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Abstract In southern China, vegetation on exposed earthen sites serves not only to mitigate erosion but also alters their visual appearance, leading to biodeterioration. However, how plants influence the properties of earthen sites is virtually unknown. This study undertook an ecological investigation of the original habitat in the east city wall of the Sanxingdui site, analyzing its soil properties and investigating plant-soil interactions. Research findings indicate that existing plant communities are not conducive to biodiversity nor site presentation. Plants exert a direct influence within a vertical range extending 0–40 cm beneath the site; root content correlates negatively with soil pH value but positively with organic matter content. The herbaceous community (E-2 and E-3) exhibits higher clay content than the arbor community (E-1) within this range. The above conclusions exhibit statistical significance. This study offers a scientific elucidation of the ecological parameters governing plant communities concerning the conservation of earthen sites, and provides an initial influence range of plant communities and biodegradation on the east city wall of the Sanxingdui sites, thereby revealing the technical potential for employing plants as a soft capping for earthen sites in the open air from the function method.

To overcome the disadvantage of the Arrhenius constitutive (AC) equation in predicting complex nonlinear flow behaviors, this work employed an artificial neural network (ANN) to introduce a proportional coefficient reflecting changes in softening mechanisms under various hot deformation conditions, thereby enhancing the applicability of the AC model. The result demonstrates that, compared to the AC model, the ANN-AC model effectively compensates for errors resulting from different softening mechanisms during hot deformation, with RMSE and MAPE decreasing by 62.47% and 63.75%, respectively. Additionally, the microstructure aligns with the evolution of the power dissipation factor (η) predicted by the ANN-AC model, indicating the map's accuracy. Microstructure analysis shows that discontinuous dynamic recrystallization (DDRX) grains nucleate adjacent to the original grain boundaries at low temperatures and high strain rates, while continuous dynamic recrystallization (CDRX) grains primarily form within original grains at high temperatures and low strain rates. The results reveal the effect of grain orientation on DRX, with //CD (compression direction) oriented grains capable of activating multiple slip systems, indicating a propensity for the CDRX mechanism, whereas //CD oriented grains, with fewer slip systems, promote DDRX through coordinated deformation via grain boundary motion.

Multistage thermomechanical treatment experiments were conducted on Cu–Ni–Co–Si–Mg alloy strip prepared by the Heating Cooling Combined Mold (HCCM) horizontal continuous casting-cold rolling process. Effects of various heat treatments on the microstructure, mechanical properties, and electrical conductivity of the alloy were studied. The strengthening mechanisms and factors influencing the performance of each process has been analyzed. The tensile strength, yield strength, and electrical conductivity of Cu–Ni–Co–Si–Mg alloy can reach 894 MPa, 855 MPa, and 47.1 %IACS after a third-stage of thermomechanical treatment (TTMT). The cold rolling in first-stage of thermomechanical treatment (FTMT) not only caused work hardening of the alloy but also promoted the precipitation of solute atoms and the growth of second phase particles, limiting the increase in strength. Second-stage of thermomechanical treatment (STMT) effectively hindered the excessive growth of second phase particles in FTMT but shortened recrystallization process. The superior performance of Cu–Ni–Co–Si–Mg alloy after TTMT was attributed to dispersive precipitation of Ni, Co, and Si elements as (Ni, Co) 2Si phases in the copper matrix, strengthening the interaction between the precipitates and dislocations. A short process of HCCM horizontal continuous casting-cold rolling-thermomechanical treatment was developed to produce a high strength and highly electrically conductive Cu–Ni–Co–Si alloy strip used in lead frames.

Inflammatory bowel disease remains a high recurrence rate and broad populations all over the world. Liquiritigenin isolated from licorice possess anti-inflammatory and antioxidative activities, suggesting its potential of treating ulcerative colitis (UC). In this study, we explored the effect of oral liquiritigenin on the DSS-induced mice colitis and underlying mechanisms in the aspect of gut microbiome and intestinal barrier dysfunction. The results showed liquiritigenin had protective effects against DSS-induced mice colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening and histological lesions. In addition, the treatment with liquiritigenin significantly reduced the plasma cytokine levels, TNF-α, IL-1β and IL-6 levels as well as the expression of iNOS and COX-2 compared to control group. Liquiritigenin supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease of myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and total Superoxide Dismutase (T-SOD) activities in the colitis mice. In regulation of mice gut microbiota, liquiritigenin augmented probiotics abundance (e.g., Akkermansia), decreased harmful bacteria (e.g., Turicibacter), and restored Firmicutes/Bacteroidetes balance. Furthermore, the mRNA levels of tight junction (TJ), including ZO-1, occludin, and claudin-1 were downregulated in colitis mice, whereas these changes were reversed by liquiritigenin. As indicated by TEM images and Endoplasmic reticulum stress (ERs) marker genes expression like GRP78, IRE1α, ATF6 and PERK that mice with colitis treated by oral liquiritigenin trended to attenuate ER stress. Collectively, the ameliorating role of liquiritigenin in gut inflammation can be attributed to intestinal barrier modulation, gut microbiome regulation, and ER stress alleviation. These findings provide a new perspective for developing liquiritigenin as a promising functional compound of food origin for preventing and mitigating UC.

ABSTRACT Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD’s therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.

Abstract Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (•OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of •OH and reduced •OH generation speed. Herein, an effective CDT is achieved by both improving •OH lifetime and long‐lasting generating •OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and Fe3O4 (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe3O4 for the appearance of ≡Cu2+ and increase in ≡Fe2+. The generated ≡Cu2+ can interact with GSH, which prolongs the lifespan of •OH, produces ≡Cu+ for higher speed •OH generation with H2O2, and induces cell ferroptosis for tumor therapy. The improved ≡Fe2+ can also improve the •OH release under H2O2 until Cu is depleted. As a result, a sustainable •OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H2O2 and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.

ObjectiveThe purpose of this systematic review and meta-analysis was to investigates whether transcranial direct current stimulation applied during physical training increases muscle strength in comparison with sham tDCS combined with physical training.MethodsRandomized controlled trials of the effects of tDCS combined physical training intervention on muscle strength and cortical excitability were collected by searching Web of Science, Pubmed, EBSCO, CNKI. The retrieval date ends in April 2024. 11 randomized controlled trials are finally included. The total sample size of the study is 338. The experimental group was subjected to tDCS combined with physical training intervention, and the control group was physical training combined with sham tDCS intervention.ResultsThere is a significant increase in maximal strength (SMD = 0.38; 95% CI: 0.09, 0.67; p = 0.01) and lower limb explosive strength (MD = 2.90; 95% CI: 1.06, 4.74; p = 0.002) when physical training was performed with tDCS, but not following physical training combined with sham tDCS. Subgroup analysis of the subject population showed an increase in muscle strength in those with training experience following tDCS combined with physical training (SMD = 0.39; 95% CI: 0.08, 0.70; p = 0.01), but not for those without training experience (SMD = 0.29; 95% CI: −0.06, 0.63; p = 0.10). Motor evoked potential (MEP) wave amplitude increased significantly following physical training with tDCS (SMD = 0.71; 95% CI: 0.18, 1.24; p = 0.008), but was not different between groups (SMD = 0.16; 95% CI: −0.33, 0.65; p = 0.52).ConclusionstDCS combined with physical training intervention can improve muscle strength, lower limb explosive strength and cerebral cortex excitability. Compared to tDCS combined with training of small muscle groups, tDCS combined with training of large muscle groups was more effective in improving muscle strength. Muscle strength was more likely to improve after tDCS combined with physical training in people with physical training experience compared with people without physical training experience. The combination of tDCS with physical training intervention and the sham-tDCS with physical training intervention both increased cortical excitability.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO, identifier (CRD42024550454).

The genus Polygala (Polygalaceae), comprising about 670 species worldwide, has more than 40 species in China. The roots of Polygala tenuifolia Willd., Polygala sibirica L., and Polygala japonica Houtt. are recorded in the Chinese Pharmacopeia. Other closely related plants of the Polygala genus are also widely used in the folk medicine of southern China, such as Polygala fallax Hemsl., Polygala arvensis Willd., and Polygala glomerata Lour. To systematically compare the chemical compositional and elucidate characteristic compounds among the Polygala genus, six Polygala species, namely P. tenuifolia, P. sibirica, P. japonica, P. fallax, P. arvensis and P. glomerata, underwent comprehensive phytochemical studies using the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass Spectrometry (UPLC-Q-TOF-MS/MS) technique, resulting in the identification of 154 compounds, consisting of 62 oligosaccharide esters (40.26 %), 58 saponins (37.66 %), 29 xanthones (18.83 %), and 5 other chemicals (3.25 %). Based on the Masslynx computational tool, a comprehensive comparative phytochemical profiling was achieved and revealed differences in composition among the six Polygala species. P. sibirica exhibited higher levels of specific compounds and was more closely related to P. tenuifolia. Meanwhile, P. japonica showed greater similarity to P. fallax, P. arvensis, and P. glomerata. Oligosaccharide esters and triterpene saponins were more abundant in P. sibirica and P. tenuifolia than in other species. Furthermore, the antioxidant activities (1,1-diphenyl-2-acrylohydrazide [DPPH], 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt [ABTS], copper ion reducing antioxidant capacity [CUPRAC], and ferric ion-reducing antioxidant power [FRAP]) of the six species were evaluated. Among them, P. tenuifolia demonstrated superior antioxidant potential, with a lower half-maximal inhibitory concentration (IC50) value for scavenging DPPH radicals and excellence in CUPRAC (119.85 ± 16.28 μM/0.01 g) compared to other plants. P. japonica showed higher ABTS (98.94 ± 0.03 μM/0.01 g) and FRAP (42.58 ± 0.08 μM/0.01 g). Total flavonoids showed remarkable antioxidant capabilities among the six medicinal plants. Total saponins and phenolics also contributed to the antioxidant potential of these plants. The systematic data and results obtained may provide methodological support for further evaluating the potential use of folk Polygala plants as new effective materials in various commercial sectors, including food, cosmetic, and pharmaceutical industries.

Sepsis is defined as a dysregulated host response to infection resulting in life-threatening organ dysfunction. Sepsis-associated encephalopathy (SAE) is the main manifestation of sepsis. Inflammation, peroxidation stress injury, and apoptosis are the main factors involved in the pathogenesis of SAE. A growing body of evidence has proved that P2X7 receptor (P2X7R), a cationic channel receptor that is widely distributed in the body, plays a major role in the occurrence and development of inflammatory injury. Therefore, this review mainly describes the activation of P2X7R in sepsis, which leads to the recruitment of inflammatory cells to the cerebral vasculature, the destruction of the blood–brain barrier, the activation of microglial cells in the brain, the apoptosis of brain cells, and other damage processes. This review also illustrates the potential therapeutic value of P2X7R inhibition in SAE.

ABSTRACT: This study evaluated 75 strains of lactic acid bacteria (LAB) isolated from traditional dairy products in western China for their probiotic properties. Among them, Limosilactobacillus fermentum WXZ 2-1, Lactiplantibacillus plantarum TXZ 2-35, Companilactobacillus crustorum QHS 9, and Companilactobacillus crustorum QHS 10 demonstrated potential probiotic characteristics. The antioxidant capacity of these 4 strains was assessed, revealing that L. fermentum WXZ 2-1 exhibited the highest antioxidant capacity. Furthermore, when cocultured with Streptococcus salivarius ssp. thermophilus and Lactobacillus delbrueckii ssp. bulgaricus, L. fermentum WXZ 2-1 demonstrated a synergistic effect in growth medium and goat milk. To explore its effect on goat milk fermentation, different amounts of L. fermentum WXZ 2-1 were added to goat milk, and its physicochemical properties, antioxidant activity, flavor substances, and metabolomics were analyzed. The study found that the incorporation of L. fermentum WXZ 2-1 in goat milk fermentation significantly improved the texture characteristics, antioxidant capacity, and flavor of fermented goat milk. These findings highlight the potential of L. fermentum WXZ 2-1 as a valuable probiotic strain for enhancing the functionality and desirability of fermented goat milk, contributing to the development of novel functional foods with improved health benefits and enhanced quality attributes.

ObjectiveThe study aimed to compare the differences in the performance of seven session-rating of perceived exertion (RPE)-derived metrics (coupled and uncoupled acute: chronic workload ratio (ACWR), weekly ratio of workload change, monotony, standard deviation of weekly workload change, exponentially weighted moving average (EWMA), and robust exponential decreasing index (REDI)) in classifying the performance of an injury prediction model after taking into account the time series (no latency, 5-day latency, and 10-day latency).DesignThe study documented the RPE of eight curlers in their daily training routine for 211 days prior to the Olympic Games.MethodsSeven Session-RPE (sRPE)-derived metrics were used to build models at three time series nodes using logistic regression and multilayer perceptron. Receiver operating characteristic plots were plotted to evaluate the model’s performance.ResultsAmong the seven sRPE-derived metrics multilayer perceptron models, the model without time delay (same-day load corresponding to same-day injury) exhibited the highest average classification performance (86.5%, AUC = 0.773). EMWA and REDI demonstrated the best classification performance (84.4%, p

Background: Bladder cancer (BLCA) presents as a heterogeneous epithelial malignancy. Progress in the early detection and effective treatment of BLCA relies heavily on the identification of novel biomarkers. Therefore, the primary goal of this study is to pinpoint potential biomarkers for BLCA through the fusion of single-cell RNA sequencing and RNA sequencing assessments. Furthermore, the aim is to establish practical clinical prognostic models that can facilitate accurate categorization and individualized therapy for patients. Methods: In this research, training sets were acquired from the TCGA database, whereas validation sets (GSE32894) and single-cell datasets (GSE135337) were extracted from the GEO database. Single-cell analysis was utilized to obtain characteristic subpopulations along with their associated marker genes. Subsequently, a novel BLCA subtype was identified within TCGA-BLCA. Furthermore, an artificial neural network prognostic model was constructed within the TCGA-BLCA cohort and subsequently verified utilizing a validation set. Two machine learning algorithms were employed to screen hub genes. QRT-qPCR was performed to detect the gene expression levels utilized in the construction of prognostic models across various cell lines. Additionally, the cMAP database and molecular docking were utilized for searching small molecule drugs. Results: The results of single-cell analysis revealed the presence of epithelial cells in multiple subpopulations, with 1579 marker genes selected for subsequent investigations. Subsequently, four epithelial cell subtypes were identified within the TCGA-BLCA cohort. Notably, cluster A exhibited a significant survival advantage. Concurrently, an artificial neural network prognostic model comprising 17 feature genes was constructed, accurately stratifying patient risk. Patients categorized in the low-risk group demonstrated a considerable survival advantage. The ROC analysis suggested that the model has strong prognostic ability. Furthermore, the findings of the validation group align consistently with those from the training group. Two types of machine learning algorithms screened NFIC as hub genes. Forskolin, a small molecule drug that binds to NFIC, was identified by employing a cMAP database and molecular docking. Conclusion: The analysis results supplement the research on the role of epithelial cells in BLCA. An artificial neural network prognostic model containing 17 characteristic genes demonstrates the capability to accurately stratify patient risk, thereby potentially improving clinical decision-making and optimizing personalized therapeutic approaches.

Abstract Background This study aimed to investigate the clinical value and prognostic significance of the alanine aspartate aminotransferase‐to‐lymphocyte ratio index (ALRI) in patients diagnosed with acute myocardial infarction (AMI). Methods Clinical indices of patients with AMI were collected from the Medical Information Mark for Intensive Care (MIMIC) III database and Wuhan Sixth Hospital. Cox regression analysis was used to explore whether ALRI was a risk factor for a worse prognosis in patients with AMI, and a nomogram including ALRI was created to estimate its predictive performance for 28‐day mortality. Results Based on clinical data from the MIMIC‐III database, we found that a high ALRI was closely associated with a variety of clinical parameters. It was an important risk factor for 28‐day survival in patients with AMI (HR = 5.816). ALRI had a high predictive power for worse 28‐day survival in patients with AMI (area under the curve [AUC] = 0.754). Additionally, we used clinical data from the Wuhan Sixth Hospital to verify the predictive power of ALRI in patients with AMI, and a high level of ALRI remained an independent risk factor for worse survival in patients with AMI (HR = 4.969). The AMI nomogram, including ALRI, displayed a good predictive performance for 28‐day mortality in both the MIMIC‐III (AUC = 0.826) and Wuhan Sixth Hospital cohorts (AUC = 0.795). Conclusion The ALRI is closely related to the survival outcomes of patients with newly diagnosed AMI, indicating that it could serve as a novel biomarker for risk stratification such patients.

Limitations on data volume and quality are key bottlenecks in using machine learning for property prediction and property-oriented composition design of non-oriented silicon steel. In response, this study employed a Gaussian Mixture Model (GMM) to generate virtual samples for enhancing the in-house experimental data, by which the generated virtual data well captured the distribution of the raw experimental data. As a result, compared with the model without data augmentation, the enhanced prediction model (composition → property) fitted by virtual samples improved its R2 value from 0.52 to 0.86. Based on this model, a multi-properties-oriented (yield strength σs, magnetic induction B50, and iron loss P10/400) composition prediction model (property → composition) was established to rapidly discover high-performance non-oriented silicon steel. Experimental characterization and theory calculation of the explored candidate alloys exhibited that their yield strength was above 750 MPa, which primarily results from solid solution strengthening (50 %) and precipitation strengthening (36 %). Moreover, the alloys possessed magnetic induction B50 of over 1.72 T and low core losses with P10/400 of 12.1 W/kg (0.2 mm) and 17.0 W/kg (0.35 mm). Further microstructural characterization exhibited that such satisfactory performance is associated with copper (Cu)-rich nanoprecipitates that dramatically improved the yield strength without deteriorating the magnetic properties.

Abstract The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient’s prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.

Damping alloys serve as key materials in the domain of shock and noise reduction and find wide-ranging applications across several industries. Aluminum alloy, a commonly used engineering material, offers distinct advantages such as low cost and light weight. However, the damping property of aluminum alloy falls short of requisite standards. Thus, efforts toward enhancing the damping and mechanical properties of cast aluminum alloy carry considerable engineering implications. In this paper, the mechanical and damping properties of AlSi10Sn4Mgx (x mass fraction is 0–4.0%) alloy have been investigated, and the mechanisms underlying the enhancement of the damping and mechanical properties have been analyzed by examining the effect of Mg on the wettability of Al/Sn and the alloy’s structure. The results of the mechanical property test reveal that the tensile strength of the AlSi10Sn4Mgx alloy increases proportionally with Mg mass fraction within the range of 0% to 1.0%, whereas the fracture elongation undergoes a negligible change. With the Mg mass fraction rising to 1.0%, the tensile strength of the alloy reaches 161 MPa, and the fracture elongation stands at 3.4%. Subsequent increases in Mg content lead to remarkable enhancements in the strength of the samples. When the Mg mass fraction increases to 1.5%, the tensile strength of the alloy stands at 188 MPa, albeit with a remarkable decrease in fracture elongation. The damping properties of the alloy initially increase and subsequently decrease with the increase in Mg mass fraction. The alloy containing 1.0% Mg displays excellent damping properties at high temperatures and high frequencies. Specifically, the damping loss factor tanh at 25 ℃/1 Hz, 200 ℃/1 Hz and 25 ℃/40 Hz measures 0.038, 0.058, and 0.069, respectively. Further research suggests that the addition of a small amount of Mg can effectively improve the wettability of Al/Sn. The mean wetting angles of AlSi10 and AlSi10Mg1 alloy samples with pure Sn are 141.2° and 116.8°, respectively. The exceptional wettability of Al/Sn facilitates the distribution of the small-sized β-Sn phase along grain boundaries within the AlSi10Sn4Mgx alloy. Meanwhile, a small amount of Mg can also modify and spheroidize the eutectic Si phase in AlSi10Sn4Mgx alloys, leading to the formation of the Mg2Si strengthened phase. These two factors are primarily responsible for the excellent damping and mechanical properties of the alloy. However, excessive Mg will generate bulky Mg2Si structures, which will impair the wettability of Al/Sn, leading to the deterioration of the damping and mechanical properties of AlSi10Sn4Mg4 alloy.

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage.Case descriptionWe presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding.ConclusionMinor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.

Objective: Helicobacter pylori (H. pylori) plays a major role in causing and advancing gastrointestinal illnesses. Our aim is to analyze the unique makeup and functional changes in the gastric microbiota of patients with chronic non-atrophic gastritis (CNAG), regardless of the presence of H. pylori, and to determine the potential signaling pathways. Methods: We performed metagenomic sequencing on gastric mucosa samples collected from 17 individuals with non-atrophic gastritis, comprising 6 cases were infected with H. pylori (H. pylori-infected case group) and 11 cases without (control group). The species composition was evaluated with DIAMOND software, and functional enrichment was assessed utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We analyzed antibiotic resistance patterns using the Comprehensive Antibiotic Resistance Database as a reference (CARD). Results: The presence of H. pylori colonization in CNAG patients was associated with increased diversity in the gastric microbiota. The Phylum Firmicutes was found to be less prevalent, while the Phylum Proteobacteria showed an increase. Functionally, pathways associated with metabolic pathways, including vitamins, auxiliaries, amino acid residue, carbon hydrate, and metabolic energy pathways, were enriched in CNAG patients with H. pylori infection. Additionally, antibiotic resistance genes correlated with antibiotic efflux pump were enriched. Conclusions: From a holistic genomic perspective, our findings offer fresh perspectives into the gastric microbiome among CNAG patients carrying H. pylori, which is valuable for future research on CNAG.

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

In order to evaluate the bone density improvement function and safety of the Malugu capsule, rats were divided into sham surgery group, model control group (oophorectomy model), high-dose calcium carbonate group (positive control), and groups with different doses of Malugu capsule (200, 400 and 1200 mg/kg·bw) by 90 days of gavage administration. The bone mineral density of the left femur and the calcium content of the right femur was measured to evaluate the performance of the Malugu capsule in increasing bone density. The acute toxicity test of the Malugu capsule at the dose of 15 g/kg·bw was carried out. Moreover, the genotoxicity test and 4-week feeding test of rats were also performed to evaluate the safety of the Malugu capsule. The results showed that there was no significant difference in body weight of rats among the groups of Malugu capsule treatment compared with the model control group (P>0.05). The bone mineral density of the left femur in the three doses of Malugu capsule groups were 0.6651, 0.6560 and 0.6605 g/cm3, respectively, which was significantly higher than that of 0.6307 g/cm3 (P

ObjectivesAiming at the high-precision recovery guidance control requirements of current stern ramp recovery technology, a self-adaptive cascade tracking control method for unmanned surface vessels (USVs) is proposed specifically for stern ramp recovery. MethodsBased on the technical requirements of stern ramp recovery, a motion model of an underactuated USV is established, and the generalized Kalman filter (GKF) algorithm is used to predict the navigation state and recovery position of the mother ship. Introducing the idea of constant bearing guidance combined with the sliding mode variable structure control theory, a stable cascade control system is constructed to solve tracking control problems during the recovery process. ResultsIt is proven that the USV can stably track the target, by analyzing the stability of the system through the Lyapunov theory and cascade theorem. ConclusionsThe simulation results show that the proposed control method gives the USV stable tracking performance and strong robustness against uncertain disturbances.

Objective To investigate the value of three hemolysis tests and carboxyhemoglobin (COHb) level in the diagnosis of hemolytic disease of the fetus and newborn (HDFN). Methods From January 1, 2019 to December 31, 2022, the neonates hospitalized in the Department of Neonatology of Hebei Provincial Children's Hospital with suspected hemolytic disease who had serological testing were retrospectively enrolled in the study. They were distributed into HDFN group and non-HDFN group according to the final diagnosis. Their clinical and laboratory data were collected and analyzed, and the COHb level was detected by blood gas analyzer. Results A total of 378 neonates with HDFN and 217 neonates without HDFN were included in the study. Most of the neonates in HDFN group were full-term infants (348/378, 92.1%), with median gestational age of 39.1 (38.3, 40.0) weeks. Three hundred and fifty-four cases (354/378, 93.7%) were ABO-HDFN and the rest were Rh HDFN. There were significant differences in the level of serum total bilirubin, hemoglobin, COHb and reticulocyte percentage at admission between the two groups(P0.05) . Conclusion The three hemolysis tests are important in the diagnosis of HDFN, among which the antibody release test has the highest sensitivity. COHb has certain value for the diagnosis of HDFN, but joint testing cannot improve the diagnosis effectiveness of three hemolysis tests. Hemolysis tests and/or COHb detection should be conducted for neonates at risk of hemolysis as early as possible after birth.

Oxidative stress is a common phenomenon in poultry production. Several molecules, including antioxidant genes, miRNAs, and gut microbiota metabolites, have been reported to participate in redox regulation. Lactiplantibacillus plantarum P8 (P8) was shown to improve the antioxidant capacity of chickens, but the specific molecular mechanisms remain unclear. In this study, 400 broilers were allocated to 4 treatment groups: control diet (Con group), control diet + dexamethasone injection (DEX group), control diet containing 1 × 108 CFU/g P8 (P8 group), and control diet containing 1 × 108 CFU/g P8 + DEX injection (DEX_P8 group). Integrated analysis of the microbiome, metabolomics, and miRNAomics was conducted to investigate the roles of P8 in oxidative stress in broilers. Results demonstrated that P8 supplementation significantly improved growth performance, jejunal morphology, and antioxidant function in DEX-treated broilers. Analysis of the gut microbiota revealed a higher abundance of Barnesiella (P = 0.01) and Erysipelatoclostridium (P = 0.05) in the DEX_P8 group than in the DEX group. Functional prediction indicated that certain pathways, including the phenylacetate degradation pathway, were enriched in the DEX_P8 group compared to the DEX group. Metabolites in the cecal contents were distinct between the groups. P8 supplementation increased the content of metabolites with antioxidant capacity, e.g., urobilinogen (P

Abstract Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2–21 segment of HBx (HBx2–21) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 “K4me3-K9me3” readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx2-21, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.

Objective: To establish a quantitative analysis of multi-components by single marker (QAMS) method for the determination of lovastatin and lovastatin acid for the quality control of Hongqu Fuling tablets. Methods: Lovastatin as a control, the RP-HPLC method was used to establish the relationship between the correction factor of lovastatin and lovastatin acid, and to simultaneously quantify both lovastatin and lovastatin acid in the Hongqu Fuling tablets by QAMS. Results: The negative sample had no interference, the specificity of the sample detection method was good, the linear relationship between lovastatin and lovastatin acid was good within the corresponding linear range, R2>0.9999, the precision and repeatability RSD values were less than 3%, and the recovery was 98.43%～103.18%. The relative correction factor of lovastatin acid and lovastatin was 0.9000, and the repeatability was good. The average content of lovastatin acid was 0.3563 mg/g determined by QAMS, and the average content of lovastatin acid determined by external standard method was 0.3668 mg/g, and the average content of lovastatin was 1.1113 mg/g, which indicated that the constructed QAMS method could be used for the multi-component quality evaluation research of Hongqu Fuling Tablets. Conclusion: The QAMS method established in this study was stable, accurate and specific, and would provide a scientific basis for the quality control and in-depth development of Hongqu Fuling tablets.

Background. Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays a central role in the pathogenesis of hepatic fibrosis. Our study aimed to investigate the pharmacological effect and potential mechanism of pirfenidone (PFD) and andrographolide (AGP) separately and together on liver fibrosis of BA. Materials and Methods. The bile ducts of male C57BL/6J mice were ligated or had the sham operation. The in vivo effects of PFD and/or AGP on liver fibrosis of BA were evaluated. Human hepatic stellate cells (LX-2) were also treated with PFD and/or AGP in vitro. Results. PFD and/or AGP ameliorates liver fibrosis and inflammation in the mice model of BA, as evidenced by significant downregulated in the accumulation of collagen fibers, hepatic fibrosis markers (α-SMA, collagen I, and collagen IV), and inflammatory markers (IL-1β, IL-6, and TNF-α). Moreover, compared with monotherapy, these changes are more obvious in the combined treatment of PFD and AGP. Consistent with animal experiments, hepatic fibrosis markers (α-SMA, collagen I, and CTGF) and inflammatory markers (IL-1β, IL-6, and TNF-α) were significantly decreased in activated LX-2 cells after PFD and/or AGP treatment. In addition, PFD and/or AGP inhibited the activation of HSCs by blocking the TGF-β/Smad signaling pathway, and the combined treatment of PFD and AGP synergistically inhibited the phosphorylation of Smad2 and Smad3. Conclusion. The combined application of PFD and AGP exerted superior inhibitive effects on HSC activation and liver fibrosis by mediating the TGF-β/Smad signaling pathway as compared to monotherapy. Therefore, the combination of PFD and AGP may be a promising treatment strategy for liver fibrosis in BA.

ABSTRACT: Poultry meat has a high polyunsaturated fatty acids content, making it vulnerable to oxidative stress. Mitophagy participates in the regulation of oxidative stress and the nucleotide-binding and oligomerization domain (NOD)-like receptor family as well as pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Lactiplantibacillus plantarum P8 (P8) is a probiotic strain with an antioxidant capacity. In the present study, we investigated the effects of P8 on oxidative stress, mitochondrial function, mitophagy, and NLRP3 inflammasome in the breast meat of oxidatively stressed broilers. Four hundred 1-day-old male broilers were assigned to a 2 × 2 factorial design with 2 P8 levels (0 or 1 × 108 cfu/g), either with or without dexamethasone (DEX) injection, for a 21-day experimental period. DEX was injected intraperitoneally once daily from d 16 to 21. The breast meat was collected on d 21. The results showed that P8 supplementation decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and activated the Keap1-Nrf2 pathway in DEX-injected broilers. Moreover, P8 supplementation downregulated mitochondrial DNA (mtDNA) copy number and increased the expressions of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), silent information regulator 1 (SIRT1), mitochondrial fusion protein 1 (Mfn1), and optic atrophy protein 1 (OPA1) in DEX-treated broilers. In addition, the decreased mitophagy level in DEX-treated broilers was elevated with P8 supplementation, as reflected by the increased gene expression of autophagy-related gene 5 (ATG5), Bcl-2-interacting protein (Becline-1), Parkin, PTEN-induced kinase 1 (PINK1), light chain 3 II (LC3II)/LC31, and the protein expression of Parkin as well as decreased p62 expression. In addition, P8 supplementation inhibited NLRP3 inflammasome activation by decreasing the transcription of NLRP3, IL-18, cysteinyl aspartate-specific proteinase-1 (Caspase-1), and the expression of NLRP3 and IL-18 in DEX-treated broilers. In conclusion, dietary P8 supplementation alleviates oxidative stress, improves mitophagy, and inhibits NLRP3 inflammasome activation in the breast meat of oxidatively stressed broilers.

AbstractBackground Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD.Method Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters.Result The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone.Conclusions Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD.

Abstract Desiccation cracking is a common deterioration that occurs in archaeological excavation sites and greatly threatens long-term preservation. The aim of this research is to comprehensively evaluate the development degree of desiccation cracking (DOC) and explore the relationships between soil properties and its development. Seven indicators are selected to comprehensively describe the DOC, and principal component analysis (PCA) is applied to calculate the weight of each indicator. Linear correlation analysis (LCA) is adopted to calculate the correlations of six soil properties and DOC. The results showed that each indicator has an influence on the DOC. The clay particle content, clay mineral content, and plasticity index showed a positive correlation with the DOC, and the moisture content showed a negative correlation. This research proposed a comprehensive evaluation method to describe the development degree of deterioration at the earthen site, and the results revealed the internal factors influencing desiccation cracking from a qualitative perspective, which can lay a foundation for further conservation research.

Because of its high strength and good fracture toughness, 6013 aluminum alloy is widely used in auto and aircraft parts, such as the outer hood, outer decklid, and outer fuselage skin. An aluminum alloy must have good plastic forming ability in forming auto and aircraft parts and must have high deformation resistance in service. These performance requirements mainly depend on the yield ratio, that is, the ratio of yield strength to tensile strength. A lower yield ratio means larger deformation from the start of plastic deformation to the final fracture, which benefits formability. A higher yield ratio means higher plastic deformation resistance, which benefits service safety. In this paper, the mechanical properties and microstructure of the extruded 6013 aluminum alloy after natural aging, artificial aging, and retrogression re-aging are studied using microhardness tests, tensile tests, scanning electron microscopy, and transmission electron microscopy. The samples after the solid solution were naturally aged at room temperature and artificially aged at 170, 180, and 190 °C to determine the peak aging time. Then, after natural peak aging, the samples were heat-treated using the retrogression and re-aging process (retrogression at 200/210 °C for 0.5 h and re-aging at 170 °C). The results show that the tensile strength was 286 MPa, the yield strength was 158 MPa, and the yield ratio was 0.54 after natural peak aging for 16 d, which is suitable for plastic forming. The tensile strength was 362 MPa, the yield strength was 336 MPa, and the yield ratio reached 0.92 after the retrogression and re-aging process (retrogression at 210 °C for 0.5 h and peak re-aging at 170 °C for 2 h); the plastic deformation resistance was considerably enhanced. Compared with single-stage artificial aging, retrogression and re-aging can enhance the yield strength of 6013 aluminum alloy more substantially to break through the yield ratio limit in single-stage aging. Because the size of the precipitated phase decreases and the number density increases considerably after retrogression and re-aging, the precipitation strengthening effect is considerably enhanced. Precipitation strengthening has different effects on yield strength and tensile strength, so the yield strength ratio can be regulated by aging heat treatment. In other words, the plastic deformation and anti-deformation abilities of the alloy can be improved by natural peak aging and the retrogression and re-aging process, respectively.

Cu-1.3 wt%Ni-1.0 wt%Co-0.9 wt%Si-0.1 wt%Mg alloy strip with 10 mm in thickness produced by heating-cooling combined mold (HCCM) horizontal continuous casting was cold rolled. Microstructure evolution and mechanical properties of the cold-rolled alloy strips with different reduction were studied, and the deformation mechanism was clarified. The results showed that the continuous casting strips had axial columnar grain with main orientations and straight small angle grain boundaries, the elongation after fracture was up to 25.0%, which can be directly processed by large deformation cold rolling, and the maximum cumulative cold deformation was up to 99%.When the reduction was 40% and 60%, the dislocation bands crossed each other and shear bands formed, and the alternating distribution of soft/hard oriented grains were conducive to improve the deformation coordination ability of micro-region under high strain. When the deformation exceeded 80%, deformation twins formed and the twins had strong interaction with the shear band and grain boundaries, resulting in strong shear and rotation of the local grains. The tensile strength and hardness increased from 464 MPa to 137HV of the as-cast strip to 629 MPa and 208HV with reduction 90%, respectively, while the elongation decreased from 25.0% to 4.1%. These results can lay a foundation for the development of compact method for producing high performance Cu–Ni–Co–Si alloy strips.

Oxidative stress is a state of imbalance between oxidation and antioxidation. It is caused by excess levels of free radicals and leads to the damage of DNA, proteins, and lipids. The crucial role of gut microbiota in regulating oxidative stress has been widely demonstrated. Studies have suggested that the redox regulatory effects of gut microbiota are related to gut microbiota metabolites, including fatty acids, lipopolysaccharides, tryptophan metabolites, trimethylamine-N-oxide and polyphenolic metabolites. In recent years, the potential benefits of probiotics have been gaining increasing scientific interest owing to their ability to modulate gut microbiota and oxidative stress. In this review, we summarise the adverse health effects of oxidative stress and discuss the role of the gut microbiota and its metabolites in redox regulation. Based on the influence of gut microbiota metabolites, the roles of probiotics in preventing oxidative stress are highlighted.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease, with an estimated incidence of 0.2%–6%, and is the main cause of sudden cardiac death (SCD) in young athletes. Left ventricular apical aneurysm (LVAA) is a rare subtype of HCM, accounting for about 5% of HCM patients, and has a higher incidence of cardiovascular adverse events. In cases of hypertrophic obstructive cardiomyopathy with LVAA (HOCM-LVAA) that do not respond adequately to optimized medical therapy, the echocardiography-guided percutaneous intra-myocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) emerges as a promising and effective novel therapeutic approach. In this case report, we present for the first time a comprehensive application of echocardiographic techniques, including TTE, 2-D STE, and contrast enhancement, in the diagnosis, treatment, surgical guidance, and assessment of therapeutic outcomes in a case of HOCM-LVAA.

Abstract LINC00941 is a novel long noncoding RNA (lncRNA) and emerging as an important factor in cancer development. However, the exact function and relative regulatory mechanism of LINC00941 in carcinogenesis of esophageal squamous cell carcinoma (ESCC) remain to be further clarified. The present study was to investigate the expression level, functions, and mechanisms of LINC00941 in ESCC tumorigenesis. LINC00941 was significantly upregulated in ESCC, and upregulated LINC00941 was correlated with dismal patient outcomes. LINC00941 functioned as an oncogene by promoting cells proliferation, stemness, migration, and invasion in ESCC. In terms of mechanisms, SOX2 could bind directly to the promoter region of LINC00941 and activate its transcription. In turn, LINC00941 upregulated SOX2 through interacting with interleukin enhancer binding factor 2 (ILF2) and Y-box binding protein 1 (YBX1) at the transcriptional and post-transcriptional levels. LINC00941 recruited ILF2 and YBX1 to the promoter region of SOX2, leading to upregulation of the transcription of SOX2. Moreover, LINC00941 could promote the binding ability of ILF2 and YBX1 on mRNA of SOX2 and further stabilize SOX2 mRNA. Therefore, LINC00941 contributed to the malignant behaviors of ESCC cells via the unrestricted increase in SOX2 expression. In conclusion, our data indicate that LINC00941 exacerbates ESCC progression through forming a LINC00941-ILF2/YBX1-SOX2 positive feedback loop, and LINC00941 may be a promising prognostic and therapeutic target for ESCC.

The greenhouse effect has always been a problem troubling various country, many fields have made corresponding technological improvements and regulations, and the shipping industry is no exception. In the shipping field, governments are actively looking for viable low-carbon/zero-carbon alternative fuels to reduce their dependence on traditional fossil fuels. This paper discusses the challenges and opportunities of replacing fuel oil with clean energies. Firstly, the alternative fuels that have been proposed frequently and widely in recent years are summarized, and their sources, adaptive power systems, and relationships among fuels are systematically summarized. Secondly, when evaluating the advantages and future development trends of each energy, the environmental, economic and safety factors are digitally quantified. Results show that the analysis focuses on the efficiency and economics of carbon reduction. Hydrogen, ammonia and nuclear energy show advantages in environmental quantification factors, while LNG, biofuels and alcohols show benefits in economic quantification factors considering calorific value and fuel price, and LNG and alcohols received high scores in safety assessment. Finally, the study predicts the evolution and development trend of ship fuels in the future, and evaluates the most suitable energy for ship development in different periods.

Rosa rugosa, a perennial shrub belonging to family Rosaceae, is a well-known ornamental plant. Its petals contain an abundance of essential oils and anthocyanins with enormous economic and health benefits when used as edible or cosmetic ingredients. The whole genome of R. rugosa was sequenced in 2021, which provided opportunities and challenges for gene regulation. However, many gene functions remain unknown. Therefore, an analytical platform named RoseAP (http://www.gzybioinformatics.cn/RoseAP/index.php) for the functional analysis of R. rugosa genes was constructed. It improved the gene annotation rate by integrating and analyzing genomic and transcriptomic datasets. First, 38,815 genes, covering 97.76% of the coding genes, were annotated functionally and structurally using a variety of algorithms and rules. Second, a total of 33 transcriptome samples were integrated, including 23 samples from our lab and 10 samples from the SRA database. A co-expression network containing approximately 29,657 positive or negative gene pairs, covering 74.7% of the coding genes, was constructed based on PCC and MR algorithms. Network analysis revealed that the DFR function was closely related to anthocyanin metabolism. It demonstrated the reliability of the network. Several SAUR genes of R. rugosa shared similar expression patterns. RoseAP was used to determine the sequence, structure, functional annotation, expression profile, regulatory network, and functional modules at the transcriptional and protein levels by inputting gene IDs. In addition, auxiliary analytical tools, including BLAST, gene set enrichment, orthologue conversion, gene sequence extraction, gene expression value extraction, and JBrowse, were utilized. Regular updates to RoseAP are expected to facilitate mining of gene function and promote genetic improvement in R. rugosa.

The large-span, relaxed antenna network is a large deformation flexible structure due to its low pre-tension level of the wires. Its dynamic analysis under a wind load belongs to dynamic and geometric nonlinear problems, which is very complex to accurately calculate and solve. This paper explores the possibility of the finite particle method (FPM) to the aeolian vibration analysis of a large-span, low stress-tensioned antenna cable net. In the FPM, the antenna network structure is discretized into a group of finite particles, where the motions of all particles follow Newton’s second law and can be solved dynamically using a central difference scheme. The effectiveness and applicability of the FPM were verified by comparing the calculation results of the finite element method and FPM. The FPM was used to study the effects of wind speed and the distribution of vibration on the aeolian vibration of antenna cable nets. The results showed that this method is suitable for studying the aeolian vibration of a large-span, low stress-tensioned antenna network and has high computational efficiency and accuracy.

Abstract Background One of the most challenging aspects of colon cancer (CC) prognosis and treatment is liver-tropic metastasis. Astragalus mongholicus Bunge—Curcuma aromatica Salisb. (AC) is a typical medication combination for the therapy of many malignancies. Our previous studies found that AC intervention inhibits liver metastasis of colon cancer (LMCC). Nevertheless, the comprehensive anti-metastasis mechanisms of AC have not been uncovered. Methods In bioinformatics analysis, RNA-seq data of CC and LMCC patients were collected from TCGA and GEO databases, and differentially expressed genes (DEGs) were identified. The biological processes and signaling pathways involved in DEGs were enriched by GO and KEGG. The protein–protein interaction (PPI) network of DEGs was established and visualized using the Cytocape software, followed by screening Hub genes in the PPI network using Degree value as the criterion. Subsequently, the expression and survival relevance of Hub gene in COAD patients were verified. In the experimental study, the effects of AC on the inhibition of colon cancer growth and liver metastasis were comprehensively evaluated by cellular and animal models. Finally, based on the results of bioinformatics analysis, the possible mechanisms of AC inhibition of colon cancer EMT and liver metastasis were explored by in vivo and in vitro pharmacological experiments. Results In this study, we obtained 2386 DEGs relevant to LMCC from the COAD (colon adenocarcinoma) and GSE38174 datasets. Results of GO gene function and KEGG signaling pathway enrichment analysis suggested that cellular EMT (Epithelial-mesenchymal transition) biological processes, Cytokine-cytokine receptor interaction and PI3K/Akt signaling pathways might be closely related to LMCC mechanism. We then screened for CXCL8, the core hub gene with the highest centrality within the PPI network of DEGs, and discovered that CXCL8 expression was negatively correlated with the prognosis of COAD patients. In vitro and in vivo experimental evidence presented that AC significantly inhibited colon cancer cell proliferation, migration and invasion ability, and suppressed tumor growth and liver metastasis in colon cancer orthotopic transplantation mice models. Concomitantly, AC significantly reduced CXCL8 expression levels in cell supernatants and serum. Moreover, AC reduced the expression and transcription of genes related to the PI3K/AKT pathway while suppressing the EMT process in colon cancer cells and model mice. Conclusions In summary, our research predicted the potential targets and pathways of LMCC, and experimentally demonstrated that AC might inhibit the growth and liver metastasis in colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway, which may facilitate the discovery of mechanisms and new therapeutic strategies for LMCC.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

IntroductionActinobacillus pleuropneumoniae (A. pleuropneumoniae) is a member of Actinobacillus in family Pasteurellaceae. It is the causative agent of porcine pleuropneumonia, which has caused huge economic losses to pig industry over the world. Cysteine is a precursor of many important biomolecules and defense compounds in the cell. However, molecular mechanisms of cysteine transport in A. pleuropneumoniae are unclear.MethodsIn this study, gene-deleted mutants were generated and investigated, to reveal the roles of potential cysteine/cystine transport proteins FliY and YdjN of A. pleuropneumoniae.ResultsOur results indicated that the growth of A. pleuropneumoniae was not affected after fliY or ydjN single gene deletion, but absence of both FliY and YdjN decreased the growth ability significantly, when cultured in the chemically defined medium (CDM) supplemented with cysteine or cystine as the only sulfur source. A. pleuropneumoniae double deletion mutant ΔfliYΔydjN showed increased sensitivity to oxidative stress. Besides, trans-complementation of YdjN into ΔfliYΔydjN and wild type leads to increased biofilm formation in CDM. However, the virulence of ΔfliYΔydjN was not attenuated in mice or pigs.DiscussionThese findings suggest that A. pleuropneumoniae FliY and YdjN are involved in the cysteine/cystine acquisition, oxidative tolerance, and biofilm formation, but not contribute to the pathogenicity of A. pleuropneumoniae.

Summary: Background: The great heterogeneity of patients with chronic critical illness (CCI) leads to difficulty for intensive care unit (ICU) management. Identifying subphenotypes could assist in individualized care, which has not yet been explored. In this study, we aim to identify the subphenotypes of patients with CCI and reveal the heterogeneous treatment effect of fluid balance for them. Methods: In this retrospective study, we defined CCI as an ICU length of stay over 14 days and coexists with persistent organ dysfunction (cardiovascular Sequential Organ Failure Assessment (SOFA) score ≥1 or score in any other organ system ≥2) at Day 14. Data from five electronic healthcare record datasets covering geographically distinct populations (the US, Europe, and China) were studied. These five datasets include (1) subset of Derivation (MIMIC-IV v1.0, US) cohort (2008–2019); (2) subset Derivation (MIMIC-III v1.4 ‘CareVue’, US) cohort (2001–2008); (3) Validation I (eICU-CRD, US) cohort (2014–2015); (4) Validation II (AmsterdamUMCdb/AUMC, Euro) cohort (2003–2016); (5) Validation III (Jinling, CN) cohort (2017–2021). Patients who meet the criteria of CCI in their first ICU admission period were included in this study. Patients with age over 89 or under 18 years old were excluded. Three unsupervised clustering algorithms were employed independently for phenotypes derivation and validation. Extreme Gradient Boosting (XGBoost) was used for phenotype classifier construction. A parametric G-formula model was applied to estimate the cumulative risk under different daily fluid management strategies in different subphenotypes of ICU mortality. Findings: We identified four subphenotypes as Phenotype A, B, C, and D in a total of 8145 patients from three countries. Phenotype A is the mildest and youngest subgroup; Phenotype B is the most common group, of whom patients showed the oldest age, significant acid-base abnormality, and low white blood cell count; Patients with Phenotype C have hypernatremia, hyperchloremia, and hypercatabolic status; and in Phenotype D, patients accompany with the most severe multiple organ failure. An easy-to-use classifier showed good effectiveness. Phenotype characteristics showed robustness across all cohorts. The beneficial fluid balance threshold intervals of subphenotypes were different. Interpretation: We identified four novel phenotypes that revealed the different patterns and significant heterogeneous treatment effects of fluid therapy within patients with CCI. A prospective study is needed to validate our findings, which could inform clinical practice and guide future research on individualized care. Funding: This study was funded by 333 High Level Talents Training Project of Jiangsu Province (BRA2019011), General Program of Medical Research from the Jiangsu Commission of Health (M2020052), and Key Research and Development Program of Jiangsu Province (BE2022823).

Abstract Background Hypertension is an urgent public health problem. Consistent summary from natural and quasi-experiments employed to evaluate interventions that aim at preventing or controlling hypertension is lacking in the current literature. This study aims to summarize the evidence from natural and quasi-experiments that evaluated interventions used to prevent or control hypertension. Methods We searched PubMed, Embase and Web of Science for natural and quasi-experiments evaluating interventions used to prevent hypertension, improve blood pressure control or reduce blood pressure levels from January 2008 to November 2018. Descriptions of studies and interventions were systematically summarized, and a meta-analysis was conducted. Results Thirty studies were identified, and all used quasi-experimental designs including a difference-in-difference, a pre-post with a control group or a propensity score matching design. Education and counseling on lifestyle modifications such as promoting physical activity (PA), promoting a healthy diet and smoking cessation consultations could help prevent hypertension in healthy people. The use of computerized clinical practice guidelines by general practitioners, education and management of hypertension, the screening for cardiovascular disease (CVD) goals and referral could help improve hypertension control in patients with hypertension. The educating and counseling on PA and diet, the monitoring of patients’ metabolic factors and chronic diseases, the combination of education on lifestyles with management of hypertension, the screening for economic risk factors, medical needs, and CVD risk factors and referral all could help reduce blood pressure. In the meta-analysis, the largest reduction in blood pressure was seen for interventions which combined education, counseling and management strategies: weighted mean difference in systolic blood pressure was − 5.34 mmHg (95% confidence interval [CI], − 7.35 to − 3.33) and in diastolic blood pressure was − 3.23 mmHg (95% CI, − 5.51 to − 0.96). Conclusions Interventions that used education and counseling strategies; those that used management strategies; those that used combined education, counseling and management strategies and those that used screening and referral strategies were beneficial in preventing, controlling hypertension and reducing blood pressure levels. The combination of education, counseling and management strategies appeared to be the most beneficial intervention to reduce blood pressure levels.

Abstract The historian studies revealed during Mendel’s later research period when mainly focusing on the constant hybrid in Hieracium, he had to be intervened to conduct the controlled pollination experiments in Mirabilis jalapa. Two letters to Nageli recorded the experimental aim was to disprove Darwin’s opinion regarding three pollen grains required for one fertilization (note: that could completely destroy his previous discovery of segregation inheritance in variable hybrid in Pisum, for it was expressed in a mathematical equation). The experimental results of single pollen grain pollination confirmed the referenced view of one pollen cell uniting one egg cell in plant fertilization; the further pedigree introduction of the single and of the designed two pollen grain experiment succeeded in exemplifying that one hereditary factor carried by one gamete (pollen cell or egg cell) can independently transmit a trait to offspring. Here we coined the observation as the Gamete Theory of Inheritance. Remarkably, in contrast with the bulked pollination experiment, in this system, Mendel could easily manipulate a hereditary factor by merely taking a gamete as a carrier. Then, Mendel’s work in M. jalapa together with the previous Pisum study was able to jointly suppport his second lecture content that regarded “gamete formation, fertilization, and seed development” and also regarded hereditary factors in the processes. All in all, the 1866 paper was published during a rapid burst of interest in hybrid species likely induced by Darwin, and Mendel’s attempts at accommodation of the two incompatible inheritances of segregation in variable hybrids versus of nonsegregation in constant hybrids might be responsible for some historical controversies when understanding his discovery of inheritance.

Vanillin holds significant importance as a flavoring agent in various industries, including food, pharmaceuticals, and cosmetics. The CoA-dependent pathway for the biosynthesis of vanillin from ferulic acid involved feruloyl-CoA synthase (Fcs) and enoyl-CoA hydratase/lyase (Ech). In this research, the Fcs and Ech were derived from Streptomyces sp. strain V-1. The sequence conservation and structural features of Ech were analyzed by computational techniques including sequence alignment and molecular dynamics simulation. After detailed study for the major binding modes and key amino acid residues between Ech and substrates, a series of mutations (F74W, A130G, A130G/T132S, R147Q, Q255R, ΔT90, ΔTGPEIL, ΔN1-11, ΔC260-287) were obtained by rational design. Finally, the yield of vanillin produced by these mutants was verified by whole-cell catalysis. The results indicated that three mutants, F74W, Q147R, and ΔN1-11, showed higher yields than wild-type Ech. Molecular dynamics simulations and residue energy decomposition identified the basic residues K37, R38, K561, and R564 as the key residues affecting the free energy of binding between Ech and feruloyl-coenzyme A (FCA). The large changes in electrostatic interacting and polar solvating energies caused by the mutations may lead to decreased enzyme activity. This study provides important theoretical guidance as well as experimental data for the biosynthetic pathway of vanillin.

Abstract The Guangyuan Thousand-Buddha grotto is of great value in researching the spread of Buddhism in China. To explore a scientific deterioration degree evaluation method, the authors selected 11 grottos from the middle Tang Dynasty in the Guangyuan Thousand-Buddha grotto as survey objects; a traditional deterioration investigation was undertaken, and an analytic hierarchy process (AHP method) was applied to build a system to calculate the weight of 15 deterioration criteria and evaluate the deterioration degree of the grotto. The results showed that 15 deteriorations can be classified into two categories: stability deterioration and weathering deterioration. Each deterioration has its own weight on affecting the preservation condition of the grotto. In contrast to realistic conditions, the calculation results can quantitatively reflect the preservation condition of the grotto. The results offer a quantitative basis for determining the priority of grotto conservation and verifying the feasibility of the AHP method in helping conservators identify major deteriorations or judge conservation orders. This research proposes a quantitative evaluation method for the deterioration degree of the grotto, which can lay the foundation for further conservation of the grotto. Graphical Abstract

The unsaturated permeability coefficients are often used to solve geotechnical problems associated with unsaturated soils. But it is very difficult to measure. However, the unsaturated permeability coefficients can be predicted by the Soil-water Characteristic Curves (SWCCs). The Van Genuchten Model (VG model) is very rife as it's smooth and good fitting, thus, it has the most research data. Therefore, the research data on VG model parameters (α, n, θs and θr) of Malan loess in Chinese Loess Plateau are collected in the past two decades to obtain the spatial distribution characteristics of parameters. The trend surface analysis method is employed to clarify the regional scale distribution and the variation regular pattern on ArcGIS. Then the linear regression method is utilized to fit the relationship between suction and water content in three different regions of Chinese Loess Plateau, which is divided according to the properties and particle gradation. By using this relationship and the trend surface analysis contour map, the unsaturated permeability coefficient of the sample can be predicted after measuring the saturated permeability coefficient. The example verification shows that the difference between the prediction results and the experimental results is very small when the sample has the lower saturation, and the deviation is slightly larger if it has the higher saturation, but they are all within the acceptable range. This method not only saves the test cost, but also considers the physical properties of the loess in the three different regions of the Loess Plateau. With the improvement of data and the gradual improvement of sampling density, the prediction accuracy will gradually improve. It can provide convenience for solving the engineering problems of loess and water and other engineering applications.

Climate change is becoming increasingly severe. Today, several studies have found that climate change substantially influences the increasing number of forest fires. Regional climate models (RCMs) are currently a vital tool for climate forecasting in researching how to combat forest fires. As China’s forest fire area, Yunnan province has frequent forest fires that generate significant losses, so it is a crucial area for forest fire prevention in China. Therefore, this study uses meteorological observational data from 25 stations in Yunnan over the period 2004–2018 to compares and evaluates the Regional Climate Forecast Model (RegCM) and Weather Research and Forecasting model (WRF) in multiple dimensions. The optimal RCM is then determined for the forest area of Yunnan. The results show that the deviations of RegCM predictions from the spatial mean of the real temperature are less than 3°C, whereas the deviations of WRF are all greater than 3°C. In addition, the RegCM correlation coefficient exceeds 0.8, whereas the WRF correlation coefficient exceeds 0.75. In terms of precipitation, the deviation of RegCM predictions for the whole territory is less than 2 mm, whereas the overall deviation of WRF predictions is great. The correlation coefficient for RegCM and WRF are both less than 0.5, but the RegCM correlation coefficient exceeds that of the WRF. We thus conclude that RegCM is more suitable for predicting the climate of the forest area of Yunnan. This study also provides references for related climate forecasting and research into forest fire dynamics in general.

IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy.