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ABSTRACT: This study investigated the effect of Ethylenediamine dihydroiodide (EDDI) on growth performance, immune function and intestinal health of meat ducks challenged with Avian pathogenic Escherichia coli (APEC). A total of 360 one-day-old Cherry Valley ducks with similar body weight were randomly allocated to 6 treatments (6 floor cages, 10 birds/cage). A 3 × 2 factor design was used with 3 dietary iodine levels (0, 8, 16 mg/kg in the form EDDI and whether APEC was challenged or not at 7-day-old ducks. The feeding period lasted for 20 d. The results showed that the addition of EDDI reduced APEC-induced decrease of the 20-d weight loss of meat ducks (P < 0.05), and alleviated the inflammatory response of liver tissue induced by APEC challenge in meat ducks. In terms of immune function, EDDI supplementation reduced the immune organ index and increased the immune cell count of meat ducks, reduced the level of endotoxins in the serum of meat ducks (P < 0.05), as well as inhibited the expression levels of liver and spleen inflammatory factors and TLR signaling pathway related genes induced by APEC (P < 0.05). In terms of intestinal health, EDDI inhibited APEC-induced decreases in ZO-3 genes expression and increases in IL-1β and TNF-α expression, increased relative abundance of beneficial bacteria in the cecum and content of metabolites. Pearson correlation analysis showed that there was a significant correlation between liver inflammatory factors and TLR4 signaling pathway genes, and there might be a significant correlation between intestinal microbial flora and other physiological indexes of meat ducks, which indicated that EDDI could reduce the damage to immune function and intestinal health caused by APEC challenge through regulating the structure of intestinal flora. Collectively, our findings suggest that the EDDI can promote growth performance, improve immune function and the intestinal barrier in APEC-challenged meat ducks, which may be related to the suppression of NF-κB signal.

In plants, the lysine and histidine transporter (LHT) family represent a class of proteins that mediate the uptake, translocation, and utilization of amino acids. The tea plant (Camellia sinensis) is a perennial evergreen with a relatively high level of amino acids. However, systematic identification and molecular characterization of the LHT gene family has rarely been reported in tea plants. In this study, 22 CsLHTs were identified from the ‘Shuchazao’ genome and classified into two groups. The modeled three-dimensional structure and the conserved domains presented a high similarity among the LHTs proteins. Moreover, it was predicted that a few genes were conserved through the analysis of the physiochemical characters, structures and cis-elements in promoters. The expression patterns in tea plants revealed that CsLHT7 was mainly expressed in the roots, and CsLHT4 and CsLHT11 exhibited relatively high expression in both the roots and leaves. Moreover, the expression of all three genes could be induced by organic nitrogen. Additionally, heterogeneous expression of CsLHT4, CsLHT7 and CsLHT11 in Arabidopsis thaliana decreased the aerial parts biomass compared with that in WT plants while significantly increased the rosette biomass only for CsLHT11 transgenic plants versus WT plants. Overall, our results provide fundamental information about CsLHTs and potential genes in N utilization for further analysis in tea plants.

Abstract Background COVID-19 is continuing to ravage globally and has resulted in a huge health and financial burden. Chinese proprietary medicines, such as Lianhua Qingwen (LHQW) and Huoxiang Zhengqi (HXZQ) capsules, have been recommended for non-high-risk patients with COVID-19 in China. Based on this, we described the baseline information, using status of LHQW and HXZQ capsules and inoculation history of quarantined patients in the second half of 2022 in Macao. Additionally, we analyzed the underlying association among medicines administration, vaccination and COVID-19 indices, in order to explore novel clues for the regular control and prevention of local epidemic situation in the future. Methods A total of 976 patients in Macao quarantine hotels from June to August 2022 were included in the present study, of which, 857 subjects were followed-up for prognosis evaluation. During quarantine, the baseline demographic information, including sex, age, BMI, occupation and personal habits were collected. Additionally, the inoculation history, medicine employment status and cycle threshold (Ct) values were also reported. We interviewed the patients for collection of their symptoms at the beginning and end of quarantine, as well as prognostic ones. Basic statistical description of baseline information, vaccination history and medication were displayed. Chi-squared test or with continuous correction test was employed for comparison of dichotomous data between two or multiple groups. Binary logistic regression was applied to reveal the correlation between potential risk factors and Ct values or prognosis symptoms. We also used Cox regression model to identify the effect of different types of vaccine products on Ct value altering rate. Results Patients who were female (52.0%), engaged in service industry (31.8%), from Macao native (65.8%), never took physical exercises (33.6%) and preferred irritated diet (59.5%) enjoyed more dominant proportions. Over 80% of participants were inoculated and 74.6% of them chose inactivated COVID-19 vaccine produced by China National Biotech Group (CNBG). Participants used LHQW capsules accounted for 92.1% and the duration of medicating lasted for one to two weeks. All of the reported symptoms were significantly ameliorated after quarantine and the duration of quarantine was concentrated on 21 days. People with different age, sex, occupation and region had different choices of HXZQ administration and vaccination. Additionally, middle dose (4–5 boxes) of LHQW capsules exhibited evidently negative association with positive Ct values (adjusted, − 0.037 ± 0.19, p = 0.04). Two doses of CNBG and one dose of mRNA vaccine had obvious protective effect on reducing Ct positive rate (p = 0.041). Meanwhile, symptoms after quarantine were significantly positive correlated with those in prognosis (adjusted, 1.38 ± 0.18, p

Abstract Background Zinc glycine chelate (Zn-Gly) has anti-inflammation and growth-promoting properties; however, the mechanism of Zn-Gly contribution to gut barrier function in Cherry Valley ducks during intestinal inflammation is unknown. Three-hundred 1-day-old ducks were divided into 5 groups (6 replicates and 10 ducks per replicate) in a completely randomized design: the control and dextran sulfate sodium (DSS) groups were fed a corn-soybean meal basal diet, and experimental groups received supplements of 70, 120 or 170 mg/kg Zn in form of Zn-Gly. The DSS and treatment groups were given 2 mL of 0.45 g/mL DSS daily during d 15–21, and the control group received normal saline. The experiment lasted 21 d. Results Compared with DSS group, 70, 120 and 170 mg/kg Zn significantly increased body weight (BW), villus height and the ratio of villus to crypt, and significantly decreased the crypt depth of jejunum at 21 d. The number of goblet cells in jejunal villi in the Zn-Gly group was significantly increased by periodic acid-Schiff staining. Compared with control, the content of intestinal permeability marker D-lactic acid (D-LA) and fluxes of fluorescein isothiocyanate (FITC-D) in plasma of DSS group significantly increased, and 170 mg/kg Zn supplementation significantly decreased the D-LA content and FITC-D fluxes. Compared with control, contents of plasma, jejunum endotoxin and jejunum pro-inflammatory factors IL-1β, IL-6 and TNF-α were significantly increased in DSS group, and were significantly decreased by 170 mg/kg Zn supplementation. Dietary Zn significantly increased the contents of anti-inflammatory factors IL-10, IL-22 and sIgA and IgG in jejunum. Real-time PCR and Western blot results showed that 170 mg/kg Zn supplementation significantly increased mRNA expression levels of CLDN-1 and expression of OCLN protein in jejunum, and decreased gene and protein expression of CLDN-2 compared with DSS group. The 120 mg/kg Zn significantly promoted the expressions of IL-22 and IgA. Dietary Zn-Gly supplementation significantly decreased pro-inflammatory genes IL-8 and TNF-α expression levels and TNF-α protein expression in jejunum. Additionally, Zn significantly reduced the gene and protein expression of TLR4, MYD88 and NF-κB p65. Conclusions Zn-Gly improved duck BW and alleviated intestinal injury by regulating intestinal morphology, barrier function and gut inflammation-related signal pathways TLR4/MYD88/NF-κB p65.

Abstract Background Allostatic load (AL) reflects the collective load of chronic stress during lifetime. Previous studies have shown that higher AL is associated with poor clinical outcomes among breast cancer patients. However, the relationship between AL and breast cancer risk is still unclear. Methods To fill the gap, we analyzed the association between AL and the development of breast cancer in 181,455 women identified from the UK Biobank. Results During the follow-up from 2006 to 2020, 5,701 women were diagnosed with incident breast cancer. Significantly higher AL was observed among incident breast cancer cases than all study participants (mean: 2.77 vs. 2.63, P

Abstract Accelerating biomass improvement is a major goal of Miscanthus breeding. The development and implementation of genomic‐enabled breeding tools, like marker‐assisted selection (MAS) and genomic selection, has the potential to improve the efficiency of Miscanthus breeding. The present study conducted genome‐wide association (GWA) and genomic prediction of biomass yield and 14 yield‐components traits in Miscanthus sacchariflorus. We evaluated a diversity panel with 590 accessions of M. sacchariflorus grown across 4 years in one subtropical and three temperate locations and genotyped with 268,109 single‐nucleotide polymorphisms (SNPs). The GWA study identified a total of 835 significant SNPs and 674 candidate genes across all traits and locations. Of the significant SNPs identified, 280 were localized in mapped quantitative trait loci intervals and proximal to SNPs identified for similar traits in previously reported Miscanthus studies, providing additional support for the importance of these genomic regions for biomass yield. Our study gave insights into the genetic basis for yield‐component traits in M. sacchariflorus that may facilitate marker‐assisted breeding for biomass yield. Genomic prediction accuracy for the yield‐related traits ranged from 0.15 to 0.52 across all locations and genetic groups. Prediction accuracies within the six genetic groupings of M. sacchariflorus were limited due to low sample sizes. Nevertheless, the Korea/NE China/Russia (N = 237) genetic group had the highest prediction accuracy of all genetic groups (ranging 0.26–0.71), suggesting that with adequate sample sizes, there is strong potential for genomic selection within the genetic groupings of M. sacchariflorus. This study indicated that MAS and genomic prediction will likely be beneficial for conducting population‐improvement of M. sacchariflorus.

To explore the axial compressive mechanical properties of steel tube recycled steel fiber reinforced concrete short columns (STRSFRCSCs), axial compression tests were conducted on ten STRSFRCSCs and two steel tube reinforced concrete short columns (STRCSCs), mainly analyzing the effects of recycled steel fiber (RSF) content, steel content, and concrete strength grade on their mechanical properties. The results showed that different RSF contents had no significant effect on the failure mode of the specimens, while the concrete strength grade and steel content had a significant effect on the failure mode. When the steel content was 2.84%, the specimens experienced shear failure, while when the steel content was 4.24%, they experienced waist drum failure. As the RSF content increased, the peak strain during the loading process of the specimens decreased, and the transverse deformation coefficient at the peak decreased. The addition of RSF significantly improved the ductility performance of the specimens. When the volume fraction of RSF was 2%, the bearing capacity of the specimens increased the most, reaching 13.4%, and the ductility coefficient gradually increased. The axial compressive bearing capacity and combined elastic modulus of the specimens increased with the increase in concrete strength grade, RSF content, and steel content.

Adopting zero-carbon fuels, like hydrogen, can significantly reduce environmental harm and pave the way for a decarbonised trajectory with zero carbon emissions. The hydrogen internal combustion engine (ICE) technology has demonstrated its reliability and capacity to seamlessly integrate into the current ICE platform, originally designed for diesel and gasoline operation. The direct utilisation of pure hydrogen eradicates steady-state carbon dioxide and hydrocarbon emissions. It is important to highlight that efforts to comprehend and comprehensively tackle NOx emissions are underway. A comprehensive study was carried out to assess the NOx emissions for a hydrogen ICE with different injection modes from gasoline. The study involved varying the relative air-to-fuel ratio (AFR) from stoichiometric to the lean-burn limit in a boosted spark ignition (SI) engine fuelled with gasoline or hydrogen. A fast NOx emissions analyser was employed to measure the instantaneous NO and NO2 emissions in the engine exhaust. The study provides a detailed analysis of NOx emissions, including steady-state averaged emissions, average crank angle domain NOx distribution and emissions, in-cylinder pressure analysis, as well as time and cycle analyses of NOx emissions’ temporal and cyclic variations. The primary discovery was that NOx emissions are almost zero between lambda 2.75 and 3.7, and hydrogen produces 13.8% less NOx emissions than gasoline at stoichiometric operation. Finally, the full NOx time analysis revealed that the consistency of NOx emissions is higher with hydrogen than with gasoline by using a novel approach by identifying the coefficient of variation of the NOx emission of each cycle.

This paper introduces a hybrid readout system for a cross-strip position-sensitive anode detector that combines a lookup table and weighted averaging. The lookup table approach is used to identify event channels and select appropriate weights based on the corresponding index code for calculating the centroid of the electron cloud. This effectively enhances the readout system’s processing speed while preserving the high-resolution advantage of the cross-strip position-sensitive anode. Simulations were performed to evaluate the performance of the system. Experimental results demonstrate that this readout method achieves an event processing speed exceeding 10 MHz while maintaining a resolution of 17.96 lp/mm.

BackgroundThere currently exists some controversy about the efficacy of oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative diseases.AimThis study compares the application effects of OLIF and TLIF in lumbar degenerative diseases by reviewing the literature and using meta-analysis.MethodsWe included randomized controlled trials and cohort studies comparing TLIF and OLIF in the treatment of lumbar degenerative diseases. We searched for words such as “intervertebral disc degeneration,” “spinal fusion,” and “lumbar vertebrae” in the PubMed, Embase, and Cochrane Library databases. The search date was set from the establishment date of the database to October 2023. Two authors independently conducted document screening, data abstraction, and qualitative assessment. A meta-analysis was performed and adapted to RevMan5.3 software. The odds ratio (OR), weighted mean difference (WMD), and 95% CI were calculated by adopting a fixed-effect model (FEM) or a random-effect model (REM).ResultsA total of 18 cohort studies were included with 1,550 patients, of whom 806 patients underwent TLIF (TLIF group) and 744 patients underwent OLIF (OLIF group). There were no significant differences found in the fusion rate [OR = 1.58 (0.95, 2.64), P = 0.08], complication rate [OR = 1.25 (0.93, 1.68), P = 0.14], and visual analog scale for back pain (VAS-BP) [WMD = 0.00 (−0.13, 0.14), P = 0.96] between the two groups. Compared with the TLIF group, the OLIF group had a lower Oswestry disability index (ODI) [WMD = −0.62 (−1.03, −0.20), P = 0.003], a higher foramen height (FH) [WMD = 2.03 (1.42, 2.46), P

Many studies on horizontally loaded energy piles have tended to ignore the impact of axial frictional resistance in the analysis processes or lacked experimental validation. The effect of axial frictional resistance may be considered by conveniently calculating the frictional resistance and revealing the mechanism of axial frictional resistance. Our proposed displacement analysis approach takes into account pile-sand axial friction during heating. Validation was carried out through a centrifuge test case. Subsequent parametric analyses explored the influence of pile diameter and Young's modulus on the lateral response of the pile. Comparative results between the centrifuge test and proposed approach underscored its effectiveness in capturing the impact of friction resistance on energy piles during heating. The parametric analyses show that the increase in pile diameter from 0.5 m to 0.7 m and Young's modulus from 10 GPa to 20 GPa led to a decrease in normalized pile top displacement by 50.68% and 28.33%, a decrease in maximum soil pressure in front of the pile by 16.18% and 11.59%, and a decrease in maximum bending stress of the pile by 3.27% and an increase by 14.48%, respectively.

Sustainable energy solutions are paramount in the urgent global drive against climate change, especially in transportation. This research focuses on second-generation biogasolines and their potential in the context of decarbonisation. Two biogasolines, 99 RON E20 and 95 RON E20, were rigorously tested in a downsized single-cylinder engine. Their performance, combustion, and emissions were compared against the conventional fossil fuel, 95 RON E10, under varying engine loads. Additionally, a comprehensive injection parameter sweep was conducted for both biofuels at low and high loads, shedding light on their unique operational characteristics and operational regimes. This research significantly enhances our knowledge about the potential of these new biofuels and their implications for a more sustainable energy future. The findings of the experiments demonstrate no substantial difference between the tested biofuels and fossil fuels. Biofuel with a higher octane number provides more knock resistance than fossil fuel, resulting in increased thermal efficiency due to spark advance ability. However, more significant hydrocarbon emissions were detected for biofuels than fossil fuels due to more extensive aromatic content. Both biofuels have stable combustion in low and high-load operations under varying injection pressures and injection start times. 99 Bio E20 has a wider operational range than 95 Bio E20. However, due to very high HC emissions, especially at high-load operations, an early injection start with more significant injection pressure is not recommended for biofuel. From a broader perspective, both biofuels exhibit the promising potential to serve as drop-in replacements in spark ignition engines.

Based on Boyd’s “Observation Orientation-Decision-Action (OODA)” aerial combat theory and the principles of operational success, an analysis of the operational division patterns for cross-generational human-machine collaboration was conducted. The research proposed three stages in the development of aerial combat human-machine fusion intelligence: “Human-Machine Separation, Functional Coordination,” “Human-Machine Trust, Task Coordination,” and “Human-Machine Integration, Deep Fusion.” Currently, the transition from the first stage to the second stage is underway, posing challenges primarily related to the lack of effective methods guiding experimental research on human-machine fusion interaction and trust. Building upon the principles of decision neuroscience and the theory of supply and demand relationships, the study analyzed the decision-making patterns of human-machine fusion intelligence under different states. By investigating the correlations among aerial combat mission demands, dynamic operational limits of human-machine tasks, and aerial combat mission performance, a theoretical model of human-machine fusion interaction and trust was proposed. This model revealed the mechanistic coupling of human-machine interactions in aerial tasks, aiming to optimize the decision-making processes of human-machine systems to enhance mission performance. It provides methodological support for the design and application of intelligent collaborative interaction modes in aviation equipment.

BackgroundImmune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC).MethodsFifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively.ResultsA comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival.ConclusionsThese results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Excessive exposure to manganese in the environment or workplace is strongly linked to neurodegeneration and cognitive impairment, but the precise pathogenic mechanism and preventive measures are still not fully understood. The study aimed to investigate manganese -induced oxidative damage in the nervous system from an epigenetic perspective, focusing on the H3K36ac-dependent antioxidant pathway. Additionally, it sought to examine the potential of curcumin in preventing manganese-induced oxidative damage. Histopathology and transmission electron microscopy revealed that apoptosis and necrosis of neurons and mitochondrial ultrastructure damage were observed in the striatum of manganese-exposed rats. manganese suppressed the expression of mitochondrial antioxidant genes, leading to oxidative damage in the rats' striatum and SH-SY5Y cells. With higher doses of manganese, levels of histone acetyltransferase lysine acetyltransferase 2 A (KAT2A) expression and H3K36ac level decreased. ChIP-qPCR confirmed that H3K36ac enrichment in the promoter regions of antioxidant genes SOD2, PRDX3, and TXN2 was reduced in SH-SY5Y cells after manganese exposure, leading to decreased expression of these genes. Overexpression of KAT2A confirms that it attenuates manganese-induced mitochondrial oxidative damage by regulating H3K36ac levels, which in turn controls the expression of antioxidant genes SOD2, PRDX3, and TXN2 in the manganese-exposed cell model. Furthermore, curcumin might control H3K36ac levels by influencing KAT2A expression, boosting antioxidant genes expression, and reducing manganese-induced mitochondrial oxidative damage. In conclusion, the regulation of mitochondrial oxidative stress by histone acetylation may be an important mechanism of manganese-induced neurotoxicity. This regulation could be achieved by reducing the level of H3K36ac near the promoter region of mitochondrial-associated antioxidant genes via KAT2A. Curcumin mitigates manganese-induced oxidative damage in mitochondria and plays a crucial protective role in manganese-induced oxidative injury in the nervous system.

This study was to investigate the effects of Alpinia officinarum Hance stems and leaves extract (AOE) on the growth, non-specific immunity, intestinal microflora of shrimp (Litopenaeus vannamei). A total of 540 juvenile L. vannamei (2.69 ± 0.03 g) were randomly divided into six groups, and feed experiment with diet supplement of 0 g/kg (CG), 0.1 g/kg (AO-1), 0.2 g/kg (AO-2), 0.3 g/kg (AO-3), 0.5 g/kg (AO-4) and 0.7 g/kg(AO-5) AOE was carried out for 8 weeks, respectively. Compared with the control group (CG), the WGR and SGR of the AO-1, AO-3, and AO-4 groups were significantly increased. Crude protein content in the muscle of L. vannamei in AO-2 was significantly increased, while the water content was significantly decreased. The crude lipid content of each extract group was significantly decreased. Compared with the control group, activities of GSH-Px, SOD, and T-AOC in the cell-free hemolymph of AO-3 group were significantly enhanced, and the MDA content of each extract group was significantly decreased. Activities of CAT, SOD, and T-AOC in the hepatopancreas of AO-2 group were significantly increased. Gene expression levels of lvcat, lvgsh-px, and lvmn-sod in AO-3 group were obviously higher than those in the control group, while lvpropo expression was dramatically higher in AO-2 and AO-3 groups. Moreover, AOE addition in feed changed the composition and species abundance of intestinal microflora of L. vannamei at phylum and genus levels. Through α diversity analysis, the biodiversity of the flora was improved, while β diversity analysis changed the similarity of the flora between the control and addition groups. Therefore, addition of 0.2–0.3 g/kg AOE could improve the growth, immunity and optimize the composition of intestinal microorganisms of L. vannamei.

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.

BackgroundThe increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in China presents a significant public health concern. Traditional ultrasound, commonly used for fatty liver screening, often lacks the ability to accurately quantify steatosis, leading to insufficient follow-up for patients with moderate-to-severe steatosis. Transient elastography (TE) provides a more quantitative diagnosis of steatosis and fibrosis, closely aligning with biopsy results. Moreover, machine learning (ML) technology holds promise for developing more precise diagnostic models for NAFLD using a variety of laboratory indicators. ObjectiveThis study aims to develop a novel ML-based diagnostic model leveraging TE results for staging hepatic steatosis. The objective was to streamline the model’s input features, creating a cost-effective and user-friendly tool to distinguish patients with NAFLD requiring follow-up. This innovative approach merges TE and ML to enhance diagnostic accuracy and efficiency in NAFLD assessment. MethodsThe study involved a comprehensive analysis of health examination records from Suzhou Municipal Hospital, spanning from March to May 2023. Patient data and questionnaire responses were meticulously inputted into Microsoft Excel 2019, followed by thorough data cleaning and model development using Python 3.7, with libraries scikit-learn and numpy to ensure data accuracy. A cohort comprising 978 residents with complete medical records and TE results was included for analysis. Various classification models, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost), were constructed and evaluated based on the area under the receiver operating characteristic curve (AUROC). ResultsAmong the 916 patients included in the study, 273 were diagnosed with moderate-to-severe NAFLD. The concordance rate between traditional ultrasound and TE for detecting moderate-to-severe NAFLD was 84.6% (231/273). The AUROC values for the RF, LightGBM, XGBoost, SVM, KNN, and LR models were 0.91, 0.86, 0.83, 0.88, 0.77, and 0.81, respectively. These models achieved accuracy rates of 84%, 81%, 78%, 81%, 76%, and 77%, respectively. Notably, the RF model exhibited the best performance. A simplified RF model was developed with an AUROC of 0.88, featuring 62% sensitivity and 90% specificity. This simplified model used 6 key features: waist circumference, BMI, fasting plasma glucose, uric acid, total bilirubin, and high-sensitivity C-reactive protein. This approach offers a cost-effective and user-friendly tool while streamlining feature acquisition for training purposes. ConclusionsThe study introduces a groundbreaking, cost-effective ML algorithm that leverages health examination data for identifying moderate-to-severe NAFLD. This model has the potential to significantly impact public health by enabling targeted investigations and interventions for NAFLD. By integrating TE and ML technologies, the study showcases innovative approaches to advancing NAFLD diagnostics.

BackgroundAn insufficient number of intratumoral CD8+ T lymphocytes is a major barrier to antitumor immunity and immunotherapy. High endothelial venules (HEVs) are the major sites through which lymphocytes enter tumors; however, the molecular mechanism through which HEVs mediate CD8+ T lymphocyte infiltration remains poorly understood.MethodsForty-two patients with stage IIIA lung adenocarcinoma, who underwent surgery, were recruited. Multiplex immunohistochemical staining was conducted on tumor tissues to detect the immune checkpoint ligands (ICLs) expressed in the HEVs, blood vessels, and lymphatics. A new ICL score model was constructed to evaluate ligand expression. The relationship between ICL score, tumor-infiltrating CD8+ T cell frequency, and survival of patients was investigated.ResultsMature HEVs, but not blood vessels or lymphatics, mediated CD8+ T cell infiltration. However, the ICLs expressed on mature HEVs could negatively regulate CD8+ T cell entry into tertiary lymphoid structures (TLSs). In addition, according to the results obtained using our ICLtotal score model, the expression of ICLs on HEVs was observed to be a predictor of both CD8+ T cell infiltration and survival, in which a high ICLtotal score > 1 represent a weak CD8+ T cell infiltration and a high ICLtotal score > 2 predicts poor survival.ConclusionUsing the ICL score model, we discovered that ICLs expressed on HEVs are indicative of CD8+ T cell subset infiltration in TLSs, as well as of patient survival with lung cancer.

BackgroundThe infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas.MethodsDoxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining.ResultsDoxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells.ConclusionsThese results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

Demyelination is a pathological feature commonly observed in various central nervous system diseases. It is characterized by the aggregation of oligodendrocyte progenitor cells (OPCs) in the lesion area, which face difficulties in differentiating into mature oligodendrocytes (OLGs). The differentiation of OPCs requires the presence of Sox10, but its expression decreases under pathological conditions. Therefore, we propose a therapeutic strategy to regulate OPCs differentiation and achieve myelin repair by endogenously loading Sox10 into exosomes. To accomplish this, we generated a lentivirus-armed Sox10 that could anchor to the inner surface of the exosome membrane. We then infected HEK293 cells to obtain exosomes with high expression of Sox10 (exosomes-Sox10, ExoSs). In vitro, experiments confirmed that both Exos and ExoSs can be uptaken by OPCs, but only ExoSs exhibit a pro-differentiation effect on OPCs. In vivo, we administered PBS, Exos, and ExoSs to cuprizone-induced demyelinating mice. The results demonstrated that ExoSs can regulate the differentiation of PDGFRα+ OPCs into APC+ OLGs and reduce myelin damage in the corpus callosum region of the mouse brain compared to other groups. Further testing suggests that Sox10 may have a reparative effect on the myelin sheath by enhancing the expression of MBP, possibly facilitated by the exosome delivery of the protein into the lesion. This endogenously loaded technology holds promise as a strategy for protein-based drugs in the treatment of demyelinating diseases.

Non aqueous reactive polymer materials produced by the reaction of isocyanate and polyol have been widely used in infrastructure construction, which may be subjected to explosion loads during complex service conditions. The blast response of composite materials is a crucial aspect for applications in engineering structures potentially subjected to extreme loadings. In this work, damage caused to rebar reinforced polymer slabs by surface explosive charges was studied experimentally and numerically. A total of 6 field tests were carried out to investigate the performances of the failure modes of rebar reinforced polymer slabs under contact and near-field explosions. The influence of explosive quantity (10–40 g) and stand-off distances (0–20 cm) at the damage modes were studied. The results show that the failure modes of rebar reinforced polymer slabs under near-field explosion mainly were bending and surface spalling, while under the impact of contact explosion, the failure modes were craters of the top surface, spalling of the bottom surface, and middle perforation. Furthermore, a detailed fully coupled model was developed and validated with the test data. The influences of explosive quantity and slab thickness on rebar reinforced polymer slabs under contact explosion were studied. Based on this, the calculation formula between breach diameter, explosive quantity, and slab thickness is fitted.

Abstract Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.

Mpox (monkeypox) virus (MPXV), which causes a mild smallpox-like disease, has been endemic in Africa for several decades, with sporadic cases occurring in other parts of the world. However, the most recent outbreak of mpox mainly among men that have sex with men has affected several continents, posing serious global public health concerns. The infections exhibit a wide spectrum of clinical presentation, ranging from asymptomatic infection to mild, severe disease, especially in immunocompromised individuals, young children, and pregnant women. Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models. However, the continued evolution of MPXV has produced multiple lineages, leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines. MPXV infections in various animal models have provided a central platform for identification and comparison of diseased pathogenesis between the contemporary and historic isolates. In this review, we discuss the susceptibility of various animals to MPXV, and describe the key pathologic features of rodent, rabbit and nonhuman primate models. We also provide application examples of animal models in elucidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs. These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures. Finally, we list some remaining scientific questions of MPXV that can be resolved by animal models.

Abstract Background The surgical approach and prognosis for invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA) of the lung differ. However, they both manifest as identical ground‐glass nodules (GGNs) in computed tomography images, and no effective method exists to discriminate them. Methods We developed and validated a three‐dimensional (3D) deep transfer learning model to discriminate IAC from MIA based on CT images of GGNs. This model uses a 3D medical image pre‐training model (MedicalNet) and a fusion model to build a classification network. Transfer learning was utilized for end‐to‐end predictive modeling of the cohort data of the first center, and the cohort data of the other two centers were used as independent external validation data. This study included 999 lung GGN images of 921 patients pathologically diagnosed with IAC or MIA at three cohort centers. Results The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). The model had high diagnostic efficacy for the training and validation groups (accuracy: 89%, sensitivity: 95%, specificity: 84%, and AUC: 95% in the training group; accuracy: 88%, sensitivity: 84%, specificity: 93%, and AUC: 92% in the internal validation group; accuracy: 83%, sensitivity: 83%, specificity: 83%, and AUC: 89% in one external validation group; accuracy: 78%, sensitivity: 80%, specificity: 77%, and AUC: 82% in the other external validation group). Conclusions Our 3D deep transfer learning model provides a noninvasive, low‐cost, rapid, and reproducible method for preoperative prediction of IAC and MIA in lung cancer patients with GGNs. It can help clinicians to choose the optimal surgical strategy and improve the prognosis of patients.

The foundation parents play key roles in the genetic improvement of both yield potential and end-use quality in wheat. Characterizing the genetic basis that underlies certain beneficial traits in the foundation parents will provide theoretical reference for molecular breeding by a design approach. ‘Kenong 9204’ (KN9204) is a candidate foundation parent characterized by ideotype, high yield potential, and particularly high nitrogen fertilizer utilization. To better understand the genetic basis of its high yield potential, high throughput whole-genome re-sequencing (10×) was performed on KN9204, its parental lines and its derivatives. A high-resolution genetic composition map of KN9204 was constructed, which showed the parental origin of the favorable genomic segments based on the identification of excellent yield-related quantitative trait loci (QTL) from a bi-parental mapping population. Xiaoyan 693 (XY693), a wheat–Thinopyrum ponticum partial amphidiploid, contributed a great deal to the high yield potential of KN9204, and three major stable QTLs from XY693 were fine mapped. The transmissibility of key genomic segments from KN9204 to its derivatives were delineated, indicating that haplotype blocks containing beneficial gene combinations were conserved along with directional selection by breeders. Evidence for selection sweeps in the breeding programs was identified. This study provides a theoretical reference for the breeding of high-yield wheat varieties by a molecular design approach.

Abstract Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis‑related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis‑related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis‑related genes in HCC.

Abstract The soil-borne fungus Verticillium dahliae, the most notorious plant pathogen of the Verticillium genus, causes vascular wilts in a wide variety of economically important crops. The molecular mechanism of V. dahliae pathogenesis remains largely elusive. Here, we identify a small ubiquitin-like modifier (SUMO)-specific protease (VdUlpB) from V. dahliae, and find that VdUlpB facilitates V. dahliae virulence by deconjugating SUMO from V. dahliae enolase (VdEno). We identify five lysine residues (K96, K254, K259, K313 and K434) that mediate VdEno SUMOylation, and SUMOylated VdEno preferentially localized in nucleus where it functions as a transcription repressor to inhibit the expression of an effector VdSCP8. Importantly, VdUlpB mediates deSUMOylation of VdEno facilitates its cytoplasmic distribution, which allows it to function as a glycolytic enzyme. Our study reveals a sophisticated pathogenic mechanism of VdUlpB-mediated enolase deSUMOylation, which fortifies glycolytic pathway for growth and contributes to V. dahliae virulence through derepressing the expression of an effector.

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

The interior permanent magnet synchronous motor (IPMSM) is known for its high output torque, strong overload capacity, and high power density, making it a popular choice in the electric vehicle industry. This paper proposes an improved multi-objective artificial hummingbird algorithm that combines chaotic mapping, adaptive weights, and dynamic crowding entropy. An optimization strategy that combines the Taguchi method with the Improved Multi-Objective Artificial Hummingbird Algorithm (IMOAHA), is proposed to minimize torque ripple and back electromotive force in the interior permanent magnet synchronous motor while simultaneously increasing the average torque of the motor. Taking the 8-pole 48-slot interior permanent magnet synchronous motor as an example, the optimization objectives include back electromotive force, average torque, and torque ripple. The rotor-related structural parameters are used as optimization variables. First, the Taguchi method is employed to identify parameters that significantly influence the optimization objectives. Subsequently, response surface fitting is used to establish the relationship between the optimization objectives and parameters. Finally, the multi-objective artificial hummingbird algorithm is utilized for optimization. By comparing the finite element analysis of the motor models before and after optimization, it is evident that the improved multi-objective artificial hummingbird algorithm can effectively enhance the performance of the interior permanent magnet synchronous motor.

With strong support from national and local government policies for prefabricated buildings, China’s prefabricated buildings have entered a period of rapid development. This article analyses the literature from various countries and establishes a structural model of the prefabricated building supply chain under the Engineering Procurement Construction (EPC) mode. It analyzes the factors that affect the prefabricated building supply chain under the EPC model from eight aspects: design stage, prefabricated component production and manufacturing stage, procurement stage, and EPC general contracting stage, etc. Then, it establishes an AHP fuzzy comprehensive evaluation model that combines qualitative and quantitative methods to evaluate the entire lifecycle supply chain of prefabricated buildings, providing reference for the robustness and resilience evaluation of prefabricated building supply chains, and further achieving green management of cost reduction and efficiency improvement in prefabricated building supply chains.

Power-barrier option is a typical exotic option formed by attaching some restrictions to the power option, where the power option evolves from standard European option with the strike price and underlying good price attached to some power. Compared with the ordinary options, power-barrier option can provide investors with stable leverage and premium income. Therefore, power-barrier option is more favored by investors. This paper mainly discusses the pricing problems of power-barrier option in uncertain financial market. The fluctuation of stock price is regarded as an uncertain process and the interest rate is floating. The uncertain differential equation is invoked to simulate this fluctuation in an uncertain environment. Then, the clear pricing formulas of power-barrier option are given. Finally, the corresponding numerical examples and a real data example are put forward to illustrate the method.

Carotenoids are an important component of the human diet, and fruit is a primary source of carotenoids. The synthesis and regulation of carotenoids in fruit are important contributors to the formation of fruit quality. In China, strawberry is one of the main seasonal fruits grown in the winter. Previous studies have shown that light has a significant effect on the metabolism of anthocyanins, sugars, and polyphenols in strawberry. However, the understanding of the role of light in regulating the metabolism of carotenoids in strawberry remains limited. This study investigated the effects of blue, red, yellow-green, and white light on carotenoid metabolism in strawberry. Blue light treatment promoted the synthesis of multiple carotenoids, including lutein, compared with the other three treatment groups. The RNA sequencing data revealed that blue light treatment promoted the expression of lycopene ε-cyclase (LCYE), and the transient overexpression of LCYE in strawberry fruit promoted lutein accumulation in strawberry. Overall, the results suggest that blue light can promote the synthesis of lutein in strawberry by inducing the expression of LCYE.

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is one of the greatest threats to soybean production, and both trend analysis and periodic analysis of its population dynamics are important for integrated pest management (IPM). Based on systematically investigating soybean aphid populations in the field from 2018 to 2020, this study adopted the inverse logistic model for the first time, and combined it with the classical logistic model to describe the changes in seasonal population abundance from colonization to extinction in the field. Then, the increasing and decreasing phases of the population fluctuation were divided by calculating the inflection points of the models, which exhibited distinct seasonal trends of the soybean aphid populations in each year. In addition, multifactor logistic models were then established for the first time, in which the abundance of soybean aphids in the field changed with time and relevant environmental conditions. This model enabled the prediction of instantaneous aphid abundance at a given time based on relevant meteorological data. Taken as a whole, the successful approaches implemented in this study could be used to build a theoretical framework for practical IPM strategies for controlling soybean aphids.

Many attentions have been previously focused to identify the multiple biochemical components related to tea quality and health benefits, however, the natural variation of biochemical components present in tea germplasm has not been adequately evaluated. In this study, the main biochemical components, leaf morphological and yield characteristics were evaluated for four rounds of tea leaves in a panel of 87 elite tea cultivars suitable for black, green, or oolong tea. Significant variations were observed among the tea cultivars, as well as seasonal differences in the levels of the free amino acid (FAA), caffeine (CAF), tea polyphenols (TP), water extract (WE) and TP to FAA ratio (TP/FAA). Results showed that the average levels of FAA showed a seasonal change, with the highest level of 4.0% in the 1st spring tea in the cultivars suitable for green tea and the lowest of 3.2% in summer tea in the cultivars suitable for black tea. The average CAF content was highest 3.2% in the cultivars suitable for oolong tea in the 1st spring and the lowest 2.5% in the cultivars suitable for green tea in summer. Limited seasonal and varietal variations were noticed in the average levels of WE among the three categories of tea. In addition, significant natural variation of the morphological characteristics, bud length varying from 2.5 cm to 8.7 cm, bud density from 190.3 buds · m-2 to 1 730.3 buds · m-2, mature leaves biomass from 128.4 kg · hm-2 to 2 888.4 kg · hm-2, and yield component traits of 100 buds (one bud with two leaves) dry weight from 3.7 g to 37.7 g, tea yield/round from 444.6 kg · hm-2 to 905.3 kg · hm-2, were observed. The aim of our evaluation was not only to identify the advantages of seasonal and clonal variations but also to provide a new viewpoint for their further application. Representative accessions were selected from the germplasm to promote the establishment of an inherent biochemical constituent expressing the quality of black, green, and oolong tea. The findings might be utilized to establish early selection criteria to enhance the tea breeding and production program.

Abstract Background The skeletal muscle of pigs is vulnerable to oxidative damage, resulting in growth retardation. Selenoproteins are important components of antioxidant systems for animals, which are generally regulated by dietary selenium (Se) level. Here, we developed the dietary oxidative stress (DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation. Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation, which is accompanied by mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and protein and lipid metabolism disorders. Supplementation with Se (0.3, 0.6 or 0.9 mg Se/kg) in form of hydroxy selenomethionine (OH-SeMet) linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins, which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle, and the mitigation of mitochondrial dysfunction and ER stress. What's more, selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle. However, several parameters such as the activity of GSH-Px and T-SOD, the protein abundance of JNK2, CLPP, SELENOS and SELENOF did not show dose-dependent changes. Notably, several key selenoproteins such as MSRB1, SELENOW, SELENOM, SELENON and SELENOS play the unique roles during this protection. Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress, recover protein and lipid biosynthesis, thus alleviate skeletal muscle growth retardation. Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.

Aiming at the problem of how to give full play to the reverse extrusion ability of bolt to the surrounding rock to make the interface stress balance quickly and enhance the active support effect, we propose the anchorage method of radial pressurization. By adding expansion agent into cement grout to form self-stress slurry, radial expansion stress is generated on the pore wall under the constraint of rock mass, and the stress state of surrounding rock is improved. Under the constraint of thin-walled steel pipe, the radial expansion stress generated by the cement slurry stone body mixed with different amounts of expansion agent is used as a different pressurization variable, and the expansion stress of steel tube wall was measured by static strain gauge and the deformation law of radial stress in stone body with different expansion agent content was analyzed. The finite element software ABAQUS is used to simulate the deformation characteristics of the surrounding rock under different pressurization variables, and the stress field and displacement field of the surrounding rock under stress and deformation are systematically studied. The results show that the radial stress and strength of cement slurry stone with 7% expansion agent are better than those of other proportions, and the compressive stress between cement slurry stone and pore wall increases obviously, resulting in expansion effect. With the increase of radial stress of grout stone body, the compressive stress increases by 65% and the deformation increases by 71% on average, and the radial stress of surrounding rock decreases with the increase of distance from drilling hole.

Highlights An atomically dispersed catalyst with unprecedented N8V4 Co-Ni dual-metal sites is synthesized, which shows interesting asymmetric in situ structural evolution and serves as a quasi-bifunctional catalyst for water splitting. The flexible C–OH groups generated by in situ oxidation can reversibly turn on/off the hydrogen-bonding interaction with the oxygen evolution reaction intermediates to break the conventional scaling relationship.

Abstract Miscanthus is a high‐yielding bioenergy crop that is broadly adapted to temperate and tropical environments. Commercial cultivation of Miscanthus is predominantly limited to a single sterile triploid clone of Miscanthus × giganteus, a hybrid between Miscanthus sacchariflorus and M. sinensis. To expand the genetic base of M. × giganteus, the substantial diversity within its progenitor species should be used for cultivar improvement and diversification. Here, we phenotyped a diversity panel of 605 M. sacchariflorus from six previously described genetic groups and 27 M. × giganteus genotypes for dry biomass yield and 16 yield‐component traits, in field trials grown over 3 years at one subtropical location (Zhuji, China) and four temperate locations (Foulum, Denmark; Sapporo, Japan; Urbana, Illinois; and Chuncheon, South Korea). There was considerable diversity in yield and yield‐component traits among and within genetic groups of M. sacchariflorus, and across the five locations. Biomass yield of M. sacchariflorus ranged from 0.003 to 34.0 Mg ha−1 in year 3. Variation among the genetic groups was typically greater than within, so selection of genetic group should be an important first step for breeding with M. sacchariflorus. The Yangtze 2x genetic group (=ssp. lutarioriparius) of M. sacchariflorus had the tallest and thickest culms at all locations tested. Notably, the Yangtze 2x genetic group's exceptional culm length and yield potential were driven primarily by a large number of nodes (>29 nodes culm−1 average over all locations), which was consistent with the especially late flowering of this group. The S Japan 4x, the N China/Korea/Russia 4x, and the N China 2x genetic groups were also promising genetic resources for biomass yield, culm length, and culm thickness, especially for temperate environments. Culm length was the best indicator of yield potential in M. sacchariflorus. These results will inform breeders' selection of M. sacchariflorus genotypes for population improvement and adaptation to target production environments.

The pancreas is a rare metastatic site for lung cancer. We report the case of a 66-year-old male with pulmonary sarcomatoid carcinoma (PSC) with pancreatic and right posterior renal fascia metastases treated with immunotherapy and platinum-based chemotherapy. A pathological biopsy of the right posterior fascial mass showed lung invasive adenocarcinoma and sarcomatoid carcinoma metastasis. Immunohistochemistry staining showed that PD- L1 expression was high and next-generation sequencing revealed KRAS and TP53 mutations. Camrelizumab and chemotherapy were administered, and the metastasis disappeared. Immunotherapy combined with platinum-based chemotherapy is effective in treating PSC with pancreatic metastases.

Abstract This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase‐5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual‐combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event‐free survival at 6 months and all‐cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low‐risk group, 35 in the intermediate‐low‐risk group, 91 in the intermediate‐high‐risk group, and 44 in the high‐risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT‐proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO‐FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low‐risk criteria (from 5.7% to 13.5%). Among the low‐risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate‐low‐risk group exhibited significant enhancements in WHO‐FC and tricuspid annular plane systolic excursion. For those in the intermediate‐high and high‐risk groups, there were marked improvements in activity tolerance, as reflected by WHO‐FC and 6MWD. The event‐free survival rate at 6 months stood at 88%. Over the long‐term follow‐up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Abstract Improving seed germination under drought stress has the potential to increase crop yield in dry direct‐seeded rice. In this study, a genome‐wide association study (GWAS) was conducted to determine the genetic basis of seed germination under drought stress in a panel of 165 rice accessions using a multi‐locus compressed variance‐component mixed model, 3VmrMLM. A total of 33 quantitative trait nucleotides (QTNs) were identified in association with drought tolerance during seed germination. Around these QTNs, eight were found to be co‐localized with known drought‐related genes. Furthermore, a causal candidate gene, OsGA2ox5, which encodes a gibberellin (GA) 2‐oxidase, was identified for QTN‐Chr07_242906 by integrating linkage disequilibrium (LD) analysis and gene expression analysis. Knockout mutation of OsGA2ox5 resulted in delayed seed germination and retarded seedling growth under drought stress. RNA‐seq analysis revealed that OsGA2ox5 regulates drought tolerance during seed germination mainly by modulating carbohydrate metabolism. Additionally, a non‐synonymous coding variant in OsGA2ox5, SNP‐Chr07_218893, was found to be strongly associated with drought tolerance level during seed germination. These findings provide valuable information for further exploration of novel drought‐related genes and genetic improvement of rice drought tolerance in the future.