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Total knee arthroplasty (TKA) is a well‐established treatment for end‐stage knee osteoarthritis. However, in patients with concomitant extra‐articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra‐articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra‐articular deformities.

AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P

Abstract As online learning and teaching are becoming an educational trend, online students’ engagement will directly impact the learning and teaching effects and outcomes. A scientific application of gamification in online learning, teaching, and online course design will improve online learners’ learning experience and help build a better virtual learning context for online learners worldwide. This study focuses on how gamification can engage online students from skills, emotional, participation, and performance perspectives. The gamification components investigated in this study are Points (also called Anar Seeds in the context of this study) and Badges, the most widely used components in gamification design in education, and online instructors have primarily used them to motivate students’ learning and acknowledge their achievements by timely rewarding specific learning behavior or performance. A mixed method has been applied to explore further the relationships between gamification components and online students’ engagement and how online students perceive the impacts of gamification on their online learning experience. The findings show a significant correlation between Points and online students’ skills, emotional, participation, and performance engagement, while it exists only between Badges and online students’ participation engagement. The findings also reveal mixed perceptions of online students towards gamification. Study limitations regarding lack of age criterion, limited measurement indicators, and oversimplification of survey responses have also been discussed. It is suggested that future research can be conducted from either the instructors’ or the gamification designers’ perspectives to determine any other factors that might contribute to the implementation of gamification in the online learning context.

Abstract Background The impact of extra-articular deformities (EADs) on lower limb alignment and collateral ligament integrity during total knee arthroplasty (TKA) poses significant challenges, increasing surgical complexity. Our study aims to evaluate the influence of EADs on mechanical axis alignment and the risk of collateral ligament injury during TKA using an AI-assisted surgical planning system, with the goal of minimizing ligament damage through precise and scientific planning. Methods A healthy volunteer underwent CT and MRI scans of the lower limbs. The scan images were imported into Mimics 20.0 software, and the reconstructed models were spatially aligned using 3-maticResearch 11.0 software. Using Unigraphics NX9.0 software, 50 three-dimensional models of femoral lateral joint deformities with varying positions and angles were created. Finally, TKA was simulated using the AI JOINT preoperative planning system. Results The larger the deformity angle and the closer it is to the knee joint, the more pronounced the deviation of the mechanical axis. During MA-aligned osteotomy, nine types of deformities can damage the collateral ligaments. After adjusting the varus/valgus of the prosthesis within a safe range of 3° and leaving a residual 3° varus/valgus in the lower limb alignment, only the 25° varus and 25° valgus deformities located at 90% of the femoral anatomical axis remain uncorrected. Conclusion For patients with osteoarthritis and concurrent EAD undergoing TKA, using reconstructed 3D models of the collateral ligaments for preoperative planning helps visually assess collateral ligament damage, providing a practical solution. Minimizing intra-articular osteotomies within a safe range and allowing some residual alignment deviation can reduce the risk of collateral ligament injury.

Abstract Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Abstract Background Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. Methods We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U‐13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. Results The metabolomics analysis in myotubes revealed insulin‐like growth factor‐1 (IGF‐1)‐induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose‐5‐phosphate/ribulose‐5‐phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: −36.8%; P = 0.009). Like the hypertrophy stimulation with IGF‐1 in myotubes in vitro, the concentration of the dipeptide l‐carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose‐6‐phosphate, fructose‐6‐phosphate or glucose‐1‐phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF‐1‐stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U‐13C6]glucose is increasingly incorporated by ~13% (P = 0.001) into the non‐essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P

Practice is acknowledged as a crucial facilitator for musicians to achieve performance excellence. Despite the rich literature on incorporating musical imagery intentionally to improve one’s practice efficacy, limitations remain in the understanding of voluntary musical imagery (VMI) in the context of musical practice. Therefore, our aims in this review are threefold. First, we enriched the interpretation of VMI in the context of music practice through the lens of embodied cognition. Second, we integrated neuroscientific findings to elucidate how the deliberate use of musical imagery parallels physical practice in effectiveness. Third, we synthesize work on the application of VMI in enhancing musical learning from both theoretical and practical perspectives. By providing an integrated overview of voluntary musical imagery, we highlight gaps in the literature and encourage further research on (1) the impact of embodied experiences on VMI formation, (2) optimal imagery content and ratio combination to establish a personalized intervention protocol for more effective musical pedagogy, and (3) on physiological measures to access VMI effectiveness. Additionally, we highlight the crucial implications of VMI for researchers, performers, and music educators.

Abstract The dense mechanoreceptors in human fingertips enable texture discrimination. Recent advances in flexible electronics have created tactile sensors that effectively replicate slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. However, the influence of dermatoglyphic structures on tactile signal transmission, such as the effect of fingerprint ridge filtering on friction‐induced vibration frequencies, remains unexplored. A novel multi‐layer flexible sensor with an artificially synthesized skin surface capable of replicating arbitrary fingerprints is developed. This sensor simultaneously detects pressure (SA response) and vibration (RA response), enabling texture recognition. Fingerprint ridge patterns from notable historical figures – Rosa Parks, Richard Nixon, Martin Luther King Jr., and Ronald Reagan – are fabricated on the sensor surface. Vibration frequency responses to assorted fabric textures are measured and compared between fingerprint replicas. Results demonstrate that fingerprint topography substantially impacts skin‐surface vibrational transmission. Specifically, Parks' fingerprint structure conveyed higher frequencies more clearly than those of Nixon, King, or Reagan. This work suggests individual fingerprint ridge morphological variation influences tactile perception and can confer adaptive advantages for fine texture discrimination. The flexible bioinspired sensor provides new insights into human vibrotactile processing by modeling fingerprint‐filtered mechanical signals at the finger‐object interface.

Background/Aims Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract The root-associated microbiota plays an important role in the response to environmental stress. However, the underlying mechanisms controlling the interaction between salt-stressed plants and microbiota are poorly understood. Here, by focusing on a salt-tolerant plant wild soybean (Glycine soja), we demonstrate that highly conserved microbes dominated by Pseudomonas are enriched in the root and rhizosphere microbiota of salt-stressed plant. Two corresponding Pseudomonas isolates are confirmed to enhance the salt tolerance of wild soybean. Shotgun metagenomic and metatranscriptomic sequencing reveal that motility-associated genes, mainly chemotaxis and flagellar assembly, are significantly enriched and expressed in salt-treated samples. We further find that roots of salt stressed plants secreted purines, especially xanthine, which induce motility of the Pseudomonas isolates. Moreover, exogenous application for xanthine to non-stressed plants results in Pseudomonas enrichment, reproducing the microbiota shift in salt-stressed root. Finally, Pseudomonas mutant analysis shows that the motility related gene cheW is required for chemotaxis toward xanthine and for enhancing plant salt tolerance. Our study proposes that wild soybean recruits beneficial Pseudomonas species by exudating key metabolites (i.e., purine) against salt stress.

Abstract In their natural habitats, microbes rarely exist in isolation; instead, they thrive in consortia, where various interactions occur. In this study, a defined synthetic co-culture of the cyanobacterium S. elongatus cscB, which supplies sucrose to the heterotrophic P. putida cscRABY, is investigated to identify potential interactions. Initial experiments reveal a remarkable growth-promoting effect of the heterotrophic partner on the cyanobacterium, resulting in an up to 80% increase in the growth rate and enhanced photosynthetic capacity. Vice versa, the presence of the cyanobacterium has a neutral effect on P. putida cscRABY, highlighting the resilience of pseudomonads against stress and their potential as co-culture partners. Next, a suitable reference process reinforcing the growth-promoting effect is established in a parallel photobioreactor system, which sets the basis for the analysis of the co-culture at the transcriptome, proteome, and metabolome levels. In addition to several moderate changes, including alterations in the metabolism and stress response in both microbes, this comprehensive multi-OMICs approach strongly hints towards the exchange of further molecules beyond the unidirectional feeding with sucrose. Taken together, these findings provide valuable insights into the complex dynamics between both co-culture partners, indicating multi-level interactions, which can be employed for further streamlining of the co-cultivation system.

Abstract Background miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. Methods To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. Results miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. Conclusions Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.

Abstract Poa pratensis L. (Poaceae) is a valuable grass across the north hemisphere, inhabiting diverse environments with wide altitudinal span, where ubiquitous various kinds of stresses. Phytohormones would be helpful to improve tolerance to abiotic and biotic stresses, but the responses of transcriptome regulation of P. pratensis to exogenous phytohormones application remain unclear. In this study, we explored the alteration of plant physiological responses by the application of phytohormones. Aiming to achieve this knowledge, we got full-length transcriptome data 42.76 Gb, of which 74.9% of transcripts were completed. Then used 27 samples representing four treatments conducted at two time points (1 h and 6 h after application) to generate RNA-seq data. 371 and 907 common DEGs were identified in response to four phytohormones application, respectively, these DEGs were involved in “plant hormone signal transduction”, “carbon metabolism” and “plant-pathogen interaction”. Finally, P. pratensis basic research can gain valuable information regarding the responses to exogenous application of phytohormones in physiological indicators and transcriptional regulations in order to facilitate the development of new cultivars.

Abstract Multi‐drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH‐sensitive photosensitizer‐drug conjugates (CyR‐SS‐L) are designed and synthesized. CyR‐SS‐L localized in the mitochondria then is cleaved into CyR‐SG and SG‐L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR‐SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG‐L part is used for chemotherapy. CyR‐SS‐L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR‐SS‐L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

BackgroundPrevious studies have explored the role of plasma proteins on osteonecrosis. This Mendelian randomization (MR) study further assessed plasma proteins on osteonecrosis whether a causal relationship exists and provides some evidence of causality.MethodsSummary-level data of 4,907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals by the deCODE Genetics Consortium. The outcome data for osteonecrosis were sourced from the FinnGen study, comprising 1,543 cases and 391,037 controls. MR analysis was conducted to estimate the associations between protein and osteonecrosis risk. Additionally, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets.ResultsWe totally assessed the effect of 1,676 plasma proteins on osteonecrosis risk, of which 71 plasma proteins had a suggestive association with outcome risk (P < 0.05). Notably, Heme-binding protein 1 (HEBP1) was significant positively associated with osteonecrosis risk with convening evidence (OR, 1.40, 95% CI, 1.19 to 1.65, P = 3.96 × 10−5, PFDR = 0.044). This association was further confirmed in other MR analysis methods and did not detect heterogeneity and pleiotropy (all P > 0.05). To comprehensively explore the health effect of HEBP1, the phenome-wide MR analysis found it was associated with 136 phenotypes excluding osteonecrosis (P < 0.05). However, no significant association was observed after the false discovery rate adjustment.ConclusionThis comprehensive MR study identifies 71 plasma proteins associated with osteonecrosis, with HEBP1, ITIH1, SMOC1, and CREG1 showing potential as biomarkers of osteonecrosis. Nonetheless, further studies are needed to validate this candidate plasma protein.

Objectives: Research shows a close association between aberrant immune reactions in osteonecrotic tissues and immune cell infiltration. However, due to limitations in sample size and dataset comprehensiveness, the causal relationship between them is not fully established. This study aims to determine whether there is a causal relationship using a larger and more diverse dataset. Methods: We conducted a comprehensive Mendelian Randomization (MR) analysis to investigate the causal relationship between immune cell characteristics and osteonecrosis. Utilizing publicly available genetic data, we explored the causal relationships between 731 immune cell features and 604 cases from the FinnGen Finnish database, as well as 257 cases from the UK Biobank database with osteonecrosis data. The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. In addition, considering data from the two databases used in this study, a meta-analysis was conducted on the significant immune cells associated with osteonecrosis (FDR

Abstract The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound‐triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Abstract Objective Early identification of cognitive impairment in neurodegenerative diseases like Alzheimer's disease (AD) is crucial. Neurofilament, a potential biomarker for neurological disorders, has gained attention. Our study aims to investigate the relationship between serum neurofilament light (sNfL) levels and cognitive function in elderly individuals in the United States. Methods This cross‐sectional study analyzed data from participants aged 60 and above in the National Health and Nutrition Examination Survey (2013–2014). We collected sNfL levels, cognitive function tests, sociodemographic characteristics, comorbidities, and other variables. Weighted multiple linear regression models examined the relationship between ln(sNfL) and cognitive scores. Restricted cubic spline (RCS) visualization explored nonlinear relationships. The stratified analysis examined subgroups' ln(sNfL) and cognitive function association. Results The study included 446 participants (47.73% male). Participants with ln(sNfL) levels between 2.58 and 2.81 pg/mL (second quintile) performed relatively well in cognitive tests. After adjusting for multiple factors, ln(sNfL) levels were negatively correlated with cognitive function, with adjusted β (95% CI) as follows: immediate recall test (IRT): −0.763 (−1.301 to −0.224), delayed recall test (DRT): −0.308 (−0.576 to −0.04), animal fluency test (AFT): −1.616 (−2.639 to −0.594), and digit symbol substitution test (DSST): −2.790 (−4.369 to −1.21). RCS curves showed nonlinear relationships between ln(sNfL) and DRT, AFT, with inflection points around 2.7 pg/mL. The stratified analysis revealed a negative correlation between ln(sNfL) and cognition in specific subgroups with distinct features, with an interaction between diabetes and ln(sNfL). Interpretation Higher sNfL levels are associated with poorer cognitive function in the elderly population of the United States. sNfL shows promise as a potential biomarker for early identification of cognitive decline.

Abstract In the field of the Internet of Things, image acquisition equipment is the very important equipment, which will generate lots of invalid data during real-time monitoring. Analyzing the data collected directly from the terminal by edge calculation, we can remove invalid frames and improve the accuracy of system detection. SSD algorithm has a relatively light and fast detection speed. However, SSD algorithm do not take full advantage of both shallow and deep information of data. So a multiscale feature fusion attention mechanism structure based on SSD algorithm has been proposed in this paper, which combines multiscale feature fusion and attention mechanism. The adjacent feature layers for each detection layer are fused to improve the feature information expression ability. Then, the attention mechanism is added to increase the attention of the feature map channels. The results of the experiments show that the detection accuracy of the optimized model is improved, and the reliability of edge calculation has been improved.

BackgroundNewer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterize extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.MethodsPrimary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterization was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analyzed by high-resolution mass spectrometry.ResultsWe observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR-323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer-associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.ConclusionOur results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.

Electrospun fibre has shown great potential in tissue engineering and regenerative medicine due to its high specific surface area and extracellular matrix-mimicking structure. However, fabricating an electrospun fibrous scaffold with controllable complex 3D macroscopic configuration remains a challenge. In the present study, a novel method was designed to transform 2D electrospun poly (L-lactic acid) (PLLA) fibrous membrane to tubular PLLA fibrous scaffolds with 3D complex but tailored configuration. The electrospun PLLA fibrous membrane was rolled around a designed mould and then treated with acetone. Treated vascular grafts’ length, diameter, and shape can be tailored by the mould parameters. Moreover, treated vascular grafts achieve favourable mechanical properties (Young’s modulus = 155 MPa, tensile stress = 8.79 MPa and radial force = 2.2 N) and the mechanical properties could be engineered on demand. In addition, treated vascular grafts kept their initial structure and size during long-term in vitro experiments once they were formed. In addition, with the acetone-induced recrystallization of PLLA, pristine solid PLLA fibres were changed to hierarchical porous PLLA fibres with ultra-high specific surface area (28.9 m2/g) and wettability (water contact angle = 101.32°), which has positive effects on cell adhesion and proliferation ability. A7r5 in vitro experiment shows that the proliferation rate of treated vascular grafts increased 153% at day 4 and 170.6% at day 7 compared with pristine vascular grafts.

The desert grassland has low precipitation, high evaporation and a limited soil water supply. Thus the tension between water shortage and sustainable vegetation restoration is increasingly evident. Change in total transpirable soil water (TTSW) reflects the water utilization and extraction capacity of plant communities, which are the basis for maintaining productivity and stability in communities, as well as the key ecological processes alleviating the above tension. Change in TTSW is influenced by precipitation, vegetation and soil. Quantifying the relative contribution of these factors to change in TTSW is key to the sustainable restoration of desert grassland. However, the current understanding of such effects remains limited. This study examined four typical plant communities in the Ningxia desert grassland, monitoring soil water content and evaluating plant community characteristics and diversity over three consecutive years. Using redundancy analysis and hierarchical partitioning methods, the influence of annual precipitation, vegetation (functional and species diversity, community characteristics) and soil physical properties on TTSW variation were investigated. Findings revealed: (1) The factors contributing to TTSW variation were annual precipitation (41 %-68 %,), vegetation (29 %-45 %), and soil physical properties (0 %-6.7 %). Specifically, community-weighted mean traits (CWM) and functional diversity (FD) explained TTSW variation by 24–37 % and 0.25–11 % respectively. In Gramineae communities, the influence of annual precipitation and vegetation on TTSW variation was consistent across soil depths. However, in degraded Sophora alopecuroides + Artemisia scoparia (SA) communities, the influence of vegetation (CWM, FD, community composition and community function) on TTSW variation was more pronounced in shallow soils (45 %) than in deeper soils (33 %), while annual precipitation effects were more substantial in the deep soil layers (66 %) than in the shallow soil layers (42 %). (2) Annual precipitation and CWM were the main biological and abiotic factors affecting TTSW. Interestingly, increased annual precipitation was negatively correlated with TTSW. Similarly, the primary controlling factor, CWM, also showed a significant negative relationship with TTSW. This relationship varied across community types and could be linear or quadratic, highlighting the need to understand the selection effects mediated by CWM in ensuring sustainable vegetation restoration. This research offers insights into the relationship between plant functional diversity and soil water retention function.

IntroductionBacteria inhabit the in- and outside of the human body, such as skin, gut or the oral cavity where they play an innoxious, beneficial or even pathogenic role. It is well known that bacteria can secrete membrane vesicles (MVs) like eukaryotic cells with extracellular vesicles (EVs). Several studies indicate that bacterial membrane vesicles (bMVs) play a crucial role in microbiome-host interactions. However, the composition of such bMVs and their functionality under different culture conditions are still largely unknown.MethodsTo gain a better insight into bMVs, we investigated the composition and functionality of E. coli (DSM 105380) bMVs from the culture media Lysogeny broth (LB) and RPMI 1640 throughout the different phases of growth (lag-, log- and stationary-phase). bMVs from three time points (8 h, 54 h, and 168 h) and two media (LB and RPMI 1640) were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis (NTA), cryogenic electron microscopy (Cryo-EM), conventional transmission electron microscopy (TEM) and mass spectrometry-based proteomics (LC–MS/MS). Furthermore, we examined pro-inflammatory cytokines IL-1β and IL-8 in the human monocyte cell line THP-1 upon bMV treatment.ResultsParticle numbers increased with inoculation periods. The bMV morphologies in Cryo-EM/TEM were similar at each time point and condition. Using proteomics, we identified 140 proteins, such as the common bMV markers OmpA and GroEL, present in bMVs isolated from both media and at all time points. Additionally, we were able to detect growth-condition-specific proteins. Treatment of THP-1 cells with bMVs of all six groups lead to significantly high IL-1β and IL-8 expressions.ConclusionOur study showed that the choice of medium and the duration of culturing significantly influence both E. coli bMV numbers and protein composition. Our TEM/Cryo-EM results demonstrated the presence of intact E. coli bMVs. Common E. coli proteins, including OmpA, GroEL, and ribosome proteins, can consistently be identified across all six tested growth conditions. Furthermore, our functional assays imply that bMVs isolated from the six groups retain their function and result in comparable cytokine induction.

Oxidative stress is closely linked to tumor initiation and development, conferring a survival advantage to cancer cells. Therefore, understanding cancer cells’ antioxidant molecular mechanisms is crucial to cancer therapy. In this study, we discovered that H2O2-induced oxidative stress increased Nrf3 expression in colon cancer cells. Overexpression of Nrf3 decreased H2O2-mediated cytotoxicity and apoptosis. Furthermore, Nrf3 reduced reactive oxygen species levels and malondialdehyde concentrations after H2O2 treatment. Mechanistically, H2O2-mediated cell apoptosis involves multiple signaling proteins, including Akt, bcl-2, JNK, and p38. An increase in Nrf3 expression in colon cancer cells treated with H2O2 partly reversed Akt/Bcl-2 inhibition, whereas it decreased activation of p38 and JNK. In addition, we found that increasing Nrf3 decreased stress-associated chemical-induced cell death, resulting in drug resistance. According to these results, Nrf3 is critical for drug resistance and oxidant adaptation.

A deflector installed on the side of the cold aisle was proposed to address the issue of poor air distribution uniformity in the vertical direction of the underfloor air supply cold aisle of the closed data center. The orthogonal experimental method was employed to investigate the three factors (height, shape, roughness) and four levels (height:2/2.1/ 2.2/2.3 m; shapes:flat panel, curved panel, equal step height, equal airflow step; surface roughness:smooth, rough, ribbed) of the deflector. Two thermal performance evaluation indicators, the return heat index (IRH) and the return temperature index (IRT) of the supply air, were calculated through numerical simulation for each experimental group. The range analysis method was used to determine the influence weight of each factor, and further numerical simulation analysis was conducted to verify the optimal structural combination of the deflector. The results indicate that the geometric shape of the deflector is the main factor affecting the thermal performance of the data center, followed by roughness and height size, which have the smallest impact. The IRH of the optimal structural combination is 0.372, and the IRT is 1.69, indicating that it has a good optimization effect on the vertical uniformity of the airflow organization in the data center. When setting up deflectors in practical engineering, priority can be given to curved surfaces.

Abstract The gastric human pathogen Helicobacter pylori has developed mechanisms to combat stress factors, including reactive oxygen species (ROS). Here, we present a comprehensive study on the redox switch protein HP1021 regulon combining transcriptomic, proteomic and DNA-protein interactions analyses. Our results indicate that HP1021 modulates H. pylori’s response to oxidative stress. HP1021 controls the transcription of 497 genes, including 407 genes related to response to oxidative stress. 79 proteins are differently expressed in the HP1021 deletion mutant. HP1021 controls typical ROS response pathways (katA, rocF) and less canonical ones, particularly DNA uptake and central carbohydrate metabolism. HP1021 is a molecular regulator of competence in H. pylori, as HP1021-dependent repression of the comB DNA uptake genes is relieved under oxidative conditions, increasing natural competence. Furthermore, HP1021 controls glucose consumption by directly regulating the gluP transporter and has an important impact on maintaining the energetic balance in the cell.

Abstract Background the prevalence of physical and multidimensional frailty and their prognostic impact on clinical outcomes in patients with atrial fibrillation (AF) is unclear. Objective to evaluated frailty in a cohort of patients with AF according to different criteria, and studied the prevalence and its prognostic impact on clinical outcomes. Methods in this multicenter prospective cohort, 197 inpatients ≥ 65 years old with AF were recruited from September 2018 to April 2019.We used Fried Frailty phenotype (Fried) to assess physical frailty, and comprehensive geriatric assessment-frailty index (CGA-FI) to assess multidimensional frailty. The primary outcome was a composite of all-cause mortality or rehospitalization. Results the prevalence of frailty was determined as 34.5% by Fried, 42.6% by CGA-FI. Malnutrition and ≥ 7 medications were independently associated with frailty. Kaplan-Meier survival curve showed that the presence of frailty by CGA-FI had significantly lower all-cause mortality or rehospitalization survival rate (log-rank P = 0.04) within 1 year. Multivariate Cox regression adjusted for age and sex showed that the frailty by CGA-FI was significantly associated with the risk of all-cause mortality or rehospitalization within 1 year (HR 1.79, 95% CI 1.10–2.90). However, those associations were absent with the physical frailty. After broader multivariate adjustment, those associations were no longer statistically significant for both types of frailty. Conclusions in older people with AF, Multidimensional frailty is more significantly associated with a composite of all-cause mortality or rehospitalization within 1 year than physical frailty, but these association are attenuated after multivariate adjustment. Clinical trial registration ChiCTR1800017204; date of registration: 07/18/2018.

Abstract In this paper, a method combining random demodulator (RD) and discrete fractional Fourier transform (DFRFT) dictionary is suggested to directly estimate the parameters of linear frequency modulation (LFM) signals from compressed sampling data. First, the RD system parameters are modified in accordance with the characteristics of the LFM signal to produce effective compressed sampling data. Next, a DFRFT dictionary is built using the fractional Fourier transform theory, and sparse representation coefficients are obtained by reconstructing the compressed sampling data using the recovery algorithm and DFRFT dictionary. The signal exhibits characteristics that make it pulse under the best fractional transform order, so the problem of signal parameter estimation can be reduced to searching for the location of the maximum value of sparse representation coefficients. The location is determined by a parameter optimization algorithm, and from there, the initial frequency and Chirp rate of the LFM signal can be estimated. Lastly, simulation and real data tests are performed to confirm that the suggested method can directly be utilized to estimate the parameter of LFM signals using compressed sampling data in addition to having high sparse representation ability for LFM signals.

Mitochondria play a key role in the cerebral ischemia-reperfusion injury. Although the extracellular signal-regulated kinase 1/2 inhibitor PD98059 (PD) is a selective and reversible flavonoid that can protect the mitochondria in a rat model of cardiac arrest/cardiopulmonary resuscitation, its role requires further confirmation. In this study, we investigated whether PD could maintain mitochondrial homeostasis and decrease reactive oxygen species (ROS) production in neuroblastoma (SH-SY5Y) cells exposed to oxygen–glucose deprivation/reperfusion (OGD/R). PD improved the mitochondrial morphology and function, reversed the increase in ROS production and cell apoptosis, and reduced total-superoxide dismutase and Mn-superoxide dismutase activities induced by OGD/R. PD decreases ROS production and improves mitochondrial morphology and function, protecting SH-SY5Y cells against OGD/R-induced injury.

The interfacial interaction between Kevlar nanofiber modified by epichlorohydrin (m-KNFs) and carboxylated nitrile butadiene rubber (XNBR), and m-KNFs and styrene-butadiene rubber (SBR), and the effect of m-KNFs on the property of the composite were studied by experiment and molecular simulation. The research results showed that m-KNFs had a significant enhancing effect on rubber systems; compared with the m-KNFs/SBR and m-KNFs/XNBR/SBR systems, there were the most hydrogen bonds in the m-KNFs/XNBR system; compared with XNBR, tensile strength of m-KNFs/XNBR nanocomposite increased by 182%, mainly due to the strong hydrogen bonding network structure formed between m-KNF and XNBR matrix, which had the strongest interfacial interaction and the best compatibility.

Abstract A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Using a synthetic gut bacterial community, we aimed to study the role of individual members in community assembly, identify putative keystone species and test their influence across different environments. Single-species dropout experiments reveal that bacterial strain relationships strongly vary not only in different regions of the murine gut, but also across several standard culture media. Mechanisms involved in environment-dependent keystone functions in vitro include exclusive access to polysaccharides as well as bacteriocin production. Further, Bacteroides caecimuris and Blautia coccoides are found to play keystone roles in gnotobiotic mice by impacting community composition, the metabolic landscape and inflammatory responses. In summary, the presented study highlights the strong interdependency between bacterial community ecology and the biotic and abiotic environment. These results question the concept of universally valid keystone species in the gastrointestinal ecosystem and underline the context-dependency of both, keystone functions and bacterial interaction networks.

In order to improve the unit scaling and core corrosion caused by circulating water quality in the practical application of evaporative cooling air conditioning, water quality of three different evaporative cooling air conditioning units, including direct evaporative cooling open-cycle cooling water system, indirect evaporative cooling open-cycle cooling water system, and indirect-direct evaporative cooling closed-cycle cooling water system was tested and analyzed. The scaling and corrosion trends of each unit were obtained, and targeted water treatment methods were provided accordingly. It was found that the evaporative cooling air conditioning units with direct evaporative cooling open-cycle cooling water systems have already experienced scaling problems, accompanied by a relatively low occurrence of bacterial and algal growth. It is recommended to use chemical dosing or electrochemical water treatment methods for water quality treatment. The evaporative cooling air conditioning units with indirect evaporative cooling open-cycle cooling water systems have a clear scaling trend, and it is suggested to choose the high-frequency electromagnetic field method, high-voltage electrostatic field method, or a combination of both with chemical dosing method for water quality treatment. The evaporative cooling air conditioning units with indirect-direct evaporative cooling closed-cycle cooling water systems have the most obvious scaling trend and a high possibility of scaling under corrosion. It is recommended to use the high-frequency electromagnetic field method in combination with chemical dosing method or the high-voltage electrostatic field method in combination with chemical dosing method for water quality treatment.

Cadmium (Cd) contamination poses a substantial threat the environment, necessitating effective remediation strategies. Phytoremediation emerges as a cost-efficient and eco-friendly approach for reducing Cd levels in the soil. In this study, the suitability of A. venetum for ameliorating Cd-contaminated soils was evaluated. Mild Cd stress promoted seedling and root growth, with the root being identified as the primary tissue for Cd accumulation. The Cd content of roots ranged from 0.35 to 0.55 mg/g under treatment with 10–50 µM CdCl2·2.5 H2O, and the bioaccumulation factor ranged from 28.78 to 84.43. Transcriptome sequencing revealed 20,292 unigenes, and 7507 nonredundant differentially expressed genes (DEGs) were identified across five comparison groups. DEGs belonging to the “MAPK signaling pathway-plant,” “monoterpenoid biosynthesis,” and “flavonoid biosynthesis pathway” exhibited higher expression levels in roots compared to stems and leaves. In addition, cytokinin-related DEGs, ROS scavenger genes, such as P450, glutathione-S-transferase (GST), and superoxide dismutase (SOD), and the cell wall biosynthesis-related genes, CSLG and D-GRL, were also upregulated in the root tissue, suggesting that Cd promotes root development. Conversely, certain ABC transporter genes, (e.g, NRAMP5), and some vacuolar iron transporters, predominantly expressed in the roots, displayed a strong correlation with Cd content, revealing the mechanism underlying the compartmentalized storage of Cd in the roots. KEGG enrichment analysis of DEGs showed that the pathways associated with the biosynthesis of flavonoids, lignin, and some terpenoids were significantly enriched in the roots under Cd stress, underscoring the pivotal role of these pathways in Cd detoxification. Our study suggests A. venetum as a potential Cd-contaminated phytoremediation plant and provides insights into the molecular-level mechanisms of root development promotion and accumulation mechanism in response to Cd stress.

C17H13ClN2O2, monoclinic, P21/c (no. 14), a = 5.3601(4) Å, b = 10.6233(7) Å, c = 25.2125(16) Å, β = 92.920(5)°, V = 1433.96(17) Å3, Z = 4, Rgt(F) = 0.0495, wRref (F2) = 0.1143, T = 173(10) K.

Abstract Background Psychological health risk is one of the most severe and complex risks in manned deep-space exploration and long-term closed environments. Recently, with the in-depth research of the microbiota–gut–brain axis, gut microbiota has been considered a new approach to maintain and improve psychological health. However, the correlation between gut microbiota and psychological changes inside long-term closed environments is still poorly understood. Herein, we used the “Lunar Palace 365” mission, a 1-year-long isolation study in the Lunar Palace 1 (a closed manned Bioregenerative Life Support System facility with excellent performance), to investigate the correlation between gut microbiota and psychological changes, in order to find some new potential psychobiotics to maintain and improve the psychological health of crew members. Results We report some altered gut microbiota that were associated with psychological changes in the long-term closed environment. Four potential psychobiotics (Bacteroides uniformis, Roseburia inulinivorans, Eubacterium rectale, and Faecalibacterium prausnitzii) were identified. On the basis of metagenomic, metaproteomic, and metabolomic analyses, the four potential psychobiotics improved mood mainly through three pathways related to nervous system functions: first, by fermenting dietary fibers, they may produce short-chain fatty acids, such as butyric and propionic acids; second, they may regulate amino acid metabolism pathways of aspartic acid, glutamic acid, tryptophan, etc. (e.g., converting glutamic acid to gamma–aminobutyric acid; converting tryptophan to serotonin, kynurenic acid, or tryptamine); and third, they may regulate other pathways, such as taurine and cortisol metabolism. Furthermore, the results of animal experiments confirmed the positive regulatory effect and mechanism of these potential psychobiotics on mood. Conclusions These observations reveal that gut microbiota contributed to a robust effect on the maintenance and improvement of mental health in a long-term closed environment. Our findings represent a key step towards a better understanding the role of the gut microbiome in mammalian mental health during space flight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew mental health during future long-term human space expeditions on the moon or Mars. This study also provides an essential reference for future applications of psychobiotics to neuropsychiatric treatments. Video Abstract

Abstract Aims Frailty in older patients with stage B heart failure with preserved ejection fraction (HFpEF) has not been fully explored. We evaluated the prevalence and prognostic significance of frailty in older patients diagnosed with stage B HFpEF. Methods Our prospective cohort study included inpatients aged ≥65 years who were followed up for 3 years. Stage B HFpEF was defined as cardiac structural or functional abnormalities with a left ventricular ejection fraction (LVEF) ≥ 50% without signs or symptoms. Frailty was assessed using the Fried phenotype. The primary outcome was 3‐year all‐cause mortality or readmission. Results Overall, 520 older inpatients diagnosed with stage B HFpEF [mean ± standard deviation age: 75.5 ± 6.25 years, male: 222 (42.7%)] were included in the study. Of these, 145 (27.9%) were frail. Frail patients were older (78.5 ± 6.23 vs. 74.3 ± 6.22 years, P

"Rubber blending was an effective way to develop new rubber materials that could achieve better properties than those of single components. The properties of blend could be precisely controlled by using different types of rubbers. However, most blends tended to phase separation, which led to deterioration in mechanical properties. Graphene oxide (GO) could be used as a novel compatibilizer to improve compatibility between rubbers［1-2］. In this work, GO was added to the blends of carboxylated nitrile butadiene rubber (XNBR) and styrene-butadiene rub-ber (SBR). The XNBR/SBR blend with different blend ratios were designed, and the effect of GO on the mechanical properties of GO/XNBR/SBR blended systems was analyzed in detail by a combination of molecular dynamics (MD) simulations and experiments. The formulation of rubber compounds was XNBR/SBR 100 phr (in mass, the same below), GO 0 or 3.0 phr, antideteriorant 4010 NA 2.0 phr, zinc oxide 2.0 phr, stearic acid 2.4 phr, accelerator CZ 2.2 phr and sulfur 1.5 phr. The mass ratios of XNBR/SBR were 25/75, 50/50 and 75/25, respectively. Through MD simulation, the number of hydrogen bonds of GO/XNBR/SBR blends was shown in Fig 1. The results showed that plenty of hydrogen bonds existed in GO/XNBR/SBR blends, and both the total number of hydrogen bonds and the number of interfacial hydrogen bonds increased with increasing XNBR content, indicating that the interfacial interaction of GO/XNBR/SBR blends was enhanced. After adding 75 phr of XNBR, the number of hydrogen bonds was the highest［3］. ■ Fig 1 Number of hydrogen bonds of GO/XNBR/SBR blends Tensile strength of XNBR/SBR and GO/XNBR/SBR blends were shown in Fig 2. It could be seen that the tensile strength of XNBR/SBR blend increased gradually with the growing of XNBR content, mainly due to the higher strength of XNBR compared to SBR. The higher the proportion of XNBR rubber was, the better the mechanical properties of the blends were. Compared to that of XNBR/SBR blend, the tensile strength of GO/XNBR/SBR blend increased by 86% when adding XNBR of 75 phr. The strong interfacial interactions, such as hydrogen bonds, may lead to a remarkable increase in the mechanical properties of the blend. ■ Fig 2 Tensile strength of XNBR/SBR and GO/XNBR/SBR blends"

Present study reports the application potential of a natural down fiber in the fields of oil-water separation and interfacial dye adsorption. The dripping experiment shows that the blue water droplets can maintain a spherical shape on the surface of the fiber with a contact angle of 155.8°, while the contact angle of oils was 0°, indicating that the fiber has superhydrophobic and ultralipophilic characteristics. Further studies reveal that this fiber has excellent absorption capacities for various oils with 120.11 g/g (vacuum pump oil), 102.11 g/g (heat transfer oil), 99.27 g/g (engine oil), and oil retention capacities after 24 hours with 94.51%, 94.29% and 92.14% respectively. The oil absorption ratios after ten cycles of use are respectively 52.75%, 60.30%, 64.79% of the initial value. More importantly, as an oil-water separation and interfacial adsorption material, down fiber with a separation efficiency as high as 97.7% and dye removal efficiency are 88.70% (Methylene blue) and 88.39% (Rhodamine B). Therefore, this natural fiber can be used as a recyclable oil-water separation and adsorption material to protect water resources.

Abstract Cu2O has been intensively studied as an efficient catalyst for CO2 reduction reaction (CO2RR). By various methods for fine-tuning the morphology and surface modification, high selectivity and activity of different products can be achieved. Here, we report a novel Cu2O nanostructure design by facet-controlled etching, during which the catalyst structure switched from a cuboctahedron architecture to a hollow dice-like structure. The as-etched catalysts exhibit a high Faradic efficiency of formic acid, reaching 75.1% at a low potential of -1.0 V. Further characterizations indicate that the performance enhancement is attributed to the increased oxygen vacancies induced by the etching process. Our Cu2O nanostructure design provides a new approach for high-efficiency catalysts for formic acid production at low potentials.

Abstract Adipogenesis is a complex cascade involved with the preadipocytes differentiation towards mature adipocytes, accelerating the onset of obesity. Histone methyltransferase SET and MYND domain-containing protein 2 (Smyd2), is involved in a variety of cellular biological functions but the epigenetic regulation of Smyd2 in adipogenesis and adipocyte differentiation remains unclear. Both Smyd2 siRNA and LLY-507, an inhibitor of Smyd2, were used to examine the effect of Smyd2 on adipogenesis and adipocyte differentiation in vitro. Smyd2 heterozygous knockout (Smyd2 +/−) mice were also constructed to validate the relationship between Smyd2 and adipogenesis in vivo. We found that Smyd2 is abundant in white adipose tissue and closely correlated with adipocyte differentiation. Knockdown or inhibition of Smyd2 restrained adipocyte differentiation in vitro, which requires the phosphorylation of STAT3. In vivo functional validation, Smyd2 +/− mice exert significant fat loss but not susceptible to HFD-induced obesity. Taken together, our findings revealed that Smyd2 is a novel regulator of adipocyte differentiation by regulating the phosphorylation of STAT3, which provides insights into the effects of epigenetic regulation in adipogenesis. Inhibition of Smyd2 might represent a viable strategy for anti-adipogenesis and maybe further alleviate obesity-related diseases in humans.

Abstract Background Along with the wide spread application and technical development of the flexible and rigid bronchoscopy, the airway foreign body removing method cme to the specific technique for different foreign bodies from the single foreign body forceps. Methods Selected 633 children who were diagnosed as airway foreign bodies by the Department of Respiratory Intervention, Children's Hospital affiliated to Shandong University from January 1st, 2018 to December 31st, 2021, and the airway foreign bodies were diagnosed using bronchoscopy. After comprehensive assessment of the foreign body nature in the airway, the foreign bodies were removed by freezing, laser, electrocoagulation, balloon and other techniques, the success rate of the foreign body removed from the airway was observed, the percentage of the foreign body removed using different techniques, the operation time, and the incidence of post-adverse reactions during operation. Results The success rate using flexible bronchoscope alone to remove foreign bodies in the airway was 99.2%. After flexible bronchoscopy, 19 cases of foreign bodies were removed by vacuum suction alone, 513 cases were removed by foreign body forceps alone, 62 cases were combined with cryotherapy, 2 cases were electrocoagulation, 6 cases were mesh baskets, 3 cases were balloons, 5 cases were laser, and various 18 cases of foreign bodies were invloved by technical combination. 5 cases of flexible bronchoscope combined with rigid bronchoscope combined to remove foreign bodies. The operation time was from 5 min to 1 h, with an average of 20 min. There were 17 cases of hypoxemia (2.7%) during operation, 36 cases (5.7%) of bleeding caused by airway mucosa injury after treatment, and 70 cases (11.2%) of laryngeal edema. The total incidence of adverse reactions was 19.6%, there were no deaths due to foreign bodies and treatment. Conclusions According to different properties of airway foreign bodies, it is safe and effective to select appropriate techniques to remove foreign bodies using the flexible bronchoscope, which can increase the removal rate of airway foreign bodies and reduce the occurrence of serious complications.

Introduction Heart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial effects of sodium–glucose cotransporter 2 inhibitors among patients with HFpEF, the mechanisms remain unclear. Basic research suggests that empagliflozin inhibits myocardial fibrosis. Myocardial extracellular volume (ECV) can be calculated using cardiac MRI (CMRI), which can reflect the degree of diffuse myocardial fibrosis. Studies show that empagliflozin can reduce ECV and left ventricular mass (LVM) assessed by CMRI in patients with diabetes with coronary heart disease and patients without diabetes with HF with reduced ejection fraction. However, whether empagliflozin reduces ECV and LVM among patients with HFpEF is unclear. This study intends to use CMRI to evaluate ECV and LVM, combined with echocardiography and an assessment of related biomarkers, to determine whether empagliflozin can improve myocardial fibrosis and left ventricular remodelling in patients with HFpEF.Methods and analysis This report describes the study design of a prospective, multicentre, randomised, double-blind, placebo-controlled and parallel-group clinical study. A total of 180 participants with HFpEF aged 40–80 years old who meet the inclusion and exclusion criteria will be randomly divided into an empagliflozin treatment group or a placebo control group. The empagliflozin treatment group will receive 10 mg of empagliflozin per day for 6 months in addition to guideline-directed medical treatment, while the control group will receive placebo oral administration with guideline-directed medical therapy for 6 months. The primary outcomes are ECV and LVM changes measured by CMRI after 6 months of treatment.Ethics and dissemination The study design is approved by the ethical committee of Beijing Hospital (2022BJYYEC-070-02). The trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn). The trial results will be published in peer-reviewed journals and conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200060862).

ABSTRACT Vesiculation is a process employed by Gram-negative bacteria to release extracellular vesicles (EVs) into the environment. EVs from pathogenic bacteria play functions in host immune modulation, elimination of host defenses, and acquisition of nutrients from the host. Here, we observed EV production of the bacterial speck disease causal agent, Pseudomonas syringae pv. tomato (Pto) DC3000, as outer membrane vesicle release. Mass spectrometry identified 369 proteins enriched in Pto DC3000 EVs. The EV samples contained known immunomodulatory proteins and could induce plant immune responses mediated by bacterial flagellin. Having identified two biomarkers for EV detection, we provide evidence for Pto DC3000 releasing EVs during plant infection. Bioinformatic analysis of the EV-enriched proteins suggests a role for EVs in antibiotic defense and iron acquisition. Thus, our data provide insights into the strategies this pathogen may use to develop in a plant environment. IMPORTANCE The release of extracellular vesicles (EVs) into the environment is ubiquitous among bacteria. Vesiculation has been recognized as an important mechanism of bacterial pathogenesis and human disease but is poorly understood in phytopathogenic bacteria. Our research addresses the role of bacterial EVs in plant infection. In this work, we show that the causal agent of bacterial speck disease, Pseudomonas syringae pv. tomato, produces EVs during plant infection. Our data suggest that EVs may help the bacteria to adapt to environments, e.g., when iron could be limiting such as the plant apoplast, laying the foundation for studying the factors that phytopathogenic bacteria use to thrive in the plant environment.

The “compressed sensing” theory is the foundation for the compressed sampling system’s design. In addition to the sparse representation and observation matrix, more studies in compressed sensing theory focus on signal reconstruction and recovery. Only a small number of research studies estimate the original signal parameter information using the compressed sample data. In this research, we propose a linear frequency modulation (LFM) signal parameter estimation approach based on the Gabor transform for the enhanced Modulated Wideband Converter (MWC) system, which can directly estimate the parameters of an LFM signal utilizing compressed sampling data. Based on the MWC system prototype, a better MWC system based on Gabor transform is created by fusing the Gabor transform with compressed sensing theory, and the system’s structure, function, parameter settings, and viability are all examined. Finally, we show through a simulation experiment that the proposed method is capable of accurately estimating the parameter information of a huge broadband LFM signal by merely restoring Gabor coefficients.

To ensure the normal passage of an ascending road during the construction of a pipe-jacking tunnel, trains generally run at low speeds during the construction phase and adopt normal speeds later. Using Jingjiu Road, Xi’an, China, as an engineering case, this study evaluated and predicted the dynamic response of a tunnel structure and soil mass when trains run at low to normal speeds. When the train speed was controlled in the range of 30–60 km/h, the soil deformation change rate around the shallow-buried pipe-jacking tunnel was 0.41%. The maximum tensile stress growth rate of the pipe-jacking tunnel structure was 0.037%, the maximum compressive stress growth rate was 0.128%, and the maximum increase in the stress of the pipe-jacking structure was 1.82%. Thus, the soil and structure of the pipe-jacking tunnel were in a safe-stress state. The results show that the influence of train speed on soil and structural stress is small and can be ignored.

With mine drainage and activities, the hydrogeochemical environments has greatly changed in Kongjiagou coalmine, Sichuan Province, southwest China. This study aimed to summarize an ideal model of coalmine hydrogeochemical zonation and evolution. In total, 24 groundwater samples from different depth were collected to analyze their components, with the combination of methods such as ion sources, normalization index, ions ratios, cation exchange and inverse modeling. The hydrogeochemical formation main factor was water–rock reactions and more weathering by sulfuric acid. Dissolution and pyrite oxidation were the main sources of , whereas carbonate weathering was the dominant source of . The vertical extent could be distinguished to three zones by mean and standard deviation of burial depth. The normalization index, ions ratios, cation exchange and water types exhibited clear vertical zonation. In shallow groundwater, dissolution led to a Ca- type water and overall stable concentrations of ions. Redox reactions in the middle region have caused significant increases in the total dissolved solids (TDS) and and a considerable reduction in pH; hence, Ca + Mg-SO4 + HCO3 became the dominant type. Re-dissolution and cation exchange played important roles at depth and caused the pH and TDS to increase slowly. The , Ca2+, and Mg2+ concentrations increased rapidly, whereas the concentration remained basically unchanged, and the water type was either Ca + Mg-HCO3 + SO4 or Na-HCO3 + SO4. This study will be of great significance to coalmine safety production and water environments protection. HIGHLIGHTS Distinguished vertical zonation based on mean and standard deviation of burial depth.; Introduced ions normalization index for hydrogeochemical analysis.; PHREEQC was used to calculate the amount transferred from shallow to deep.; The main reactions from shallow to deep were dissolution, redox, re-dissolution and cation exchange.; Summarized an ideal vertical zoning model and mechanism of coal mine hydrogeochemically.;

The design and synthesis of porous framework materials with strong affinity and selectivity for uranyl ion are extremely appealing for the efficient extraction of uranium from seawater. Herein, rectangular porous framework cage(denoted as Co16) is prepared by using p-tert-butylsulfonylcalix［4］arene, CoCl2·6H2O and 1,3-bis(2H-tetrazol-5-yl)benzene (H2L) ligands under solvothermal conditions. Further, the Co16 is used for uranium extraction. As the result, the Co16 exhibits short adsorption equilibrium time(≈90 min) and is in accordance with the pseudo-second-order kinetic model. Robust framework and active U(Ⅵ) adsorption in the wide pH range are displayed. Besides, Co16 adsorbents exhibit high U(Ⅵ) uptake capacity(547.31 mg/g) and well fit the Langmuir model. Adsorption thermodynamics research has clearly demonstrated that the adsorption process is endothermic and spontaneous. Furthermore, Co16 achieves a high uranium adsorption capacity(4.88 mg/g) after immersing in real seawater for 20 days. Overall, these advantages of Co16 adsorbents highlight the potential candidate for the selective capture of U(Ⅵ) from seawater.

In this paper, we propose a compressive sampling and reconstruction system based on the shift-invariant space associated with the fractional Gabor transform. With this system, we aim to achieve the sub-Nyquist sampling and accurate reconstruction for chirp-like signals containing time-varying characteristics. Under the proposed scheme, we introduce the fractional Gabor transform to make a stable expansion for signals in the joint time-fractional-frequency domain. Then the compressive sampling and reconstruction system is constructed under the compressive sensing and shift-invariant space theory. We establish the reconstruction model and propose a block multiple response extension of sparse Bayesian learning algorithm to improve the reconstruction effect. The reconstruction error for the proposed system is analyzed. We show that, with considerations of noises and mismatches, the total error is bounded. The effectiveness of the proposed system is verified by numerical experiments. It is shown that our proposed system outperforms the other systems state-of-the-art.

Objective To investigate the role of long non-coding RNA double homeobox A pseudogene 9 (DUXAP9) in head and neck squamous cell carcinoma (HNSCC) and to evaluate the expression level, molecular function and mechanism of DUXAP9 in HNSCC cells. Methods Differential expression of lncRNAs between normal and tumor tissues in HNSCC tissues were screened using lncRNA microarray, the expression level of DUXAP9 in HNSCC tissues and its relationship with prognosis were analyzed in the TCGA database. The expression levels of DUXAP9 in HNSCC tissues and cell lines were detected using qRT-PCR. The function in HNSCC cells after DUXAP9 silencing was evaluated using the CCK-8 assay, wound healing assay, Transwell migration assay and subcutaneous xenograft assay in nude mice. Changes in the transcription and translation of epithelial-mesenchymal transition (EMT)-related proteins in head and neck squamous cell carcinoma cells after DUXAP9 silencing were detected using qRT-PCR and Western blot. Results lncRNA microarray results showed that, compared to adjacent normal tissues, DUXAP9 was abnormally upregulated in HNSCC tissues. Analysis from TCGA database showed that, compared to HNSCC patients with low DUXAP9 expression, HNSCC patients with high DUXAP9 expression had poorer survival. The relative expression of DUXAP9 in HNSCC tissues and 4 HNSCC cell lines increased compared to paired adjacent normal tissues as detected using qRT-PCR. Silencing DUXAP9 significantly inhibited the proliferation, migration and expression of EMT-related genes in HNSCC cells. The silencing of DUXAP9 significantly inhibited subcutaneous tumorigenesis of the HNSCC cell line CAL27 in nude mice. Conclusion Silencing DUXAP9 significantly inhibited the proliferation of HNSCC cells and subcutaneous xenografts in nude mice. DUXAP9 may mediate the migration of head and neck squamous cell carcinoma cells via the EMT pathway.