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In this study, CrNiTiMo high-entropy alloys films were prepared on 304 stainless steel and silicon wafer substrates by direct current magnetron sputtering and the effects of bias voltages (0 to −200 V) on microstructure, chemical composition, hardness and corrosion resistance were investigated. The results showed that the surface of the CrNiTiMo HEAs films exhibited equiaxed nanoparticles and are composed of uniformly distributed Cr, Ni, Ti, and Mo elements. Meanwhile, the films developed a columnar structure and formed a biphasic structure with body-centered cubic solid solution and amorphous phases. The roughness decreased and then increased with increasing bias voltage, and the film deposited at −50 V had the lowest roughness (1.02 ± 01 nm), which also had a maximum hardness of approximately 9.52 ± 0.2 GPa and a maximum elastic modulus of approximately 187 ± 6 GPa. In addition, all films showed better corrosion resistance compared to 304 stainless steel substrates at 3.5 wt% NaCl solution. The corrosion current density (icorr) of the films decreased and then increased with increasing bias voltages and reached the lowest icorr of about 2.49 × 10−8A/cm2, indicating that the films deposited at a bias voltage of −50 V had the best corrosion resistance. These was attributed to the formation of the passivation films mainly composed of TiO2 and Cr2O3 and the improvement of the surface quality of the film as well as the refinement of the columnar structure and particles.

Abstract Background The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC). Methods We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability. Results We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53–0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63–0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32–0.55) and regorafenib (HR = 0.46, 95% CI: 0.31–0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33–0.57), ramucirumab (HR = 0.44, 95% CI: 0.34–0.57), and regorafenib (HR = 0.44, 95% CI: 0.38–0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40–42.98) and S-1 (OR = 8.68, 95% CI: 1.4–154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48–6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54–4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures. Conclusions Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.

Abstract Background Cognitive dysfunction caused by infection frequently emerges as a complication in sepsis survivor patients. However, a comprehensive understanding of its pathogenesis remains elusive. Methods In our in vivo experiments, an animal model of endotoxemia was employed, utilizing the Novel Object Recognition Test and Morris Water Maze Test to assess cognitive function. Various techniques, including immunofluorescent staining, Western blotting, blood‒brain barrier permeability assessment, Limulus Amebocyte Lysate (LAL) assay, and Proximity-ligation assay, were employed to identify brain pathological injury and neuroinflammation. To discern the role of Caspase-11 (Casp11) in hematopoietic or non-hematopoietic cells in endotoxemia-induced cognitive decline, bone marrow chimeras were generated through bone marrow transplantation (BMT) using wild-type (WT) and Casp11-deficient mice. In vitro studies involved treating BV2 cells with E. coli-derived outer membrane vesicles to mimic in vivo conditions. Results Our findings indicate that the deficiency of Casp11-GSDMD signaling pathways reverses infection-induced cognitive dysfunction. Moreover, cognitive dysfunction can be ameliorated by blocking the IL-1 effect. Mechanistically, the absence of Casp11 signaling significantly mitigated blood‒brain barrier leakage, microglial activation, and synaptic damage in the hippocampal CA3 region, ultimately leading to improved cognitive function. Conclusion This study unveils the crucial contribution of Casp11 and GSDMD to cognitive impairments and spatial memory loss in a murine sepsis model. Targeting Casp11 signaling emerges as a promising strategy for preventing or treating cognitive dysfunction in patients with severe infections.

Abstract British scholar Peter Taylor constructed the World City Network by analyzing the office networks of multinational companies, enabling a network perspective on world cities. However, this method has long been hindered by data deficiencies and update delays. In this study, we utilized publicly available, real-time updated data on global routes to construct the World City Network, thereby addressing the issues of data insufficiency and delayed updates in the existing model. For the first time, advanced Graph Convolutional Networks were employed to analyze the World City Network, and we introduced GCNRank. Finally, we compared GCNRank with other centrality measures and found that GCNRank provides a more detailed representation of city rankings and effectively avoids local optima.

Abstract The rapid rise in the availability and scale of scRNA-seq data needs scalable methods for integrative analysis. Though many methods for data integration have been developed, few focus on understanding the heterogeneous effects of biological conditions across different cell populations in integrative analysis. Our proposed scalable approach, scParser, models the heterogeneous effects from biological conditions, which unveils the key mechanisms by which gene expression contributes to phenotypes. Notably, the extended scParser pinpoints biological processes in cell subpopulations that contribute to disease pathogenesis. scParser achieves favorable performance in cell clustering compared to state-of-the-art methods and has a broad and diverse applicability.

Objective In situ leaching is a uranium extraction process in which a solution reacts with uranium-bearing minerals in a saturated aquifer and then uranium in the flowing solution is extracted through exchange. To understand the internal structure and seepage path of the 512 deposits, Methods representative wallrock and ore cores of the deposit were selected for CT scanning, and the pore throat parameters were obtained via image noise reduction filtering, image segmentation to extract pores, and the construction of pore network models. The changes in the absolute permeability, tortuosity and seepage velocity are simulated with Avizo software. Results The results showed that the porosity of the wallrock was 15.42%, the connected porosity was 9.61%, the ore porosity was 15.18%, the connected porosity was 13.82%, and the water permeability was better than that of the wallrock. The high-density materials in the wallrock are metal minerals, accounting for approximately 0.54%, and most of the high-density minerals in the ore are secondary uranium minerals, accounting for 1.06%. It can be fully in contact with the solution during the leaching process. Conclusion There is strong heterogeneity inside the pores, which causes the flow rate to gradually decrease in the flow path. The number of large pores connecting the wallrock and ore is greater than that of small pores, indicating that large pores are the main factors determining the degree of pore development. According to the velocity streamlines, although there is a blockage area in the wallrock and ore, the circulation area is dominant.

Abstract Background Elucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai’s animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province’s population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep. Result In this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8. Conclusion By genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.

Producing renewable e-methanol from e-hydrogen and diverse carbon sources is an essential way for clean methanol preparation. Despite this, the technical and economic feasibility of different e-methanols has yet to be thoroughly compared, leaving the most promising pathway to achieve commercialization yet evident. This paper reports a preliminary analysis of the lifecycle greenhouse gas (GHG) emissions and costs of four renewable e-methanols with different carbon sources: bio-carbon, direct air capture (DAC), fossil fuel carbon capture (FFCC), and fossil. The results indicate that renewable e-methanol costs (4167−10250 CNY/tonne) 2−4 times the market rate of grey methanol. However, with the carbon tax and the projected decline in e-H2 costs, blue e-methanol may initially replace diesel in inland navigation, followed by a shift from heavy fuel oil (HFO) to green e-methanol in ocean shipping. Furthermore, the e-H2 cost and the availability of green carbon are vital factors affecting cost-effectiveness. A reduction in e-H2 cost from 2.1 CNY/Nm3 to 1.1 CNY/Nm3 resulting from a transition from an annual to a daily scheduling period, could lower e-methanol costs by 1200 to 2100 CNY. This paper also provides an in-depth discussion on the challenges and opportunities associated with the various green carbon sources.

Abstract In carbonate reservoirs characterized by the fracture‐cavity system as storage spaces, the drilling process is highly prone to the loss of drilling fluid. This not only affects drilling efficiency but can also lead to severe accidents, such as blowouts. Therefore, it is crucial to understand the distribution pattern of these fractures. However, the formation of carbonate rock fracture‐cavity system systems, being controlled by various factors, is difficult to precisely identify. This limitation hampers the efficient development of such types of oil and gas fields. This paper presents a case study of the M55 sub‐section carbonate gas reservoir in the Sulige gasfield, proposing an improved You Only Look Once v5s (YOLOv5s) deep learning algorithm. It utilizes enhanced training with conventional logging data to identify response characteristics of fractures in the carbonate reservoirs. And its identification results have been confirmed to be accurate by various fracture data obtained through different means, such as the core samples, cast thin section photographs, imaging logging data, and seismic attributes. This method incorporates the Ghost convolution module to replace the Conv module in the backbone network of the YOLOv5s model, and modifies the C3 module into a Ghost Bottleneck module, effectively making the model more lightweight. Additionally, a Convolutional Block Attention Module is integrated into the Neck network, enhancing the model's feature extraction capabilities. Finally, the method employs the Efficient Intersection over Union Loss function instead of the Complete Intersection over Union Loss, reducing the network's regression loss. The validation results using actual data demonstrate that this method achieves an average recognition accuracy of 87.3% for the fracture‐cavity system, which is a 3% improvement over the baseline model (YOLOv5s). This enhancement is beneficial for precisely locating the drilling fluid loss positions in carbonate reservoirs.

Abstract Background Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. Methods In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. Results The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. Conclusions High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.

Abstract Background The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive. Results A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-β, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir’s role in the ceRNA regulatory network mechanism, we identified 113 circRNA–miRNA pairs and 14 miRNA–mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1. Conclusions Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed.

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu2+, although the underlying mechanism of this enhancement remains unclear. In this study, we investigated the mechanistic basis of Cu2+-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate (CuET) complex. CuET exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of action. However, despite its potent activity, CuET suffered from poor solubility and limited permeability, as revealed by our druggability studies. To overcome these intrinsic limitations, we developed a scalable method to prepare CuET nanocrystals (CuET NCs) using a metal coordination-driven self-assembly approach. Pharmacokinetic studies demonstrated that CuET NCs exhibited a 6-fold improvement in bioavailability. Notably, CuET NCs exhibited high biodistribution in the intestine, suggesting their potential application for the treatment of inflammatory bowel diseases (IBDs). To evaluate their therapeutic efficacy in vivo, we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis symptoms. Our findings highlight the discovery of CuET as a potent anti-pyroptotic agent, and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

Abstract Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI. Graphical Abstract

Abstract Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.

Abstract Background Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. Methods The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. Results Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. Conclusions Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Rapid, reliable and non-destructive detection of the quality of maize silage is essential to high-efficiency animal husbandry and food safety. In this study, the colorimetric sensor array (CSA) integrated with chemometric methods is innovatively proposed for qualitative discrimination of maize silage. First, 12 color-sensitive dyes were selected to fabricate colorimetric sensor arrays to be used as artificial olfactory sensors for obtaining odor fingerprints of maize silage. Machine vision algorithms were utilized to extract the color features, and principal component analysis was applied to reduce the dimensionality of the obtained data. Finally, the PCA results were input variables to develop different qualitative discrimination models. These models involve support vector machines (SVM), extreme learning machine (ELM), and random forest (RF). The analysis results show the 100% correct identification rate for independent samples. The general results sufficiently reveal that olfactory visualization technology integrated with chemometrics analysis has promising applications for high-precision discrimination of maize silage.

Abstract Background As the largest group of healthcare professionals, nurses play an indispensable and crucial role in disaster response. The enhancement of nurses’ disaster literacy is imperative for effective disaster emergency management. However, there is currently a lack of knowledge regarding nurses’ disaster literacy. This study represents the first attempt to explore the key components and characteristics of disaster literacy among nurses. Methods A qualitative descriptive design was employed, and the reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (refer to File S1). The purposive sampling method was utilized. Thirty-one rescue nurses from 31 medical institutions across 25 provinces and regions in China were recruited to participate in the study. The respondents were requested to share their experiences and insights regarding disaster rescue operations. Inductive content analysis was employed for data examination. Results The results indicated that rescue nurses universally recognized that there was a pressing need to enhance the level of disaster literacy among nurses. The disaster literacy of nurses encompasses nine dimensions: physical and mental quality, disaster rescue general knowledge, professional and technical competence, professional ethics, teamwork, emotional ability, information literacy, leadership, and knowledge transformation. Conclusions To ensure national sustainability, government departments, healthcare organizations, and hospital administrators can accurately evaluate the disaster literacy of individual clinical nurses, groups, and the workforce as a whole through nine dimensions, which also can provide evidence to support the development of precision strategies to strengthen the disaster literacy of nurses.

Abstract Background Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. Methods For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. Results We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02–2.55, P = 4.07 × 10–2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53–0.89, P = 5.74 × 10–3) and CD19 (OR = 0.59, 95%CI = 1.02–2.55, P = 4.07 × 10–2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01–1.09, P = 1.19 × 10–2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00–1.08, P = 2.83 × 10–2). Conclusions Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.

Superoxide dismutase (SOD) is widely present in plants and plays a crucial role in defending against oxidative stress and preventing tissue damage. This study discovered that the PagSOD2a gene in 84K poplar (Populus alba × P. glandulosa) exhibits a distinct capacity to be induced in response to salt stress. To delve into the pivotal role of PagSOD2a in conferring salt tolerance, the entire PagSOD2a fragment was successfully cloned from 84K poplar and the potential function of PagSOD2a was explored using bioinformatics and subcellular localization. PagSOD2a was found to encode a CuZn-SOD protein localized in chloroplasts. Furthermore, six CuZn-SOD family members were identified in poplar, with closely related members displaying similar gene structures, indicating evolutionary conservation. Morphological and physiological indexes of transgenic 84K poplar overexpressing PagSOD2a (OE) were compared with non-transgenic wild-type (WT) plants under salt stress. The OE lines (OE1 and OE3) showed improved growth performance, characterized by increased plant height and fresh weight, along with reduced malondialdehyde (MDA) content and electrolyte leakage rate under salt stress. Meanwhile, overexpression of PagSOD2a significantly augmented CuZn-SOD and total SOD enzyme activities, leading to a reduction in superoxide anion accumulation and an enhancement of salt tolerance. Additionally, co-expression and multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PagSOD2a constructed using transcriptome data revealed that PagSOD2a gene may be directly regulated by SPL13, NGA1b and FRS5, as well as indirectly regulated by MYB102 and WRKY6, in response to salt stress. These findings provide a theoretical and material foundation for further elucidating the function of PagSOD2a under salt stress and for developing salt-tolerant poplar varieties.

The thermal error of machine tool has always been an important reason affecting the accuracy of machine tool. In modern methods to reduce thermal error, thermal error compensation method and thermal error isolation method are two methods with high operability. Thermal error compensation method emphasizes predicting deformation in advance and then compensating in advance. Thermal error isolation method emphasizes the reduction of numerical value in thermal error propagation path. In this paper, the machine tool swing head is taken as the research object, and the above two methods are innovatively combined; Build an experimental platform and a simulation model to ensure the accuracy of the experiment through mutual verification; The POA-LSTM prediction model is established to predict the expansion of the swing head shell structure caused by thermal load accumulation, and compared with the LSTM prediction model. The results show that the prediction accuracy of the POA-LSTM prediction model in Z direction and X direction is 98.89 % and 98.38 %, respectively, which is higher than that of LSTM's 89.33 % and 89.47 %. The experiment for shell structure optimization is designed to reduce the thermal expansion of the pendulum and improve the machining accuracy. As a result, the thermal expansion inhibition effect on the whole pendulum is 26.14 %, and the thermal expansion inhibition effects on the X-direction, Y-direction and Z-direction are 34.93 %, 33.35 % and 30.24 % respectively.

Obesity has shown a global epidemic trend. The high-lipid state caused by obesity can maintain the heart in a prolonged low-grade inflammatory state and cause ventricular remodeling, leading to a series of pathologies, such as hypertrophy, fibrosis, and apoptosis, which eventually develop into obese cardiomyopathy. Therefore, prolonged low-grade inflammation plays a crucial role in the progression of obese cardiomyopathy, making inflammation regulation an essential strategy for treating this disease. Cyy-272, an indazole derivative, is an anti-inflammatory compound independently synthesized by our laboratory. Our previous studies revealed that Cyy-272 can exert anti-inflammatory effects by inhibiting the phosphorylation and activation of C-Jun N-terminal kinase (JNK), thereby alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI). The current study aimed to evaluate the potential of Cyy-272 to mitigate the occurrence and progression of obese cardiomyopathy through the inhibition of the JNK signaling pathway. Our results indicate that the compound Cyy-272 has encouraging therapeutic effects on obesity-induced cardiac injury. It significantly inhibits inflammation in cardiomyocytes and heart tissues induced by high lipid concentrations, further alleviating the resulting hypertrophy, fibrosis, and apoptosis. Mechanistically, the protective effect of Cyy-272 on obese cardiomyopathy can be attributed to its direct inhibition of JNK protein phosphorylation. In conclusion, we identified a novel compound, Cyy-272, capable of alleviating obese cardiomyopathy and confirmed that its effect is achieved through direct inhibition of JNK.

BackgroundTemporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear.MethodsGenome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects.ResultsThe analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD.ConclusionThe research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.

In the pursuit of economic growth, the role of innovation has become increasingly important, posing dilemmas for subnational governments as they navigate the balance between expenditure competition and long-term investments in innovation. This study aimed to investigate the intricate relationship between fiscal pressures and the pursuit of innovation goals faced by regional authorities. To achieve this, a systematic literature review was conducted, synthesizing more than 150 studies published within the past 15 years. Keyword searches were conducted across multiple databases, and additional scholarly articles were incorporated through citation tracking. Rigorous qualitative analysis techniques, including inductive coding and thematic analysis, were employed to distill conceptual insights from the literature. The analysis performed in this review reveals extensive discussions regarding the influence of competition on innovation outcomes, encompassing a wide range of perspectives. The potential advantages of localization are emphasized by some viewpoints, while others caution against the risks of inadequate investment. The effective coordination of policies across multiple levels of governance to maximize synergies between national and subnational innovation systems emerges as a complex yet crucial challenge. It is observed that collaborative networks, which facilitate knowledge exchange through industrial clustering and public-private linkages, play a significant role in leveraging regional innovation assets. Strategic approaches that successfully balance competition with long-term capacity development have been demonstrated by leading jurisdictions. These findings highlight the significance of tailored policy frameworks that account for the unique contexts of each region, providing opportunities to harness competitive motivations while sustaining investments in innovation. Ongoing coordination is essential to strike a balance between responsiveness and coherence across diverse territories. This study offers practical guidance and academic insights on strategies to align decentralized imperatives, aiming to optimize prosperity through knowledge creation within evolving multi-level innovation systems. By shedding light on these strategies, the research contributes to both practical and academic understandings of how to effectively navigate and capitalize on the dynamics of such systems.

To investigate the substitutability of the simulation results using the single-dome combustor as the computational domain to the triple-dome combustor, three-dimensional numerical simulations were conducted on both models and the differences in various performances between the two combustors were compared and analyzed. The findings reveal that the simulation results obtained using the single-dome combustor as the computational domain can effectively substitute for those of the triple-dome combustor in terms of critical performance metrics, including velocity distribution in the central cross-section, morphology and size of back-flow regions, total pressure loss coefficient, combustion efficiency, outlet temperature distribution and pollutant emissions. Under takeoff conditions, the flame tube outlet of the single-dome combustor exhibits higher OTDF and RTDF values compared to the triple-dome combustor, with similar radial temperature distribution shapes. Additionally, the NOx emissions of the flame tube outlet are slightly lower in the single-dome combustor compared to the triple-dome combustor, while the Soot emissions are slightly higher. However, both the NOx and Soot emissions are within the same order of magnitude for both combustors. Under idle conditions, both the single-dome and triple-dome combustors show almost zero CO emissions at the flame tube outlet section.

As an upright tree with multifunctional economic application, Machilus pauhoi is an excellent choice in modern forestry from Lauraceae. The growth characteristics is of great significance for its molecular breeding and improvement. However, there still lack the information of WUSCHEL-related homeobox (WOX) and Auxin response factor (ARF) gene family, which were reported as specific transcription factors in plant growth as well as auxin signaling. Here, a total of sixteen MpWOX and twenty-one MpARF genes were identified from the genome of M. pauhoi. Though member of WOX conserved in the Lauraceae, MpWOX and MpARF genes were unevenly distributed on 12 chromosomes as a result of region duplication. These genes presented 45 and 142 miRNA editing sites, respectively, reflecting a potential post-transcriptional restrain. Overall, MpWOX4, MpWOX13a, MpWOX13b, MpARF6b, MpARF6c, and MpARF19a were highly co-expressed in the vascular cambium, forming a working mode as WOX-ARF complex. MpWOXs contains typical AuxRR-core and TGA-element cis-acting regulatory elements in this auxin signaling linkage. In addition, under IAA and NPA treatments, MpARF2a and MpWOX1a was highly sensitive to IAA response, showing significant changes after 6 hours of treatment. And MpWOX1a was significantly inhibited by NPA treatment. Through all these solid analysis, our findings provide a genetic foundation to growth mechanism analysis and further molecular designing breeding in Machilus pauhoi.

Additively manufactured a low carbon Fe–Cr–Ni–Al Corrax stainless steel has ultra-high strength, but the mechanism at work when the steel cracks is still unclear. In this study, Corrax stainless steel was tensile tested to fracture and cracks in the vicinity of the fracture surface were analyzed by scanning electron microscope and electron-backscattered diffraction. The results show that the cracks propagated at angles of 45–60° to the tensile axis. Some cracks were transgranular, and high-angle grain boundaries had little effect on crack propagation. Crack propagation was inhibited in regions with lower Taylor factors. Kernel average misorientation value analysis established that the crack propagation process is accompanied by significant plastic deformation. The influence of particles and unfused pores on crack propagation is also discussed.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress. Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells. However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation. In this study, we observed significant upregulation of TrxR1 specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer. Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification. We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC. Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression. Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS). Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis. Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts. Remarkably, LW-216 exhibited superior antitumor activity compared to Auranofin in vivo. Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC.

Enhancing cavern sealing is crucial for improving the efficiency of compressed air energy storage (CAES) in hard rock formations. This study introduced a novel approach using a nano-grade organosilicon polymer (NOSP) as a sealant, coupled with an air seepage evaluation model that incorporates Knudsen diffusion. Moreover, the initial coating application methods were outlined, and the advantages of using NOSP compared to other sealing materials, particularly regarding cost and construction techniques, were also examined and discussed. Experimental results indicated a significant reduction in permeability of rock specimens coated with a 7–10 μm thick NOSP layer. Specifically, under a 0.5 MPa pulse pressure, the permeability decreased to less than 1 nD, and under a 4 MPa pulse pressure, it ranged between 4.5×10−6–5.5×10−6 mD, marking a 75%–80% decrease in granite permeability. The sealing efficacy of NOSP surpasses concrete and is comparable to rubber materials. The optimal viscosity for application lies between 95 and 105 KU, and the coating thickness should ideally range from 7 to 10 μm, applied to substrates with less than 3% porosity. This study provides new insights into air transport and sealing mechanisms at the pore level, proposing NOSP as a cost-effective and simplified solution for CAES applications.

Abstract This work addresses the ongoing challenge of optimizing sand control screens, attributed to a limited understanding of screen blocking. A novel one‐way computational fluid dynamics and discrete element method (CFD–DEM) coupling technique is presented to analyze the structural parameters of unconsolidated prepacked gravel screens (PPGS). CFD–DEM involves systematically investigating the width of the punched slot on the outer protective screen, the size of the gravel, and the efficiency of gravel packing to improve the antiblocking capability of unconsolidated PPGS. Results from numerical simulations reveal that under conditions of effective sand control, the amount of sand entering the gravel layer to the bridge (referred to as the sand pass rate) is positively correlated with the antilocking ability (referred to as oil productivity index) for unconsolidated PPGS. The efficiency of gravel packing has the most substantial effect on the antilocking performance of unconsolidated PPGS. The data suggest that appropriately reducing the efficiency of gravel packing can enhance the antilocking capability of unconsolidated PPGS. To design an unconsolidated PPGS with enhanced antilocking capability, the efficiency of gravel packing be determined first. Then, the gravel size is designed based on this efficiency, and the width relative to the gravel size is decided. This contemporary design principle diverges considerably from previous design principles for gravel‐packed sand control screens. Supporting validation experiments agree with simulation outcomes, suggesting the established one‐way CFD–DEM coupling method in this paper is suitable for analyzing the plugging mechanism of unconsolidated PPGS. Thus, the CFD–DEM coupling method improves the design of such screens for improved antiblocking performance.

Objective: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. Methods: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. Results: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. Conclusion: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

Abstract Multi-parametric MRI (mpMRI) is widely used for prostate cancer (PCa) diagnosis. Deep learning models show good performance in detecting PCa on mpMRI, but domain-specific PCa-related anatomical information is sometimes overlooked and not fully explored even by state-of-the-art deep learning models, causing potential suboptimal performances in PCa detection. Symmetric-related anatomical information is commonly used when distinguishing PCa lesions from other visually similar but benign prostate tissue. In addition, different combinations of mpMRI findings are used for evaluating the aggressiveness of PCa for abnormal findings allocated in different prostate zones. In this study, we investigate these domain-specific anatomical properties in PCa diagnosis and how we can adopt them into the deep learning framework to improve the model’s detection performance. We propose an anatomical-aware PCa detection Network (AtPCa-Net) for PCa detection on mpMRI. Experiments show that the AtPCa-Net can better utilize the anatomical-related information, and the proposed anatomical-aware designs help improve the overall model performance on both PCa detection and patient-level classification.

Abstract As a major component of the digestive system malignancies, tumors originating from the hepatic and biliary ducts seriously endanger public health. The kinesins (KIFs) are molecular motors that enable the microtubule-dependent intracellular trafficking necessary for mitosis and meiosis. Normally, the stability of KIFs is essential to maintain cell proliferation and genetic homeostasis. However, aberrant KIFs activity may destroy this dynamic stability, leading to uncontrolled cell division and tumor initiation. In this work, we have made an integral summarization of the specific roles of KIFs in hepatocellular and biliary duct carcinogenesis, referring to aberrant signal transduction and the potential for prognostic evaluation. Additionally, current clinical applications of KIFs-targeted inhibitors have also been discussed, including their efficacy advantages, relationship with drug sensitivity or resistance, the feasibility of combination chemotherapy or other targeted agents, as well as the corresponding clinical trials. In conclusion, the abnormally activated KIFs participate in the regulation of tumor progression via a diverse range of mechanisms and are closely associated with tumor prognosis. Meanwhile, KIFs-aimed inhibitors also carry out a promising tumor-targeted therapeutic strategy that deserves to be further investigated in hepatobiliary carcinoma (HBC).

Pepper (Capsicum spp.) belongs to the genus Capsicum in the Solanaceae family and is widely cultivated around the world as a vegetable and spice crop. In addition to its application as a cooking ingredient and spice, pepper also has a wide range of uses in the pharmaceutical and cosmetic fields. Carotenoids are a class of natural pigments involved in many important metabolic processes in plants, such as photosynthesis, photoprotection, photomorphogenesis and growth and development. Carotenoid is one of the main nutrients of pepper fruit, which has various biological activities. To cultivate varieties with higher carotenoid content, it is necessary to understand its biosynthesis and molecular mechanism of regulation. The development of molecular biology and biotechnology has promoted the identification of carotenoid biosynthesis genes, providing opportunities for breeding new varieties of pepper with higher carotenoid content. In this review, the physiological role of carotenoid, carotenoid and pepper fruit color, carotenoid biosynthesis pathway, structural genes and regulatory factors of carotenoid biosynthesis pathway, molecular genetics of pepper fruit color and QTL sites related to pepper fruit color are described. GGPS, PSY, PDS, ZDS, LCY, CCS are port enzymes and rate-limiting enzymes in the carotenoid biosynthesis pathway of pepper, and the expression abundance and activity of them directly regulate the carotenoid content in pepper. Transcription factors such as MYB306, DIVARICATA1 and BBX20 are involved in the regulation of carotenoid biosynthesis in pepper. The diversity of carotenoid biosynthesis and regulatory genes determines the amount and content of carotenoid monomer and affects the color of pepper fruit. Based on the current research progress, future research on carotenoid metabolism of pepper is prospected in order to provide new ideas for breeding new varieties of biofortified pepper rich in carotenoids in the future.

Abstract The alkaline phosphatase-to-albumin ratio (APAR) is correlated to worse prognosis in coronary artery disease, cancer, and acute renal failure. However, the relationship between APAR and sepsis prognosis has received little research. The content of this research was to investigate the prognostic relationship between APAR and sepsis. And validate the stability of the correlation in 90-days and 1-year mortality. Retrospective cohort research was conducted basing MIMIC-IV database (version 2.0). The hazard ratio (HR) and 95% confidence interval (Cl) were computed using multivariate Cox regression analysis. In addition, plots of survival curves and subgroup analyzes were conducted. Receiver operating characteristic (ROC) curves were also used. 9741 participants were included in this investigation. The 90-days mortality was 32.8%, and the 1-year mortality was 42.0%. After controlling for confounders, the adjusted HRs (95% CI) for tertile 2 (2.2–3.8) and tertile 3 (> 3.8) were 1.37 (1.25–1.51) and 1.74 (1.58–1.91), respectively. The Kaplan–Meier curve analysis showed a higher probability of 90-days death in the higher APAR group. The area under the curve (AUC) of APAR was 0.674 and could reach 0.709 after combining the Oxford Acute Severity of Illness Score (OASIS). This study demonstrates that APAR is significantly related to bad clinical outcomes in sepsis.

Abstract Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH)2/NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm−2). Importantly, thanks to the “transferred” oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H2-integrated CO2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness.

Abstract Extracellular matrix (ECM) remodeling has been implicated in the tumor malignant progression and immune escape in glioblastoma (GBM). Runt-related transcription factor 1 (RUNX1) is a vital transcriptional factor for promoting tumorigenesis and invasion in mesenchymal subtype of GBM. But the correlation between RUNX1 and ECM genes expression and regulatory mechanism of RUNX1 on ECM genes expression remain poorly understood to date. In this study, by using integral analysis of chromatin immunoprecipitation-sequencing and RNA sequencing, we reported that RUNX1 positively regulated the expression of various ECM-related genes, including Fibronectin 1 (FN1), Collagen type IV alpha 1 chain (COL4A1), and Lumican (LUM), in GBM. Mechanistically, we demonstrated that RUNX1 interacted with Nucleophosmin 1 (NPM1) to maintain the chromatin accessibility and facilitate FOS Like 2, AP-1 Transcription Factor Subunit (FOSL2)-mediated transcriptional activation of ECM-related genes, which was independent of RUNX1’s transcriptional function. ECM remodeling driven by RUNX1 promoted immunosuppressive microenvironment in GBM. In conclusion, this study provides a novel mechanism of RUNX1 binding to NPM1 in driving the ECM remodeling and GBM progression.

MYB transcription factors (TF) are recognized as significant regulators in facilitating plant adaptation to various biotic and abiotic stresses. In order to elucidate the involvement of MYB TFs in the growth, development, and salt tolerance of poplar, PagMYB73A was cloned from 84K poplar (Populus alba × P. glandulosa) and utilized as the target gene for generating PagMYB73A overexpressing transgenic lines (OE-1 , OE-8 , OE-12). Compared to the wild type (WT) plants under normal conditions, the OE lines exhibited enhanced plant height and increased leaf number. While under NaCl treatment, the OE lines displayed elongated adventitious roots but reduced plant height compared to WT. At the transcriptional level, the expression of four genes associated with adventitious root growth and development was examined, revealing higher expression levels in WT compared to OE under normal conditions, but the opposite pattern was observed under salt stress. Physiological index analysis demonstrated a significant decrease in stomatal density of WT under salt stress, whereas the reduction was not significant in OE lines. Furthermore, OE lines exhibited decreased content of malondialdehyde (MDA), a marker of cellular membrane damage, compared to WT under salt stress. In summary, this study preliminarily revealed the regulatory function of PagMYB73A in poplar growth and salt stress resistance, highlighting its active role in the adaptation of poplar to salt stress.

To enhance the resistance of SiCf/SiC to hydrothermal corrosion in the pressurized water reactor (PWR) environment, structurally tunable Ti3SiC2-based corrosion mitigation coatings for SiCf/SiC were prepared using molten salt synthesis. The influence of various process parameters, such as Si/Ti molar ratio in raw materials, annealing time, and annealing temperature, on the phase composition and the structure of the coatings was explored. Through the process control, the fabricated coatings can be either Ti3SiC2 monolithic structure or TiC/Ti3SiC2 and TiC/Ti3SiC2/Ti5Si3Cx multi-layered structures. The coatings demonstrate strong bonding to the substrate due to in-situ reaction, exhibiting tensile and shear strength of at least 26.9 and 30.8 MPa, respectively. Incorporating TiC as a transition layer further enhances the tensile and shear strength to 41.3 and 51.4 MPa, respectively. Monolithic Ti3SiC2 coatings enhance the thermal conductivity of SiCf/SiC by 10%–12%. Notably, Ti3SiC2 coatings effectively protect SiCf/SiC from hydrothermal corrosion, demonstrating an 83% strength retention rate compared to 71% in the control group after corrosion. However, the Ti5Si3Cx layer exhibits unsatisfactory corrosion mitigation. The Ti3SiC2 monolithic coating has higher thermal conductivity, TiC/Ti3SiC2 multi-layered coating has higher bonding strength, and both have desirable resistance to the hydrothermal corrosion.

Abstract In this study, a robust adaptive event‐triggered iterative learning control (ET‐ILC) method is developed for discrete‐time non‐repetitive nonlinear systems with both time‐varying system parameters and time‐iteration‐varying non‐parametric uncertainty. The proposed method utilizes an iteration‐varying dead‐zone function to estimate both parametric and non‐parametric uncertainties simultaneously. Moreover, an event‐triggered control mechanism including a mixed triggering strategy is employed to minimize the unnecessary usage of communication resource. This strategy updates the controller only when the triggering condition is met, thereby reducing the frequency of controller actions. The results are also extended to a class of multiple‐input–multiple‐output (MIMO) non‐repetitive nonlinear systems. The designed robust adaptive ET‐ILC algorithm not only guarantees perfect learning convergence in the iteration domain but also contributes to saving the system resources. The effectiveness of the presented method is demonstrated by virtue of the rigorous theoretical analysis and the illustrative simulation examples.

Abstract Background Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. Methods The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. Results The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. Conclusions These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Remote sensing image acquisition is an essential way to obtain information. However, research on remote sensing images mainly focuses on object detection or image classification. The emergence of remote sensing image captioning (RSIC) has enabled understanding and inference of remote sensing images, thus attracting considerable attention. There are still challenges in RSIC: the features used in RSIC are mostly based on grid features, and this form of features makes it difficult for the model to determine the main description targets. Hence, a more effective cross-modal matching method is needed for better text generation. Thus, we propose a region-guided transformer in response to the aforementioned issues. We extracted region features to enhance the ability of the model to focus on the main targets. To address the issue of information loss caused by region feature extraction, we proposed environment features to supplement background information. To improve the matching between text and image features, we propose a region-guided decoder that enhances the model's perception of different features through a weighted cross-attention mechanism. Meanwhile, we introduce region-guided information to guide the text-generation process. The effectiveness and superiority of our model have been demonstrated through extensive experiments.

With the development of lightweight aerospace equipment, magnesium alloys are receiving increasing attention. Wire-arc directed energy deposition (Wire-arc DED) is a highly promising manufacturing method for magnesium alloy parts, but its development has been severely restricted by the problems of coarse grain size and low mechanical properties. To address these issues, a hammer-forging assisted Wire-arc DED technology for magnesium alloy AZ91 is proposed. The effects of interlayer hammer-forging and synchronous hammer-forging on macrostructure, microstructure and mechanical properties of the Wire-arc DED samples are compared, and the microstructure evolution and performance enhancement mechanism are discussed. The results show that the maximum plastic deformation caused by hammer forging reaches 11.7%. Hammer forging can significantly refine grains, and the average grain size decreases from 27.7 μm to 13.5 μm. Synchronous hammer-forging is better than interlayer hammer-forging in terms of performance enhancement, the UTS reaches 301.8 MPa, an increase of 10.9%, which is comparable to that of traditional forged parts, mainly attributed to the grain refinement and increased dislocation density.

AbstractA kind of highly dispersed ZrO2 modified Cs/SiO2-based catalyst was prepared via ligand–assisted impregnation strategy. The catalyst was then used to the aldol condensation reaction of methyl acetate (MAc) with formaldehyde (FA) to produce methyl acrylate (MA). The effect of highly dispersed ZrO2 promotion on Cs/SiO2 catalyst selectivity and activity was studied as well. Various techniques such as XRD, FT-IR, TEM, XPS, NH3-TPD, CO2-TPD, N2 physical adsorption, and solid-state MAS NMR were used to characterize the structural features, Cs species states, and acid–base properties of these catalysts. The use of Zr(acac)4 as a zirconium source for modifying Cs/SiO2 could be considered optimal for ligand-assisted impregnation. By modifying the highly dispersed ZrO2, more Cs–O–Si species and a suitable balance of acid–base sites were formed in the Zr–Cs/SiO2 catalyst. As a result, the catalyst showed significant improvements in selectivity and yield of MA under optimized reaction conditions. This study is beneficial for the development and optimization of catalysts for aldol condensation and provides a reference for future industrial applications.

AbstractObjective This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways.Method Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes.Results Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia.Conclusion Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Background Despite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy. Tumor microenvironment (TME) strongly correlates with the efficacy of CAR-T therapy. V-domain Ig suppressor of T-cell activation (VISTA), which exerts a multifaceted and controversial role in regulating the TME, acts not only as a ligand on antigen-presenting cells but also functions as a receptor on T cells. However, the characteristics and underlying mechanisms governing endogenous T-cell activation by VISTA, which are pivotal for reshaping the TME, remain incompletely elucidated.Methods The immunocompetent B acute lymphoblastic leukemia (B-ALL), lymphoma, and melanoma murine models were employed to investigate the characteristics of endogenous T cells within the TME following CD19 and hCAIX CAR-T cell therapy, respectively. Furthermore, we examined the role of VISTA controlled by interferon (IFN)-γ signaling in regulating endogenous T-cell activation and functionality in B-ALL mice.Results We demonstrated that the administration of CD19 CAR-T or hCAIX CAR-T cell therapy elicited augmented immune responses of endogenous T cells within the TME of B-ALL, lymphoma, and melanoma mice, thereby substantiating the efficacy of CAR-T cell efficacy. However, in the TME lacking IFN-γ signaling, VISTA levels remained elevated, resulting in attenuated cytotoxicity of endogenous T cells and reduced B-ALL recipient survival. Mice treated with CD19 CAR-T cells exhibited increased proportions of endogenous memory T cells during prolonged remission, which possessed the tumor-responsive capabilities to protect against B-ALL re-challenge. Compared with wild-type (WT) CAR-T treated mice, the administration of IFN-γ−/− CAR-T to both WT and IFN-γ−/− recipients resulted in a reduction in the numbers of endogenous CD4+ and CD8+ effectors, while exhibiting increased populations of naïve-like CD4+ T and memory CD8+ T cells. VISTA expression consistently remained elevated in resting or memory CD4+ T cells, with distinct localization from programmed cell death protein-1 (PD-1) expressing T subsets. Blocking the VISTA signal enhanced dendritic cell-induced proliferation and cytokine production by syngeneic T cells.Conclusion Our findings confirm that endogenous T-cell activation and functionality are regulated by VISTA, which is associated with the therapeutic efficiency of CAR-T and provides a promising therapeutic strategy for relapse cases in CAR-T therapy.

Objective: The objective of this study is to investigate the aggressive infiltration of glioblastoma into adjacent brain tissue, considering its challenging prognosis. Initially classified as an intergenic non-coding RNA, we aim to elucidate the functional implications of LINC01138 in glioblastoma. Method: Glioma grading was performed utilizing H&E staining, which unveiled distinct nuclear morphology in high-grade gliomas. The downregulation of LINC01138 in glioma tissues was corroborated through qRT-PCR and gel electrophoresis, concurrently identifying two previously unrecognized LINC01138 isoforms. Expression profiling of all four LINC01138 isoforms was executed in glioma cell lines (A172, SHG-44, U251, U87-MG). The impact of LINC01138 overexpression in U87-MG and U251 cells was evaluated for cell proliferation, migration, and invasion through cell counting, CCK-8 analysis, and Transwell assays. Furthermore, the suppression of LINC01138 in SHG-44 cells substantiated its involvement in fostering tumor malignancy. Transcriptome sequencing revealed the inhibitory influence of LINC01138 on IGF1 expression. These findings contribute to an enriched comprehension of glioma biology by exploring the engagement of LINC01138 through diverse methodologies, thereby elucidating its potential therapeutic significance. Results: Our investigation elucidates the intricate involvement of LINC01138 in gliomas. High-grade gliomas are characterized by elevated cell density and distinctive nuclear features. LINC01138 demonstrates a substantial downregulation in glioma tissues, with the identification of two novel isoforms. The expression of all four LINC01138 isoforms is notably diminished in both glioma tissues and cell lines. Elevated expression of LINC01138 demonstrates inhibitory effects on tumor cell proliferation, migration, and invasion, while its downregulation exacerbates malignancy. The regulatory function of LINC01138 as a repressor of IGF1 expression was elucidated through transcriptome sequencing. Conclusion: The LINC01138 isoforms display notable tumor-suppressive effects, suggesting a promising potential for impeding glioma progression.