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Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

In this study, the prepared dish Kung Pao Chicken with soy protein artificial meat (SPAM-KPC) was developed to satisfy the higher demand for nutritious healthy and diversified convence food, and the changes in storage quality of SPAM-KPC at different storage temperatures (4, 25 and 37 ℃) were compared. The shelf life prediction model of the SPAM-KPC was established based on the total number of bacteria as the key quality factor affecting the shelf life of the product. The results showed that the total colony count of SPAM-KPC samples stored at three temperatures for 15 days increased from 0.67 lg(CFU/g) to 2.73, 3.37 and 4.33 lg(CFU/g), respectively. While pH (from 6.22 to 5.88, 5.87, 5.69) and sensory scores (from 25.12 to 22.67, 19.52, 16.84) gradually decreased, as well as hardness and springiness decreased. The shelf life of SPAM-KPC products at three storage temperatures was 28, 20 and 17 days, respectively. According to the findings, low-temperature storage at 4 ℃ was the best storage temperature for SPAM-KPC products. This work could provide a theoretical reference for the application of plant-based protein meat in the field of prepared dishes processing.

Abstract Accurate forecasting of electric vehicle (EV) load is essential for grid stability and energy management. EV load forecasting is influenced by multiple factors. At present, the load forecasting model for EVs mainly uses collected sample data to build a data‐driven model. But these algorithms need to collect all the data together to train the model, ignoring the privacy of each data collection source. In a competitive market environment, each device service provider is not willing to share the sample data they store. Aiming at this problem, this paper proposes an EV load diagnosis algorithm considering data privacy. Firstly, a convolutional neural network with dual attention mechanism is constructed as the basic time series forecasting model. The association rule algorithm is used to select weather data with strong associations as the inputs of the model. Each service provider uses local data to perform deep learning network. All models are then trained using a federated learning framework. During the entire training process, historical data is stored locally, and only model parameter information is shared and interacted; thus data privacy is protected. Finally, the validity of the algorithm in this paper is verified by using real collected EV load data.

Abstract Liquid formulations are ubiquitous yet have lengthy product development cycles owing to the complex physical interactions between ingredients making it difficult to tune formulations to customer-defined property targets. Interpolative ML models can accelerate liquid formulations design but are typically trained on limited sets of ingredients and without any structural information, which limits their out-of-training predictive capacity. To address this challenge, we selected eighteen formulation ingredients covering a diverse chemical space to prepare an open experimental dataset for training ML models for rinse-off formulations development. The resulting design space has an over 50-fold increase in dimensionality compared to our previous work. Here, we present a dataset of 812 formulations, including 294 stable samples, which cover the entire design space, with phase stability, turbidity, and high-fidelity rheology measurements generated on our semi-automated, ML-driven liquid formulations workflow. Our dataset has the unique attribute of sample-specific uncertainty measurements to train predictive surrogate models.

Timely inspection of defects on the surfaces of wind turbine blades can effectively prevent unpredictable accidents. To this end, this study proposes a semi-supervised object-detection network based on You Only Looking Once version 4 (YOLOv4). A semi-supervised structure comprising a generative adversarial network (GAN) was designed to overcome the difficulty in obtaining sufficient samples and sample labeling. In a GAN, the generator is realized by an encoder- decoder network, where the backbone of the encoder is YOLOv4 and the decoder comprises inverse convolutional layers. Partial features from the generator are passed to the defect detection network. Deploying several unlabeled images can significantly improve the generalization and recognition capabilities of defect-detection models. The small-scale object detection capacity of the network can be improved by enhancing essential features in the feature map by adding the concurrent spatial and channel squeeze and excitation (scSE) attention module to the three parts of the YOLOv4 network. A balancing improvement was made to the loss function of YOLOv4 to overcome the imbalance problem of the defective species. The results for both the single- and multi-category defect datasets show that the improved model can make good use of the features of the unlabeled images. The accuracy of wind turbine blade defect detection also has a significant advantage over classical object detection algorithms, including faster R-CNN and DETR.

Based on a large number of newly added deep well data in recent years, the subsidence of the Ordos Basin in the Mid-Late Triassic is systematically studied, and it is proposed that the Ordos Basin experienced two important subsidence events during this depositional period. Through contrastive analysis of the two stages of tectonic subsidence, including stratigraphic characteristics, lithology combination, location of catchment area and sedimentary evolution, it is proposed that both of them are responses to the Indosinian Qinling tectonic activity on the edge of the craton basin. The early subsidence occurred in the Chang 10 Member was featured by high amplitude, large debris supply and fast deposition rate, with coarse debris filling and rapid subsidence accompanied by rapid accumulation, resulting in strata thickness increasing from northeast to southwest in wedge-shape. The subsidence center was located in Huanxian–Zhenyuan–Qingyang–Zhengning areas of southwestern basin with the strata thickness of 800–1 300 m. The subsidence center deviating from the depocenter developed multiple catchment areas, until then, unified lake basin has not been formed yet. Under the combined action of subsidence and Carnian heavy rainfall event during the deposition period of Chang 7 Member, a large deep-water depression was formed with slow deposition rate, and the subsidence center coincided with the depocenter basically in the Mahuangshan–Huachi–Huangling areas. The deep-water sediments were 120–320 m thick in the subsidence center, characterized by fine grain. There are differences in the mechanism between the two stages of subsidence. The early one was the response to the northward subduction of the MianLüe Ocean and intense depression under compression in Qinling during Mid-Triassic. The later subsidence is controlled by the weak extensional tectonic environment of the post-collision stage during Late Triassic.

Abstract To reveal the influence mechanism of the grinding surface quality of 20CrMnTi steel components on the tribological characteristics and contact fatigue performance, accelerated tests for sliding friction wear and fatigue damage were carried out. Tribological characteristics and contact fatigue performance get worse with increasing surface roughness while getting better with increasing surface microhardness. Residual compressive stress is conducive to inhibiting the initiation and propagation of cracks and promoting contact fatigue performance. Additionally, mechanical friction, abrasive wear, adhesive wear and fatigue damage coexist and form a competing failure mechanism under the synergistic effect of frictional wear and contact fatigue failure. The damage process mainly manifests as wear, stress concentration induced fatigue, microcracks, pitting, and spalling in the shallow layer. This study is more beneficial to promote the 20CrMnTi steel transmission parts manufacturing products for high precision, low damage, and long life.

Abstract Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis. Graphical Abstract

Abstract Acute ST-segment elevation myocardial infarction (STEMI) is a severe cardiovascular disease that poses a significant threat to the life and health of patients. This study aimed to investigate the predictive value of triglyceride glucose index (TyG) combined with neutrophil-to-lymphocyte ratio (NLR) for in-hospital cardiac adverse event (MACE) after PCI in STEMI patients. From October 2019 to June 2023, 398 STEMI patients underwent emergency PCI in the Second People's Hospital of Hefei. Stepwise regression backward method and multivariate logistic regression analysis were used to screen the independent risk factors of MACE in STEMI patients. To construct the prediction model of in-hospital MACE after PCI in STEMI patients: Grace score model is the old model (model A); TyG combined with NLR model (model B); Grace score combined with TyG and NLR model is the new model (model C). We assessed the clinical usefulness of the predictive model by comparing Integrated Discrimination Improvement (IDI), Net Reclassification Index (NRI), Receiver Operating Characteristic Curve (ROC), and Decision Curve Analysis (DCA). Stepwise regression and multivariate logistic regression analysis showed that TyG and NLR were independent risk factors for in-hospital MACE after PCI in STEMI patients. The constructed Model C was compared to Model A. Results showed NRI 0.5973; NRI + 0.3036, NRI − 0.2937, IDI 0.3583. These results show that the newly developed model C predicts the results better than model A, indicating that the model is more accurate. The ROC analysis results showed that the AUC of Model A for predicting MACE in STEMI was 0.749. Model B predicted MACE in STEMI with an AUC of 0.685. Model C predicted MACE in STEMI with an AUC of 0.839. For DCA, Model C has a better net return between threshold probability 0.1 and 0.78, which is better than Model A and Model B. In this study, by combining TyG, NLR, and Grace score, it was shown that TyG combined with NLR could reasonably predict the occurrence of MACE after PCI in STEMI patients and the clinical utility of the prediction model.

This paper proposes an improved You Only Look Once (YOLOv3) algorithm for automatically detecting damaged apples to promote the automation of the fruit processing industry. In the proposed method, a clustering method based on Rao-1 algorithm is introduced to optimize anchor box sizes. The clustering method uses the intersection over the union to form the objective function and the most representative anchor boxes are generated for normal and damaged apple detection. To verify the feasibility and effectiveness of the proposed method, real apple images collected from the Internet are employed. Compared with the generic YOLOv3 and Fast Region-based Convolutional Neural Network (Fast R-CNN) algorithms, the proposed method yields the highest mean average precision value for the test dataset. Therefore, it is practical to apply the proposed method for intelligent apple detection and classification tasks.

Objective The embedded granularity of target minerals refers to their particle size and distribution in ore, which directly influences the design and effectiveness of ore beneficiation processes. Therefore, the measurement of embedded granularity of target minerals is a crucial task in process mineralogy research. In traditional process mineralogy research, the main method for observing and analysing ore samples is to use a polarized light microscopy. However, this approach generally suffers from problems such as long processing times, susceptible to subjective factors, and difficulties in achieving automation and large-scale applications. To overcome these limitations, this paper proposes a method for detecting the embedded granularity of metal minerals under the microscope based on based on deep learning. Methods This method takes specimens from the Shuichang magnetic ore deposit in Tangshan City, Hebei Province as the object. We take photographs under the reflected light conditions using a polarized light microscope to create a dataset, and design a mineral recognition network model based on the Deeplabv3+ network. Thereby it enables automated feature extraction and intelligent recognition of the target metal minerals. This method achieves segmentation of the target minerals by generating binary images of the desired metal minerals. Finally, the analysis and measurement of the embedded granularity of the target metal minerals are completed by combining the maximum Feret diameter. Results Compared with traditional manual microscopic measurement methods, the application of image measurement based on deep learning in mineral particle analysis has increased the processing speed by approximately 119.8 times and the measurement accuracy 169.5 times when measuring the same mineral particles, demonstrating its significant improvement in terms of processing efficiency and measurement accuracy. Conclusion The deep learning-based method for detecting the embedded granularity of metal minerals under a microscope significantly reduces the detection time and enhances the detection accuracy for mineral embedded granularity. Moreover, it eliminates the influence of subjective factors, which is of great significance for promoting the intelligent development of process mineralogy.

Abstract Background The magnitude of the risk of death and cardiac arrest associated with emergency surgery and anesthesia is not well understood. Our aim was to assess whether the risk of perioperative and anesthesia-related death and cardiac arrest has decreased over the years, and whether the rates of decrease are consistent between developed and developing countries. Methods A systematic review was performed using electronic databases to identify studies in which patients underwent emergency surgery with rates of perioperative mortality, 30-day postoperative mortality, or perioperative cardiac arrest. Meta-regression and proportional meta-analysis with 95% confidence intervals (CIs) were performed to evaluate global data on the above three indicators over time and according to country Human Development Index (HDI), and to compare these results according to country HDI status (low vs. high HDI) and time period (pre-2000s vs. post-2000s). Results 35 studies met the inclusion criteria, representing more than 3.09 million anesthetic administrations to patients undergoing anesthesia for emergency surgery. Meta-regression showed a significant association between the risk of perioperative mortality and time (slope: -0.0421, 95%CI: from − 0.0685 to -0.0157; P = 0.0018). Perioperative mortality decreased over time from 227 per 10,000 (95% CI 134–380) before the 2000s to 46 (16–132) in the 2000–2020 s (p

Abstract Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH. Graphical Abstract

The rapid development of Chinese potato processing industry can be attributed to the implementation of the potato staple food industrialization strategy. Potato protein, known for its high nutritional value and functionality, exhibits exceptional solubility and contains a significant amount of tyrosines that are scarce in other plant proteins. Consequently, potato protein holds immense potential for various market applications. This paper provides a comprehensive review of the composition, functional properties, modification methods, and modification applications of potato protein. Potato protein exhibits good solubility, foaming and emulsifying properties, gelation, and antioxidant activity. Currently, enzyme treatment and microbial fermentation are the focus of potato protein modification research. Additionally, this article provides an overview of the main issues commonly found in potato protein and proposes future development prospects based on current research progress. In the future, it is necessary to further investigate the relationship between the molecular structure of potato protein and its functional activities. Enhancing the utilization of potato protein and plant proteins, enzymatic methods and microbial fermentation shows promise as a future direction for modification. By harnessing microbial resources, the cost of modification can be effectively reduced.

Abstract Objectives Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. Methods Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. Results In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). Conclusions Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Abstract Background N1-methyladenosine (m1A), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of m1A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m1A modification characteristics with biological functions. This model could predict the prognosis for patients with HCC. Methods An integrated analysis of the TCGA-LIHC database was performed to explore the gene signatures and clinical relevance of 10 m1A regulators. Furthermore, the biological pathways regulated by m1A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m1A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m1A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m1A levels and the expression of DEGs from the risk model in HCC tissues and paracancer tissues using tissue microarray. Results The risk model, constructed from five DEGs (CDK5R2, TRIM36, DCAF8L, CYP26B, and PAGE1), exhibited significant prognostic value in predicting survival rates among individuals with HCC. Moreover, HCC tissues showed decreased levels of m1A compared to paracancer tissues. Furthermore, the low m1A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m1A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. Conclusions The risk model, comprising m1A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m1A may represent a potential target for anti-HCC strategies.

Basement buried hill reservoirs represent significant emerging prospects among the newly discovered growth poles in the deepwater areas of the northern South China Sea. Addressing the unclear key factors contributing to their formation, this study dissects successful global exploration cases of basement buried hill reservoirs and analyzes the common characteristics of basement reservoir accumulation under different basin types, structural backgrounds, basement lithologies, and oil and gas geological conditions. A three-element coupling relationship, termed “source-reservoir-cap”, is proposed as the dominant mechanism controlling basement buried hill reservoir formation. The genesis of these reservoirs requires adequate oil and gas supply, appropriately sized accumulation bodies, and effective sealing layers. The optimal configuration of the “source-reservoir-cap” relationship directly influences the efficient charging and preservation of oil and gas within basement buried hill reservoirs. Four configurations are identified, including circumstances such as the source-underlying low-positioned basement buried hill with a “source-reservoir cover docking migration type”, the source-border middle-positioned basement buried hill with a “source-reservoir lateral window docking migration type”, and the source-outside high-positioned basement buried hill with both “source-reservoir short-distance transport and migration type” and “source-reservoir long-distance transport and migration type”. The first to three models present favorable accumulation conditions. Based on the “source-reservoir-cap” three-element coupled model, this study identifies the Yunkai basement buried hill in the Pearl River Mouth Basin, the central depression in the Qiongdongnan Basin, and the northern and southern basement buried hills belts as crucial exploration targets in the deepwater areas of the northern South China Sea.

Abstract Background Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea were investigated with tracking of potential sources in Wenzhou City, China. Methods A total of 1032 children were recruited, 684 of whom had diarrhea and 348 without, from Yuying Children’s Hospital in Wenzhou, China. Samples of stool were collected from each participant, followed by extraction of DNA, genotyping, and molecular identification of Cryptosporidium species and subtypes. Results Twenty-two of the 1032 (2.1%) children were infected with Cryptosporidium spp. with 2.5% (17/684) and 1.4% (5/348) in diarrhoeic and asymptomatic children, respectively. Four Cryptosporidium species were identified, including C. parvum (68.2%; 15/22), C. felis (13.6%; 3/22), C. viatorum (9.1%; 2/22), and C. baileyi (9.1%; 2/22). Two C. parvum subtypes named IIdA19G1 (n = 14) and IInA10 (n = 1), and one each of C. felis (XIXa) and C. viatorum (XVaA3g) subtype was found as well. Conclusions This is the first research that identified Cryptosporidium in children of Wenzhou, China, using PCR. Identification of zoonotic C. parvum, C. felis, C. viatorum, and their subtypes indicate potential cross-species transmission of Cryptosporidium between children and animals. Additionally, the presence of C. baileyi in children suggests that this species has a wider host range than previously believed and that it possesses the capacity to infect humans.

Abstract Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

Abstract We have previously shown that nucleosome assembly protein 1-like 1 (NAP1L1) plays an important role in the abnormal proliferation of hepatocellular carcinoma (HCC) cells. However, the effects of NAP1L1 on the malignant behaviour of HCC cells, including cell migration, invasion and apoptosis, remain unclear. Baculoviral IAP repeat-containing 2 (BIRC2) plays a key role in initiating the abnormal proliferation, apoptotic escape and multidrug resistance of HCC cells; however, the mechanisms through which its stability is regulated in HCC remain elusive. Here, we found that knockdown of NAP1L1 inhibited the proliferation of HCC cells and activated apoptotic pathways but did not remarkably affect the migratory and invasive abilities of HCC cells. In addition, knockdown of NAP1L1 did not alter the expression of BIRC2 at the transcriptional level but substantially reduced its expression at the translational level, suggesting that NAP1L1 is involved in the post-translational modification (such as ubiquitination) of BIRC2. Furthermore, BIRC2 was highly expressed in human HCC tissues and promoted the proliferation and apoptotic escape of HCC cells. Co-immunoprecipitation (Co-IP) assay and mass spectrometry revealed that NAP1L1 and BIRC2 did not bind to each other; however, ubiquitin protein ligase E3 component n-recognin 4 (UBR4) was identified as an intermediate molecule associating NAP1L1 with BIRC2. Knockdown of NAP1L1 promoted the ubiquitin-mediated degradation of BIRC2 through the ubiquitin–protein junction of UBR4, which in turn inhibited the proliferation and apoptotic escape of HCC cells and exerted anti-tumour effects. In conclusion, this study reveals a novel mechanism through which NAP1L1 regulates the ubiquitination of BIRC2 through UBR4, thereby determining the progression of HCC. Based on this mechanism, suppression of NAP1L1 may inhibit tumour progression in patients with HCC with high protein expression of NAP1L1 or BIRC2.

Ajania flavida, a new species from western Sichuan and eastern Xizang, China, is described and illustrated. It is readily assigned to A. sect. Ajania owing to its straw-colored, glossy involucres and marginally whitish scarious phyllaries. Within the section, it is distinct in being a shrub of 1−2 m in height, and in having creamy yellow florets. It is superficially similar to A. ramosa in A. sect. Phaeoscyphus, but can easily be distinguished by, among other characters, the plant height, color of the florets and margins of the phyllaries. In addition, we provide a distribution map of the new species.

Abstract Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

Abstract Novel methods are required to enhance lung cancer detection, which has overtaken other cancer-related causes of death as the major cause of cancer-related mortality. Radiologists have long-standing methods for locating lung nodules in patients with lung cancer, such as computed tomography (CT) scans. Radiologists must manually review a significant amount of CT scan pictures, which makes the process time-consuming and prone to human error. Computer-aided diagnosis (CAD) systems have been created to help radiologists with their evaluations in order to overcome these difficulties. These systems make use of cutting-edge deep learning architectures. These CAD systems are designed to improve lung nodule diagnosis efficiency and accuracy. In this study, a bespoke convolutional neural network (CNN) with a dual attention mechanism was created, which was especially crafted to concentrate on the most important elements in images of lung nodules. The CNN model extracts informative features from the images, while the attention module incorporates both channel attention and spatial attention mechanisms to selectively highlight significant features. After the attention module, global average pooling is applied to summarize the spatial information. To evaluate the performance of the proposed model, extensive experiments were conducted using benchmark dataset of lung nodules. The results of these experiments demonstrated that our model surpasses recent models and achieves state-of-the-art accuracy in lung nodule detection and classification tasks.

A simple and efficient method for the synthesis of spiropyridazine-benzosultams has been developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation.

Ligularia lushuiensis, a new species from northwestern Yunnan, China, is described and illustrated. It was tentatively placed in L. sect. Ligularia ser. Ligularia on the basis of the pinnate-palmate leaf venation, racemose synflorescence and pappus which is as long as tubular corolla. Within the series, it appeared somewhat close to both L. lamarum and L. pseudolamarum. However, L. lushuiensis can be easily distinguished from the latter two species by, among other characters, the leaf margin, bract size, involucre shape and size, and number and width of ray florets. Morphologically, L. lushuiensis is also superficially similar to L. secunda but differs readily by having distally shortly yellowish and brownish puberulent stems, palmately-pinnately veined leaves regularly dentate at margin, scarious, brown and larger bracts, and larger ray laminae. In addition, a distribution map and a diagnostic key to Chinese species of L. ser. Ligularia are also provided.

Abstract It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression and transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi‐immune pathway regulation strategy through PD‐L1, collagen, and TGF‐β co‐depression. Then, IR‐LND is prepared by combining the mitochondria‐targeted molecule IR‐68 with LND, which then is loaded with liposomes (Lip) to create IR‐LND@Lip nanoadjuvants. By doing this, IR‐LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition. In conclusion, the combined treatment of RT and IR‐LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.

Hip arthroscopy has become a predominant treatment for hip disorders such as femoroacetabular impingement syndrome and labral injury, and appropriate distraction for the hip joint is necessary for successful surgery. The traditional distraction method uses a perineal post but may cause complications such as perineum injury and nerve damage. For this reason, some surgeons have proposed postless distraction techniques, but they usually require additional equipment purchase and cost, which is not conducive to application. Therefore, we developed a post-free distraction technique without additional equipment. This method uses only surgical draw sheets, safety straps, a hip fracture table, and a hip distractor that are routinely provided in the operating room, and postless hip distraction can be achieved by using the Trendelenburg position, which is reliable, simple, and reproducible to be used in hip arthroscopy.

Colon cancer is a common gastrointestinal malignancy that ranks third in incidence among gastrointestinal cancers. Therefore, screening bioactive compounds for treatment of colon cancer is urgently needed. Sanguisorba officinalis L. (SO) has been demonstrated that the extractions or monomers possess potential anti-tumor effect. In this study, we firstly used cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled with (quadrupole) time-of-flight mass spectrometry (UHPLC-(Q) TOF-MS/MS) to identify a novel active ingredient, octyl gallate (OG), from SO methanol extract (SO-MtOH). HCT116 and SW620 cells lines were used for in vitro research, which showed OG presents great anti-colon cancer effect by inhibiting proliferation, inducing apoptosis, and repressing the migration and invasion. Furthermore, SW620 bearing athymic nude mice was used to investigate the potential antitumor activity in vivo, which exhibited OG treatment remarkably lessened the tumor volume. Mechanism studies showed that OG downregulated the PI3K/AKT/mTOR signaling axis and induced apoptosis by upregulating the Bax/Bcl-2 protein and the cleaved caspase-3, caspase-9. In conclusion, our research innovatively applied the method of CMC to intriguingly unearth the potential anti-colon cancer ingredient OG and demonstrated its the great antineoplastic activity, which provide a new insight for researchers efficiently developing the novel apoptosis-inducing compound for colon cancer therapy.

Abstract Objective Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90‐day interval in AIS patients. Methods A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) from total cholesterol (TC). Results Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90‐day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90‐day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p‐overall = .011). Conclusions Including RC as a contributing element may refine the prediction of poor 90‐day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.

Coordinated siting and sizing for energy stations and supply networks in urban integrated energy system (UIES) is significant for economic improvement and carbon emissions reduction. A station-network cooperative planning method of UIES based on energy flow model is proposed. First, an operation model of heat network based on energy flow theory is proposed, which solves the problem that the temperature mixing equation in the traditional operation model cannot be applied to heat network planning. On this basis, a bi-level model for station-network cooperative planning of UIES is constructed, in which the upper level optimizes the siting and sizing of the energy station and the topology of the supply network, and the lower level optimizes the operation of the UIES and feeds back the operation cost of the UIES to the upper level. Finally, a solution method of cooperative planning based on the Karush-Kuhn-Tucher condition is proposed, to transform the bi-level nonlinear optimization model into a single-level linear optimization model for efficient solution. Case studies on the 55-node and 77-road urban topology show that the proposed method can perform an effective planning on energy supply network topology and rationally configure the capacity of various devices in the energy station.

Gaia mission offers opportunities to search for compact binaries not involved in binary interactions (hereafter inert compact binaries), and results in the discoveries of binaries containing one black hole (BH) or one neutron star (NS), called "Gaia BHs'' and "Gaia NSs'', respectively. We have assessed if Gaia BHs and NSs can be formed in open clusters through dynamical interactions. In order to obtain a large number of inert compact binaries similar to Gaia BHs and NSs, we have performed gravitational $N$-body simulations for a large number of open clusters whose total mass is $1.2 \times 10^8 M_\odot$. These clusters have various masses, metallicities, densities, and binary fractions. We have found that open clusters form Gaia BHs ($10^{-6}$-$10^{-5} M_\odot^{-1}$) much more efficiently than Gaia NSs ($\lesssim 10^{-7} M_\odot^{-1}$) for any cluster parameters. This is quite inconsistent with observational results, because the reported numbers of Gaia BHs and NSs are $3$ and $21$, respectively. Additionally, we have switched off NS natal kicks for $10^4$ open clusters each weighing $10^3 M_\odot$ in order to retain a large number of NSs in open clusters. Then, open clusters form inert NS binaries originating from primordial binaries rather than formed through dynamical interactions. This means that Gaia NSs are formed dominantly on isolated fields, not in open clusters, if there is no NS natal kick. We have concluded that Gaia BHs can be dominantly formed in open clusters, however Gaia NSs cannot.

Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.

Abstract Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Abstract Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24–2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05–1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.

Abstract Background The postponement of parenthood is a global public health issue that has received attention of many public health experts. However, few studies have investigated the postponement in marriage age, marriage and conception interval, and pregnancy age in terms of demographic and regional heterogenicities. Methods This is a cross-sectional, registry-based study, and a total of 13 894 601 nulliparous couples who participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013–2019 were included. We calculated annual percentage change and forest plots for marriage age, marriage and conception interval, and pregnancy age. Results Late marriage (marriage age ≥ 35 years), long marriage and conception interval (marriage and conception interval ≥ 2 years), and advanced pregnancy (pregnancy age ≥ 35 years) increased from 1.20%, 22.01%, and 1.88% in 2013 to 1.69%, 32.75%, and 2.79% in 2019, respectively. The corresponding annual percentage changes were 6.55%, 8.44%, and 8.17%. Participants without higher education had a higher annual percentage change, but comparable prevalence for long marriage and conception interval with participants with higher education. Participants residing in second- or new first-tier cities, and the northeast of China who had a higher prevalence of parenthood postponement also had higher corresponding annual percentage changes. Conclusions Structural postponement of parenthood with demographic and regional heterogenicities was observed among Chinese nulliparous couples with planned pregnancies during 2013–2019. Inclusive and comprehensive parenting support should be developed and implemented in mainland China to minimize the negative health effects arising from the postponement, especially for couples without higher education and living in new first/second-tier cities or the northeast China.

Different levels of hydroxypropyl methylcellulose (HPMC), xanthan gum (XG) and Glucose oxidase (GOX) were applied to germination brown rice-wheat flour (1:1) to evaluate the effects of improvers on the dough properties and Chinese steamed bread (CSB) quality. With no improver as control, thermo-mechanical and alveograph properties of different dough were analyzed, and the overall quality of different steamed bread was evaluated by color, texture, specific volume, height/diameter ratio and sensory score. The results showed that the addition of HPMC significantly (P

Duodenal stump fistula (DSF) is a serious complication of radical gastrectomy for gastric cancer. Herein, we illustrated an innovative choice for treating duodenal stump fistulas by placing a modified sump drainage through trocar puncture into the DSF-related abscess (DSF-abscess) cavity. We retrospectively analyzed 974 consecutive patients who underwent gastrectomy for gastric cancer between 2011 and 2021. Of these patients, 34 who developed postoperative duodenal stump fistulas postoperatively were enrolled into our study, and their clinical data were retrospectively assessed. From January 2011 to December 2017, 15 patients received conventional treatments (percutaneous catheter drainage, PCD group) known as the traditional percutaneous method, and 19 patients from January 2018 to December 2021 received new treatments (Troca's SD group) consisting of conventional therapies and placement of a modified sump drainage through trocar puncture into DSF-abscess cavity. The demographics, clinical characteristics and treatment outcomes were compared between two groups. Compared with the PCD group, the rates of postoperative complications, duodenostomy creation, subsequent surgery, fistula healing rates of the DSF, and length of postoperative hospital stay were significantly decreased in the Troca SD group. However, there was no significant difference in the abscess recurrence rate and mortality rates. Trocar puncture with a modified sump drainage is an safe, effective, and technically feasible treatment for duodenal stump fistula after radical gastrectomy for gastric cancer. This novel technique should be further investigated using large-scale RCT research.

Abstract Human social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions.

The imprudent cultivation of Pinus sylvestris var. mongolica has led to degradation in the watersheds surrounding Chongli County. This study investigates the artificial forests of P. sylvestris var. mongolica in the Xiaotaojiagou watershed, Chongli County. Twenty-five subplots measuring 20 m × 20 m were established at upper, upper-middle, middle, and lower positions within the watershed. Spatial distribution patterns and fractal characteristics of P. sylvestris var. mongolica were analyzed using univariate pair correlation function g(r), marked correlation functions (marked correlation function Kmm(r), marked variation function γm(r), and Schlather’s Im(r) function), and fractal dimensions (box-counting dimension, information dimension). The findings are as follows: (1) P. sylvestris var. mongolica in the middle section of the watershed displayed the largest average diameters at breast height and tree height, while those in the lower section exhibited the largest average crown width. (2) P. sylvestris var. mongolica populations in the upstream, middle, and downstream sections of the watershed exhibited three alternating states: aggregated distribution, uniform distribution, and random distribution. However, with increasing spatial scale, the distribution gradually tended towards randomness. P. sylvestris var. mongolica in the upper-middle section of the watershed showed aggregated distribution at scales of 1.5–32.5 m, transitioning to random distribution and then to uniform distribution with increasing spatial scale. (3) Individual attributes of P. sylvestris var. mongolica (diameter at breast height, tree height, and crown width) exhibited high correlation and facilitation in the upstream and upper-middle sections at small-to-medium scales, whereas negative correlations and inhibitions were observed in the middle and lower sections. These attributes tended to be uncorrelated with increasing spatial scale. (4) Fractal dimensions indicated that the degree of aggregation of P. sylvestris var. mongolica population was lowest in the downstream section of the watershed. In conclusion, spatial distribution patterns and intraspecies relationships of P. sylvestris var. mongolica populations are influenced by spatial scale and environmental conditions, particularly in more resource-competitive downstream areas. Effective management and protection of P. sylvestris var. mongolica populations require targeted measures such as adjusting afforestation density, improving soil conditions, and implementing differentiated ecological restoration strategies to alleviate intraspecies competitive pressures and promote population health and sustainable development.

Abstract Based upon mixed linear model and incomplete diallel cross between different strains of Macrobrachium nipponense, the additive‐genetic correlations of growth and morphometrics with meat yield traits in M. nipponense were estimated using the minimum norm quadratic unbiased estimation procedure. Path analysis method was utilized to investigate the overall additive‐genetic determinations of growth and morphometric traits on the meat yield traits. Results indicated that growth and morphometrics were genetically positively correlated with abdominal meat weight (p 0.05) in both sexes. Growth and morphometrics were genetically positively correlated (p

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

To meet the urgent need for a new design concept and solve the inaccuracy of existing performance prediction algorithms for high-speed turbomolecular pumps (TMPs), a new algorithm based on a novel twisted rotor blade is proposed. In this algorithm, the blade angle of the turbine rotor row progressively decreases from the root to the tip of the blade tooth. The feasibility and accuracy of the simulation algorithm were verified through experiments. The dependence of the simulation results on the number of simulated molecules was discussed. Both theoretical analysis and simulations confirmed the necessity of setting a twisted rotor blade in the turbine combined blade row. A comparative analysis on the performance of conventional straight-blade and twisted-blade structures based on the first-four stages of turbine combined blade rows of the F-63/55 TMP was conducted. The results indicated that the maximum pumping speed coefficient and maximum compression ratio of the optimised twisted-blade structure increased by 4.59% and 22.26%, respectively. This novel blade structure overcomes the limitations of the conventional straight-blade structure. Progressively decreasing the rotor blade angle from the root to the tip of the blade tooth is beneficial for improving the performance of TMPs. This study provides a new design concept and performance prediction algorithm for the structural optimisation of high-speed TMPs.

ABSTRACTMarine ecosystems contain an immense diversity of phages, many of which infect cyanobacteria (cyanophage) that are largely responsible for primary productivity. To characterize the genetic diversity and biogeographic distribution of the marine T4-like cyanophage community in the northern South China Sea, the T4-like cyanophage portal protein gene (g20) was amplified. Phylogenetic analysis revealed that marine T4-like cyanophages were highly diverse, with g20 operational taxonomic units being affiliated with five defined clades (Clusters I–V). Cluster II had a wide geographic distribution, Cluster IV was the most abundant in the open sea, and Cluster I was dominant in coastal shelf environments. Our results showed T4-like cyanophages (based on g20) community was generally shaped via heterogeneous selection. Highly variable environmental factors (such as salinity and temperature) can heterogeneously select different cyanophage communities. Nevertheless, the dominant drivers of the T4-like cyanophage community based on the g20 and g23 (T4-like phage major capsid protein gene) were different, probably due to different coverages by the primer sets. Furthermore, the community assembly processes of T4-like cyanophages were affected by host traits (abundance and distribution), viral traits (latent period, burst size, and host range), and environmental properties (temperature and salinity).IMPORTANCECyanophages are abundant and ubiquitous in the oceans, altering population structures and evolution of cyanobacteria, which account for a large portion of global carbon fixation, through host mortality, horizontal gene transfer, and the modulation of host metabolism. However, little is known about the biogeography and ecological drivers that shape the cyanophage community. Here, we use g20 and g23 genes to examine the biogeographic patterns and the assembly mechanisms of T4-like cyanophage community in the northern part of the South China Sea. The different coverages of primer sets might lead to the different dominant drivers of T4-like cyanophage community based on g20 and g23 genes. Our results showed that characteristics of viral traits (latent period, burst size, and host range) and host traits (abundance and distribution) were found to either limit or enhance the biogeographic distribution of T4-like cyanophages. Overall, both virus and host properties are critical to consider when determining rules of community assembly for viruses.

Background: Qing-Jin-Hua-Tan decoction (QJHTD) is a classic traditional Chinese medicine (TCM) prescription that first appeared in the ancient book Yi-Xue-Tong-Zhi. QJHTD has shown effectiveness for treating chronic obstructive pulmonary disease (COPD), although its mechanisms of action are still perplexing. The molecular mechanisms underlying the curative effects of QJHTD on COPD is worth exploring. Methods: In vitro antiapoptotic and antiinflammatory activities of QJHTD were evaluated using cell viability, proliferation, apoptosis rate, and expression of IL-1β and TNF-α in BEAS-2B and RAW264.7 cells challenged with cigarette smoke (CS) extract (CSE) and lipopolysaccharide (LPS). In vivo therapeutic activities of QJHTD were evaluated using respiratory parameters (peak inspiratory flow (PIFb) and peak expiratory flow (PEFb) values), histopathology (mean linear intercept, MLI), and proinflammatory cytokine (IL-1β and TNF-α) and cleaved caspase-3 (c-Casp3) levels in the lung tissue of CS–LPS-exposed BALB/c mice. Network pharmacology-based prediction, transcriptomic analysis, and metabolic profiling were employed to investigate the signaling molecules and metabolites pertinent to the anti-COPD action of QJHTD. Results: Increased cell viability and proliferation with decreased apoptosis rate and proinflammatory cytokine expression were noted after QJHTD intervention. QJHTD administration elevated PEFb and PIFb values, reduced MLI, and inhibited IL-1β, TNF-α, and c-Casp3 expression in vivo. Integrated network pharmacology–transcriptomics revealed that suppressing inflammatory signals (IL-1β, IL-6, TNF, IκB–NF-κB, TLR, and MAPK) and apoptosis contributed to the anti-COPD property of QJHTD. Metabolomic profiling unveiled prominent roles for the suppression of apoptosis and sphingolipid (SL) metabolism and the promotion of choline (Ch) metabolism in the anti-COPD effect of QJHTD. Integrative transcriptomics–metabolomics unraveled the correlation between SL metabolism and apoptosis. In silico molecular docking revealed that acacetin, as an active compound in QJHTD, could bind with high affinity to MEK1, MEK2, ERK1, ERK2, Bcl2, NF-κB, and alCDase target proteins. Conclusion: The therapeutic effect of QJHTD on COPD is dependent on regulating inflammatory signals and apoptosis-directed SL metabolism. These findings provide deeper insights into the molecular mechanism of action of QJHTD against COPD and justify its theoretical promise in novel pharmacotherapy for this multifactorial disease.

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

Background: In recent years, with the rapid development of mobile Internet and Web3D technologies, a large number of web-based online 3D visualization applications have emerged. Web3D applications, including Web3D online tourism, Web3D online architecture, Web3D online education environment, Web3D online medical care, and Web3D online shopping are examples of these applications that leverage 3D rendering on the web. These applications have pushed the boundaries of traditional web applications that use text, sound, image, video, and 2D animation as their main communication media, and resorted to 3D virtual scenes as the main interaction object, enabling a user experience that delivers a strong sense of immersion. This paper approached the emerging Web3D applications that generate stronger impacts on people's lives through “real-time rendering technology”, which is the core technology of Web3D. This paper discusses all the major 3D graphics APIs of Web3D and the well-known Web3D engines at home and abroad and classify the real-time rendering frameworks of Web3D applications into different categories. Results: Finally, this study analyzed the specific demand posed by different fields to Web3D applications by referring to the representative Web3D applications in each particular field. Conclusions: Our survey results show that Web3D applications based on real-time rendering have in-depth sectors of society and even family, which is a trend that has influence on every line of industry.

Abstract Background Contrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital. Methods The diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto’s thyroiditis influence the assessment of CEUS. Results This research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto’s thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P

Abstract The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP2), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP2, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2.