conversion, establish a green, low-carbon and sustainable economic system, provide new impetus for tackling climate change and environmental protection recovery, and help China and the world to achieve the Carbon Peak and Carbon Neutrality goal.

Summary: The continuous monitoring of vital signs is one of the hottest topics in healthcare. Recent technological advances in sensors, signal processing, and image processing spawned the development of no-contact techniques such as remote photoplethysmography (rPPG). To solve the common problems of rPPG including weak extracted signals, body movements, and generalization with limited data resources, we proposed a dual-path estimation method based on video magnification and deep learning. First, image processes are applied to detect, track, and magnificate facial ROIs automatically. Then, the steady part of the wave of each processed ROI is used for the extraction of features including heart rate, PTT, and features of pulse wave waveform. The blood pressures are estimated from the features via a small CNN. Results comply with the current standard and promise potential clinical applications in the future.

In this paper, a solid-state circuit breaker (SSCB) suitable for high-voltage DC systems is presented. A single gate driver is used to drive multiple series-connected power semiconductor devices, leading to a compact, reliable, and cost-effective design. An accelerating capacitor in parallel with a diode is used to charge the gate capacitors of the upper devices without an additional gate driving circuit. Simultaneous turn-on and turn-off are realized similarly to the structure with individual gate drivers. It can achieve good static and dynamic voltage balancing with the help of metal oxide varistors (MOV). Compared to the conventional single gate driver structures, negative gate voltages for all the devices are guaranteed during the entire OFF state simply by using two transient-voltage-suppression (TVS) diodes. Thus, the notorious gate voltage oscillation and the severe voltage unbalance problems during the voltage recovery process are eliminated. An 800 V/100 A SSCB simulation and experimental prototype based on two series-connected IGBTs are built to verify the effectiveness of the proposed structure.

The parallel interleaved three-phase inverters are suitable for high-power applications due to the current ripple canceling effect. The power density and efficiency can be further improved with the current ripple prediction (CRP) based high frequency zero-voltage switching (ZVS). However, the variable switching frequency increases rapidly as the power decrease, resulting in higher turn-off loss at light load despite the elimination of turn-on loss. In this paper, a phase-shedding control strategy is proposed along with the CRP based ZVS method to improve the light load efficiency. Only four phase-legs of the two parallel inverters operate at light load to reduce the switching frequency and the circulating current between the two clamping phase-legs. The proposed method can achieve full-range ZVS for all the switches without any auxiliary circuits or high frequency sensors. Current sharing can also be realized between the two clamping phase-legs based on accurate gate signal modulation. A 5 kW simulation and experimental prototype using SiC devices interfacing 400 V dc with three-phase 110 V ac grid is developed to verify the effectiveness of the proposed control strategy.

Abstract Background Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. Methods Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. Results The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. Conclusions The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Background: Myogenin is well known as a crucial transcription factor in skeletal muscle development, yet its other biological functions remain unexplored. Previous research showed that myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes, and offered a new perspective on myogenin’s role in cardioprotection. However, the detailed mechanism of this cardioprotection, especially under oxidative stress, is still unclear. Methods: In this study, hydrogen peroxide (H2O2) was used to generate reactive oxygen species in myogenin-overexpressing cardiomyocytes. The apoptosis was examined by flow cytometry. Transcriptome sequencing (RNA-seq) was performed to identify genes regulated by myogenin. Western blotting was used to detect the protein level of DUSP13 and the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). The dual-luciferase reporter assay and ChIP assay were used to confirm the binding of myogenin to the promoter region of DUSP13. DUSP13 overexpression and knockdown assays were performed to study its anti-apoptotic role. Results: Flow cytometry analysis of apoptosis showed that overexpressing myogenin for 24 and 48 hours decreased the apoptotic ratio by 47.9% and 63.5%, respectively, compared with untreated controls. Transcriptome sequencing performed on cardiomyocytes that expressed myogenin for different amounts of time (6, 12, 24, and 48 hours) identified DUSP13 as being up-regulated by myogenin. Western blotting showed that overexpression of myogenin increased the expression of DUSP13 and decreased the phosphorylation level of p38 MAPK. A dual-luciferase reporter assay proved that myogenin bound directly to the promoter region of DUSP13 and led to strong relative luciferase activity. Direct expression of DUSP13A and DUSP13B significantly reduced the rates of apoptosis and necrosis in cells treated with H2O2. Knockdown of DUSP13B significantly increased the rate of apoptosis in cells treated with H2O2. Conclusions: The present findings suggest that myogenin might attenuate apoptosis induced by reactive oxygen species by up-regulating DUSP13 and inactivating the p38 MAPK pathway.

Significant advancements in ultra-precision machining technology have forced a re-examination of the spindle perpendicularity errors’ impact on the milled surface quality at the micro-nano scale. In this paper, a method of spindle precision adjustment is proposed to enhance surface finish quality. Sensitive errors in the machining process are identified using multi-body kinematic theory, with the milling process serving as an example. A two-degree-of-freedom (2-DOF) rotation platform is designed, optimized, and fabricated. The platform’s static model is established based on elastic beam theory and verified by finite element analysis. Structural parameters are optimized via the response surface method in combination with the Pareto front. Experimental results reveal the effects of spindle speed, voltage amplitude, vibration frequency, cutting depth, and feed rate on the platform’s modulation performance. The static modulation experiment shows that the perpendicularity error between the spindle and the guideway can be reduced from 92.5 μ rad to 0.25 μ rad. Finally, milling experiments show that the surface quality can be improved by 37.6% after spindle modulation.

IntroductionThe emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak.MethodsA retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement.ResultsPediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group.DiscussionThe clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients.

Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.

Green ceramsite concrete is an environmentally friendly sound-absorbing material for high-speed railway sound barriers. However, given its low sound absorption, this material is not widely used. Therefore, this study proposes a triple-hole structure to improve the sound absorption of green ceramsite concrete. The triple-hole structure comprised micro-sized holes in the ceramsite, medium-sized holes between the ceramsite, and surface macro-sized holes. The surface macro-sized holes were obtained by changing the mold shape, and the other holes were formed by formula control. The influence of the surface macro-sized holes on the acoustic performance of the triple-hole structure was analyzed using an impedance tube test. Results showed that the sound absorption coefficient increased when the hole diameter decreased or the surface porosity increased. The optimal surface macro-sized holes increased the average sound absorption coefficient by 83 %. The surface macro-sized holes improved the acoustic performance by absorbing the reflection of incident sound and not by resonance effect. This effect was attenuated when the relative surface area was increased by more than 100 %. Compared with the ANN method, the finite element simulation method cannot accurately reflect the acoustic effects of the triple hole structure. Back propagation neural network was used to predict the effect and can realize an accuracy of 95.5 %. Thus, this study proposes a reference for the design of sound-absorbing concrete based on frequency.