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Abstract GH 3230 superalloy is a solution strengthening nickel-based superalloy and it is commonly used for fabricating hot components with the service temperature of above 900 ℃. In order to further improve high-temperature performance, nickel-based alloy matrix composites (NMCs) were proposed. Meanwhile, it is known that laser additive manufacturing is an optional method for fabricating nickel-based composites. However, the research on ceramic-reinforced GH 3230 fabricated by laser metal deposition (LMD) are highly lacking. The aim of this study is to develop TiC ceramic particle reinforced GH 3230 composites using laser metal deposition (LMD) method and study the effect of TiC content on their microstructure and tensile properties. The results showed that TiC particles not only changed the intensity and position of the X-ray diffraction peaks of the alloy matrix but also had a significant effect on the refinement of the cellular dendrites. Meanwhile, it was found that an interfacial layer with sub-micrometer thickness was formed between the TiC ceramic particle and the superalloy matrix, which was identified to be (W, Ti)C1-x phase by the TEM. In terms of the as-built composites, the ultimate tensile strength (UTS) and yield strength (YS) gradually increased, but elongation (EL) decreased with the increase of TiC content. For the as-LMDed 10 vol.% TiC/GH3230 composites, UTS and EL reached 1077.0 MPa and 12.4%, respectively. The enhancement of the tensile strength for composites was attributed to the combined effect of grain refinement strengthening, Orowan strengthening, dislocation strengthening and loading-bearing strengthening.

Abstract Wireless local area network (WLAN) has gained widespread application as a convenient network access method, demanding higher network efficiency, stability, and responsiveness. High-performance filters are crucial components to meet these needs. Film bulk acoustic resonators (FBARs) are ideal for constructing these filters due to their high-quality factor (Q) and low loss. In conventional air-gap type FBAR, aluminum nitride (AlN) is deposited on the sacrificial layer with poor crystallinity. Additionally, FBARs with single-crystal AlN have high internal stress and complicated fabrication process. These limit the development of FBARs to higher frequencies above 5 GHz. This paper presents the design and fabrication of FBARs and filters for WLAN applications, combining the high electromechanical coupling coefficient ( $${K}_{{\rm{t}}}^{2}$$ K t 2 ) of Al0.8Sc0.2N film with the advantages of the thin film transfer process. An AlN seed layer and 280 nm-thick Al0.8Sc0.2N are deposited on a Si substrate via physical vapor deposition (PVD), achieving a full width at half maximum (FWHM) of 2.1°. The ultra-thin film is then transferred to another Si substrate by wafer bonding, flipping, and Si removal. Integrating conventional manufacturing processes, an FBAR with a resonant frequency reaching 5.5 GHz is fabricated, demonstrating a large effective electromechanical coupling coefficient ( $${{k}}_{{\rm{eff}}}^{2}$$ k eff 2 ) of 13.8% and an excellent figure of merit (FOM) of 85. A lattice-type filter based on these FBARs is then developed for the Wi-Fi UNII-2 band, featuring a center frequency of 5.5 GHz and a −3 dB bandwidth of 306 MHz, supporting high data rates and large throughputs in WLAN applications.

Abstract Abundant residual heat from industrial emissions may provide energy resource for CO2 conversion, which relies on H2 gas and cannot be accomplished at low temperatures. Here, we report an approach to store electrons and hydrogen atoms in catalysts using sunlight and water, which can be released for CO2 reduction in dark at relatively low temperatures (150−300 °C), enabling on-demand CO2 conversion. As a proof of concept, a model catalyst is developed by loading single Cu sites on hexagonal tungsten trioxide (Cu/WO3). Under light illumination, hydrogen atoms are generated through photocatalytic water splitting and stored together with electrons in Cu/WO3, forming a metastable intermediate (Cu/HxWO3). Subsequent activation of Cu/HxWO3 through low-temperature heating releases the stored electrons and hydrogen atoms, reducing CO2 into valuable products. Furthermore, we demonstrate the practical feasibility of utilizing natural sunlight to drive the process, opening an avenue for harnessing intermittent solar energy for CO2 utilization.

Abstract Background Acetate is an important chemical feedstock widely applied in the food, chemical and textile industries. It is now mainly produced from petrochemical materials through chemical processes. Conversion of lignocellulose biomass to acetate by biotechnological pathways is both environmentally beneficial and cost-effective. However, acetate production from carbohydrate in lignocellulose hydrolysate via glycolytic pathways involving pyruvate decarboxylation often suffers from the carbon loss and results in low acetate yield. Results Escherichia coli BL21 (DE3) was confirmed to have high tolerance to acetate in this work. Thus, it was selected from seven laboratory E. coli strains for acetate production from lignocellulose hydrolysate. The byproduct-producing genes frdA, ldhA, and adhE in E. coli BL21 (DE3) were firstly knocked out to decrease the generation of succinate, lactate, and ethanol. Then, the genes pfkA and edd were also deleted and bifunctional phosphoketolase and fructose-1,6-bisphosphatase were overexpressed to construct an EP-bifido pathway in E. coli BL21 (DE3) to increase the generation of acetate from glucose. The obtained strain E. coli 5K/pFF can produce 22.89 g/L acetate from 37.5 g/L glucose with a yield of 0.61 g/g glucose. Finally, the ptsG gene in E. coli 5K/pFF was also deleted to make the engineered strain E. coli 6K/pFF to simultaneously utilize glucose and xylose in lignocellulosic hydrolysates. E. coli 6K/pFF can produce 20.09 g/L acetate from corn stover hydrolysate with a yield of 0.52 g/g sugar. Conclusion The results presented here provide a promising alternative for acetate production with low cost substrate. Besides acetate production, other biotechnological processes might also be developed for other acetyl-CoA derivatives production with lignocellulose hydrolysate through further metabolic engineering of E. coli 6K/pFF.

Hydroclimate over the Tibetan Plateau (TP) notably influences the eco-environment of the Northern Hemisphere. Given its high elevation and complex topography, the climate in the TP shows a high sensitivity to anthropogenic warming and volcanic-induced cooling. The mechanism by which a future volcanic or similar radiative perturbation affects precipitation in the TP under an anthropogenic warming climate must be addressed not only to enable regional adaptation but deepen our understanding of how a climate system evolves under such a dual force. Here, based on the Community Earth System Model version 1.2 and ensemble simulations under pre-industrial and RCP8.5 scenarios, we showed that a Tambora-sized volcanic perturbation led to severe rainfall reduction over the south TP in the following summer (June–August). Evaporation response accounted for a minor and relatively constant share of precipitation reduction following the Clausius–Clapeyron scaling, whereas dynamic processes triggered an El Niño-like response in the eastern equatorial Pacific, which suppressed the Walker and Hadley circulation and contributed to drying anomalies. Global warming renders the post-Tambora hydroclimate responses with 30% higher severity as a result of the increased climatological moisture content and intensified El Niño response, which enhanced hydroclimate sensitivity and attenuated monsoon circulation. The results illustrate the amplification effect of global warming on the plateau's hydroclimate responses to external forcings, which may add another layer of uncertainty on climate adaptation in this already complex region.

Abstract Alzheimer’s Disease (AD) is a neurodegenerative disorder, and various molecules associated with PANoptosis are involved in neuroinflammation and neurodegenerative diseases. This work aims to identify key genes, and characterize PANoptosis-related molecular subtypes in AD. Moreover, we establish a scoring system for distinguishing PANoptosis molecular subtypes and constructing diagnostic models for AD differentiation. A total of 5 hippocampal datasets were obtained from the Gene Expression Omnibus (GEO) database. In total, 1324 protein-encoding genes associated with PANoptosis (1313 apoptosis genes, 11 necroptosis genes, and 31 pyroptosis genes) were extracted from the GeneCards database. The Limma package was used to identify differentially expressed genes. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify gene modules significantly associated with AD. The ConsensusClusterPlus algorithm was used to identify AD subtypes. Gene Set Variation Analysis (GSVA) was used to assess functional and pathway differences among the subtypes. The Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithms were used to select the three PANoptosis-related Key AD genes (PKADg). A scoring model was constructed based on the Boruta algorithm. PANoptosis diagnostic models were developed using the RF, SVM-RFE, and Logistic Regression (LR) algorithms. The ROC curves were used to assess the model performance. A total of 48 important genes were identified by intersecting 725 differentially expressed genes and 2127 highly correlated module genes from WGCNA with 1324 protein-encoding genes related to PANoptosis. Machine learning algorithms identified 3 key AD genes related to PANoptosis, including ANGPT1, STEAP3, and TNFRSF11B. These genes had strong discriminatory capacities among samples, with Receiver Operating Characteristic Curve (ROC) analysis indicating Area Under the Curve (AUC) values of 0.839, 0.8, and 0.868, respectively. Using the 48 important genes, the ConsensusClusterPlus algorithm identified 2 PANoptosis subtypes among AD patients, i.e., apoptosis subtype and mild subtype. Apoptosis subtype patients displayed evident cellular apoptosis and severe functionality damage in the hippocampal tissue. Meanwhile, mild subtype patients showed milder functionality damage. These two subtypes had significant differences in apoptosis and necroptosis; however, there was no apparent variation in pyroptosis functionality. The scoring model achieved an AUC of 100% for sample differentiation. The RF PANoptosis diagnostic model demonstrated an AUC of 100% in the training set and 85.85% in the validation set for distinguishing AD. This study identified two PANoptosis-related hippocampal molecular subtypes of AD, identified key genes, and established machine learning models for subtype differentiation and discrimination of AD. We found that in the context of AD, PANoptosis may influence disease progression through the modulation of apoptosis and necrotic apoptosis.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by massive neuronal loss in the brain. Both cortical glutamatergic neurons and basal forebrain cholinergic neurons (BFCNs) in the AD brain are selectively vulnerable. The degeneration and dysfunction of these two subtypes of neurons are closely associated with the cognitive decline of AD patients. The determination of cellular and molecular mechanisms involved in AD pathogenesis, especially in the early stage, will largely facilitate the understanding of this disease and the development of proper intervention strategies. However, due to the inaccessibility of living neurons in the brains of patients, it remains unclear how cortical glutamatergic neurons and BFCNs respond to pathological stress in the early stage of AD. In this study, we established in vitro differentiation systems that can efficiently differentiate patient-derived iPSCs into BFCNs. We found that AD-BFCNs secreted less Aβ peptide than cortical glutamatergic neurons did, even though the Aβ42/Aβ40 ratio was comparable to that of cortical glutamatergic neurons. To further mimic the neurotoxic niche in AD brain, we treated iPSC-derived neurons with Aβ42 oligomer (AβO). BFCNs are less sensitive to AβO induced tau phosphorylation and expression than cortical glutamatergic neurons. However, AβO could trigger apoptosis in both AD-cortical glutamatergic neurons and AD-BFCNs. In addition, AD iPSC-derived BFCNs and cortical glutamatergic neurons exhibited distinct electrophysiological firing patterns and elicited different responses to AβO treatment. These observations revealed that subtype-specific neurons display distinct neuropathological changes during the progression of AD, which might help to understand AD pathogenesis at the cellular level.

Abstract Background Whey, which has high biochemical oxygen demand and chemical oxygen demand, is mass-produced as a major by-product of the dairying industry. Microbial fermentation using whey as the carbon source may convert this potential pollutant into value-added products. This study investigated the potential of using whey powder to produce α-ketoisovalerate, an important platform chemical. Results Klebsiella oxytoca VKO-9, an efficient L-valine producing strain belonging to Risk Group 1 organism, was selected for the production of α-ketoisovalerate. The leucine dehydrogenase and branched-chain α-keto acid dehydrogenase, which catalyzed the reductive amination and oxidative decarboxylation of α-ketoisovalerate, respectively, were inactivated to enhance the accumulation of α-ketoisovalerate. The production of α-ketoisovalerate was also improved through overexpressing α-acetolactate synthase responsible for pyruvate polymerization and mutant acetohydroxyacid isomeroreductase related to α-acetolactate reduction. The obtained strain K. oxytoca KIV-7 produced 37.3 g/L of α-ketoisovalerate from lactose, the major utilizable carbohydrate in whey. In addition, K. oxytoca KIV-7 also produced α-ketoisovalerate from whey powder with a concentration of 40.7 g/L and a yield of 0.418 g/g. Conclusion The process introduced in this study enabled efficient α-ketoisovalerate production from low-cost substrate whey powder. Since the key genes for α-ketoisovalerate generation were integrated in genome of K. oxytoca KIV-7 and constitutively expressed, this strain is promising in stable α-ketoisovalerate fermentation and can be used as a chassis strain for α-ketoisovalerate derivatives production.

China is accelerating the development of sodium-cooled fast reactor technology. For nuclear reactors, whether it is a pressurized water reactor or a fast reactor, core flow distribution is a key concern, which directly determines whether the reactor can operate safely and reliably. Sodium-cooled fast reactor core adopts a three-stage flow distribution method consisting of diagrid, distribution headers and assemblies. Distribution headers are installed on diagrid, and various types of assemblies are installed on distribution headers. Pressure drop of the core is composed of distribution header pressure drop and assembly pressure drop. The distribution header pressure drop itself affects the flow distribution of the assemblies, thereby affecting the safety of the core. Therefore, it is of great significance to study the impact of distribution header pressure drop on the flow distribution of assemblies for the sodium-cooled fast reactors. In order to reduce the flow distribution deviation of assemblies caused by the distribution header pressure drop, it is necessary to carry out a reasonable assembly pressure drop design. Based on the mechanism of flow distribution deviation of assemblies caused by distribution header pressure drop, a theoretical calculation model was proposed, and an optimized design of assembly pressure drop was carried out for the China Experimental Fast Reactor (CEFR) core. Based on the actual layout of CEFR core, the maximum deviation of flow distribution of fuel assemblies was obtained, and the optimization direction of nominal assembly pressure drop was determined, indicating that optimization design of nominal assembly pressure drop should be carried out for the first five rings. After adjusting the nominal pressure drop of the first five rings of assemblies from 250 kPa (the original nominal pressure drop) to 249 kPa, 248.5 kPa, and 248 kPa, respectively, the maximum deviation of flow distribution of fuel assemblies firstly decreases from −0.99% to −0.95%, and then increases to −1.02% and −1.08%, which indicates that nominal assembly pressure drop should be elaborately determined to obtain a minimum flow distribution deviation of fuel assemblies. In conclusion, when conducting core thermal hydraulic design for sodium-cooled fast reactors, it is necessary to analyze the optimization direction of nominal assembly pressure drop based on actual core layout, and sensitivity analysis should be conducted to finally determine the nominal assembly pressure drop to reduce the impact of distribution header pressure drop on flow distribution of assemblies to the lowest extent.

Abstract Objective Clinical studies have demonstrated the effectiveness of arthrocentesis in managing temporomandibular joint disorders (TMDs). However, there is a lack of consensus among these studies regarding the selection of injectables. Furthermore, an increasing number of drugs have been tested for TMDs in recent years, complicating the decision-making process for clinicians. This study conducted a network meta-analysis of randomized controlled trials (RCTs) to compare the clinical efficacy of different arthrocentesis treatment regimens. Methods We conducted a comprehensive search of Embase, PubMed, Cochrane Library, and Web of Science to gather articles on RCTs pertaining to the management of TMDs using arthrocentesis. This search spanned from inception of these databases up to July 29, 2024. We then performed a network meta-analysis using Stata 17.0 software. The outcome indicators used were VAS scores and changes in unassisted maximum opening. To determine the efficacy of each regimen, we employed surface-under the cumulative ranking curve (SUCRA) ranking. Result Forty RCTs were included, encompassing 1904 temporomandibular joints (TMJs) cases. Treatment options encompass platelet-rich plasma (PRP), hyaluronic acid (HA), corticosteroids (CS), bone marrow concentrate (BMAC), injectable platelet-rich fibrin (i-PRF), concentrated growth factor (CGF), Tenoxicam (TX), microfragmented adipose tissue (FAT), and their combination regimens. The SUCRA ranking revealed that the most effective treatment options at 1-, 3-, and 6-months post-arthrocentesis were HA + PRP, i-PRF, and BMAC, respectively. Conclusion HA + PRP, i-PRF and BMAC may represent the optimal arthrocentesis agents for the management of TMDs symptoms and restoration of TMJ function in the short, medium, and long term, respectively. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024563975.

[Introduction] Facing the advancement of the national "carbon peaking and carbon neutrality" strategy, energy in various regions of China will develop towards low-carbon utilization based on its unique resource endowment. In order to understand the development level of low-carbon energy, it is necessary to conduct evaluation research on low-carbon energy utilization. [Method] This paper first analyzed the evaluation objects of energy low-carbon utilization; then classified and organized the evaluation indicators of energy low-carbon utilization. This paper sorted out and introduced the characteristics of each evaluation method and model, and explained the role of energy low-carbon utilization evaluation research. [Result] The evaluation objects of energy low-carbon utilization can be divided into energy system evaluation and regional energy evaluation. The evaluation indicators are summarized from three aspects: energy low-carbon indicators, energy utilization indicators and energy security indicators, and the subjective and objective weighting evaluation methods are rationally used. It is possible to more comprehensively and accurately assess and understand the situation of low-carbon energy utilization. [Conclusion] The current energy low-carbon utilization evaluation is usually only reflected as a part of the evaluation index system. With the development of low-carbon energy and the increase in the proportion of clean energy, the evaluation of low-carbon energy utilization will become more and more important.

Abstract Casuarina equisetifolia trees are used as windbreaks in subtropical and tropical coastal zones, while C. equisetifolia windbreak forests can be degraded by seawater atomization (SA) and seawater encroachment (SE). To investigate the mechanisms underlying the response of C. equisetifolia to SA and SE stress, the transcriptome and metabolome of C. equisetifolia seedlings treated with control, SA, and SE treatments were analyzed. We identified 737, 3232, 3138, and 3899 differentially expressed genes (SA and SE for 2 and 24 h), and 46, 66, 62, and 65 differentially accumulated metabolites (SA and SE for 12 and 24 h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SA and SE stress significantly altered the expression of genes related to plant hormone signal transduction, plant–pathogen interaction, and starch and sucrose metabolism pathways. The accumulation of metabolites associated with the biosynthetic pathways of phenylpropanoid and amino acids, as well as starch and sucrose metabolism, and glycolysis/gluconeogenesis were significantly altered in C. equisetifolia subjected to SA and SE stress. In conclusion, C. equisetifolia responds to SA and SE stress by regulating plant hormone signal transduction, plant–pathogen interaction, biosynthesis of phenylpropanoid and amino acids, starch and sucrose metabolism, and glycolysis/gluconeogenesis pathways. Compared with SA stress, C. equisetifolia had a stronger perception and response to SE stress, which required more genes and metabolites to be regulated. This study enhances our understandings of how C. equisetifolia responds to two types of seawater stresses at transcriptional and metabolic levels. It also offers a theoretical framework for effective coastal vegetation management in tropical and subtropical regions.

Abstract The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.

This paper aimed to investigate the correlation between carbon emissions, fuel consumption, and speed limit. A theoretical model was derived based on the energy conservation law, which expresses the relationship between vehicle's fuel consumption and speed. Subsequently, a total of 40 sets of fuel consumption data were collected through field tests to verify the accuracy of the theoretical model at different speeds and different road longitudinal slope combinations. The fuel consumption was then converted to carbon emissions according to the carbon emission factors specified by Intergovernmental Panel on Climate Change (IPCC). In the field experiment, two types of cars and trucks, which are most common on the expressways in China, were selected. Finally, the travel speed under different posted speed limits was obtained through the previously established model, and the carbon emission changes of different vehicle types at different limited speeds are calculated. The results show that the speed limit has a significant impact on fuel consumption and carbon emissions. When the speed limit increased from 80 to 120 km/h, average vehicle speeds increased about 21%–27%, and fuel consumption and carbon emissions increased from approximately 33%–38%. Another interesting result was that the vehicle's fuel consumption and carbon emissions are only affected by speed. The results of the study explore the effect of speed limits on carbon emissions and provide evidence for road managers to set reasonable speed limits.

Abstract Camellia oleifera, a significant woody edible oil species, was examined using 48 germplasm resources from high-altitude regions in East Guizhou Province, China, to analyze fruit quality. The analysis aimed to identify high-performance germplasm, providing theoretical and research foundations for selecting and cross-breeding superior C. oleifera varieties in these regions. Fifteen primary traits of mature fruits were measured and analyzed, including four phenotypic traits (single fruit weight, transverse diameter, longitudinal diameter, peel thickness) and eleven quality traits (fresh seed yield rate, dry seed yield rate, dry kernel yield rate, seed kernel oil content, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, α-linolenic acid, cis-11-eicosenoic acid). A comprehensive evaluation employing cluster and principal component analyses (PCA) was conducted. The cluster analysis categorized the germplasms into five groups at a squared Euclidean distance of 14, with the first category comprising 17 germplasms, the second 28, and the third, fourth, and fifth each containing one. PCA reduced the 15 traits to five principal components (PCs), with PC1 having the highest eigenvalue of 3.57 and a contribution rate of 23.8%, mainly representing phenotypic traits. PC2, contributing 20.44%, represented linoleic acid, while PC3, PC4, and PC5, with contribution rates of 12.99%, 9.13%, and 7.45% respectively, predominantly represented seed kernel oil content, fresh seed yield, and palmitoleic acid. Employing a weighted sum method, a comprehensive evaluation function was developed to calculate total scores for each superior individual, forming the basis for rankings and selections. Notable variability was detected in single fruit weight, peel thickness, and fresh and dry seed yields, while oleic acid exhibited the lowest coefficient of variation. Dry seed yield showed a robust positive correlation with seed kernel oil content and the concentrations of palmitic and linoleic acids, whereas seed kernel oil content was inversely correlated with cis-11-eicosenoic acid levels. Five PCs with eigenvalues > 1 were identified, highlighting the top ten superior individuals: QD (Qian Dong: the code of eastern Guizhou Province)-33 > QD-34 > QD-48 > QD-38 > QD-27 > QD-15 > QD-35 > QD-5 > QD-14 > QD-36. Thus, the 48 C. oleifera germplasms from East Guizhou’s high-altitude areas demonstrate significant potential for enhancing traits such as single fruit weight, peel thickness, and fresh and dry seed yields. Specifically, QD-33, QD-34, and QD-48 exhibited superior comprehensive performance, designating them as prime candidates for variety selection and breeding.

Abstract Background This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. Materials The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. Results Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. Conclusions The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.

Abstract Background Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. Results The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. Conclusion In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.

Abstract Background Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. Methods Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. Results The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p

The study focuses on lung adenocarcinoma (LUAD), a predominant type of lung cancer. Despite advancements in diagnostics and molecular therapies, treatment remains challenging due to its low five-year survival rate. This study aims to investigate the role of the transmembrane protein TMEM164 in ferroptosis and anti-tumor immunity in LUAD, and to evaluate its potential as a therapeutic target. Through cellular experiments (such as QPCR, WB, CCK-8, EdU, Transwell, flow cytometry, CO-IP) and animal model experiments (including HE staining and IHC analysis), the relationship between TMEM164 expression and LUAD progression was explored, with particular attention to its mechanisms in ferroptosis and autophagy. The results show that TMEM164 expression is downregulated in LUAD and is associated with poor prognosis. Increasing TMEM164 expression significantly inhibits cell proliferation, migration, and invasion, while promoting an autophagy process dependent on ATG5 for autophagosome formation, thus facilitating ferroptosis. In mouse models, high TMEM164 expression combined with anti-PD-1 antibodies demonstrated synergistic anti-tumor effects. These findings highlight the critical role of TMEM164 in LUAD, suggesting that modulating TMEM164 expression could open new avenues for LUAD treatment.

Study region: Taihu Basin, China Study focus: Floods threaten humans, the environment, economic activity, and infrastructure. In this study, a new trend test and flood-frequency methods were adopted to detect extreme floods and their distributions based on flood-event identification. To fully understand the phased process of the influence of human activities on extreme hydrological processes, 12 copula functions were employed creatively in combined static and dynamic time-varying correlation aspects between extreme precipitation and floods. New hydrological insights for the region: Although both significant and insignificant increasing trends of the annual maximum water level in all three hydrological districts were examined, the periodic oscillations of all the stations were similar. Thus, it was significant to fully detect the periodical variation of floods. Extreme floods occurred mainly in the 1990s, as measured by frequency estimates. Generally, the nonstationary response relationship between heavy rain and an extreme water level was gradually strengthened; that is, a certain magnitude precipitation seemed to induce a greater-intensity flood event as time passed. Through the identification of historical flood events and the analysis of the rise and fall processes of floods, we found that the main reason for variation in the response relationship was the increase in the water level before the rising stage, rather than the water level rising in the Taihu Basin. Our study findings further existing knowledge on the regional flood-control design standard and can ensure the coexistence of humans and water systems in the future.

Acute myeloid leukemia (AML), which has distinct genetic abnormalities, has unique clinical and biological features. In this study, the incidence, clinical characteristics, induction treatment response, and outcomes of a large cohort of Chinese AML pediatric patients treated according to the BCH-AML 2005 protocol were analyzed. RUNX1-RUNX1T1 was the most common fusion transcript, followed by the CBFβ-MHY11 and KMT2A rearrangements. FLT3-ITD and KIT mutations are associated with unfavorable clinical features and induction responses, along with KMT2A rearrangements, DEK-NUP214, and CBF-AML. The 5-year event-free survival (EFS) and overall survival (OS) rates of our cohort were 53.9 ± 3.7% and 58.5 ± 3.6%, with the best survival found among patients with CBFβ-MYH11 and the worst survival among those with DEK-NUP214. In addition, we found that patients with FLT3-ITD mutation had adverse outcomes and that KIT mutation had a negative impact on OS in RUNX1-RUNX1T1+ patients. Furthermore, the risk classification and response to treatment after each induction block also influenced the prognosis, and HSCT after first remission could improve OS in high-risk patients. Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.

Supramolecular hydrogels based on host–guest interactions constitute a class of intriguing soft matter and have attracted great attention due to their unique properties, etc. In this study, we successfully synthesized 4-methylene-7-diethylaminocoumarin methacrylate (DEACMMA) monomer and carried out reversible addition-fragmentation chain transfer (RAFT) polymerization using methylated β-cyclodextrin via a host-guest encapsulation mechanism. This process led to the formation of ternary copolymer hydrogel supramolecular photoresponsive hydrogels through polymerization induced supramolecular gelation (PISG). The encapsulation of coumarin monomers by methylated cyclodextrins was confirmed using 2D ROESY NMR and fluorescence spectroscopy. We have carefully analyzed the microstructure of these supramolecular hydrogels by rheological profiles and scanning electron microscopy (SEM). Stimulated by UV light, the copolymers transition from non-luminescence to a bright fluorescent blue color, which is reminiscent of the self-transforming colors observed in jellyfish. The development of photostimuli-responsive hydrogels based on methylated β-cyclodextrin-coated coumarin esters opens new avenues in the fields of smart materials and clinical medicine.

ABSTRACTOvarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

PurposeThis study aims to optimize neoadjuvant radiotherapy target area for locally advanced rectal cancer (LARC) patients undergoing total neoadjuvant therapy (TNT) by examining local recurrence patterns.Methods and materialsWe retrospectively analyzed the clinical data of rectal cancer patients who undergone local recurrence after surgery. Recurrence sites were categorized and compared with initial diagnosis imaging, focusing on visible and suspicious lesions.ResultsOf the 126 patients who met our criteria, 186 lesions were analyzed. Within these, 75.40% of cases (95/126) and 83.33% of lesions (155/186) were located within the pelvic cavity. Conversely, 3.97% of cases (5/126) and 3.33% of lesions (6/186) occurred outside the pelvic cavity. Additionally, 20.63% of cases (26/126) and 13.44% of lesions (25/186) were found in both regions. Recurrences were predominantly observed in mesenteric regions (MR) (40.86%, 76/186) and presacral regions (PR) (32.26%, 60/186). In addition, 86.51% of patients (109/126) had recurrent lesions in HRA and the suspected lesions areas. Further analysis showed that initial CEA levels and adjuvant therapy types were identified as independent predictors for recurrence in MR/PR and initially suspected lesions. 86.51% of patients had recurrent lesions in HRA and the suspected lesions areasConclusionThe MR, PR, and areas of initial suspicious lesions are high-risk zones for post-surgical recurrence of LARC. Exploratory study of involved-field irradiation (IFI) can be carried out in the context of TNT in LARC.

ObjectivePleural effusion (PE) is a common pulmonary manifestation in patients with systemic lupus erythematosus (SLE), and is associated with disease activity. However, little is known regarding the additive effects of PE on cardiac function. Therefore, this study aimed to investigate multi-parameter cardiovascular magnetic resonance imaging (CMR) findings in SLE patients with PE and to explore whether cardiac involvement is associated with PE.MethodsPatients with SLE and age-matched/sex-matched healthy controls were included in this study. Patients with SLE were diagnosed according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. Moreover, the PE diagnosis was based on computed tomography, and the height of the effusion was > 5 mm. All enrolled individuals underwent CMR imaging, including cine and late gadolinium enhancement (LGE), T1, and T2 mapping imaging. The left and right ventricular function, LGE, T1, extracellular volume (ECV), and T2 values were evaluated.ResultsA total of 111 patients with SLE were enrolled, of whom 26 (23.42%) had PE. White cell count, hemoglobin, CRP, ESR, and lactate dehydrogenase levels were higher in SLE patients with PE than in SLE patients without PE (P

Abstract Diabetic nephropathy (DN) is a frequent and costly complication of diabetes with limited understandings of mechanisms and therapies. Emerging evidence points to the important roles of interleukin‐33 (IL‐33) in acute kidney injury, yet its contribution to DN is still unclear. We here found a ubiquitous increase of IL‐33 and its receptor (ST2) in murine models and patients with DN. Surprisingly, both IL‐33 and ST2 knockdown aggravated renal lesions in DN, while overexpression of IL‐33 also exacerbated the condition. Further population‐based analyses revealed a positive correlation of IL‐33 expression with renal dysfunction in DN patients. Individuals with high IL‐33 expression‐related polygenic risk score had a higher DN risk. These findings confirmed the harmful effects of IL‐33 on DN. Conversely, endogenous and exogenous partial reduction of IL‐33 signaling conferred renoprotective effects in vivo and in vitro. Mechanistically, IL‐33 induced senescence by regulating cell cycle factors in HK‐2 cells, and accordingly senescence led to renal cell damage through the secretion of senescence‐related secretory phenotype (SASP) including IL‐33 and prostaglandins. Together, elevated IL‐33 accelerates cellular senescence to drive DN possibly by SASP production, while a partial blockage improves renal injury and senescence. Our findings pinpoint a possible and new avenue for DN interventions.

Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.

Melon seeds have received considerable attention in recent years because of their high protein content, but they have not yet been fully used. The modification of melon seed protein (MSP) using ultrasound-assisted pH-shifting treatment was investigated in this study by analyzing structural characteristics and functional properties. The particle size, free sulfhydryl content, surface hydrophobicity, solubility, secondary structure, water-holding capacity, oil-holding capacity, emulsification activity index, and emulsification stability index of MSP were determined. MSP treated with ultrasound-assisted, pH-shifting had a smaller particle size, lower free sulfhydryl content, higher surface hydrophobicity, and solubility increased from 43.67 % to 89.12 %. The secondary structure of MSP was affected by ultrasonic treatment, manifesting as an α-helix increase and β-helix, β-turn, and random coil content decrease, which may be the reason why the protein structure became more compact after treatment. The water and oil holding capacities of MSP increased from 2.74 g/g and 3.14 g/g in untreated samples to 3.19 g/g and 3.97 g/g for ultrasound-treated samples, and further increased to 3.97 g/g and 5.02 g/g for ultrasound-assisted, pH-shifting treatment at pH 9.0, respectively. The emulsification activity index of MSP was 21.11 m2/g before treatment and reached a maximum of 32.34 m2/g after ultrasound-assisted, pH-shifting treatment at pH 9.0. The emulsification stability of MSP was maximized by ultrasonic treatment at pH 7.0. Ultrasound-assisted, pH-shifting treatment can effectively improve the functional properties of MSP by modifying the protein structure, which improves the potential application of melon seed protein in the food industry.

The entry of Cd into soil-rice systems is a growing concern as it can pose potential risks to public health. To derive regional soil Cd threshold, a total of 333 paired soil and rice samples was collected in Anhui Province, Eastern China. The results showed that the total soil Cd and soil Zn/Cd were the most significant variables contributing to Cd content in polished rice. The Chinese Soil Quality Standards might overestimate risk posed by Cd-contaminated soil for rice production in the mining area due to high Zn/Cd values of some mining-associated soils. Cd levels in polished rice can be predictable using stepwise multiple linear regression (MLR) model. However, the derived soil Cd threshold based on the MLR model would be unrealistically high. The classification and regression tree method (CART) performed well in simulating Cd levels in polished rice and can be used to derive soil Cd threshold instead of MLR to minimize the uncertainty.

The All-DC wind power generation system can effectively solve the harmonic resonance problem caused by large-scale wind power AC collection and transmission, gradually becoming a hot topic in future research. However, there are few studies on the relay protection of the All-DC wind power transmission systems. In the All-DC wind power systems, there are differences in topology, control strategies, fault characteristics, boundary characteristics, etc. At the same time, existing pilot protection has problems such as strict information synchronization requirements and selection of setting values through simulation. Therefore, the proposed pilot protection based on the similarity of the traveling wave between the quadratic fitting curve and the calculated curve for the All-DC wind power system transmission lines. Firstly, the difference of the 1-mode initial current waveform characteristics is analyzed in the time domain at both ends. Then, the least squares method is introduced to fit the differential curves of the current forward and backward traveling waves at two terminals. The differential characteristics of the differences between the fitted curve, the calculated curve, and the measured curve under the influence of internal and external errors are analyzed. Finally, the calculated value of traveling wave current during external metallicity fault is used as the standard. By comparing the fitting curve of current traveling waves and the difference in the calculation curve to distinguish internal faults from external faults. The simulation results show that the proposed protection principle can fault resistance of 2200 Ω and noise interference of 20 dB. In addition, the proposed method does not require strict data synchronization, higher sampling frequency, and setting value through simulation.

Abstract Background Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. Study design The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. Discussion The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. Trial registration Registered on clinicaltrial.gov (NCT04561739).

Abstract Introduction Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP). Objective Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules. Methods Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated. Results BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity. Conclusion From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery. Graphical abstract

Suzhou City, located in the Yangtze River Delta in China, is prone to flooding due to a complex combination of natural factors, including its monsoon climate, low elevation, and tidally influenced position, as well as intensive human activities. The Large Encirclement Flood Control Project (LEFCP) was launched to cope with serious floods in the urban area. This project changed the spatiotemporal pattern of flood processes and caused spatial diversion of floods from the urban area to the outskirts of the city. Therefore, this study developed a distributed flood simulation model in order to understand this transition of flood processes. The results revealed that the LEFCP effectively protected the urban areas from floods, but the present scheduling schemes resulted in the spatial diversion of floods to the outskirts of the city. With rainstorm frequencies of 10.0% to 0.5%, the water level differences between two representative water level stations (Miduqiao (MDQ) and Fengqiao (FQ)) located inside and outside the LEFCP area, ranged from 0.75 m to 0.24 m and from 1.80 m to 1.58 m, respectively. In addition, the flood safety margin at MDQ and the duration with the water level exceeding the warning water level at FQ ranged from 0.95 m to 0.43 m and from 4 h to 22 h, respectively. Rational scheduling schemes for the hydraulic facilities of the LEFCP in extreme precipitation cases were developed according to flood simulations under seven scheduling scenarios. This helps to regulate the spatial flood diversion caused by the LEFCP during extreme precipitation.