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Abstract Prostate cancer is the most common solid malignant tumor in men, characterized by high morbidity and mortality. While current screening tools, such as prostate-specific antigen (PSA) testing and digital rectal examination, are available for early detection of prostate cancer, their sensitivity and specificity are limited. Tissue puncture biopsy, although capable of offering a definitive diagnosis, has poor positive predictive rates and burdens the patient more. Therefore, more reliable molecular diagnostic tools for prostate cancer urgently need to be developed. In recent years, microRNAs (miRNAs) have attracted much attention in prostate cancer research. miRNAs are extensively engaged in biological processes such as cell proliferation, differentiation, apoptosis, migration, and invasion by modulating gene expression post-transcriptionally. Dysregulation of miRNA expression in cancer is considered a critical factor in tumorigenesis and progression. This review first briefly introduces the biogenesis of miRNAs and their functions in cancer, then focuses on tumor-promoting miRNAs and tumor-suppressor miRNAs in prostate cancer. Finally, the potential application of miRNAs as multifunctional tools for cancer diagnosis, prognostic assessment, and therapy is discussed in detail. The concluding section summarizes the major points of the review and the challenges ahead.

In order to solve the problem of the large deviation between the classical option pricing model and the actual price data, based on the BS option pricing model, the Fast Fourier Transform (FFT) combined with the Transformer's multi-head attention mechanism of deep learning algorithm was used to conductthe empirical research on the 300ETF options and Shanghai gold options data. The model was quadratically trained by the improved Transformer algorithm on the residual values between the option pricing model based on the FFT algorithm and the option price data of the actual financial market. The results show that compared with other algorithms (BS model, FFT-BS model) and other hybrid algorithm models (FFT-BS+ARIMA model, FFT-BS+LSTM model), the proposed model has a good performance in the statistical indexes such as R2, MSE, NRMSE and MAE, and the hybrid algorithm model achieves a better performance for different volatilitiesand different varieties of options. The study innovatively applies the improved Transformer algorithm to option pricing, which compensates for the shortcomings of the classical option pricing model and provides a more accurate option pricing model.

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

This is an article in the field of mineral processing engineering. The study objects are a spodumene waste rock in Sichuan. According to the mineral characteristics of thisspodumene waste rock, heavy medium separation tests were carried out at three different feed particle sizes (-15+0.5 mm, -10+0.5 mm, -5+0.5 mm) of the spodumene waste rock in laboratory. The test results show that the application of heavy medium separation in beneficiation of spodumene waste rock is very effective, and when -10+0.5 mm is used as the feed particle size range of the subsequent waste rock in heavy medium separation, and 2.70 g/cm3 is selected as the separation density, the results of heavy medium separation effect is relatively good. However, according to the actual production of heavy medium separation test results, the separation index is relatively good when the selected particle size is -15+0.5 mm and the medium density is 2.0 g/cm3.

Abstract Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.

Abstract Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 μs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.

To date, the exploration of multi-principal element alloys (MPEAs) has rarely ventured into the realm of hexagonal close-packed (HCP) structures. In this research, we embarked on a pioneering systematic comparison between a single-phase Ti-Zr-Hf HCP-MPEA and Ti regarding their dislocation activities and mesoscale deformation homogeneity. Through large-area high-resolution quasi-in-situ slip trace analysis and crystal plasticity finite element modeling, we identified HCP-MPEA’s significantly enhanced pyramidal slip activities—resulted from minimized disparities among different deformation modes—notably improve the material’s intragranular deformation homogeneity. Alongside MPEA’s intrinsically high slip resistance, it renders HCP-MPEA an outstanding strength-toughness combination relative to its conventional HCP counterparts.

Pseudorabies virus (PRV) poses a significant threat to the global swine industry, characterized by high morbidity and a range of sequelae in infected pigs. Mitochondria serve as a crucial platform for innate immunity, playing a pivotal role in a wide array of antiviral responses. In our recent study, we revealed that PRV infection induces mitochondrial disruption, which in turn triggers PINK1/PARKIN-mediated mitophagy. We also show that this process leads to the degradation of the mitochondrial antiviral signaling protein (MAVS) and the inhibition of antiviral interferon production and signaling, ultimately facilitating viral replication.

This study was conducted to investigate the hydrostatic stability of a steel slag porous asphalt mixture (SSPA) under freeze-thaw cycles in seasonal frozen soil areas and thereafter, compare its (SSPA) characteristic properties and advantages with a traditional porous asphalt pavement. In the study, the freeze-thaw stability of SSPA was tested through multiple freeze-thaw cycle splitting, scattering loss, and trabecular bending tests under various cyclic temperature water immersion conditions including quantitatively analyzing the SSPA volumetric changes. In addition, the scanning electron microscope (SEM) and energy dispersive spectrometer (EDS) tests were used to analyze the microscopic damage mechanism of SSPA after being subjected to various cyclic temperature water immersion conditions. The corresponding test results indicated that: (a) the long-term freeze-thaw cycles had significant adverse effects on the hydrostatic stability, physical/mechanical properties, and volume stability of SSPA; and (b) when the melting temperature was increased, both the hydrostatic stability and mass gain/loss ratio of SSPA decreased whilst the void ratio increased. On the other hand, the SEM and EDS results showed that an increase in the number of freeze-thaw cycles or melting temperature led to a corresponding increase in the width of the steel slag-asphalt transition zone. This resulted in a weakening of the mechanical connection and anchorage between steel slag and asphalt, as well as the destruction of their adhesion bond. However, the short-term freeze-thaw cycles had little effect on the hydrostatic stability of SSPA because the steel slag-asphalt interfacial strength was enhanced by short-term freeze-thaw cycles.

BackgroundThe high prevalence of noncommunicable diseases and the growing importance of social media have prompted health care professionals (HCPs) to use social media to deliver health information aimed at reducing lifestyle risk factors. Previous studies have acknowledged that the identification of elements that influence user engagement metrics could help HCPs in creating engaging posts toward effective health promotion on social media. Nevertheless, few studies have attempted to comprehensively identify a list of elements in social media posts that could influence user engagement metrics. ObjectiveThis systematic review aimed to identify elements influencing user engagement metrics in social media posts by HCPs aimed to reduce lifestyle risk factors. MethodsRelevant studies in English, published between January 2006 and June 2023 were identified from MEDLINE or OVID, Scopus, Web of Science, and CINAHL databases. Included studies were those that examined social media posts by HCPs aimed at reducing the 4 key lifestyle risk factors. Additionally, the studies also outlined elements in social media posts that influenced user engagement metrics. The titles, abstracts, and full papers were screened and reviewed for eligibility. Following data extraction, narrative synthesis was performed. All investigated elements in the included studies were categorized. The elements in social media posts that influenced user engagement metrics were identified. ResultsA total of 19 studies were included in this review. Investigated elements were grouped into 9 categories, with 35 elements found to influence user engagement. The 3 predominant categories of elements influencing user engagement were communication using supportive or emotive elements, communication aimed toward behavioral changes, and the appearance of posts. In contrast, the source of post content, social media platform, and timing of post had less than 3 studies with elements influencing user engagement. ConclusionsFindings demonstrated that supportive or emotive communication toward behavioral changes and post appearance could increase postlevel interactions, indicating a favorable response from the users toward posts made by HCPs. As social media continues to evolve, these elements should be constantly evaluated through further research.

Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Serum uric acid (SUA), a product of purine metabolism, has been implicated in HF progression. However, the association between hyperuricaemia and the short-term readmission and mortality in patients with HF remains controversial.Methods In this retrospective cohort study, we analysed data from a HF database specific to the Chinese population. The primary endpoint was short-term readmission or all-cause mortality within 90 days. Participants with HF were categorised into normouricaemia group (NUA) and hyperuricaemia group (HUA) based on a SUA threshold of 420 µmol/L. The association between SUA and primary endpoint was evaluated using Kaplan-Meier survival curves and Cox regression analysis.Results Baseline characteristics revealed significant differences between NUA and HUA groups, with the latter exhibiting a higher prevalence of males, chronic kidney disease (CKD) and elevated levels of various biomarkers. During a 90-day follow-up, 493 (26.6%) participants reached the primary endpoint, with a higher incidence observed in the HUA group at 31.2%, compared with 20.1% in the NUA group. When a threshold effect was identified at 420 µmol/L, a non-linear association was observed between SUA and the primary endpoint. After adjusting for gender, age, New York Heart Association class, CKD, systolic blood pressure (SBP) and potassium, the HUA group exhibited a higher risk for the primary endpoint compared with the NUA group (HR: 1.40, 95% CI: 1.14 to 1.72, p=0.001). Additionally, the risk increased across quartiles of SUA (P for trend=0.002). Furthermore, stratified analyses indicated a stronger association in patients without CKD (P interaction=0.033).Conclusion Hyperuricaemia is independently associated with an increased risk of short-term readmission and mortality in patients with HF. Our findings suggest that monitoring and managing SUA could be crucial in improving patient with HF outcomes.

Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.

Retroreflectors can scatter the arbitrarily incident wave back to incoming direction, demonstrating great potential in wireless communication. However, there are limitations in adaptive retroreflection and polarization modulation with the existing retroreflectors. In this paper, a novel metasurface array with a reconfigurable transmission line (TL) network has been proposed to flexibly achieve multiple manipulation functions of electromagnetic wave including upper half-space cross-polarized retroreflection and circularly polarized retroreflection in the diagonal planes and radar cross section (RCS) reduction. To accomplish these capabilities, a novel transmission mode for ferrite circulators has been developed, enabling precise phase control of the TL. By adjusting the operation states of the circulators, multiple phase differences between forward and reverse transmission directions including ±90° and ±180° are generated. With the obtained phase differences, the metasurface array can flexibly achieve the adaptive retroreflection fields with multiple polarization characteristics based on the spatial field superposition and the RCS reduction based on the phase cancellation. To validate the concept and feasibility of the proposed reconfigurable retrodirective metasurface, an X-band prototype has been fabricated and measured. Good agreement between the simulation and the experiment is observed to verify the effectiveness of our retrodirective design in upper half-space wave manipulation.

Abstract The potential for off-target mutations is a critical concern for the therapeutic application of CRISPR-Cas9 gene editing. Current detection methodologies, such as GUIDE-seq, exhibit limitations in oligonucleotide integration efficiency and sensitivity, which could hinder their utility in clinical settings. To address these issues, we introduce OliTag-seq, an in-cellulo assay specifically engineered to enhance the detection of off-target events. OliTag-seq employs a stable oligonucleotide for precise break tagging and an innovative triple-priming amplification strategy, significantly improving the scope and accuracy of off-target site identification. This method surpasses traditional assays by providing comprehensive coverage across various sgRNAs and genomic targets. Our research particularly highlights the superior sensitivity of induced pluripotent stem cells (iPSCs) in detecting off-target mutations, advocating for using patient-derived iPSCs for refined off-target analysis in therapeutic gene editing. Furthermore, we provide evidence that prolonged Cas9 expression and transient HDAC inhibitor treatments enhance the assay’s ability to uncover off-target events. OliTag-seq merges the high sensitivity typical of in vitro assays with the practical application of cellular contexts. This approach significantly improves the safety and efficacy profiles of CRISPR-Cas9 interventions in research and clinical environments, positioning it as an essential tool for the precise assessment and refinement of genome editing applications.

Abstract With its high energy consumption and pollutant emissions, the iron and steel industry is a significant source of air pollution and carbon emissions in the Beijing–Tianjin–Hebei (BTH) region. To improve air quality and reduce greenhouse gas emissions, a series of policies involving ultra-low emission, synergistic reduction of pollution, and carbon application have been implemented in the region. This study has assessed air pollutant and CO2 emission patterns in the iron and steel industry of the region by employing co-control effects coordinate system, marginal abatement cost curve, and numerical modeling, along with the synergistic benefits of typical technologies. The results have demonstrated that: (1) the intensive production activities pertinent to iron and steel enterprises has contributed greatly to the emission in Tangshan and Handan, where the sintering process is the main source of SO2, NOx, PM2.5, and CO, accounting for 64.86%, 55.15%, 29.98%, and 46.43% of the total emissions, respectively. (2) Among the typical pollution control and reduction measures, industrial restructuring and adjustment of the energy-resource structure have led to the greatest effects on emission reduction. Technologies exhibiting great potential in emission reduction and high-cost efficiency such as Blast Furnace Top Gas Recovery Turbine Unit (TRT) need to be promoted. (3) In Tangshan city with the highest level of steel production, the iron and steel production activities contributed to the concentration of 30.51% of PM2.5, 50.67% of SO2, and 42.54% of NO2 during the non-heating period. During the heating period, pollutants pertinent to the combustion of fossil energy for heating have increased, while iron and steel induced emissions have decreased to 23.7%, 34.32%, and 29.13%, respectively. By 2030, it is speculated that the contribution of the iron and steel industry to air quality will be significantly decreased as result of successful implementation of ultra-low emission policies and typical synergistic reduction technologies.

Abstract Background There are numerous complex barriers and facilitators to continuously wearing hearing protection devices (HPDs) for noise-exposed workers. Therefore, the present study aimed to investigate the relationship between HPD wearing behavior and hearing protection knowledge and attitude, HPD wearing comfort, and work-related factors. Method A cross-sectional study was conducted with 524 noise-exposed workers in manufacturing enterprises in Guangdong Province, China. Data were collected on hearing protection knowledge and attitudes, HPD wearing comfort and behavior, and work-related factors through a questionnaire. Using structural equation modeling (SEM), we tested the association among the study variables. Results Among the total workers, 69.47% wore HPD continuously, and the attitudes of hearing protection (26.17 ± 2.958) and total HPD wearing comfort (60.13 ± 8.924) were satisfactory, while hearing protection knowledge (3.54 ± 1.552) was not enough. SEM revealed that hearing protection knowledge had direct effects on attitudes (β = 0.333, p

Abstract Exploring the molecular packing and interaction between chiral molecules, no matter single enantiomer or racemates, is important for recognition and resolution of chiral drugs. However, sensitive and non‐destructive analysis methods are lacking. Herein, an intermolecular‐charge transfer (ICT) based spectroscopy is reported to reveal the differences in interaction between the achiral acceptor 1,2,4,5‐tetracyanobenzene (TCNB) and the chiral donors, including S, R, and racemic naproxen (S/R/rac‐NAP). In this process, S‐NAP+TCNB and R‐NAP+TCNB display a narrower band gap attributed to the newly formed ICT state. In contrast, the mixed rac‐NAP and TCNB exhibit almost no significant change due to the strong affinity between the stereoisomers according to the Wallach's rule. Thus, S/R‐NAP can be easily distinguished from rac‐NAP based on significantly different optical behavior. The single crystal analysis, infrared spectroscopy, fluorescence spectroscopy, and theoretical calculation of naproxen confirm the importance of carboxyl for this differentiation in molecular packing and interaction. In addition, the esterification derivatization of naproxen achieves the manipulation of the intermolecular interaction model of racemates from the absolute Wallach's rule to a coexisting form of Wallach's rule and ICT. Further, visualized chiral purification of naproxen by the simple cocrystallization method is achieved through the collaboration of ICT and Wallach's rule.

BackgroundDespite increasing awareness, silica dust–induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. ObjectiveWe aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. MethodsBetween May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission’s risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. ResultsKaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust–exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. ConclusionsChinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners’ working environment, and reduce the risk of silicosis.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. Conclusions: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

Microvascular angina (MVA) is the most common cause of cardiac ischemic chest pain in patients without obstructive coronary artery disease (CAD) and lacks of effective treatment means. Medicine food homology (MFH) involves substances with both nutritional and medicinal qualities that have the potential to improve MVA symptoms as medicines, dietary supplements. However, research on MFH formula (MFHF) for MVA is not available. The study aims to generate a core MFHF for MVA through data mining and offer scientific backing for the utilization of edible medications in the prevention and alleviation of MVA. 11 databases were utilized to construct a database of MFH drugs, and the MFHF was generated through frequency analysis, association rule analysis, and clustering analysis. The composition of the formula is Codonopsis Radix, Astragali Radix, Platycodonis Radix, Persicae Semen, Glycyrrhizae Radix Et Rhizoma, Angelicae Sinensis Radix, and Allii Macrostemonis Bulbus. Through network pharmacology and molecular docking, we identified five major active components of MFHF: Adenosine, Nonanoic Acid, Lauric Acid, Caprylic Acid, and Enanthic Acid, along with nine core targets (NFKB1, ALB, AKT1, ACTB, TNF, IL6, ESR1, CASP3, and PTGS) for the improvement of MVA. These 5 active components have various biological activities, such as reducing oxidative stress, anti-inflammation, analgesia effect, inhibiting platelet aggregation, vasodilatation, vascular endothelial protection, and cardio-protection. GO and KEGG enrichment analyses revealed that MFHF mainly acted on the response to xenobiotic stimulus, integrative component of the plasma membrane, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, pathways in cancer, lipid and atherosclerosis, human cytomegalovirus infection, and the PI3K-Akt signaling pathway, which are the main pathogenesis of MVA.

BackgroundTunneling technique has shown preliminary promise in lung segmentectomy which requires the use of staplers in specific procedures. However, the obstacle when staples pass is the most obvious factor hindering the implementation and development of this technique. This study investigated whether the obstacle of the technology could be addressed by using an innovative self-designed stapler tractor and analyzed the combined and respective advantages of them.MethodsThe clinical data of patients with lung nodules located near anatomical sites with potential tunnel creation treated by segmentectomy were analyzed in this retrospective case-control study. The data were divided into four groups according to four distinct surgical strategies: In Group A, the tunneling technique was performed with a stapler tractor; in Group B, the tunneling technique was performed without a stapler tractor; in Group C, didn’t perform the tunneling technique but using stapler tractor in a normal approach; and in Group D, neither performed the technique nor used the stapler tractor. The general linear data, operation times, intraoperative adverse events, postoperative recovery and complications were compared.ResultsCompared with other groups, Group A exhibited the best surgical outcomes in comprehensive aspects. Separately, the tunnel groups (Group A&B) had better outcomes in the macro implementation of operation, including resection margin, the number of sampled intrapulmonary lymph nodes and resected subsegments, while the staple tractor groups (Group A&C) performed better on details of the procedure, including operation time, conversion to thoracotomy, and intraoperative bleeding (p < 0.05). Both of them were beneficial for shorter hospital stay, and the tunnel group was more advantageous.ConclusionThe tunneling technique is an advanced and beneficial surgical strategy for performing precise resection of lung segments while a stapler tractor can promote and facilitate it as a supplementary instrument. They show more combined benefits in effectively minimizing the occurrence of erroneous injuries and enhancing the operational efficacy.

Abstract Axially chiral thioethers and sulfoxides emerge as two pivotal classes of ligands and organocatalysts, which have remarkable features in the stereoinduction of various asymmetric transformations. However, the lack of easy methods to access such molecules with diverse structures has hampered their broader utilization. Herein, an oxidative kinetic resolution for sulfides using a chiral bifunctional squaramide as the catalyst with cumene hydroperoxide as the terminal oxidant is established. This asymmetric approach provides a variety of axially chiral thioethers as well as sulfoxides bearing both axial and central chirality, with excellent diastereo‐ and enantioselectivities. This catalytic system also successfully extends to the kinetic resolution of benzothiophene‐based sulfides. Preliminary mechanism investigation indicates that the multiple hydrogen bonding interactions between the bifunctional squaramide catalyst and substrates play a crucial role in determining the enantioselectivity and reactivity.

Joining dissimilar metals is a major challenge in joining technology; the weldability of immiscible systems is especially challenging. In this study, a design methodology for dissimilar welding is suggested. The Miedema model and Toop model are developed to calculate the thermodynamics of quaternary alloy systems (Mg-Fe-Al-Cu). Finite element modelling (FEM) of temperature fields and the calculation of phase diagrams (CALPHAD) are combined to provide prerequisite information for modelling. As a test subject, laser welded lap configuration joints of AZ31B magnesium alloy and DP590 steel with a copper coating were put into the design scheme. The interfacial elemental diffusion and formation of intermetallics (IMCs) along the interface during the welding process are predicted. This simulation design scheme predicts the interfacial reaction kinetics and identifies whether the intermediate element works or not. The effects of the Cu coating thickness on the weld constitution, interfacial microstructures and mechanical properties were studied. Cu coating promotes the weld formation fostering the metallurgical reaction of the fusion zone (FZ) with the steel brazing interface. The mechanism of interfacial reactions during the welding-brazing process has been clarified. The Vickers hardness distribution across the interface shows that the Cu-IMCs are ductile.

Abstract Nanoclusters with atomically precise structures and discrete energy levels are considered as nanoscale semiconductors for artificial intelligence. However, nanocluster electronic engineering and optoelectronic behavior have remained obscure and unexplored. Hence, we create nanocluster photoreceptors inspired by mantis shrimp visual systems to satisfy the needs of compact but multi-task vision hardware and explore the photo-induced electronic transport. Wafer-scale arrayed photoreceptors are constructed by a nanocluster-conjugated molecule heterostructure. Nanoclusters perform as an in-sensor charge reservoir to tune the conductance levels of artificial photoreceptors by a light valve mechanism. A ligand-assisted charge transfer process takes place at nanocluster interface and it features an integration of spectral-dependent visual adaptation and circular polarization recognition. This approach is further employed for developing concisely structured, multi-task, and compact artificial visual systems and provides valuable guidelines for nanocluster neuromorphic devices.

The periodic layered structure (PLS) composed of alternative arrangement of Cr–Al–B MAB phase and FeAl3 was formed at the (Cr, Fe)2B/Al interface during hot-dip aluminizing (HDA) of Fe–Cr–B cast steel in molten Al. However, the effect of alloying element in the Al melt on the PLS was still unknown. This work focused on the effect of Ti on the interfacial reaction between Fe–Cr–B cast steel and molten Al–Ti–B alloy. The Ti atoms in Al–Ti–B alloy melt could partially replace the Cr atoms in the M-sites of the Cr–Al–B MAB phase contained in the PLS after it formed in-situ, leading to the formation of (Cr, Ti)–Al–B MAB phase solid solution. The B atoms in the melt absorbed by the Cr–Al–B MAB phase also accounted for the blackening of the Cr–Al–B MAB phase. It was the first time that the M-site MAB phase solid solution in the Cr–Al–B system was prepared by hot-dip aluminizing.

Abstract Background CRISPR-Cas9 technology has advanced in vivo gene therapy for disorders like hemophilia A, notably through the successful targeted incorporation of the F8 gene into the Alb locus in hepatocytes, effectively curing this disorder in mice. However, thoroughly evaluating the safety and specificity of this therapy is essential. Our study introduces a novel methodology to analyze complex insertion sequences at the on-target edited locus, utilizing barcoded long-range PCR, CRISPR RNP-mediated deletion of unedited alleles, magnetic bead-based long amplicon enrichment, and nanopore sequencing. Results We identified the expected F8 insertions and various fragment combinations resulting from the in vivo linearization of the double-cut plasmid donor. Notably, our research is the first to document insertions exceeding ten kbp. We also found that a small proportion of these insertions were derived from sources other than donor plasmids, including Cas9-sgRNA plasmids, genomic DNA fragments, and LINE-1 elements. Conclusions Our study presents a robust method for analyzing the complexity of on-target editing, particularly for in vivo long insertions, where donor template integration can be challenging. This work offers a new tool for quality control in gene editing outcomes and underscores the importance of detailed characterization of edited genomic sequences. Our findings have significant implications for enhancing the safety and effectiveness of CRISPR-Cas9 gene therapy in treating various disorders, including hemophilia A.

Abstract Purpose Intraoperative frozen section pathology (FS) is widely used to guide surgical strategies while the accuracy is relatively low. Underestimating the pathological condition may result in inadequate surgical margins. This study aims to identify CT imaging features related to upgraded FS and develop a predictive model. Methods Collected data from 860 patients who underwent lung surgery from January to December 2019. We analyzed the consistency rate of FS and categorized the patients into three groups: Group 1 (n = 360) had both FS and Formalin-fixed Paraffin-embedded section (FP) as non-invasive adenocarcinoma (IAC); Group 2 (n = 128) had FS as non-IAC but FP as IAC; Group 3 (n = 372) had both FS and FP as IAC. Clinical baseline characteristics were compared and propensity score adjustment was used to mitigate the effects of these characteristics. Univariate analyses identified imaging features with inter-group differences. A multivariate analysis was conducted to screen independent risk factors for FS upgrade, after which a logistic regression prediction model was established and a receiver operating characteristic (ROC) curve was plotted. Results The consistency rate of FS with FP was 84.19%. 26.67% of the patients with non-IAC FS diagnosis were upgraded to IAC. The predictive model’s Area Under Curve (AUC) is 0.785. Consolidation tumor ratio (CTR) ≤ 0.5 and smaller nodule diameter are associated with the underestimation of IAC in FS. Conclusion CT imaging has the capacity to effectively detect patients at risk of upstaging during FS.

The rapid development of wireless communication systems demands extremely high reliability in transmission links. However, non-ideal characteristics of RF links, such as carrier frequency offset (CFO) and IQ mismatch (IQM), can lead to RF impairments, severely affecting system performance. Advanced signal processing techniques are indispensable to mitigate the non-ideal characteristics of RF links. Within signal processing, synchronization issues, including CFO estimation schemes for frequency synchronization, should be prioritized. However, the traditional CFO estimation schemes are susceptible to interference from the harmonics caused by IQM, resulting in severe performance degradation. Therefore, based on the least squares (LS) interpolation method, we develop a CFO estimation scheme robust to IQM by using $2l _{0}+1$ ( $l _{0}\geqslant ~3$ ) discrete Fourier transform (DFT) coefficients. The proposed estimator combines a coarse estimation and a fine estimation. In the first stage, the peak position of the signal amplitude spectrum is detected to provide a rough frequency estimation. In the second stage (fine estimation), an LS equation relationship between the observation vector and the observation matrix is established with observed DFT samples and DFT rotation factors. The precise frequency is extracted using the LS principle from the equation, utilizing $2l _{0}+1$ ( $l _{0}\geqslant ~3$ ) DFT sample points. Because the IQM interference structure is considered in the equation, the proposed method can combat IQI. Test results based on the RF verification platform indicate that the proposed method improves accuracy by at least 20 dB at an input power of −45 dBm. Accuracy improves by at least 9 dB at an input power of −65 dBm. Complexity analysis shows that the proposed method increases by at most 10.74% compared to the traditional LS-based methods.

Natural language processing (NLP) is a research field that provides huge potential to automate accounting tasks dealing with text data. This research studies the application of NLP in automatically categorizing invoices based on the invoice text description. The study employs semantic enrichment, data augmentation, and deep learning to address the NLP unique issues posed by the inherent short text and multi-class imbalance nature of invoice descriptions. Semantic enrichment was done using labels as an information source. Training data was artificially increased with either WordNet synonym replacement, Global Vectors for Word Representation (GloVe) word replacement, or the Bidirectional Encoder Representations from Transformers (BERT) word replacement method. Each training dataset was then supplied for training with one nondeep learning classifier and two deep learning classifiers respectively, namely Linear Support Vector Machine (LSVM), Bidirectional Long Short-Term Memory (Bi-LSTM), and BERT. Overall, the semantically enriched, WordNet augmented training set paired with the BERT classifier yielded the best results, successfully preserving semantics, reducing noise and overfitting while improving accuracy per class, achieving an increase of performance up to 20 percentage points (ppts) for macro F1 score and 6.7 ppts for accuracy.

The incidence rate of gastroesophageal reflux is high. Qingre Jiangni Formula has shown good clinical efficacy. In this study, the therapeutic effect of this formula on inflammation was analyzed in the gastroesophageal reflux model. A rat model of gastroesophageal reflux was constructed using surgical methods. The successful construction of the rat model was confirmed through case testing. The model rats were treated with Qingre herbs, Jiangni herbs, and Qingre + Jiangni herbs for 2 weeks, followed by hematoxylin-eosin staining (HE), Western Blot (WB), enzyme linked immunosorbent assay (Elisa) and polymerase chain reaction (PCR) assays. SPSS 22.0 statistical software was used for analysis. The modeling of gastroesophageal reflux reduced the levels of testosterone and androsterol. The Qingre Jiangni formula helped to improve testosterone and androsterol to normal levels. Treatments in the Qingre group, Jiangni group, and Qingre + Jiangni group can all decrease inflammatory factor levels (interleukin IL-1B, IL-6, IL-8), and lead to a decreasing trend in p38, Claudin-4, Occludin and ZO_S. In addition, the three groups also showed decreased inflammation pathological levels compared with those in the model group (p < 0.01). Qingre Jiangni Formula is helpful for male hormones (testosterone and androsterol) and can decrease gastroesophageal reflux disease inflammation, thereby treating gastroesophageal reflux disease.

The purpose of the study was to explore effect of four different strains on quality characteristics of soy yogurt. The results showed that four strains were all related to the genus Lactobacillus and N1 was Lacticaseibacillus rhamnosus, N2 was Lacticaseibacillus paracasei, N3 was Lacticaseibacillus plantarum, and N4 was Lacticaseibacillus acidophilus. The result analysis of biochemical, sensory, nutritional, functional and safety properties of fermentation process and end products showed that the soy yogurt fermented with L. rhamnosus N1 had the highest isoflavone content and the lowest phytic acid content; the soy yogurt fermented with L. paracasei N2 had the highest content of free amino acids and oligosaccharides, the lowest content of trypsin inhibitors; the soy yogurt fermented with L. plantarum N3 had the lowest oil content; the soy yogurt fermented with L. acidophilus N4 had optimal functional properties. In summary, N4 was suitable as a fermentation strain for soymilk.

BackgroundLung segmentectomy has gained much more attention as an important surgical method for treating early-stage lung cancer. However, incomplete fissures increase the difficulty of lung segmentectomy. The aim of this study was to analyze the safety and efficacy of the fissure-first approach in precision resection of lung segments for patients with incomplete fissures.MethodsThe clinical data of patients with incomplete fissures who underwent lung segmentectomy were retrospectively analyzed. Date was divided into fissure-first approach in lung segmentectomy group (group A) and fissure-last approach in lung segmentectomy group (group B). The general linear data, operation times, intraoperative adverse events, postoperative recovery dates and complications were compared.ResultsA total of 122 patients with complete clinical data were included. Patients in group B had more COPD (p < 0.05), and the lesions in group A were more closely related to the hilum of the lung (p < 0.05). Compared to Group B, Group A achieved better surgical outcomes, such as operation time, postoperative hospital stays, intraoperative bleeding, number of intrapulmonary lymph nodes sampled, counts of resected subsegments (except the upper lobe of the right lung), and rate of conversion to thoracotomy (all p < 0.05).ConclusionThe fissure-first approach is a safe and effective surgical approach in lung segmentectomy for patients with incomplete fissures. This approach can reduce the counts of resected subsegments and improve techniques in lung segmentectomy for patients with lung incomplete fissures.

Abstract A 53‐year‐old man undergoing painless colonoscopy for long‐term diarrhea. After colonoscopy withdrawing to the sigmoid colon, a local perforation was found, about 3 cm in size, oval in shape. We used a two‐channel endoscope and grip to pull the edges of the intestinal wall on both sides of the perforation site to close together, and then repair the 3 cm oval perforation of the colon through multiple ordinary titanium clips. The patient had no obvious infection after surgery and recovered well after 1 month of follow‐up. Preliminary experience has shown that using multiple titanium clips under dual‐channel endoscope to zipper suture can effectively repair 3 cm iatrogenic colonic perforations.

To achieve the enormous potential of gene-editing technology in clinical therapies, one needs to evaluate both the on-target efficiency and unintended editing consequences comprehensively. However, there is a lack of a pipelined, large-scale, and economical workflow for detecting genome editing outcomes, in particular insertion or deletion of a large fragment. Here, we describe an approach for efficient and accurate detection of multiple genetic changes after CRISPR/Cas9 editing by pooled nanopore sequencing of barcoded long-range PCR products. Recognizing the high error rates of Oxford nanopore sequencing, we developed a novel pipeline to capture the barcoded sequences by grepping reads of nanopore amplicon sequencing (GREPore-seq). GREPore-seq can assess nonhomologous end-joining (NHEJ)-mediated double-stranded oligodeoxynucleotide (dsODN) insertions with comparable accuracy to Illumina next-generation sequencing (NGS). GREPore-seq also reveals a full spectrum of homology-directed repair (HDR)-mediated large gene knock-in, correlating well with the fluorescence-activated cell sorting (FACS) analysis results. Of note, we discovered low-level fragmented and full-length plasmid backbone insertion at the CRISPR cutting site. Therefore, we have established a practical workflow to evaluate various genetic changes, including quantifying insertions of short dsODNs, knock-ins of long pieces, plasmid insertions, and large fragment deletions after CRISPR/Cas9-mediated editing. GREPore-seq is freely available at GitHub (https://github.com/lisiang/GREPore-seq) and the National Genomics Data Center (NGDC) BioCode (https://ngdc.cncb.ac.cn/biocode/tools/BT007293).

A series of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) systems have been engineered for genome editing. The most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus aureus. However, a comparison of their detailed gene editing outcomes is still lacking. By characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells (iPSCs) and K562 cells, we found that SaCas9 could edit the genome with greater efficiencies than SpCas9. We also compared the effects of spacer lengths of single-guide RNAs (sgRNAs; 18–21 nt for SpCas9 and 19–23 nt for SaCas9) and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9, respectively. However, the optimal spacer length for a particular sgRNA was 18–21 nt for SpCas9 and 21–22 nt for SaCas9. Furthermore, SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end-joining (NHEJ) +1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif (PAM), indicating a characteristic of a staggered cut. Accordingly, editing with SaCas9 led to higher efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide (dsODN) insertion or homology-directed repair (HDR)-mediated adeno-associated virus serotype 6 (AAV6) donor knock-in. Finally, GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with SpCas9. Our work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.

A crack-free high-Mn TWIP steel welding joint with comparable strength and superplastic was obtained via vacuum electron beam welding (VEBW) where the microstructural evolution, mechanical behaviors and strengthening mechanism of welding joint were investigated. The results indicated that the welding joint with a typical nail-shaped welding cross-section was divided into three zones including the base metal (BM), heat-affected zone (HAZ) and fusion zone (FZ). Massive fine AlN-type precipitates with the hexagonal crystal structure were observed in welding join. The orientation relationship between the γ-austenite matrix and AlN precipitates was determined as [001]γ//[2110]AlN. In FZ, small-sized cellular grains or columnar grains with consistent growth directions were combined into large-sized columnar grains with obvious preferential orientation. Compared with the base mantal, the yield strength, ultimate strength and elongation of the VEBWed specimen were slightly reduced by 6.03%, 4.7% and 13.23%, respectively. However, the impact toughness was obviously decreased from the 87.90 J–68.97 J after the VEBW process, which was mainly attributed to the brittle AlN precipitates, inhomogeneous microstructure and back stress induced by the plastic mismatch between gradient grains. The strength contributions of different regions to overall strength including of BM, HAZ and FZ in welding joint were calculated. Here, the dislocation strengthening and precipitation strengthening were the dominant strengthening mechanisms of FZ, which was attributed to the high level of density and massive fine AlN precipitates induced by micro-elements segregations during the VEBW process.

Abstract Capacitive deionization is a promising desalination technique to tackle with freshwater scarcity, due to its facile, energy-efficient and eco-friendly operation. Carbon materials are primary electrode materials in capacitive deionization devices; however, their practical applications are limited by the low salt adsorption capacity and poor cycling stability. Here, we report a pre-oxidized strategy to significantly improve the salt adsorption capacity and cycling lifespan of carbon clothes. By the simple pre-oxidation treatment, it creates abundant ultramicropores and a superhydrophilic surface, which lead to a high salt adsorption capacity (31.5 mg g−1 and 13 mg cm−3) in 0.01 M NaCl aqueous solution. Moreover, the surface of each carbon fiber is oxidized, combined with a high mechanical strength, resulting in a stable surface during the cycling process. The retention rate is 74% even after 5000 adsorption/desorption cycles in diluted seawater. This work provides a new avenue to the design of high-performance, low-cost, and durable electrodes for capacitive deionization applications.

Abstract Background Natural killer (NK) cells hold great promise in treating diverse hematopoietic and solid tumors. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells offer an 'off-the-shelf' solution. Hematopoietic stem and progenitor cells (HSPCs) derived from cord blood pose no risk to the newborn or mother and are virtually ideal sources for NK cell differentiation. Methods We developed a modified protocol to differentiate HSPCs to NK cells under serum-free conditions using defined factors. The HSPC-derived NK (HSC-NK) cells could be expanded in a K562 feeder cell-dependent manner. Furthermore, using lentivirus transduction, chimeric antigen receptor (CAR)-modified HSPCs could be differentiated into NK cells, leading to the establishment of CAR-NK cells. Results The efficiency of NK cell differentiation from HSPCs was increased through the simple modulation of osmotic pressure by the addition of sodium chloride or glucose. Furthermore, the hyperosmosis-primed HSC-NK cells exhibited enhanced proliferation capacity and maintained normal functional characteristics, including transcriptome and antitumor efficacy. The optimized protocol yielded approximately 1.8 million NK cells from a single CD34-positive cell within a 28-day cycle, which signifies more than a ten-fold increase in efficiency relative to the conventional methods. This optimized protocol was also suitable for generating CAR-NK cells with high yields compared to standard conditions. Conclusions The results of this study establish high osmotic pressure as a simple yet powerful adjustment that significantly enhances the efficiency and functionality of HSC-NK cells, including CAR-NK cells. This optimized protocol could lead to cost-effective, high-yield NK cell therapies, potentially revolutionizing cancer immunotherapy strategies.

Epidemiological studies show that individuals with obesity are more likely to develop Alzheimer's disease (AD) than those who do not have obesity. However, the mechanisms underlying the relationship between obesity and AD are not entirely unclear. Here, we have reviewed and analyzed relevant articles published in the literature and found that obesity has correlation or potential increase in the levels of β-amyloid (Aβ) protein, which may explain why people with obesity are more likely to suffer from AD. Additionally, the published findings point to the roles of obesity-related metabolic disorders, such as diabetes, inflammation, oxidative stress, and imbalance in gut microbiota in Aβ accumulation caused by obesity. Therefore, in-depth experimental and clinical studies on these mechanisms in the future may help shed light on appropriate prevention and treatment strategies for AD, such as dietary changes and regular exercise to reverse or prevent obesity and related metabolic disorders.

Porcine rotavirus (PoRV) is a significant enteric pathogen causing gastroenteritis in piglets, which causes huge economic loss to the Chinese pig industry. In this study, six porcine rotavirus A strains were isolated from three adjacent sow farms belonging to the same company within one year, which suffered severe diarrhea outbreaks. AHBZ2303 (G11P[7]) and AHBZ2305 (G9P[23]), AHBZ2304 (G9P[23]) and AHBZ2312 (G4P[6]), AHBZ2310 (G9P[23]) and AHBZ2402 (G5P[23]) were isolated from Farm A, B and C, respectively. All six isolates were related to human rotavirus through complete genome analysis, suggesting the potential cross–species infection between humans and pigs. Evolutionary analysis revealed that AHBZ2303 and AHBZ2304 likely emerged simultaneously in Farm A and B, and then AHBZ2304 was introduced to Farm A and C, leading to the emergence of AHBZ2305 and AHBZ2310. Recombination and large variation were identified for AHBZ2312 and AHBZ2402. These findings provided insights into the transmission and evolution of PoRV among farms and underscored the need for enhanced monitoring to mitigate the risk of outbreaks from novel variants.

Objective To investigate the expression of fragile X mental retardation protein (FMRP) in Chinese patients with malignant melanoma and its correlation with hematologic ratios. Methods Lesional skin samples were collected from 23 Chinese with malignant melanoma (melanoma group), and skin samples from 10 normal subjects served as controls (normal skin group). The expression of FMRP was observed using immunohistochemical(IHC) staining, and two scoring methods (H-Score and IRS) were used to evaluate the expression levels. The relationship between FMRP and different pathological grades and stages of malignant melanoma was assessed. The association of FMRP with some hematological ratios, such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and systemic inflammatory markers (SIM) in patients with malignant melanoma were analyzed. Results The expression levels of FMRP in the melanoma were significantly higher than that in the normal skin (P0.05). Expression levels of FMRP were positively correlated with NLR and SIM, while negatively correlated with LMR. Conclusions FMRP is highly expressed in cutaneous malignant melanoma and its expression levels are significantly correlated with NLR, SIM, and LMR.

BackgroundMetabolic reprogramming plays a significant role in the advancement of lung adenocarcinoma (LUAD), yet the precise metabolic changes remain incompletely understood. This study aims to uncover metabolic indicators associated with the progression of LUAD.MethodsA total of 1083 subjects were recruited, including 670 LUAD, 135 benign lung nodules (BLN) and 278 healthy controls (HC). Gas chromatography-mass spectrometry (GC/MS) was used to identify and quantify plasma metabolites. Odds ratios (ORs) were calculated to determine LUAD risk factors, and machine learning algorithms were utilized to differentiate LUAD from BLN.ResultsHigh levels of oxalate, glycolate, glycine, glyceric acid, aminomalonic acid, and creatinine were identified as risk factors for LUAD (adjusted ORs>1.2, P

Seawater batteries are attracting continuous attention because seawater as an electrolyte is inexhaustible, eco-friendly, and free of charge. However, the rechargeable seawater batteries developed nowadays show poor reversibility and short cycle life, due to the very limited electrode materials and complicated yet inappropriate working mechanism. Here, we propose a rechargeable seawater battery that works through a rocking-chair mechanism encountered in commercial lithium ion batteries, enabled by intercalation-type inorganic electrode materials of open-framework-type cathode and Na-ion conducting membrane-type anode. The rechargeable seawater battery achieves a high specific energy of 80.0 Wh/kg at 1,226.9 W/kg and a high specific power of 7,495.0 W/kg at 23.7 Wh/kg. Additionally, it exhibits excellent cycling stability, retaining 66.3% of its capacity over 1,000 cycles. This work represents a promising avenue for developing sustainable aqueous batteries with low costs.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Abstract INTRODUCTION White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population‐based cohorts of non‐demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Low-carbon development of the iron and steel industry is critical to China’s goal of carbon neutrality and emission peaking. The carbon emissions of China’s iron and steel industry are calculated using the emission factor method in this paper, and the influencing factors of emission growth are investigated using the two-stage logarithmic mean divisia index (LMDI). The results show that carbon emissions from the steel industry continue to rise, reaching a stage peak of 1.848 billion tons in 2014 before declining. Carbon emissions fall by 52.4% during this period, energy intensity decreases by 52.9% per ton of steel; the decline in energy intensity will be much smaller in the future. The scale effect is the most important factor in the growth of carbon emission, accounting for 178.17% of the total, whereas energy intensity is the most important restraining factor, accounting for 76.02% of the total. However, the impact of energy structure and emission factors remains unclear. This is due to the small change in the energy mix and emission factors. The scale effect, which is a major contributor to rising carbon emissions, is broken down once more. Capital stock and total factor productivity drive carbon emission growth, whereas labor factors reflect the transition of the industrial population to low-carbon industries. The STIRPAT model predicts future carbon emissions from the iron and steel industry. The results of the scenario analysis show that carbon emissions will peak in 2025 under the baseline scenario, with carbon emissions totaling 1.904 billion tons. The peak time for carbon emissions in the low carbon scenario is 2021, and the peak is lower, with carbon emissions of 1.867 billion tons. Carbon emissions have already peaked in 2020 in the strong low-carbon scenario and will further decline to 1.439 billion tons in 2030, which is equivalent to 2010 carbon emissions. However, the rapid development scenario will not be able to reach a peak in carbon dioxide emissions before 2030. The forecast results show that both social and economic factors, as well as steel production factors, can have a significant impact on the overall industry’s carbon emission, implying that both the supply and demand sides must contribute to emission reductions. Controlling new capacity, transforming process structure, reducing fossil energy consumption, and promoting the use of hydrogen energy in the smelting process will be critical in the future for the industry’s low-carbon development.

Objective To analyze the clinical manifestations and histopathological features of 7 cases of dermatitis caused by benzalkonium chloride disinfectant, so as to enhance the understanding of this disease. Methods We retrospectively analyzed the clinical manifestations and pathological features of benzalkonium disinfectant-induced contact dermatitis in 7 cases who visited our clinic from August to November 2022. Results The clinical manifestations were repeated annular erythema and desquamation at the rubbing sites of the skin. The histopathological features of 4 cases were sponge formation, acanthosis and perivascular inflammation in the superficial dermis. Accumulation of neutrophils in the epidermis and the dermis was observed in 2 cases. Patients were treated with the systemic glucocorticoids and cyclosporine, and advised to avoid contact with benzalkonium chloride disinfectant. Conclusions Contact dermatitis caused by benzalkonium chloride disinfectant has specific manifestations and good response to the treatments. The skin patch test would be helpful to confirm the diagnosis.

Abstract Purpose Small cell lung cancer (SCLC) is an aggressive and rapidly progressive malignant tumor characterized by a poor prognosis. Chemotherapy remains the primary treatment in clinical practice; however, reliable biomarkers for predicting chemotherapy outcomes are scarce. Methods In this study, 78 SCLC patients were stratified into “good” or “poor” prognosis cohorts based on their overall survival (OS) following surgery and chemotherapeutic treatment. Next-generation sequencing was employed to analyze the mutation status of 315 tumorigenesis-associated genes in tumor tissues obtained from the patients. The random forest (RF) method, validated by the support vector machine (SVM), was utilized to identify single nucleotide mutations (SNVs) with predictive power. To verify the prognosis effect of SNVs, samples from the cbioportal database were utilized. Results The SVM and RF methods confirmed that 20 genes positively contributed to prognosis prediction, displaying an area under the validation curve with a value of 0.89. In the corresponding OS analysis, all patients with SDH, STAT3 and PDCD1LG2 mutations were in the poor prognosis cohort (15/15, 100%). Analysis of public databases further confirms that SDH mutations are significantly associated with worse OS. Conclusion Our results provide a potential stratification of chemotherapy prognosis in SCLC patients, and have certain guiding significance for subsequent precise targeted therapy.

Soybean protein isolate processing and production produces a large amount of soybean whey wastewater, which causes environmental pollution and waste of resources directly discharged. Soybean whey wastewater contains soybean whey proteins (SWP), soybean isoflavones, soybean oligosaccharides and other nutrients, of which soybean whey proteins application value is extremely high, rich in trypsin inhibitors, β-amylase, soybean hemagglutinin, lipoxygenase and other functional factors. Therefore, with regard to the recycling of soy whey proteins, this paper sumerizes the main components in soybean whey proteins, analyses functional properties and research purposes of each component, and sortes out the recovery methods and applications of soy whey proteins. The aim of this paper is to provide a theoretical and technical reference for high value utilisation in industrial production practice.