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Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y6R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y6R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y6R and Th1 cells mediated by IL-27. Mechanistically, P2Y6R enhanced PLCβ/p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leading to erythematous and scaly plaques of psoriasis. Interestingly, we developed a novel P2Y6R inhibitor FS-6, which bonds with the ARG266 side chain of P2Y6R, exhibited remarkable anti-psoriasis effects targeting P2Y6R. Our study provides insights into the role of P2Y6R in the pathogenesis of psoriasis and suggests its potential as a target for the development of therapeutic interventions. A novel P2Y6R inhibitor FS-6 could be developed as an anti-psoriasis drug candidate for the clinic.

Abstract The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Abstract In this study, we analyzed pooled data from two prospective population-based cohorts—the Health Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA)—to explore the association between trajectories of depressive symptoms and the risk of cardiac events. Depressive symptoms were assessed using the 8-item CES-D scale and categorized into somatic and cognitive-affective subtypes. Trajectories were tracked for four surveys from baseline. Heart disease was identified based on self-reported physician-diagnosed conditions. Hazard ratios and 95% confidence intervals were calculated with Cox proportional risk models that adjusted for potential confounders. In total, 17,787 subjects (59.7% female, median age 63 years) were enrolled at baseline. During a 10-year follow-up, 2409 cases of heart disease were identified. Participants with fluctuating (HR = 1.13, 95% CI: 1.06–1.20), increasing (HR = 1.43, 95% CI: 1.25–1.64), and consistently high (HR = 1.64, 95% CI: 1.45–1.84) depressive symptom trajectories exhibited an increased risk of heart disease compared to those with consistently low depressive symptoms, while a decreasing (HR = 1.07, 95% CI: 0.96–1.19) depressive symptom trajectory did not significantly affect the risk of heart disease. Moreover, the association between heart disease and somatic depressive symptoms was found to be stronger than with cognitive-affective symptoms. These findings suggest a significant link between depressive symptom trajectories and heart disease, with particular emphasis on stronger associations with somatic symptoms. It is recommended that the identification and management of depressive symptoms be incorporated into heart disease prevention strategies.

Abstract Background According to the 5th edition of the Japanese Guidelines for the Treatment of Gastric Cancer, proximal gastrectomy is recommended for patients with early upper gastric cancer who can retain the distal half of the residual stomach after R0 resection. However, a large number of recent clinical studies suggest that surgical indications for proximal gastrectomy in the guidelines may be too narrow. Therefore, this meta-analysis included patients with early and advanced gastric cancer and compared short- and long-term postoperative outcomes between the two groups. At the same time, we only had high-quality clinical studies such as propensity score-matched studies and randomized controlled trials, which made our research more authentic and credible. Methods Data were retrieved from PubMed, EMBASE, Medline, and Cochrane Library up to June 2023, and included treatment outcomes after proximal gastrectomy with double-tract reconstruction and total gastrectomy with Roux-en-Y reconstruction. The primary results were Early-phase complications(Anastomotic leakage, Anastomotic bleeding, Abdominal abscess, Abdominal infection, Pulmonary infection, Incision infection, Intestinal obstruction, Dumping syndrome, Pancreatic fistula), Late-phase complications(Intestinal obstruction, Anastomosis stricture, Dumping syndrome, Reoperation, Internal hernia, Incidence of endoscopic gastroesophageal reflux), Serious complications (≥ Grade III C-D score), Quality of life[Gastroesophageal reflux symptom evaluation (Visick score)(≥ III), Los Angeles classification(C or D)], Nutritional status(Hemoglobin, Receipt of vitamin B12 supplementation), Oncologic Outcomes(The 5-year overall survival rates). Secondary outcomes were surgical outcomes (Operative time, Estimated blood loss, Postoperative hospital stay, Number of harvested lymph nodes, Gas-passing, Postoperative mortality).The Cochrane risk-of-bias tool and Newcastle‒Ottawa scale were used to assess the quality of the included studies. Results After screening, 11 studies were finally included, including 1154 patients. Results from the combined literature showed that total gastrectomy had a significant advantage over proximal gastrectomy with double-tract reconstruction in mean operating time (MD = 4.92, 95% CI: 0.22∼9.61 P = 0.04). However, meta-analysis results showed that Hemoglobin (MD = 7.12, 95% CI:2.40∼11.84, P = 0.003) and Receipt of vitamin B12 supplementation (OR = 0.12, 95% CI:0.05∼0.26, P

Abstract Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at −402 mA cm−2 and a high activity up to −1 A cm−2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at −100 mA cm−2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

The advent of 3D virtual presentation technology for clothing has led to the gradual popularisation of digital virtual clothing in the modern fashion industry. However, there remains a gap between the application of this technology and the integration of cultural attributes in the field of digital communication of traditional cultural clothing. Consequently, the objective of this paper is to propose the establishment of a fusion system integrating archaeological research on traditional culture with emerging virtual presentation technology. This paper draws inspiration from the replicability and easy dissemination of digital products to combine cultural archaeology and digital technology. The aim is to provide ideas for the diversity of dissemination of cultural heritage. The research object is Diplomatic Envoys, a Chinese mural painting of the Tang Dynasty that depicts friendly exchanges between countries. The research is divided into two research stages. A CLO3D software-based digital restoration test was conducted to reproduce the costumes of officials and foreign envoys depicted in the Tang Dynasty mural. The FAHP model was employed to verify the accuracy of the restoration results. The experiment demonstrated that the digitally reconstructed clothing exhibited a high degree of similarity to the unearthed mural figure clothing object. Furthermore, the restoration result passed the credibility verification, resulting in a ‘credible’ outcome. The application of digital virtual simulation clothing restoration methods offers two key advantages. Firstly, in comparison with traditional clothing restoration methods, digital restoration enables the rapid assessment of the resulting clothing effect, thereby reducing the likelihood of secondary damage to cultural relics due to manual errors. Secondly, the benefits of digital technology facilitate the convenient storage, replication, and dissemination of clothing data information. Data can not only be extended to online exhibition halls but also to game animation, clothing production, and other fields for the purposes of creative redesign and information dissemination. Furthermore, these benefits can penetrate the education industry to disseminate information to the public through all-round display models and explanations.

ObjectiveThe objective of this study is to explore the risk factors associated with new-onset postoperative atrial fibrillation (POAF) following Sun's surgery(total arch replacement using a tetrafurcate graft with stented elephant trunk implantation) for acute type A aortic dissection(AAAD) and to develop a predictive model for assessing the likelihood of new-onset POAF in patients undergoing Sun's surgery for AAAD.MethodsWe reviewed the clinical parameters of patients diagnosed with AAAD who underwent Sun's surgery at Qilu Hospital between December 1, 2017 and December 31, 2022. The data was analyzed through univariable and multivariable logistic regression analysis. Variance inflation factor was used to investigate for variable collinearity. A nomogram for predicting new-onset POAF was developed and verified by bootstrap resampling. In addition, the calibration of our model was evaluated by the calibration curve and Hosmer-Lemeshow test. Furthermore, the clinical utility of our model was evaluated using the net benefit curve.ResultsThis study focused on a cohort of 242 patients with AAAD, among whom 42 experienced new-onset POAF, indicating an incidence rate of 17.36%. Age, left atrial diameter (LA), right atrial diameter (RA), preoperative red blood cells (RBC), and previous acute coronary syndrome (preACS) emerged as independent influences on new-onset POAF following Sun's surgery, as identified by univariable and multivariable logistic regression analysis. Collinearity analysis with demonstrated no collinearity among the variables. A user-friendly prediction nomogram for new onset POAF following Sun's surgery was formulated. The model demonstrated commendable diagnostic accuracy with an area under the curve (AUC) of 0.7852. Validation of the model through bootstrapping (1,000 repetitions) yielded an AUC of 0.8080 (95% CI: 0.8056–0.8104). affirming its robustness. Additionally, the model exhibited favorable fit, calibration, and positive net benefits in decision curve analysis.ConclusionsDrawing upon these findings, we have developed a predictive model for the occurrence of new-onset POAF. These results suggest the potential efficacy of this prediction model for identifying patients at risk of developing POAF. The visualization of this model empowers healthcare professionals to conveniently and promptly assess the risk of AF in patients, thereby facilitating the timely intervention implementation.

Abstract Purinergic signaling plays a causal role in the pathogenesis of inflammatory bowel disease. Among purinoceptors, only P2Y14R is positively correlated with inflammatory score in mucosal biopsies of ulcerative colitis patients, nevertheless, the role of P2Y14R in ulcerative colitis remains unclear. Here, based on the over-expressions of P2Y14R in the intestinal epithelium of mice with experimental colitis, we find that male mice lacking P2Y14R in intestinal epithelial cells exhibit less intestinal injury induced by dextran sulfate sodium. Mechanistically, P2Y14R deletion limits the transcriptional activity of cAMP-response element binding protein through cAMP/PKA axis, which binds to the promoter of Ripk1, inhibiting necroptosis of intestinal epithelial cells. Furthermore, we design a hierarchical strategy combining virtual screening and chemical optimization to develop a P2Y14R antagonist HDL-16, which exhibits remarkable anti-colitis effects. Summarily, our study elucidates a previously unknown mechanism whereby P2Y14R participates in ulcerative colitis, providing a promising therapeutic target for inflammatory bowel disease.

Abstract Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a tumor growth-promoting phenotype through activation of the anaplastic lymphoma kinase (ALK) signaling pathway. Targeting the RNase1/ALK axis reprograms the macrophage polarization, with increased CD8+ T- and Th1- cell recruitment. Moreover, simultaneous targeting of the checkpoint protein PD-1 unleashes cytotoxic CD8+ T-cell responses. Treatment utilizing both an ALK inhibitor and an anti-PD-1 antibody exhibits enhanced tumor regression and facilitates long-term immunity. Our study elucidates the role of RNase1 in mediating tumor resistance to immunotherapy and reveals an RNase1-mediated immunosuppressive tumor microenvironment, highlighting the potential of targeting RNase1 as a promising strategy for cancer immunotherapy in HCC.

It is crucial to develop a comprehensive method for estimating the aboveground biomass (AGB) of trees, shrubs, grasslands, and sparse tree areas in ecologically fragile dry, hot valley regions with vertical zonation. Multi-source remote-sensing data can fulfill this requirement, providing help in monitoring the health of ecosystems and providing a basis for regional biodiversity conservation and restoration. Sentinel-2A satellite imagery was used to classify the forests, shrubs, and grasslands in Yuanmou County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, China. The Gaofen-2 satellite (GF-2) was used to extract the canopy width and calculate tree biomass in the valley-type savanna region. These data were combined with remote-sensing factors and measured survey data, and random forest (RF) and extreme gradient boosting (XGBoost) models were used to estimate the biomass. Using GF-2 images to segment sparse tree areas effectively reduced the overestimation of low-resolution remote-sensing images, enabling the AGB of sparse trees to be accurately estimated. The biomass estimations based on the Sentinel-2A images attained coefficient of determination (R2) values of 0.45 and 0.47 for the forest, 0.55 and 0.61 for the shrubs, and 0.32 and 0.37 for the grasslands using RF and XGBoost models, respectively, demonstrating variable effectiveness across vegetation types. In addition, the XGBoost model was more robust than the RF model for all three vegetation types. Our methodology provides scientific support for the sustainable development of ecologically fragile dry, hot valleys and savanna areas.

Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS–AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation (n = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand–eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder (n = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation (n = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.

BackgroundMajor depressive disorder (MDD) pathogenesis may involve metalloids in a significant way. The aim of our study was to identify potential links between MDD and metalloid elements [boron (B), germanium (Ge), arsenic (As), antimony (Sb)].MethodsA total of 72 MDD cases and 75 healthy controls (HCs) were recruited from Zhumadian Second People’s Hospital in Henan Province, China. The levels of four metallic elements (B, Ge, As, and Sb) in the serum and urine were measured using inductively coupled plasma mass spectrometry (ICP-MS).ResultsIn comparison to the HCs, the B, As, and Sb levels were considerably lower in the MDD group (p < 0.05) in the serum; the MDD group had significantly higher (p < 0.05) and significantly lower (p < 0.001) B and Sb levels in the urine. After adjusting for potential confounders, serum B (OR = 0.120; 95% CI, 0.048, 0.300; p < 0.001) and Sb (OR = 0.133; 95% CI, 0.055, 0.322; p < 0.001) showed a negative correlation with MDD. Urine B had a negative correlation (OR = 0.393; 95% CI, 0.193, 0.801; p = 0.01) with MDD, while urine Sb had a positive correlation (OR = 3.335; 95% CI, 1.654, 6.726; p = 0.001) with MDD. ConclusionOur current research offers insightful hints for future investigation into the function of metalloids in connection to MDD processes.

Abstract Geometric frustration commonly occurs in materials where magnetic rare-earth ions are arranged on a two-dimensional triangular lattice. These compounds have been gaining significant attention lately, as they hold the promise of revealing unique quantum states of matter. However, little attention has been devoted to cases where spin- $$\frac{1}{2}$$ 1 2 rare-earth ions are substituted with ions exhibiting higher spin multiplicities. Here, we successfully synthesize high-quality single crystal samples of Ba3Er(BO3)3, which is part of the family of triangular lattice compounds. In our experiments, conducted at extremely low temperatures (around 100 millikelvin), we observe two sublattice exchange interactions in Ba3Er(BO3)3, resulting in the hexagonal lattice spins exhibiting a mixture of ferromagnetic and antiferromagnetic tendencies. Our theoretical analysis suggest that this behavior may be attributed to the distinct positions of magnetic ions within the crystal lattice. However, the presence of quantum effects adds an extra layer of complexity to our findings, calling for further exploration.

Abstract Background Bicarbonate Ringer’s (BR) solution is a direct liver and kidney metabolism-independent HCO3 − buffering system. We hypothesized that BR solution would be more effective in improving acid-base equilibrium and more conducive to better liver function than Acetate Ringer’s (AR) solution in conventional orthotopic liver transplantation (OLT) patients. Methods Sixty-nine adult patients underwent OLT. Patients in the bicarbonate and acetate groups received BR solution or AR solution as infused crystalloids and graft washing solution, respectively. The primary outcome was the effect on pH and base excess (BE) levels. The secondary outcome measures were the incidence and volume of intraoperative 5% sodium bicarbonate infusion and laboratory indicates of liver and kidney function. Results The pH and absolute BE values changed significantly during the anhepatic phase and immediately after transplanted liver reperfusion in the bicarbonate group compared with the acetate group (all P

Objective. We aimed to explore the long-term outcomes of bipolar transurethral enucleation and resection of the prostate (B-TUERP) in patients with benign prostatic hyperplasia (BPH). Methods. A total of 1195 patients with BPH who underwent B-TUERP from July 2006 to June 2010 were enrolled in this retrospective study. Preoperative data, particularly urodynamic study (UDS) parameters, were collected by questionnaire and examination. Postoperative follow-up was performed at 3, 6, 12, 36, 60 and 120 months, respectively. Demographic, perioperative and functional data were analysed. International Prostate Symptom Score, quality of life and overactive bladder syndrome score (OABSS) were used to assess the functional scores. Predictors of postoperative urgency incontinence were identified by univariate analysis. Results. Long-term outcomes of functional score were significantly better than the preoperative values. All UDS variables, including maximum urinary flow rate, postvoid residual urine volume, compliance, maximum cystometric capacity (MCC), bladder outlet obstruction index, prostatic urethral pressure and detrusor pressure at maximum urinary flow rate, were all significantly improved. No one required reoperation due to recurrent BPH. The postoperative rate of transient urinary incontinence was 31.7%, while the long-term incontinence rate was 0%. Retrograde ejaculation occurred in 44.3% patients who remained sexually active after operation. Patients who had transient urge incontinence were older with preoperative higher OABSS, prostate-specific antigen (PSA) and detrusor overactivity rate and lower MCC. Conclusion. B-TUERP is a safe, successful and highly effective treatment for BPH at 10-year follow-up. Increased age, OABSS, PSA level and detrusor overactivity rate are potential predictors for urge incontinence after B-TUERP.

The trees in a given stand compete with each other for light, water and nutrients, producing spatial effects. To understand spatial effects, it is critical to characterise the spatial distributions and patterns of the aboveground biomass (AGB) of individual trees and the biomass of their components (stem, bark, branches and foliage). This study investigated the spatial effects by examining the AGB of individual trees and the biomass of their components in the context of typical sub-tropical tree species in Yunnan, China, including a Pinus kesiya var. langbianensis natural forest (PN), a Pinus kesiya var. langbianensis plantation (PP), and a Eucalyptus spp. plantation (EP), using datasets for three clear-cutting plots. Ripley’s L function was employed to identify the spatial distributions and patterns of the AGB of individual trees and the biomass of their components. Then, Global and Local Moran’s I indices were utilised to analyse spatial autocorrelation, with Intra-group variance being calculated to quantify spatial heterogeneity. This led to following findings. Firstly, with increasing distance, the spatial heterogeneity of the three stands increased before stabilising at a distance of 10 m. Secondly, excluding bark, all components of the tree biomass in the PN stand exhibited significant dispersion. In contrast, all the components in the PP stand showed significant dispersion. The spatial distributions and patterns of trees and their biomass in the EP stand indicated the coexistence of clustering and dispersion. Moreover, the significant spatial autocorrelations of tree AGB and components biomass could be noticed but depending on the stands, components and distances. These findings provide theoretical support for sustainable forest management based on biomass and carbon stocks.

Abstract With the increasing number of flexible distributed energy resources, it is difficult for the distribution network to control various devices directly. Therefore, managing and dispatching the resources in a cluster way is required. This article proposes an equivalent model‐based asynchronous dispatch framework, which is composed of three layers, the distribution network, clusters, and distributed energy resources. With this framework, economic dispatch is carried out with the equivalent models of clusters, simplifying the dispatch problem of the distribution network. The numerical test results show that the proposed method can significantly reduce the calculation time and maintain high accuracy in the economic dispatch problem.

Abstract Warburg effect plays a crucial role in bladder cancer (Bca) development. However, the mechanism by which glycolysis is involved in Bca remains poorly understood. CircRNAs commonly play a regulatory role in tumor progression. Our study discovered and identified a novel circRNA, hsa_circ_0000235 (circ235), and investigated its role in the glycolytic process, which further results in the progression of Bca. We applied qRT-PCR to assess its clinicopathological relevance and evaluated its proliferation, migration, and glycolytic capacity. We investigated its mechanism using RNA immunoprecipitation, dual-luciferase reporters, and fluorescence in situ hybridization. The findings demonstrated that circ235 was dramatically increased in Bca tissues and was related to a worse prognosis. In vitro studies revealed that circ235 accelerated the rate of extracellular acidification and promoted glucose uptake and lactate manufacture in Bca cells. Additionally, it strengthened the proliferative and migratory capacities. Experiments on animals revealed that downregulating circ235 dramatically reduced carcinogenesis and tumor growth. Circ235 activates monocarboxylate transporter 4 (MCT4) by sponging miR-330-5p, which promotes glycolysis and tumor growth. In conclusion, these findings suggest that circ235 may be a viable molecular marker and therapeutic target for Bca.

Here, cytosine methylation in the whole genome of pear flower buds was mapped at a single-base resolution. There was 19.4% methylation across all sequenced C sites in the Pyrus pyrifolia cultivar ‘Sucui 1’ flower bud genome. Meantime, the CG, CHG, and CHH sequence contexts (where H = A, T or C) exhibited 47.4%, 33.3%, and 11.9% methylation, respectively. Methylation in different gene regions was revealed through combining methylome and transcriptome analysis, which presented various transcription trends. Genes with methylated promoters exhibited lower expression levels than genes with non-methylated promoters, while body-methylated genes displayed an obvious negative correlation with their transcription levels. The methylation profiles of auxin- and cytokinin-related genes were estimated. And some of them proved to be hypomethylated, with increased transcription levels, in wizened buds. More specifically, the expression of the genes PRXP73, CYP749A22, and CYP82A3 was upregulated as a result of methylation changes in their promoters. Finally, auxin and cytokinin concentrations were higher in wizened flower buds than in normal buds. The exogenous application of paclobutrazol (PP333) in the field influenced the DNA methylation status of some genes and changed their expression level, reducing the proportion of wizened flower buds in a concentration-dependent manner. Overall, our results demonstrated the relationship between DNA methylation and gene expression in wizened flower buds of P. pyrifolia cultivar ‘Sucui 1’, which was associated with changes in auxin and cytokinin concentrations.

Abstract Electrochemical CO2 conversion to methane, powered by intermittent renewable electricity, provides an entrancing opportunity to both store renewable electric energy and utilize emitted CO2. Copper-based single atom catalysts are promising candidates to restrain C-C coupling, suggesting feasibility in further protonation of CO* to CHO* for methane production. In theoretical studies herein, we find that introducing boron atoms into the first coordination layer of Cu-N4 motif facilitates the binding of CO* and CHO* intermediates, which favors the generation of methane. Accordingly, we employ a co-doping strategy to fabricate B-doped Cu-N x atomic configuration (Cu-N x B y ), where Cu-N2B2 is resolved to be the dominant site. Compared with Cu-N4 motifs, as-synthesized B-doped Cu-N x structure exhibits a superior performance towards methane production, showing a peak methane Faradaic efficiency of 73% at −1.46 V vs. RHE and a maximum methane partial current density of −462 mA cm−2 at −1.94 V vs. RHE. Extensional calculations utilizing two-dimensional reaction phase diagram analysis together with barrier calculation help to gain more insights into the reaction mechanism of Cu-N2B2 coordination structure.

For the purpose of researching the rules of combustion heat release, ammonium phosphate dry powder extinguishing agent and water-based fire extinguishing agent were utilized before and after the class A fire common wood stack ignition fuel and class B fire anhydrous ethanol ignition fuel fire extinguishing. For wood stack fire, 0.5A wood stack was used for blank combustion test, and the pan fire ignition method for the same type and scale of wood stack fire extinguishing experiment. For absolute ethanol fire, fire suppression was studied using a 13B scale. The change characteristics of the combustion field before and after action of the dry powder extinguishing agent and water system extinguishing agent were measured by thermocouple, heat flow meter and digital camera. The findings of the experiment demonstrated that in the combustion experiment of wood stack, the temperature of 0.5A wood stack of the blank group could reach 800 °C, and the temperature reduction rate of free combustion was 2.62 °C/s. It took an average of 36.5s and 2.25 kg of ammonium phosphate dry powder to put out the fire，and the temperature reduction rate was 4.18 °C/s. The average amount of water-based extinguishing agent used to extinguish a fire was 1.21 kg, yet the average time to do so was just 12.5 s, and the average rate of temperature drop was 10.14 °C/s. In the experiment where an ethanol pool fire was being burned, the typical amount of water-based fire extinguishing chemical used was 3.44 kg, and the typical extinguishing time was 18 s, the maximum temperature drop rate could reach 35.6 °C/s in the initial stage of fire extinguishing, despite the fact that the dry powder fire extinguisher containing ammonium phosphate was used, the fire was not properly controlled.

Insufficient sample data is a challenge when estimating forest aboveground biomass (AGB) using large-scale remote sensing. Extracting remote sensing information from sub-compartments could rectify such defects, but the corresponding method, its accuracy, and influencing factors still need to be clarified. We combined Landsat 8 data with a Pinus densata forest sub-compartment to extract remote sensing information that matched the sample plots. Six sub-compartment based methods, including the centroid point extraction method, and the minimum, mean, maximum, majority, and median statistic extraction methods were used to extract sub-compartment remote sensing information and compare the differences between each method and the true values. For each method, structural equation modelling (SEM) was used to explore the effect of sub-compartment topography, shape, and forest stand factors on the extraction error. Mean statistic was the best extraction method, with the highest consistency index, and the lowest mean relative error, between the extracted and true values. All three factors affected extraction accuracy, with forest stand being the dominant one. When sub-compartment data are sufficient, but sample plots are insufficient, it is an effective extrapolation method for large-scale AGB estimation.

Highlights The electrochemical techniques utilizing metal-organic frameworks (MOFs)-based catalysts for converting CO2 into chemical species are discussed. The structure–activity relationship of MOF-based catalysts in electrocatalytic CO2 reduction reactions is thoroughly reviewed The challenges and opportunities of large-scale applications of MOF-based materials in electrochemical CO2 reduction reactions are discussed, and possible directions for the future development of MOFs and their derivatives are outlined.

Abstract The removal of acetylene impurities remains important yet challenging to the ethylene downstream industry. Current thermocatalytic semihydrogenation processes require high temperature and excess hydrogen to guarantee complete acetylene conversion. For this reason, renewable electricity-based electrocatalytic semihydrogenation of acetylene over Cu-based catalysts is an attractive route compared to the energy-intensive thermocatalytic processes. However, active Cu electrocatalysts still face competition from side reactions and often require high overpotentials. Here, we present an undercoordinated Cu nanodots catalyst with an onset potential of −0.15 V versus reversible hydrogen electrode that can exclusively convert C2H2 to C2H4 with a maximum Faradaic efficiency of ~95.9% and high intrinsic activity in excess of −450 mA cm−2 under pure C2H2 flow. Subsequently, we successfully demonstrate simulated crude ethylene purification, continuously producing polymer-grade C2H4 with

The optical saturation problem is one of the main factors causing uncertainty in aboveground biomass (AGB) estimations using optical remote sensing data. It is critical for the improvement in AGB estimation accuracy to clarify the relationships between environmental factors and the variations in optical saturation values (OSVs). In this study, we obtained the OSVs for 20 districts and clarified the individual, interactive, and comprehensive effects of climate, soil, and topographical factors on the OSV variations. The results are as follows: (1) the range of the OSVs was from 104 t/hm2 to 182 t/hm2 for the 20 districts; (2) the soil factor had the greatest (−0.635) influence on the OSVs compared to climate and topography; (3) the highest interaction effect (−0.833) was between climate and soil; (4) the comprehensive effect of the three environmental factors on the OSVs was obvious, and the correlation coefficient was 0.436. Moreover, the mean temperature of the coldest quarter (MCQMean) had the highest effect on the OSVs. The results indicate that environmental factors significantly affect the variation in OSVs through their individual, interactive, and comprehensive effects. Our findings provide a valuable reference for reducing the uncertainty caused by spectral saturation in AGB estimations using optical remote sensing data.

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using μCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.

SMXL genes constitute a conserved gene family that is ubiquitous in angiosperms and involved in regulating various plant processes, including branching, leaf elongation, and anthocyanin biosynthesis, but little is known about their molecular functions in pear branching. Here, we performed genome-wide identification and investigation of the SMXL genes in 16 angiosperms and analyzed their phylogenetics, structural features, conserved motifs, and expression patterns. In total, 121 SMXLs genes were identified and were classified into four groups. The number of non-redundant SMXL genes in each species varied from 3 (Amborella trichopoda Baill.) to 18 (Glycine max Merr.) and revealed clear gene expansion events over evolutionary history. All the SMXL genes showed conserved structures, containing no more than two introns. Three-dimensional protein structure prediction revealed distinct structures between but similar structures within groups. A quantitative real-time PCR analysis revealed different expressions of 10 SMXL genes from pear branching induced by fruit-thinning treatment. Overall, our study provides a comprehensive investigation of SMXL genes in the Rosaceae family, especially pear. The results offer a reference for understanding the evolutionary history of SMXL genes and provide excellent candidates for studying fruit tree branching regulation, and in facilitating pear pruning and planting strategies.

To enhance forest carbon sequestration capacity, it is important to optimize forest structure by revealing the spatial effects of the aboveground biomass of individual trees, with particular emphasis on stand origin and tree size. Here, 0.3 ha clear-cut plots of Pinus kesiya var. langbianensis forest were selected in a typical plantation and natural stand. Then, the ordinary least squares model and spatial regression models were used to analyze the different responses between spatial position and individual tree biomass based on the stand origin and diameter at breast height (DBH) of the tree. Our study shows the following: (1) The spatial effect produced a stronger response in the natural stand than in the plantation. The amount of change in the adjusted R-squared (ΔRadj2) of tree component totaled 0.34 and 0.57 for Pinus kesiya var. langbianensis and other trees in the natural stand, compared to only 0.2 and 0.42 in the plantation; (2) Spatial effects had a stronger impact on the accuracy of the fit for the crown (ΔRadj2 = 0.52) compared to the wood and bark (ΔRadj2 = 0.03) in the plantation, and there were no significant differences in the natural stand (ΔRadj2 = 0.42, ΔRadj2 = 0.43); (3) When DBH reached a certain size, the impact of spatial effect for the crown showed a significant change from positive to negative. The sizes of DBH were 19.5 cm, 14 cm and 34.6 cm, 19 cm for branches of Pinus kesiya var. langbianensis and other tree species in the plantation and natural stand, and were 20.3 cm and 31.4 cm for the foliage of Pinus kesiya var. langbianensis. Differences in stand structure led to varied responses in the biomass of tree components to spatial effects.

ObjectiveThe main purpose of this study was to evaluate the safety and efficacy of Castor single-branched stent-graft combined with fenestrated technique in treatment of thoracic aortic disease (TAD) with unfavorable proximal landing area (PLZ) and isolated left vertebral artery (ILVA).MethodsFrom January 2018 to March 2022, 8 patients with TAD (6 patients with type B aortic dissections, 1 patient with type B intramural hematomas, and 1 patient with thoracic aortic aneurysm) underwent thoracic endovascular aortic repair with fenestrated Castor stent-graft due to the existence of ILVA and unfavorable PLZ. Demographic characteristics, surgical details, postoperative complications, follow-up and postoperative CTA imaging results were collected and analyzed.ResultsThe primary technical success rate was 100%. The mean operation time was 115 min (range, 70–180 min). All the left subclavian arteries (LSAs) and ILVAs of the eight patients were revascularized by fenestrated Castor stent-grafts. During the follow-up period, no deaths and complications were observed. No internal leakage, aortic rupture, retrograde type A dissection were found on computed tomography angiography. All of the LSAs and ILVAs maintained patency without stenosis.ConclusionCastor single-branched stent-graft implantation combined with fenestration technique may be safe and feasible for TAD patients with ILVA and unfavorable PLZ.

Abstract Psoriasis is currently an incurable skin disorder mainly driven by a chronic inflammatory response. We found that subcutaneous application of umbilical cord- derived mesenchymal stem/stromal cells (MSCs) primed by IFN-γ and TNF-α, referred to as MSCs-IT, exhibited remarkable therapeutic efficacy on imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Neutrophil infiltration, a hallmark of psoriasis, was significantly reduced after treatment with MSCs-IT. We further demonstrated that the effects of MSCs-IT were mediated by tumor necrosis factor (TNF) stimulating gene-6 (TSG-6), which was greatly upregulated in MSCs upon IFN-γ and TNF-α stimulation. MSCs transduced with TSG-6 siRNA lost their therapeutic efficacy while recombinant TSG-6 applied alone could also reduce neutrophil infiltration and alleviate the psoriatic lesions. Furthermore, we demonstrated that TSG-6 could inhibit neutrophil recruitment by decreasing the expression of CXCL1, which may be related to the reduced level of STAT1 phosphorylation in the keratinocytes. Thus, blocking neutrophil recruitment by MSCs-IT or TSG-6 has potential for therapeutic application in human psoriasis.

Abstract Background Mesenchymal stem/stromal cells (MSCs) acquire immunosuppressive capacity only in an inflammatory microenvironment. This can be recapitulated in vitro by treating MSCs with inflammatory cytokines TNFα and IFNγ, which induce indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene-6 (TSG-6). However, the signaling pathways downstream of the cytokines remain to be elucidated. Methods Inflammatory bowel disease (IBD) mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. Human UC-MSCs were pretreated with TNF-α and IFN-γ for 24 h and were then infused intravenously at day 2 of DSS administration. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay. Real-time PCR and Western blot were used to examine the mRNA level and protein expression. MSCs overexpressing constitutive active AKT or dominant negative AKT were generated and were analyzed. The glycolysis level of the MSCs was measured using Extracellular Flux Analyzer. 2-NBDG was used to monitor the uptake of glucose by MSCs. Results TNFα and IFNγ treatment led to rapid consumption of glucose and metabolic skewing toward glycolysis in MSCs, which was required for the therapeutic efficacy of MSCs on IBD. Blockade of glycolysis in MSCs inhibited the expression of immunomodulatory molecules, IDO and TSG-6, as well as the therapeutic effect on IBD. Moreover, PI3K-AKT signaling axis was rapidly activated and was required for the skewing toward glycolysis induced by TNFα and IFNγ. MSCs expressing dominant negative AKT were compromised in their therapeutic efficacy on IBD. Conclusion The glycolysis-dependent anti-inflammatory property of MSCs conferred by inflammatory cytokines is mediated by PI3K-AKT signaling pathway.

Using various biomass factors, such as biomass expansion factor (BEF) and biomass conversion and expansion factor (BCEF), yields different results for estimating forest biomass. Therefore, ensuring compatibility between total biomass and its components when employing different biomass factors is crucial for developing a set of rapid and efficient models for large-scale biomass calculation. In this study, allometric equations were utilized to construct independent models and the proportional values (root-to-shoot ratio (Rra), crown-to-stem ratio (Rcs), bark-to-wood ratio (Rbw), foliage-to-bark ratio (Rfb), and wood biomass-to-wood volume (ρ)) by using the mean height (Hm) and the mean diameter at breast height (Dg) of 98 Pinus densata plots in Shangri-La, Yunnan province, China. The compatible methods were applied to reveal the compatibility between the total biomass and each component’s biomass. The results showed the following: (1) Both the independent model and compatible model had a higher accuracy. The values were greater than 0.7 overall, but the foliage biomass accuracy was only 0.2. The total biomass and the component biomass showed compatibility. (2) The accuracy of BEF and BCEF exceeded 0.87 and the total error was less than 0.1 for most components. (3) The mean BEF (1.6) was greater than that of the Intergovernmental Panel on Climate Change (IPCC) (M = 1.3), and the mean BCEF was smaller than that of the IPCC; the values were 0.6 and 0.7, respectively. The range of BEF (1.4–2.1) and BCEF (0.44–0.89) were all within the range of the IPCC (1.15–3.2, 0.4–1.0). This study provides a more convenient and accurate method for calculating conversion coefficients (BEF and BCEF), especially when only Rcs data is available.

Abstract Background In our previous research, we found that overexpression of miR-126-3p in human umbilical cord MSCs (hucMSCs) promoted human umbilical vein endothelial cells angiogenic activities through exosome-mediated mechanisms. The present study aimed to investigate the role of miR-126-3p-modified hucMSCs derived exosomes (miR-126-3p-hucMSCs-exosomes) on the treatment of premature ovarian failure (POF). Methods Primary hucMSCs were isolated from human umbilical cords and identified by differentiation experiments and flow cytometry. miR-126-3p-hucMSCs were obtained by miR-126-3p lentivirus infection. miR-126-3p-hucMSCs-exosomes were purified by ultracentrifugation method and characterized by transmission electron microscopy and western blot analysis. Primary rat ovarian granulosa cells (OGCs) were collected from ovarian tissues and identified by cell immunohistochemistry. The effects of miR-126-3p-hucMSCs-exosomes and miR-126-3p on OGCs function were determined by cell proliferation and apoptosis assays in a cisplatin induced POF cell model. The levels of suitable target genes were analyzed by PCR and Western blot analysis and subsequent Dual-Luciferase reporter assay. The signal pathway was also analyzed by western blot analysis. A cisplatin-induced POF rat model was used to validate the therapeutic effects of miR-126-3p-hucMSCs-exosomes to treat POF. Ovarian function was evaluated by physical, enzyme-linked immunosorbent assay, and histological examinations in chemotherapy-treated rats. The angiogenesis and apoptosis of ovarian tissues were assessed by immunohistochemical staining and Western blots. Results Primary hucMSCs and miR-126-3p-hucMSCs-exosomes and primary rat OGCs were successfully isolated and identified. The cellular uptake experiments indicated that miR-126-3p-hucMSC-exosomes can be internalized into OGCs in vitro. Annexin V-FITC/PI staining and EDU assays revealed that both miR-126-3p-hucMSCs-exosomes and miR-126-3p promoted proliferation and inhibited apoptosis of OGCs damaged by cisplatin. PCR and western blot analysis and subsequent dual-luciferase reporter assay verified that miR-126-3p targets the sequence in the 3' untranslated region of PIK3R2 in OGCs. Further analysis showed that PI3K/AKT/mTOR signaling pathway took part in miR-126-3p/PIK3R2 mediated proliferation and apoptosis in OGCs. In rat POF model, administration of miR-126-3p-hucMSCs-exosomes increased E2 and AMH levels, increased body and reproductive organ weights and follicle counts, and reduced FSH levels. But more importantly, immunohistochemistry results indicated miR-126-3p-hucMSCs-exosomes significantly promoted ovarian angiogenesis and inhabited apoptosis in POF rats. Additionally, the analysis of angiogenic-related factors and apoptosis-related factors showed miR-126-3p-hucMSCs-exosomes had pro-angiogenesis and anti-apoptosis effect in rat ovaries. Conclusions Our findings revealed that hucMSCs-derived exosomes carrying miR-126-3p promote angiogenesis and attenuate OGCs apoptosis in POF, which highlighted the potential of exosomes containing miR-126-3p as an effective therapeutic strategy for POF treatment.

Electroreduction of carbon dioxide (CO2) into value-added chemicals offers an entrancing approach to maintaining the global carbon cycle and eliminating environmental threats. A key obstacle to achieving long-term and large-scale implementation of electrochemical CO2 reduction technology is the lack of active and selective catalysts. Copper (Cu) is one of the few candidates that can facilitate C–C coupling to obtain high-energy oxygenates and hydrocarbons beyond carbon monoxide (CO), but it suffers from poor selectivity for products of interest and high overpotentials. Alloying is an effective way to break the linear scaling relations and uniquely manipulate the reactivity and selectivity, which is hard to achieve by using monometallic compositions alone. By alloying Cu with other metals, one could change the catalytic properties of the catalyst by tuning the local electronic structure and modulating the adsorption strength of the reaction intermediates, thus improving the catalytic activity and selectivity. In this review, we focus on the recently developed Cu-based alloy catalysts (including conventional alloys, high-entropy alloys and single-atom alloys) that have been applied in electrocatalytic CO2 reduction (ECR). Theoretical calculations and experimental advances in understanding the key rate-limiting and selectivity-determining steps in those alloys are summarized, with a particular focus on identifying binding energy descriptors and the dynamic product formation mechanisms. In addition, we outline the opportunities and challenges in the fundamental understanding of ECR by recommending advanced in-situ characterization techniques and standardized electrochemical methods and offer atomic-level design principles for steering the reaction pathways to the desired products.

DNA methylation plays an indispensable role in genome stability, regulation of gene expression and plant stress response. It is mediated by DNA methyltransferases (MTases). Twelve putative MTases of P. betulaefolia were identified and were classified into MET1, CMT, DRM2 and Dnmt2 groups based on the organization of various characteristic domains. Three pairs of paralogous genes were identified with the Ka/Ks ratio varied from 0.232 for PbeMET1a and PbeMET1b to 0.251 for PbeCMT2 and PbeCMT3, respectively. In addition, the Ka/Ks ratio for nine pairs of orthologous gene pairs between P. betulaefolia and apple were varied from 0.053 for PbeDRM3 and MD17G1031900 to 0.278 for PbeDnmt2b and MD15G1120500, respectively. All the 12 members of MTase genes were located on nine chromosomes out of 17 P. betulaefolia chromosomes with highly conserved protein sequence structures. The isoelectric points (pI) of MTases ranged from 4.74 to 7.24, while molecular weight varied from 35.99 to 174.32. The expression profiles of MTase and other salt-responsive genes under salt stress treatment revealed their important roles involved in salt response in P. betulaefolia. Furthermore, three selected salt-responsive genes (PbeNHX2.1, PbeCBL2 and PbeAKT2) were found altered in methylation level of promoters (which contain CpG islands) under salt stress. Especially, the PbeAKT2 promoter regions showed high CHG and CHH methylation types. Our study provided a genome-wide survey of the MTase gene family and highlighted their roles in salt response. These results also provided an effective way for the breeding and improvement of salt-tolerant pear varieties.

Abstract Background The study aimed to assess the value of circulating tumor cells (CTCs) as a prognostic and treatment response marker in patients undergoing androgen deprivation therapy (ADT) plus cryosurgery vs. ADT alone for metastatic prostate cancer (mPCA). Methods This retrospective analysis included 43 patients with mPCA: 23 receiving ADT alone (control) and 20 receiving additional cryosurgery (cryosurgery group). CTCs and progression-free survival (PFS) were compared between the two groups. Cox proportional hazards regression was conducted to identify variables associated with PFS. Results Median PFS was 35 months (IQR, 33‑37) in the cryosurgery group vs. 30 months (IQR, 27‑32) in the control (p < 0.001). CTCs count was significantly lower in the cryosurgery group at both 3 months (z = 2.170, p = 0.030) and 12 months (z = 2.481; p = 0.013). In comparison to the baseline, the number of CTCs at both 3 and 12 months was lower in the cryosurgery group (p = 0.004 and p < 0.001, respectively), but not in the ADT alone group. In multivariate Cox regression, shorter PFS was associated with baseline PSA ≧100 ng/ml (HR 6.584, 95% CI, 5.309‑8.166), biopsy Gleason score ≧ 8 (HR 2.064, 95% CI, 1.608‑2.650), clinic T stage>T2b (HR 5.021, 95% CI, 3.925‑6.421), number of bone metastases>3 (HR 3.421, 95% CI, 2.786‑4.202), positive CTCs at 3 months post-treatment (HR 6.833, 95% CI, 5.176‑9.022), positive CTCs 1 year post-treatment (HR 6.051, 95% CI, 4.347‑8.424). Prostate cryosurgery was associated with longer PFS (HR 0.062, 95% CI, 0.048‑.080). Conclusions CTC was a prognostic and treatment response marker for mPCA. ADT plus cryosurgery could reduce CTCs and prolong PFS vs. ADT alone in mPCA patients with low metastatic volume.

ObjectiveSelf-injurious behavior (SIB) is a clinically challenging problem in the general population and several clinical disorders. However, the precise molecular mechanism of SIB is still not clear. In this paper, the systematic investigation of the genesis and development of SIB is conducted based on behavioral and pathophysiology studies in mink (Neovison vison) models.MethodThe night-vision video was used to observe the mink behavior, and the duration was a month. HE stain was performed to characterize the pathology change in the brain of a mink. IHC assay was performed to conduct the protein level detection of Iba-1, p-CREB, CBP, and p300 in the brain tissues. Elisa assay was used to examine the levels of NfL and NfH in serum and CSF of mink. The qRT-PCR assay was used to detect the expression of Bcl-2, NOR1, FoxO4, c-FOS, CBP, and p300 in brain tissues. Western blot was used to detect the protein levels of p-CREB, CBP, and p300 in brain tissues. We also used Evans Blue as a tracer to detect whether the blood-brain barrier was impaired in the brain of mink.ResultThe behavioral test, histopathological and molecular biology experiments were combined in this paper, and the results showed that CBP was related to SIB. Mechanism analysis showed that the dysregulation of CBP in brain-activated CREB signaling will result in nerve damage of the brain and SIB symptoms in minks. More importantly, the CBP-CREB interaction inhibitor might help relieve SIB and nerve damage in brain tissues.ConclusionOur results illustrate that the induction of CBP and the activation of CREB are novel mechanisms in the genesis of SIB. This finding indicates that the CBP-CREB axis is critical for SIB and demonstrates the efficacy of the CBP-CREB interaction inhibitor in treating these behaviors.

Abstract Weak inertia characteristics of power systems with high penetrations of renewables have become a prominent problem for frequency security. To solve this problem, a convolutional neural network (CNN)‐based deep learning approach is applied to realize rapid frequency security assessment (FSA). First, the time series frequency security feature is autonomously mined from the wide‐area measurement data to serve as the input data. By doing so, the complex construction process of frequency security feature quantity is avoided. A deep learning structure is then used to establish a non‐linear mapping relationship between time series features and frequency security indicators to realize end‐to‐end power system frequency security prediction. Next, the evaluation accuracy of the proposed approach is optimized by tuning the key parameters in the CNN‐based evaluation model. Through data measurement error analysis and a wind penetration sensitivity study, the anti‐interference performance of the proposed evaluation model is demonstrated. Finally, the effectiveness of the CNN‐based FSA is verified by case studies of a modified 16‐machine 68‐node system and the China Southern Power Grid.

BackgroundProstate cancer (PCa) is among the leading causes of cancer death worldwide. Ferroptosis refers to an iron-dependent form of regulated cell death and is involved in prostate tumorigenesis. A few ferroptosis-related gene signatures have been developed to predict the prognosis for PCa patients. However, previous signatures were typically established based on biochemical recurrence-free survival, which has proven not to be a good surrogate for overall survival (OS). This study aimed to construct a novel ferroptosis-related gene prognostic index (FRGPI) to predict disease-free survival (DFS) and response to immunotherapy for PCa patients after radical prostatectomy.MethodsGene expression and clinicopathological data on PCa patients were obtained from the TCGA database. Ferroptosis-related hub genes associated with DFS of PCa patients were identified by an in-depth bioinformatics analysis using a novel and comprehensive algorithm based on functional enrichment, consensus clustering, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. The FRGPI was established on the basis of the genes selected using multivariate cox regression analysis and further validated in two additional PCa cohorts. Next, the clinicopathological, molecular, and immune profiles were characterized and compared between FRGPI-high and FRGPI-low subgroups. Finally, the predictive role of the FRGPI in response to immunotherapy was estimated using a metastatic urothelial cancer cohort treated with an anti-PD-L1 agent.ResultsThe FRGPI was constructed based on four genes (E2F1, CDC20, TYMS, and NUP85), and FRGPI-high patients had worse DFS than FRGPI-low patients. Multivariate cox regression analysis revealed that FRGPI could act as an independent prognostic factor for PCa patients after radical prostatectomy. A prognostic nomogram comprising the FRGPI and other clinicopathological parameters was established to predict the DFS for PCa patients quantitatively. In addition, comprehensive results demonstrated that high FRGPI scores showed a significantly positive correlation with worse clinicopathological features, higher mutation counts, increased frequency of copy number variations (CNVs), higher homologous recombination deficiency (HRD) and immune scores, higher mRNAsi, and more importantly, enhanced sensitivity to immunotherapy.ConclusionsFRGPI is not only a promising and robust prognostic biomarker, but also a potential indicator of immunotherapeutic outcomes for PCa patients after radical prostatectomy.

It is essential to analyze the spatial autocorrelation and heterogeneity of aboveground biomass (AGB). But it is difficult to accurately describe due to the lack of data in clear-cutting plots. Thus, measuring the AGB directly in a clear-cutting plot can provide a reference for accurately describing the spatial variation. Therefore, a 0.3-hectare clear-cutting sample plot of Pinus kesiya var. langbianensis natural forest was selected, and the AGB was calculated by each component. The intra-group variance was quantitatively described in terms of spatial heterogeneity, and the spatial autocorrelation was explored by global and local Moran’s I. The results indicated that (1) there was different spatial heterogeneity for the different trees and organs. The intra-group variance tended to be stable after 20 m for P. kesiya var. langbianensis (PK) and other upper trees (UPs) and after 10 m for the other lower trees (LTs). (2) The spatial autocorrelation of AGB and wood biomass was similar, while the bark biomass and foliage biomass were consistent. PK and other UPs also exhibited strong spatial autocorrelation, with maximum Moran’s I values of 0.1537 and 0.1644, respectively. (3) There was spatial heterogeneity in the different components except for the bark of PK. The lowest spatial heterogeneity was found for LT.

Abstract Background Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10‐mediated acetylation modification in bladder cancer remains elusive. Methods The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10‐deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets. Results NAT10 was essential for the proliferation, migration, invasion, survival and the stem‐cell‐like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4. Conclusions In summary, these findings provide new insights into the dynamic characteristics of mRNA's post‐transcriptional modification via NAT10‐dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer. Highlights NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1. NAT10 may serve as an effective and novel therapeutic target for BLCA.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes tremendous economic losses to the swine industry worldwide. In China, novel PRRSVs have frequently emerged in recent years, but the evolutionary relationship among these viruses has remained unclear. In the present study, a 4-year PRRSV genome-monitoring study was performed on samples from a pig farm. We observed that NADC30-like PRRSVs with higher mutation rates replaced HP-PRRSVs as the epidemic strains. We monitored the variation in the same PRRSV strain evolved in a pig herd over 2 years and observed that the low genomic similarity of NADC30-like PRRSVs results from rapid mutation. We also showed that recombination events between NADC30-like and QYYZ-like PRRSVs resulted in the complex recombination patterns of PRRSVs, which have formed gradually over time. Furthermore, recombination of the same strain can occur at different locations and increase the diversity of recombination events. Overall, these findings interpret the evolutionary patterns of novel and emerging PRRSVs, information that is crucial for PRRSV control.

The fate of infiltrating neutrophils in inflamed joints determines the development of acute gouty arthritis (AGA). GPR105 highly expressed in human neutrophils is sensitive to monosodium urate crystals (MSU); nevertheless, the roles of GPR105 in AGA remain unclear. Here, we show that GPR105 is significantly upregulated in peripheral polymorphonuclear neutrophils of AGA patients. GPR105 knockout (GPR105−/−) prevented NETosis and induced apoptosis of neutrophils under MSU exposure, as well as attenuating inflammatory cascades in AGA. Mechanistically, GPR105 deletion activated cAMP-PKA signals, thereby disrupting Raf-Mek1/2-Erk1/2 pathway-mediated NADPH oxidase activation, contributing to inhibition of NETosis. Whereas, cAMP-PKA activation resulting in GPR105 deficiency modulated PI3K-Akt pathway to regulate apoptosis. More importantly, suppression of cAMP-PKA pathway by SQ22536 and H-89 restored NETosis instead of apoptosis in GPR105−/− neutrophils, promoting MSU-induced gout flares. Interestingly, lobetyolin was screened out as a potent GPR105 antagonist using molecular docking-based virtual screening and in vitro activity test, which efficiently attenuated MSU-induced inflammatory response interacting with GPR105. Taken together, our study implicated that modulating cell death patterns between NETosis and apoptosis through targeting GPR105 could be a potential therapeutic strategy for the treatment of AGA.

Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

P2Y14 nucleotide receptor is a Gi protein-coupled receptor, which is widely involved in physiological and pathologic events. Although several P2Y14R antagonists have been developed thus far, few have successfully been developed into a therapeutic drug. In this study, on the basis of two P2Y14R homology models, Glide docking-based virtual screening (VS) strategy was employed for finding potent P2Y14R antagonists with novel chemical architectures. A total of 19 structurally diverse compounds identified by VS and drug-like properties testing were set to experimental testing. 10 of them showed good inhibitory effects against the P2Y14R (IC50

While single-atom catalysts exhibit intriguing catalytic performances and electronic structures, syntheses are often tailored to a particular system. Here, authors report electrochemical deposition as a universal approach for the fabrication of single-atom catalysts over range of metals and supports.

Adipose-derived stem cells (ASCs) improve the self-renewal and survival of fat grafts in breast reconstruction after oncology surgery. However, ASCs have also been found to enhance breast cancer growth, and its role in tumor proliferation remains largely elusive. Here, we explored a novel mechanism that mediates hTERT reactivation during ASC-induced tumor growth in breast cancer cells. In this study, we found the proliferative ability of breast cancer cells markedly increased with ASC coculture. To explore the molecular mechanism, we treated cells with anibody/inhibitor and found that the activation of MEK-ERK pathway was triggered in breast cancer cells by SCF secreted from ASCs, leading to the nuclear recruitment of CBP. As a coactivator of hTERT, CBP subsequently coordinated with RFPL-3 upregulated hTERT transcription and telomerase activity. The inhibition of CBP and RFPL-3 abrogated the activation of hTERT transcription and the promotion of proliferation in breast cancer cells with cocultured ASCs in vitro and in vivo. Collectively, our study findings indicated that CBP coordination with RFPL-3 promotes ASC-induced breast cancer cell proliferation by anchoring to the hTERT promoter and upregulating telomerase activity, which is activated by the MAPK/ERK pathway.

Abstract Background Sucrose synthase (SUS) is widely considered a key enzyme participating in sucrose metabolism in higher plants and regarded as a biochemical marker for sink strength in crops. However, despite significant progress in characterizing the physiological functions of the SUS gene family, knowledge of the trajectory of evolutionary processes and significance of the family in higher plants remains incomplete. Results In this study, we identified over 100 SUS genes in 19 plant species and reconstructed their phylogenies, presenting a potential framework of SUS gene family evolution in higher plants. Three anciently diverged SUS gene subfamilies (SUS I, II and III) were distinguished based on their phylogenetic relationships and unique intron/exon structures in angiosperms, and they were found to have evolved independently in monocots and dicots. Each subfamily of SUS genes exhibited distinct expression patterns in a wide range of plants, implying that their functional differentiation occurred before the divergence of monocots and dicots. Furthermore, SUS III genes evolved under relaxed purifying selection in dicots and displayed narrowed expression profiles. In addition, for all three subfamilies of SUS genes, the GT-B domain was more conserved than the “regulatory” domain. Conclusions The present study reveals the evolution of the SUS gene family in higher plants and provides new insights into the evolutionary conservation and functional divergence of angiosperm SUS genes.

Forest biomass measurement or estimation is critical for forest monitoring at the stand scale, but errors among different estimations in stand investigation are unclear. Thus, the Pinus densata natural forest in Shangri-La City, southwestern China, was selected as the research object to investigate the biomass of 84 plots and 100 samples of P. densata. The stand biomass was calculated using five methods: stand biomass growth with age (SBA), stem biomass combined with the biomass expansion factors (SB+BEF), stand volume combined with biomass conversion and expansion factors (SV+BCEF), individual tree biomass combined with stand diameter structure (IB+SDS), and individual tree biomass combined with stand density (IB+SD). The estimation errors of the five methods were then analyzed. The results showed that the suitable methods for estimating stand biomass are SB+BEF, M+BCEF, and IB+SDS. When using these three methods (SB+BEF, SV+BCEF, and IB+SDS) to estimate the biomass of different components, wood biomass estimation using SB+BEF is unsuitable, and root biomass estimation employing the IB+SDS method was not preferred. The SV+BCEF method was better for biomass estimation. Except for the branches, the mean relative error (MRE) of the other components presented minor errors in the estimation, while MRE was lower than other components in the range from −0.11%–28.93%. The SB+BEF was more appealing for branches biomass estimation, and its MRE is only 0.31% lower than SV+BCEF. The stand biomass strongly correlated with BEF, BCEF, stand structure, stand age, and other factors. Hence, the stand biomass growth model system established in this study effectively predicted the stand biomass dynamics and provided a theoretical basis and practical support for accurately estimating forest biomass growth.