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The sharing of pathological data is highly important in various applications, such as remote diagnosis, graded diagnosis, illness treatment, and specialist system development. However, ensuring reliable, secure, privacy-preserving, and efficient sharing of pathological data poses significant challenges. This paper presents a novel solution that leverages blockchain technology to ensure reliability in pathological data sharing. Additionally, it employs conditional proxy re-encryption (C-PRE) and public key encryption with equality test technology to control the scope and preserve the privacy of shared data. To assess the practicality of our solution, we implemented a prototype system using Hyperledger Fabric and conducted evaluations with various metrics. We also compared the solution with relevant schemes. The results demonstrate that the proposed solution effectively meets the requirements for pathological data sharing and is practical in production scenarios.

PurposeThis systematic review and meta-analysis of clinical observational studies aims to clarify the correlation between the intake levels of fruits and vegetables and non-alcoholic fatty liver disease (NAFLD).Materials and methodsPubMed, Embase, Web of Science, and the Cochrane Library were searched for studies on the association between vegetable or fruit intake with the risk of NAFLD from the foundation of each database up until September 2023. The relative risk (OR) and the 95% confidence interval (CI) were pooled for both the highest and lowest consumption levels of vegetables and fruits to explore their association with the incidence of NAFLD.ResultsThe meta-analysis encompassed 11 studies with a total of 493,682 patients. A higher consumption of vegetables (OR = 0.78, 95% CI = 0.67–0.91) and fruits (OR = 0.88, 95% CI = 0.83–0.93) was found to have a negative correlation with the risk of NAFLD, denoting an inverse association. This correlation, however, varied among different ethnic groups and gender.ConclusionsOur results indicate that increased consumption of vegetables and fruits is associated with a reduced likelihood of developing NAFLD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023460430.

An improved leaf target detection method based on the YOLOv5s network is proposed to address the issues of low model detection accuracy and slow detection speed in potato leaf image target detection. Firstly, a deformable convolution replaces the standard convolution in YOLOv5s to ensure that the convolution region always covers the target region. Secondly, CBAM attention module is introduced into the convolutional module to enhance local feature extraction and fusion capability of the network, while WIoU_Loss serves as Bounding box loss function SRN-DeblurNet deblurnet is combined with YOLOv5s network to convert part of fuzzy images into clear ones before being integrated with multi-scale features for model prediction. To verify its effectiveness, we trained our model using Pytorch deep learning framework and achieved an accuracy rate of 90.3% and recall rate of 88%, which are respectively 8.6% and 8.9% higher than those obtained by YOLOv5s.

Multimodal Sentiment Analysis (MSA) is gaining attention, but faces two main challenges: efficient extraction of cross-modal features without redundancy and removing spurious correlations between sentiment labels and multimodal features. In this paper, we propose a novel multimodal learning debiasing model, named Bilateral Cross-modal Debias Multimodal sentiment analysis Model (BCD-MM), to address these issues. Specifically, BCD-MM ultimately enhances the generalisation of the model to out-of-distribution (OOD) situations by improving the ability of cross-modal low-redundancy feature extraction and reducing the reliance on non-causal correlations. First, BCD-MM utilizes an attention score-based method to preserve critical information and eliminate redundancy within modalities. It also employs a gated crossmodal attention mechanism to filter inconsistencies through modal interaction, thereby enhancing the extraction of cross-modal specific features. Second, BCD-MM incorporates a debiasing approach with double bias extraction, using a Tanh-based Mean Absolute Error (TMAE) loss function and inverse probability weighting to mitigate spurious correlations. Finally, extensive testing on three public datasets (MOSI, MOSEI, and SIMS) and two OOD datasets (OOD MOSI and OOD MOSEI) demonstrates our model’s effectiveness in both MSA and debiasing tasks.

AbstractContext Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear.Objective To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms.Materials and methods C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed.Results The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa.Discussion and conclusions XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

A two-layer scheduling method of energy storage that considers the uncertainty of both source and load is proposed to coordinate thermal power with composite energy storage to participate in the peak regulation of power systems. Firstly, considering the characteristics of thermal power deep peak regulation, a cost model of thermal power deep peak regulation is constructed and fuzzy parameters are used to manage the uncertainty of wind, photovoltaics, and load. Secondly, based on the peaking characteristics and operating costs of composite energy storage, a two-layer optimal scheduling model of energy storage is constructed. The upper layer takes pumped storage as the optimization goal to improve net load fluctuation and the optimal peak load benefit; the lower layer takes the system’s total peak load cost as the optimization goal and obtains a day-before scheduling plan for the energy storage system, using an improved gray wolf algorithm to process it. Finally, we verify the effectiveness of the proposed strategy based on an IEEE 39-node system.

Potato powdery scab is a serious disease that affects potato yield and has widespread global impacts. Due to its concealed symptoms, it is difficult to detect and control the disease once lesions appear. This paper aims to overcome the drawbacks of interactive algorithms and proposes an optimized approach using object detection for the GrabCut algorithm. We design a YOLOv7-guided non-interactive GrabCut algorithm and combine it with image denoising techniques, considering the characteristics of potato powdery scab lesions. We successfully achieve effective segmentation of potato powdery scab lesions. Through experiments, the improved segmentation algorithm has an average accuracy of 88.05%, and the highest accuracy can reach 91.07%. This is an increase of 46.28% and 32.69% respectively compared to the relatively accurate K-means algorithm. Moreover, compared to the original algorithm which could not segment the lesions independently, the improvement is more significant. The experimental results indicate that the algorithm has a high segmentation accuracy, which provides strong support for further disease analysis and control.

Abstract Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor‐κB (NF‐κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF‐κB activation on the serum levels of tumor necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO‐guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF‐κB and serum TNF‐α、IL‐1β levels were detected by enzyme‐linked immunosorbent assay. Protein expression of the MAPK/NF‐κB signaling pathway including p‐IκBα, p‐p38 MAPK, p‐NF‐κB p65, IκBα, p38 MAPK, and NF‐κB p65 was determined using western blot analysis. Compared with control group, the expression of NF‐κB in lung tissue and the levels of serum TNF‐α and IL‐1β rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF‐κB p65 were found in APMTE group rats. And UK administration reversed the APMTE‐induced increase in TNF‐α, IL‐1β, p‐IκBα, p‐MAPK, and p‐NF‐κB protein. Furthermore, the levels of NF‐κB, TNF‐α, and IL‐1β were positively correlated with mean pulmonary artery. And the levels of TNF‐α and IL‐1β were positively correlated with NF‐κB. These findings suggest that the activation of MAPK/NF‐κB pathway as a critical driver of increasing TNF‐α and IL‐1β level in APMTE rats and UK exerted protective effects against APMTE‐induced PH may be related to the downregulation of the MAPK/NF‐κB signaling pathway.

This study conducted a comparative analysis of the extraction efficiency and antioxidant potential of caffeoylquinic acids (CQAs) from Blumea aromatica using deep eutectic solvents (DESs) and traditional solvents. Utilizing UPLC-Q-Orbitrap HRMS, the quantification of seven CQAs revealed concentrations ranging from 0.46 to 7.60 mg/g, with 1,5-diCQA identified as the most abundant. DESs demonstrated significant advantages (P

Metal ions play a pivotal role in regulating and determining the functions of proteins and peptides in nature. This study aims to investigate the regulatory role of metal ions in peptide assembly and explore the influence of sequence variations and metal ions on the structure and function of resulting peptide nanoarchitectures. Dipeptide sequences with distinct charged properties (positive and negative) and functional groups (-COOH, -NH2, and phenolic hydroxyl) were meticulously selected and co-assembled with various metal ions (Au3+, Ag+, and Pt4+). The findings highlight the crucial functional role of the phenolic hydroxyl group of tyrosine in metal ion reduction, while positively charged groups promote metal ion accumulation through electrostatic forces, facilitating co-assembly. The formation of ordered structures in Au@Fmoc-YK and Au@Fmoc-YR nanoarchitectures further validates the significant interaction among metal ions, tyrosine-OH, and positively charged NH2. Notably, these nanoarchitectures possess the unique attribute of being prepared under physiological conditions, specifically at 37 °C, without the need for organic solvents or chemical modifications of peptides. This approach offers a straightforward means of constructing diverse functional nanoarchitectures based on peptides and metal ions. Moreover, Au@Fmoc-YR exhibits good performance as a nanoenzyme for detecting glucose in complex bodily fluids and plasma GSH in tumor patients, showcasing its promising potential for medical applications.

Abstract Studying plant early immunity, such as the unique immune mechanisms against pathogens, is an important field of research. Tomato wilt resulting from the infection by Fusarium oxysporum f. sp. lycopersici (Fol) is an important soil-borne vascular disease. In this study, we challenged tomato plants with Fol for a time-course RNA sequencing (RNA-seq) analysis. The result indicated that phenylpropanoid and flavonoid pathway genes were significantly enriched during the early invasion stage. Further study revealed that the flavonoids galangin and quercetin could effectively inhibit Fol growth and enhance wilt resistance in tomato. Moreover, the genes involved in plant-pathogen interactions, the MAPK signaling pathway, and plant hormone signal transduction were significantly enriched. These genes were also involved in plant pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) signaling pathways. Strikingly, the transcription levels of pathogen-related protein 1 (SlPR1) were dramatically increased at 2 days post Fol inoculation, implying that SlPR1 is important in early immunity in tomato. SlPR1 does not have direct antifungal activity. Instead, its C-terminal peptide CAPE1 could activate root defense responses, such as the reactive oxygen species (ROS) burst, salicylic acid (SA)/jasmonic acid (JA) production, and defense-related gene expression, which collectively increased tomato resistance to Fol infection. In addition, CAPE1 could induce systemic acquired resistance (SAR). Application of CAPE1 onto tomato leaves induced local resistance to the pathogen Botrytis cinerea and systemic resistance to Fol infection. These results advanced our understanding for the early immunity against Fol in tomato and provide potential strategy for tomato disease control.

Cavitation bubbles near narrow gaps widely exist within microfluidic control devices. In the present paper, a laser-induced cavitation bubble is arranged in a narrow gap composed of two parallel plates. The inception position of the bubble is set to be at the same distance from the two plates so that the dynamic behaviors of the bubble are symmetrical. The collapse and rebound dynamics of the bubble near the boundary of a narrow gap are investigated through high-speed photography. The bubble behaviors (e.g., shape deformation, translational movement, and jet characteristics) are analyzed while considering the influence of the dimensionless distance between the bubble and the boundary and the dimensionless gap width. The principal findings include the following: (1) When the dimensionless distance is small, a violent jet towards the gap is generated during the bubble collapse stage, along with a weak counter-jet towards the boundary appearing during the rebound stage. (2) As the dimensionless distance increases, the translational distance of the bubble during the collapse stage initially decreases, then increases, and finally decreases to zero. (3) Within the parameter range considered in this paper, the dimensionless width mainly affects the expansion degree and movement direction of the bubble cloud during its rebound and subsequent stages. The above research findings can provide experimental support for bubble-driven flow control, pumping, and liquid mixing in microfluidic channels.

The frequency of forest fires has increased dramatically due to climate change. The occurrence of forest fires affects the carbon and nitrogen cycles and react to climate change to form a positive feedback mechanism. These effects further impact the distribution of microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) and the soil microbial community structure. In addition, permafrost degradation can significantly affect the microorganisms in the soil. Based on these findings, this review examines the effects of fire intensity and post-fire recovery time on permafrost, the soil microbial community, MBC, MBN, and their interrelationships. This review demonstrated that (1) fires alter the condition of surface vegetation, reduce the organic layer thickness, redistribute snow, accelerate permafrost degradation, and even lead to permanent changes, where the restoration of the pre-fire state would require several decades or even centuries; (2) soil microbial community structure, soil MBC, and MBN negatively correlate with fire intensity, and the effects become more pronounced with increasing fire intensity; and (3) the structural diversity and stability of the soil microbial community were improved with time, and the amount of MBC and MBN increases as the years after a fire go by; it would still take more than ten years to recover to the pre-fire level. However, the relationship between permafrost degradation and soil microbes after forest fires is still unclear due to a lack of quantitative research on the mechanisms underlying the changes in soil microorganisms resulting from fire-induced permafrost degradation. Therefore, expanding quantitative studies and analyses of the mechanisms of interactions between forest fires, permafrost, and soil microorganisms can provide a scientific basis for understanding ecosystem carbon pools and dual-carbon targets in Arctic–boreal permafrost regions.

Abstract Background The high false‐positive rate for pulmonary nodules (PNs) from using low‐dose computed tomography (LDCT) screening can lead to overuse of invasive procedures, overtreatment, and patient anxiety. Therefore, it is very important to develop new diagnostic methods. Methods A negative enrichment‐fluorescence in situ hybridization (NE‐FISH) approach was used to detect circulating tumor cells (CTCs) in patients with PNs. We evaluated whether or not the combination of CTC counts with serum tumor marker levels (CEA, CA 125, CYFRA 21‐1, SCC) could improve the diagnostic ability for distinguishing patients with malignant pulmonary nodules (MPNs) from those with benign pulmonary nodules (BPNs). Moreover, the potential clinical application of this combination for the diagnosis of solitary pulmonary nodules (SPNs) with a diameter ≤2 cm was also investigated. Results The combination of CTC counts and tumor marker levels had a sensitivity of 80.12% and the area under the receiver operating characteristics curve (AUCROC) of 0.853 (95% confidence interval [CI]: 0.800–0.897, p

It remains a challenge to achieve satisfactory balance between biodegradability and osteogenic capacity in biosynthetic bone grafts. In this study, we aimed to address this challenge by incorporating mesoporous bioactive glass (MBG) into poly(caprolactone-co-glycolide) (PGA-PCL) at gradient ratios. MBG/PGA-PCL (PGC/M) scaffolds with MBG incorporation ratio at 0, 10%, 25% and 40% (PGC/M0-40) were synthesized using a modified solvent casting-particulate leaching method, and their physiochemical and biological properties were comprehensively evaluated. PGC/M scaffolds exhibited highly perforated porous structure with a large-pore size of 300–450 μm, with ordered MBGs of around 6.0 nm mesopores size uniformly dispersed. The increase in MBG incorporation ratio significantly improved the scaffold surface hydrophilicity, apatite-formation ability and pH stability, increased the weight loss rate while insignificantly influenced the molecular chains degradation of PGA-PCL component, and facilitated the attachment, spreading, viability and proliferation of rat bone marrow stromal cells (rBMSCs) on scaffolds. Moreover, rBMSCs cultured on PGC/M10-40 scaffolds demonstrated enhanced ALP activity and osteogenesis-related gene expression in a MBG dose-dependent manner as compared with those cultured on PGC/M0 scaffolds. When implanted to the rat cranial bone defect, PGC/M25 and PGC/M40 scaffolds induced significantly better bone repair as compared to PGC/M0 and PGC/M10 scaffolds. Besides, the biodegradability of PGC/M scaffolds correlated with the MBG incorporation ratio. These data suggested this novel PGC/M scaffolds as promising bone repair biomaterial with highly tunable hydrophilicity, bioactivity, cytocompatibility, osteogenic activity as well as biodegradability.

Marginal velopharyngeal inadequacy (MVPI) is a particular status of velopharyngeal closure after cleft palate repair. The physiological and phonological characteristics of patients with MVPI are significantly different from those with typical velopharyngeal insufficiency. The pathological mechanisms and diagnostic criteria of MVPI are still controversial, and there is limited evidence to guide the selection of surgical and non- surgical management options and a lack of recognized standards for treatment protocols. Based on a systematic study of the relevant literatures, this review identifies specific problems that are currently under-recognized in the diagnosis and treatment of MVPI and provides guidelines for further exploration of standardized and reasonable intervention protocols for MVPI.

In this study, we aimed to compare survival outcomes after receiving radiofrequency ablation (RFA) and hepatic resection (HR) for solitary hepatocellular carcinoma (HCC) with stratification by tumor size and age. A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0-2, 2-5, and > 5 cm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed. For patients >65 with tumors measuring 0-2 and 2-5 cm, the HR group had better OS and DSS compared with the RFA group. For patients >65 with tumors > 5 cm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.262 and p = 0.129, respectively). For patients ≤65, the HR group had better OS and DSS compared with the RFA group regardless of tumor size. For patients with resectable solitary HCC, regardless of age, HR is the better choice not only for tumors ≤ 2 cm, but also for tumors 2-5 cm. For resectable solitary HCC with tumors ＞5 cm, HR is the better choice for patients ≤65 but for patients >65, the issue of treatment choice needs to be further studied.

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

The motion of a continuously operating reference station is usually dominated by the long-term crustal motions of the tectonic block on which the station is located. Monitoring changes in the coordinates of reference stations located at tectonic plate boundaries allows for the calculation of velocity fields that reflect the spatial and temporal characteristics of the region. This study analyzes the spatiotemporal relationships of regional reference frame points with GNSS data from 25 reference stations in Sichuan, China, from 2015 to 2021. The common mode errors are extracted and eliminated by principal component analysis. A time series function model is developed for the reference stations and their constituent baselines for calculating the velocity field. Subsequently, the spatiotemporal characteristics of the regional reference frame in Sichuan is analyzed by a stochastic model. The results show that the influences of the common mode error on the horizontal and vertical directions of the reference stations is 2.5 mm and 4.3 mm, respectively. Generally, the horizontal motion of the reference stations in the Sichuan region tends to be in the southeast direction and the vertical motion trend is mainly uplifting. The east–west and vertical components of the baseline tend to be shortened, and the random influence among the reference stations is larger in the north–south and east–west directions—0.39 mm and 0.54 mm, respectively. Polynomial functions are more appropriate for constructing the fitted random influence covariance model.

Objective Clinical prostate cancer (PCa) is rare in men aged

Surgical correction is the optimal way of repairing a congenital cleft lip. Patients with this condition often undergo initial surgical treatment at an early age and achieve an acceptable outcome. However, their levels of satisfaction will decrease in later stages of life as facial growth and development will inevitably cause changes in long-term outcomes, especially in the nasolabial region. Therefore, it is important for surgeons to understand nasolabial development after primary treatment and tailor their surgical techniques appropriately. This review focuses on the growth patterns of the nasolabial region after primary repair, so as to provide references for operative strategy.

Bacillus velezensis (B. velezensis) is a cellulose-degrading strain that has the potential as an additive in fermented feed. B. velezensis BV-10 was isolated and screened from the termite gut. We sequenced the whole genome of this new source of B. velezensis to reveal its potential for use in cellulose degradation. Whole-genome sequencing of B. velezensis BV-10 showed that it has a circular chromosome of 3929792 bp containing 3873 coding genes with a GC content of 45.51% and many genes related to cellulose, hemicellulose, and lignin degradation. King grass silage was inoculated with B. velezensis BV-10 and mixed with other feed additives to assess the effect of B. velezensis BV-10 on the fermentation quality of silage. Six treatment groups were established: the control, B. velezensis BV-10, molasses, cellulase, B. velezensis BV-10 plus molasses, and B. velezensis BV-10 plus cellulase groups. After 30 days of silage-fermentation testing, B. velezensis BV-10 was found to rapidly reduce the silage pH value and significantly reduce the acid-detergent fiber (ADF) content (p < 0.05). The addition of B. velezensis BV-10 plus molasses and cellulase in fermented feed significantly reduced the silage neutral-detergent fiber and ADF content and promoted organic-acid accumulation (p < 0.05). The above results demonstrate that B. velezensis BV-10 promotes the fermentation quality of silage and that this effect is greater when other silage-fermentation additives are included. In conclusion, genes involved in cellulose degradation in B. velezensis BV-10 were identified by whole-genome sequencing and further experiments explored the effects of B. velezensis BV-10 and different feed additives on the fermentation quality of king grass silage, revealing the potential of Bacillus velezensis as a new silage additive.

The accuracy of autonomous robot localization using a monocular visual-inertial odometry system (VIO) is significantly reduced in an agricultural environment compared to an urban and indoor environment due to the unstructured scenes with unstable features, variation of light conditions, and rugged terrain. To address those challenges, we propose a monocular VIO system with modifications to the existing state-of-the-art monocular VIO system VINS-mono. Three modules of VINS-mono have improved in this work: vision processing front end, pose optimization, failure detection and recovery. In the vision processing front-end module, we proposed a keyframe selection algorithm base on vertical movement smoothness verification to prevent the rapid loss of feature tracks. In the pose optimization module, some feature points are removed using a depth-limited approach to improve the efficiency and accuracy of trajectory tracking. In the failure detection and recovery module, we propose a failure recovery method using the old trajectory poses, which can recover the trajectory tracking process interrupted by the failure and alleviate the orientation drift. Experiments on the Rosario dataset have shown that our system outperforms VINS-mono, and the absolute trajectory error in the agricultural environment can be at least reduced by 69% compared with the VINS-mono, which can effectively improve the localization accuracy of agriculture robots in the agricultural environment.

Pathogens utilize secretory effectors to manipulate plant defense. Fusarium oxysporum f. sp. lycopersici (Fol) is the causal agent of Fusarium wilt disease in tomatoes. We previously identified 32 secreted effector candidates by LC-MS analysis. In this study, we functionally identified one of the secreted proteins, FolAsp, which belongs to the aspartic proteases (Asp) family. The FolAsp was upregulated with host root specifically induction. Its N-terminal 1–19 amino acids performed the secretion activity in the yeast system, which supported its secretion in Fol. Phenotypically, the growth and conidia production of the FolAsp deletion mutants were not changed; however, the mutants displayed significantly reduced virulence to the host tomato. Further study revealed the FolAsp was localized at the apoplast and inhibited INF1-induced cell death in planta. Meanwhile, FolAsp could inhibit flg22-mediated ROS burst. Furthermore, FolAsp displayed protease activity on host protein, and overexpression of FolAsp in Fol enhanced pathogen virulence. These results considerably extend our understanding of pathogens utilizing secreted protease to inhibit plant defense and promote its virulence, which provides potential applications for tomato improvement against disease as the new drug target.

Pathogens utilize a panoply of effectors to manipulate plant defense. However, despite their importance, relatively little is actually known about regulation of these virulence factors. Here, we show that the effector Fol-Secreted Virulence-related Protein1 (FolSvp1), secreted from fungal pathogen Fusarium oxysporum f. sp. lycopersici (Fol), directly binds and translocates the tomato pathogenesis-related protein1, SlPR1, from the apoplast outside the plasma membrane to the host nucleus via its nuclear localization signal. Relocation of SlPR1 abolishes generation of the defense signaling peptide, CAPE1, from its C-terminus, and as a consequence, facilitates pathogen invasion of plants. The action of FolSvp1 requires covalent modification by acetylation for full virulence in host tomato tissues. The modification is catalyzed by the Fol FolArd1 lysine acetyltransferase prior to secretion. Addition of an acetyl group to one residue, K167, prevents ubiquitination-dependent degradation of FolSvp1 in both Fol and plant cells with different mechanisms, allowing it to function normally in fungal invasion. Either inactivation of FolSvp1 or removal of the acetyl group on K167 leads to impaired pathogenicity of Fol. These findings indicate that acetylation can regulate the stability of effectors of fungal plant pathogens with impact on virulence.

Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.

Backgroud:In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches.Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH.Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson’s trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling.Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy.Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH.

ObjectivesThe success of the rat model of pulmonary hypertension (PH) is primarily dependent on the measurement of pulmonary artery pressure. We herein demonstrate a novel method for measuring pulmonary artery pressure through a high-frequency ultrasound-guided transthoracic puncture in rats. The efficacy and time of this novel method are also discussed.MethodsA single subcutaneous injection of monocrotaline (MCT) was used to establish a rat model of PH. Through the heat shaping method, the tip of that puncture cannula was maintained at a certain angle after the needle core was removed. In-plane real-time guided trocar puncture of the right ventricular outflow tract was performed in the short-axis section of the parasternal aorta. The external pressure sensor was used to record the real-time waveform of right ventricular systolic pressure, pulmonary artery systolic pressure, and diastolic pressure.ResultsThe success rates of which using this novel method in the model group and the control group were 88.5 and 86.7%, respectively. The time of puncture pressure measurement was 164 ± 31 and 235 ± 50 s, respectively. The right ventricular systolic blood pressure, pulmonary systolic blood pressure, and diastolic blood pressure of the model group were higher than those of the control group.ConclusionThe modified method for trocar is helpful for accurately positioning pulmonary artery manometry. The method described in this paper has a high success rate and short operation time. It can simultaneously measure systolic blood pressure, diastolic blood pressure, and mean pressure of the right ventricle and pulmonary artery. It has a broad application prospect in verifying the rat PH model and pulmonary artery pressure monitoring.

African swine fever (ASF) is a highly contagious hemorrhagic and transboundary animal disease, and it threatens global food security. A full necropsy to harvest the sample matrices for diagnosis in the farm may lead to contamination of the premises and directly threaten to the herds. In the present study, we compared the ASFV loads of the common samples that can be collected without necropsy. The unmatched nasal, throat, rectal samples were randomly taken using cotton swabs, and inguinal lymph node samples were collected by the minimally invasive samplers from the dead pigs of an ASF field outbreak farm. The ASFV loads of the samples were detected by qPCR and the results suggested that the overall ASFV nucleic acids levels of inguinal lymph node samples were higher than the swabs. What's more, sets of matched nasal swabs, rectal swabs, throat swabs, inguinal lymph nodes, serums, spleens and lungs samples were collected from 15 dead ASFV naturally infected pigs. Similarly, the results showed that inguinal lymph node samples, together with serum, spleen and lungs samples, contained more ASFV nucleic acids than the swabs. Our findings demonstrated that the inguinal lymph node collected by minimally invasive sampler is an ideal tissue for diagnosing ASFV infection in dead pigs without necropsy.

Zanthoxylum myriacanthum Wall. ex Hook. f., a plant belonging to the Rutaceae family and the Zanthoxylum genus, is extensively utilized for its medicinal properties and as a culinary seasoning in China and Southeast Asian countries. However, the chemical composition and biological activities of Z. myriacanthum branches and leaves remain insufficiently explored. In this study, the volatile and non-volatile components of Z. myriacanthum branches and leaves were analyzed using GC-MS and UPLC-Q-Orbitrap HRMS techniques. A total of 78 volatile compounds and 66 non-volatile compounds were identified. The volatile compounds were predominantly terpenoids and aliphatic compounds, while the non-volatile compounds were primarily flavonoids and alkaloids. The branches contained 52 volatile compounds and 33 non-volatile compounds, whereas the leaves contained 48 volatile compounds and 40 non-volatile compounds. The antioxidant activities of the methanol extracts from Z. myriacanthum branches and leaves were evaluated using ABTS and DPPH free-radical-scavenging assays, both of which demonstrated certain antioxidant activity. The methanol extract of leaves demonstrated significantly higher antioxidant activity compared to that of the branches, possibly due to the higher presence of flavonoids and phenols in the leaves, with IC50 values of 7.12 ± 0.257 μg/mL and 1.22 × 102 ± 5.01 μg/mL for ABTS and DPPH, respectively. These findings enhance our understanding of the chemical composition and antioxidant potential of Z. myriacanthum. The plant holds promise as a natural source of antioxidants for applications in pharmaceuticals, cosmetics, and functional foods. Further research can explore its broader biological activities and potential applications.

Abstract Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

Pine wilt disease (PWD) poses a serious threat to the worldwide pine forest resources. Unmanned aerial vehicle (UAV) remote sensing has been widely used for PWD control, due to its flexibility and efficiency. Although pixel-level detection can obtain fine detection boundaries, there have been few related works in complex scenes because of the difficulty of setting a preset category system and the poor generalization. A preset category system establishes which categories are to be labeled, and is necessary for traditional pixel-level detection. However, the poor generalization leads to an obvious accuracy drop when detecting PWD in new scenes. In the proposed approach, to address the first issue, one-class classification (OCC) is introduced to detect diseased pixels, focusing only on the category of diseased pine trees. However, the numerous objects but low PWD pixel proportion makes the model optimization unbalanced, for which balanced unbiased detection risk estimation is proposed. To address the second issue, a novel model consisting of three-dimensional (3D) convolutional layers and transformer blocks is proposed to extract more robust features. A novel PWD detection framework based on deep OCC is finally proposed to achieve fine pixel-level PWD detection results. PWD detection experiments were conducted on eight UAV H2 (high spatial and spectral resolution) image strips. In total, 300 PWD samples from strip 1 (accounting for roughly 0.009 % of the total pixels) and 400 unlabeled pixels formed the training set. The test experiments were conducted in the remaining seven strips to validate the model generalization. Satisfactory quantitative results (F1-score greater than 0.9) were obtained for all the test strips. The results indicate that the proposed method has a powerful ability to detect PWD in pine trees, even when the PWD proportion is low, and shows better model generalization than the traditional pixel-level detection methods.

Abstract Background The fragility index (FI) of trial results can provide a measure of confidence in the positive effects reported in randomized controlled trials (RCTs). The aim of this study was to calculate the FI of RCTs supporting HCC treatments. Methods A methodological systematic review of RCTs in HCC treatments was conducted. Two-arm studies with randomized and positive results for a time-to-event outcome were eligible for the FI calculation. Results A total of 6 trails were included in this analysis. The median FI was 0.5 (IQR 0–10). FI was ≤7 in 4 (66.7%) of 6 trials; in those trials the fragility quotient was ≤1%. Conclusion Many phase 3 RCTs supporting HCC treatments have a low FI, which challenges the confidence in concluding the superiority of these drugs over control treatments.

Posterior pharyngeal flap palatoplasty (PPF) is one of the most commonly used surgical procedures to correct speech, especially for patients suffering from velopharyngeal insufficiency (VPI). During PPF, surgeons use the catheter to control the lateral velopharyngeal port on each side. Airway obstruction and sleep apnea are common after PPF. To understand the air dynamics of the upper airway after PPF, we used computational fluid dynamics (CFD) to demonstrate the airflow. In our previous study, we have revealed the expiration process of the upper airway after PPF and shown the features of how PPF successfully restores the oral pressure for speech. In this study, we focus on examining the inspiration process. Normal airway structures were included. For the normal velopharyngeal structure, one cylinder was applied to each model. For recapitulating the velopharyngeal structure after PPF, two cylinders were used in each model. The ports for borderline/inadequate closure, which can help the oral cavity get the required pressure, were chosen for this study. A real-time CFD simulation was used to capture the airflow through the ports. We found that the airflow dynamics of the upper airway’s inspiration were dependent on the velopharyngeal structure. Although the airflow patterns were similar, the velocities between one-port and two-port structures were different, which explained why patients after PPF breathed harder than before and suggested that the one-port structure might be a better choice for secondary VPI reconstruction based on the CFD analyses.

Mutations in VPS13 gene have been recently reported as a genetic cause of Parkinson's disease (PD). In this study, we isolated the skin fibroblasts from a PD patient harboring VPS13A gene mutation (c. 4282_4289delinsA) and reprogrammed the fibroblasts to a novel patient-specific induced pluripotent stem cell (iPSC) line LCPHi002-A using transgene-free episomal plasmids to express OCT3/4, SOX2, KLF4, L-MYC, and LIN28. The LCPHi002-A line showed the normal karyotype, expression of pluripotency markers, and had multi-lineage differentiation capacity in vivo. This iPSC line of LCPHi002-A could be used for studying pathogenic mechanisms of PD.

An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-β1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.

Objective(s): Ulcerative colitis (UC) is a kind of complex immune disease, and a major cause of destruction of intestinal barrier and oxidative stress in this field. In this paper, glutamine (Gln) was believed to offer protection against oxidative stress injury in colitis mice.Materials and Methods: Thirty mice were randomly assigned into control, model, LY294002 (PI3K/Akt inhibitor), Gln, Gln+LY294002 and 5-Aminosalicylic acid (5-ASA) groups. The mice in the experimental group drank 4% dextran sulfate sodium salt (DSS) for 7 consecutive days. The protective effect of Gln on oxidative stress was quantified by keeping colitis mice, involving Phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt)/mammalian target of Rapamycin (mTOR) signaling pathway, with different medications or distilled water through intragastric administration for 10 consecutive days.Results: In vivo administration of Gln, LY294002 or 5-ASA was found to ameliorate the symptoms of colitis in mice, such as reduced growth, loose stools and stool bleeding; protected DSS-induced colitis mice from goblet cell loss, lymphocytosis, mucosal erosion, loss of crypts, and neutrophil infiltration; improved the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP); decreased the content of malondialdehyde (MDA); and inhibited the activation of PI3K/Akt signaling pathway.Conclusion: Administration of Gln to the DSS-induced colitis mice led to a clearly reduction in oxidative stress-induced injury. The Gln is confirmed as inhibiting the PI3K/Akt signaling pathway activity.

Demolishing a tall chimney by directional blasting can save time and cost. However, the blasting vibration and the touchdown vibration of the parts of the chimney falling to the ground will cause noise disturbance to the local residents. To reduce the vibration effect of blasting demolition of the chimney, taking the 180 m high chimney in Jiaozuo, China, as the engineering background, the loose accumulation body with a right-angled trapezoid section 3-6 m thick was piled with three kinds of graded gravel particles as the buffer layer. According to the site restrictions, the chimney was demolished by directional blasting in two stages. The vibration propagation and attenuation rules of the blasting demolition of the chimney were analyzed and touchdown vibrations of two parts of the chimney were monitored also. Results show that the low frequency vibrations generated by the blasting and chimney touchdown have a greater impact on the surrounding environment. The vibration velocity and energy attenuation represent a form of power function. With the increase of the number of chimney touchdowns, the energy absorption rate of the loose accumulation body becomes lower. The obtained conclusions in this study can provide a reference for the similar blasting demolition practice.

The rapid development of energy consumption and carbon emissions in the construction industry poses an enormous and negative challenge for China’s energy and environment. While maintaining moderate economic growth, it is particularly important to realize energy conservation and carbon reduction. Carbon tax policy, a direct tool to reduce carbon emissions, can effectively alleviate the environmental issues caused by construction activities. However, relying solely on a single method is insufficient to handle the complicated circumstances of China’s construction industry. This study explores the influence of carbon tax on the construction industry through adjustments to tax rates via developing a Computable General Equilibrium (CGE) model. Then, it analyzes how the carbon tax affects the economic and environmental variables by designing scenarios for recycling tax revenue and improved energy efficiency. The results indicate that the carbon tax rate of 40 RMB/t-CO2 is the most appropriate. At this tax level, the negative impacts of energy demand and emissions reduction on macroeconomy and construction industry are minimized. It was also determined that carbon tax revenue recycling to households and sectoral investment will realize the “weak double dividend” effect on the construction industry. Furthermore, improving energy efficiency in the construction industry will demonstrate the additional advantages of carbon tax. This study serves as a theoretical foundation for the Chinese government to develop various energy strategies to achieve low-carbon development in the construction industry.

In the ecosystem, microbiome widely exists in soil, animals, and plants. With the rapid development of computational biology, sequencing technology and omics analysis, the important role of soil beneficial microbial community is being revealed. In this review, we mainly summarized the roles of rhizosphere microbiome, revealing its complex and pervasive nature contributing to the largely invisible interaction with plants. The manipulated beneficial microorganisms function as an indirect layer of the plant immune system by acting as a barrier to pathogen invasion or inducing plant systemic resistance. Specifically, plant could change and recruit beneficial microbial communities through root-type-specific metabolic properties, and positively shape their rhizosphere microorganisms in response to pathogen invasion. Meanwhile, plants and beneficial microbes exhibit the abilities to avoid excessive immune responses for their reciprocal symbiosis. Substantial lines of evidence show pathogens might utilize secreting proteins/effectors to overcome the emerging peripheral barrier for their advantage in turn. Overall, beneficial microbial communities in rhizosphere are involved in plant–pathogen interactions, and its power and potential are being explored and explained with the aim to effectively increase plant growth and productivity.

Craniofacial muscles emerge as a developmental novelty during the evolution from invertebrates to vertebrates, facilitating diversified modes of predation, feeding and communication. In contrast to the well-studied limb muscles, knowledge about craniofacial muscle stem cell biology has only recently starts to be gathered. Craniofacial muscles are distinct from their counterparts in other regions in terms of both their embryonic origin and their injury response. Compared with somite-derived limb muscles, pharyngeal arch-derived craniofacial muscles demonstrate delayed myofiber reconstitution and prolonged fibrosis during repair. The regeneration of muscle is orchestrated by a blended source of stem/progenitor cells, including myogenic muscle satellite cells (MuSCs), mesenchymal fibro-adipogenic progenitors (FAPs) and other interstitial progenitors. Limb muscles host MuSCs of the Pax3 lineage, and FAPs from the mesoderm, while craniofacial muscles have MuSCs of the Mesp1 lineage and FAPs from the ectoderm-derived neural crest. Both in vivo and in vitro data revealed distinct patterns of proliferation and differentiation in these craniofacial muscle stem/progenitor cells. Additionally, the proportion of cells of different embryonic origins changes throughout postnatal development in the craniofacial muscles, creating a more dynamic niche environment than in other muscles. In-depth comparative studies of the stem cell biology of craniofacial and limb muscles might inspire the development of novel therapeutics to improve the management of myopathic diseases. Based on the most up-to-date literature, we delineated the pivotal cell populations regulating craniofacial muscle repair and identified clues that might elucidate the distinct embryonic origin and injury response in craniofacial muscle cells.

Abstract Background For a better understanding of common suspension sutures during primary cleft lip nasal rhinoplasty, the biomechanical consequences of those sutures need to be demonstrated. Methods A finite element model of the infant specimen was established. The closure of cleft lip and four different specific suspension sutures were simulated by loading different forces on the model: 1. F1 to simulate the suture fastening both medial crura together; 2. F2 to simulate the suture which sewed both medial crura and the non-cleft-side upper lateral cartilage together; 3. F3 to simulate the suture elevating the alar cartilage cranially; 4. F4 to simulate the suture elevating the alar cartilage superiorly. The deformation and stress distribution consequent to each maneuver were analyzed in details. Results The deviation of columella was restored through the closure of cleft lip. Different suspension sutures had different biomechanical effects on the nasal structure. All suspension sutures had the function on elevating the alar cartilage. F2 had no function on restoring the collapse of the nasal tip. The suture which fastened both medial crura together leaded to the lowest stress on the skin envelope. Conclusions Each suspension suture had its characteristics respectively. The simulation suggested that F1, the suture which fastened both medial crura, could be the most potential maneuver for cleft lip rhinoplasty because it can symmetrically restore the shape of the nose without incurring a significant increase in stress.

BackgroundHepatocellular carcinoma (HCC) is one of the most common types of cancer that is associated with poor quality of life in patients and a global health burden. The mechanisms involved in the development and progression of HCC remain poorly understood.MethodsHepatocellular carcinoma human samples and cell lines were subjected to qRT-PCR for expression assessment. CCK-8 assay, Transwell migration and invasion assay, were applied for cell function detection. Animal experiment was used to measure the function of SNHG17 on cell growth in vivo. Western blot was conducted to evaluate the level of EMT in cells. RIP, RNA pull-down and luciferase reporter assays were performed to assess the correlation between SNHG17, miR-3180-3p and RFX1.ResultsOur study demonstrated that SNHG17 was upregulated in HCC human samples and involved cell proliferation, migration, invasion progress. SNHG17 promoted HCC cell growth and metastasis in vivo. Furthermore, we investigated the downstream factor of SNHG17, SNHG17 acted as a molecular sponge for miR-3180-3p, and SNHG17 regulated RFX1 expression via miR-3180-3p. SNHG17 promotes tumor-like behavior in HCC cells via miR-3180-3p/RFX1.ConclusionWe determined RFX1 as the target of miR-3810-3p; SNHG17 enhanced the progression of HCC via the miR-3180-3p/RFX1 axis. Taken together, our findings may provide insight into the molecular mechanism involved in the progression of HCC and develop SNHG17 as a novel therapeutic target against HCC.

Fusarium oxysporum f. sp. lycopersici (Fol) is the causal agent of Fusarium wilt disease in tomato. Proteins secreted by this pathogen during initial host colonization largely determine the outcome of pathogen-host interactions. Lysine acetylation (Kac) plays a vital role in the functions of many proteins, but little is known about Kac in Fol secreted proteins. In this study, we analyzed lysine acetylation of the entire Fol secretome. Using high affinity enrichment of Kac peptides and LC-MS/MS analysis, 50 potentially secreted Fol proteins were identified and acetylation sites determined. Bioinformatics analysis revealed 32 proteins with canonical N-terminal signal peptide leaders, and most of them were predicted to be enzymes involved in a variety of biological processes and metabolic pathways. Remarkably, all 32 predicted secreted proteins were novel and encoded on the core chromosomes rather than on the previously identified LS pathogenicity chromosomes. Homolog scanning of the secreted proteins among 40 different species revealed 4 proteins that were species specific, 3 proteins that were class-specific in the Ascomycota phylum, and 25 proteins that were more widely conserved genes. These secreted proteins provide a starting resource for investigating putative novel pathogenic genes, with 26 up-regulated genes encoding Kac proteins that may play an important role during initial symptomless infection stages.

BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA).MethodHUMSCs (1 × 106) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated.ResultsHUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely, Peyer’s patches and the lamina propria. The gene expression of TGF-β1 and IL-17A and protein expression of IL-10, TGF-β1, IL-17A, IL-22, and immunoglobulin A (IgA) were modulated in the ileum, and the serum levels of IL-10, TGF-β1, IL-17A, IL-1β, and tumor necrosis factor (TNF)-α were regulated in the rats with CIA. The relative abundances of the genera Bacteroides and Bacillus were increased in the HUMSCs-treated rat with CIA; in addition, the levels of indole, indoleacetic acid, and indole-3-lactic acid were consistently upregulated, and this upregulation was accompanied by increases in AhR gene and protein expression.ConclusionOur study demonstrates that HUMSCs play a therapeutic role in rats with CIA by regulating the interactions between host immunity and gut microbiota via the AhR.

Background: FOLFOX treatment is a method used widely to reduce tumor size in low-set rectal cancer, with variable clinical results. FOLFOX agents comprise a mixture of oxaliplatin and 5-fluorouracil, the efficacy of which might be modulated by the gut microbiome in humans. This study aimed to determine whether the bowel microbiota is a factor that influences FOLFOX treatment. Methods: To investigate the role of gut microbiota during FOLFOX treatment, we carried out comprehensive metagenomic and metabolomic analyses on 62 fecal samples collected from 37 low-set rectal cancer patients. A set of 31 samples was collected before the patients underwent treatment; another 31 samples were obtained after the treatment was completed. Among these samples, 50 were paired samples collected before and after FOLFOX treatment. The patients were divided into responder and nonresponder groups according to the treatment outcome. Metagenomic sequencing was performed on these fecal samples. Diverse bacterial taxa were identified by MetaGeneMark, Soapaligner, and DIAMOND; microbiotal data analyses were carried out in the R environment. Differences in microbial taxa and metagenomic linkage groups were observed in multiple comparative analyses. Results: The gut microbiota was altered after treatment. Compared with before treatment, the changes in bacterial diversity and microbiotal composition after treatment were more apparent in the responder group than in the nonresponder group. Bacterial species analysis revealed a group of gut bacteria in multiple comparisons, with a group of eight specific species being associated with the outcome of FOLFOX treatment. Responders and nonresponders before treatment were clearly separated based on this bacterial subset. Finally, the metagenomic linkage group network and metabolomic analyses based on the genomic data confirmed a more significant change in the gut microbiota during FOLFOX treatment in the responder group than in the nonresponder group. Conclusions: Overall, our results describe a dynamic process of gut microbiotal changes from the start to the end of FOLFOX treatment, and verified a close relationship between microbiota and treatment outcome. Recognition of the significance of microbiotal intervention before FOLFOX treatment for low-set rectal cancer may improve the effects of these agents.

This paper presents a statistics-optimized organization technique to achieve better element matching in successive approximation register (SAR) analog-to-digital converter (ADC) in smart sensor systems. We demonstrate the proposed technique ability to achieve a significant improvement of around 23 dB on a spurious free dynamic range (SFDR) of the ADC than the conventional, testing with a capacitor mismatch σu = 0.2% in a 14-bit SAR ADC system. For the static performance, the max root mean square (rms) value of differential nonlinearity reduces from 1.63 to 0.20 LSB and the max rms value of integral nonlinearity (INL) reduces from 2.10 to 0.21 LSB. In addition, it is demonstrated that by applying grouping optimization and strategy optimization, the performance boosting on the SFDR can be effectively achieved. Such a great improvement on the resolution of the ADC only requires an off-line pre-processing digital part.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

ABSTRACT GATA transcription factors (TFs) are common eukaryotic regulators, and glutathione-dependent formaldehyde dehydrogenases (GD-FDH) are ubiquitous enzymes with formaldehyde detoxification activity. In this study, the formaldehyde dehydrogenase Sclerotinia sclerotiorum Fdh1 (SsFdh1) was first characterized as an interacting partner of a GATA TF, SsNsd1, in S. sclerotiorum. Genetic analysis reveals that SsFdh1 functions in formaldehyde detoxification, nitrogen metabolism, sclerotium development, and pathogenicity. Both SsNsd1 and SsFdh1 harbor typical zinc finger motifs with conserved cysteine residues. SsNsd1 regulates SsFdh1 in two distinct manners. SsNsd1 directly binds to GATA-box DNA in the promoter region of Ssfdh1; SsNsd1 associates with SsFdh1 through disulfide bonds formed by conserved Cys residues. The SsNsd1-SsFdh1 interaction and nuclear translocation were found to prevent efficient binding of SsNsd1 to GATA-box DNA. Site-directed point mutation of these Cys residues influences the SsNsd1-SsFdh1 interaction and SsNsd1 DNA binding capacity. SsFdh1 is regulated by and functions jointly with the SsNsd1 factor, providing new insights into the complex transcriptional regulatory mechanisms of GATA factors. IMPORTANCE S. sclerotiorum is a pathogenic fungus with sclerotium and infection cushion development, making S. sclerotiorum one of the most challenging agricultural pathogens with no effective control method. We identified important sclerotium and compound appressorium formation determinants, SsNsd1 and SsFdh1, and investigated their regulatory mechanism at the molecular level. SsNsd1 and SsFdh1 are zinc finger motif-containing proteins and associate with each other in the nucleus. On other hand, SsNsd1, as a GATA transcription factor, directly binds to GATA-box DNA in the promoter region of Ssfdh1. The SsNsd1-SsFdh1 interaction and nuclear translocation were found to prevent efficient binding of SsNsd1 to GATA-box DNA. Our results provide insights into the role of the GATA transcription factor and its regulation of formaldehyde dehydrogenase in stress resistance, fungal sclerotium and compound appressorium development, and pathogenicity.

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair.