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Abstract In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2–8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents.

Architecture embodies symbolic meanings evolving across shifting socio-political landscapes. This paper investigates the multivalent transformations of Singapore’s iconic colonial landmark – the Victoria Theatre and Concert Hall (VTCH). Tracing VTCH’s metamorphosing roles, functions, and identities through historical ruptures like British rule, Japanese occupation, decolonization, and nation-building, it illuminates how the complex underwent profound changes. The analysis underscores how regimes continually reimagined this architectural palimpsest to forge national narratives, consolidate collective memories, and materialize power relations. VTCH’s transition from colonial edifice to a symbolically imbued site mirrors the intricate interplay between built environments and Singapore’s spatial politics. Once symbols of colonial dominance, the buildings later embodied sovereign nationhood and nostalgic roots. Notably, VTCH recently assumed new roles driving cultural tourism and economic growth. Through a diachronic interrogation of this singular icon, the paper elucidates broader dialectics between decolonization, nation-building, and the semiotics of heritage in (re)constructing collective identities. It offers insights into how societies redefine spatial legacies to serve evolving ideological imperatives and identity discourses. Integrating the micro-architectural and macro-national enriches understandings of the mutually constitutive relationships between the built environment, political authority and national consciousness.

Abstract Background Metabolic reprogramming plays a pivotal role in tumorigenesis and development of lung adenocarcinoma (LUAD). However, the precise mechanisms and potential targets for metabolic reprogramming in LUAD remain elusive. Our prior investigations revealed that the mitochondrial ribosomal protein MRPL12, identified as a novel mitochondrial transcriptional regulatory gene, exerts a critical influence on mitochondrial metabolism. Despite this, the role and regulatory mechanisms underlying MRPL12’s transcriptional activity in cancers remain unexplored. Methods Human LUAD tissues, Tp53 fl/fl ;Kras G12D -driven LUAD mouse models, LUAD patient-derived organoids (PDO), and LUAD cell lines were used to explored the expression and function of MRPL12. The posttranslational modification of MRPL12 was analyzed by mass spectrometry, and the oncogenic role of key phosphorylation sites of MRPL12 in LUAD development was verified in vivo and in vitro. Results MRPL12 was upregulated in human LUAD tissues, Tp53 fl/fl ;Kras G12D -driven LUAD tissues in mice, LUAD PDO, and LUAD cell lines, correlating with poor patient survival. Overexpression of MRPL12 significantly promoted LUAD tumorigenesis, metastasis, and PDO formation, while MRPL12 knockdown elicited the opposite phenotype. Additionally, MRPL12 deletion in a Tp53 fl/fl ;Kras G12D -driven mouse LUAD model conferred a notable survival advantage, delaying tumor onset and reducing malignant progression. Mechanistically, we discovered that MRPL12 promotes tumor progression by upregulating mitochondrial oxidative phosphorylation. Furthermore, we identified UBASH3B as a specific binder of MRPL12, dephosphorylating tyrosine 60 in MRPL12 (MRPL12 Y60) and inhibiting its oncogenic functions. The decrease in MRPL12 Y60 phosphorylation impeded the binding of MRPL12 to POLRMT, downregulating mitochondrial metabolism in LUAD cells. In-depth in vivo, in vitro, and organoid models validated the inhibitory effect of MRPL12 Y60 mutation on LUAD. Conclusion This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12’s oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions. Graphical Abstract

Abstract Diabetic cardiomyopathy (DCM) represents a unique myocardial disease originating from diabetic metabolic disturbances that is characterized by myocardial fibrosis and diastolic dysfunction. While recent research regarding the pathogenesis and treatment of DCM has focused primarily on myocardial cells, nonmyocardial cells—including fibroblasts, vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and immune cells—also contribute significantly to the pathogenesis of DCM. Among various therapeutic targets, fibroblast growth factor 21 (FGF21) has been identified as a promising agent because of its cardioprotective effects that extend to nonmyocardial cells. In this review, we aim to elucidate the role of nonmyocardial cells in DCM and underscore the potential of FGF21 as a therapeutic strategy for these cells.

Radioactive waste resin is generated during the operation of nuclear facilities such as nuclear fuel recycling，reactor cooling water treatment，and spent fuel pool purification. The treatment of radioactive waste resin must consider system radiation protection issues and adopt effective shielding measures to protect public and environmental safety. Design three different shielding combinations based on the type and location of shielding materials，calculate and analyze the shielding effects and applicable scenarios of each method，and provide relevant reference for engineering applications. Meanwhile，using SuperMC radiation shielding calculation software，the surface dose rate of waste resin flowing through equipment such as reactor vessels，resin grinding devices，waste resin transfer tanks，and booster pumps was calculated and analyzed with waste resin treatment facilities as the research object. The calculation results indicate that the surface dose rate of the relevant equipment is 22.13-48.64 μSv/h without shielding. The use of a lead shielding layer to shield and protect equipment with higher surface dose rates meets the requirements of a control area of 5 μSv/h or less after shielding.

Abstract National and global food security depend on both supply and demand, yet the vast majority of studies on the impact of climate change on food security have focused somewhat myopically on the supply side. Here, we assess planetary implications of the changing climate for food supply, concurrently considering implications of shifts in dietary preferences on food security. From 1990 to 2018, climate change detrimentally impacted on the food production of 92% of nations assessed. During this time, demand decreased at a greater rate than food supply in 28% of countries; food security for 35% of the global population was unperturbed by climate change. On the other hand, 2% of the global population did not benefit from positive impacts of climate change on food production, due to dietary changes faster increasing food demand. If consumers shift dietary preferences en masse towards healthier diets, detrimental impacts of the climate crisis on food security may be abated, although en mass and/or abrupt transitions in dietary preferences are unlikely.

Abstract This paper primarily explores the modeling method of n-level complex helical structures with coal mining machine cables as the research object. The paper first elaborately introduces the modeling method of n-level helix curves based on parametric equations and coordinate transformations, and compensates for the n-level helix curves with corrected pitch, which can obtain more accurate n-level helix curves and improve the accuracy of n-level helix curves modeling. Subsequently, based on this high-precision n-level helix curves modeling method, the paper elaborates on the method of solving pitch and twisting radius of multi-layer helical structure. Calculation scripts were written based on the above methods, which can be used to batch calculate the twisting radius and pitch of each layer structure in multi-layer structures when satisfying the conditions of in-layer tangency, inter-layer tangency, and extrusion deformation, and retain the actual results through logical judgment. Then, based on the above two methods, the paper developed a modeling method for braided structures based on piecewise functions containing fifth-order polynomials, which can effectively avoid the problem of insufficiently dense arrangement of braided lines and easy interference in traditional methods. Finally, a set of modeling tools was developed using C# and Python in Grasshopper to implement the modeling algorithm. Taking the MCPT-1.9/3.3 3120 + 170 + 4 * 10 coal mining machine cable as an example. The cable was modeled using both the method proposed in this paper and the traditional method. Comparative data shows that the method proposed in this paper can reduce errors by 3.31E6 times in the second-level and above helical structures. In addition this paper compares the standard line length, measured line length, and the line length established by the proposed model, showing that the relative errors are both less than 0.1941%. This paper provides a new, systematic, high-precision, and full-process cable modeling method, in which all parameters except the process parameters are accurately solved by equations. It lays a theoretical foundation for the high-precision simulation and intelligent sensing cables, which is of great significance for improving the safety, stability, and efficient development of the coal mining industry. The research results of the paper can not only be applied to the modeling of coal mining machine cables but also can be extended to the modeling of other complex multi-layer helical structures.

Abstract Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer’s disease (AD). HSV-1 infection induces β-amyloid (Aβ) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aβ deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aβ deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aβ deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aβ deposition in AD.

Abstract Existing agricultural nitrogen datasets in China are mostly developed using coarse national or provincial statistics. A crop‐specific nitrogen rate dataset based on the finest‐scale agricultural nitrogen statistics at the county level remains lacking. Here, we constructed a new dataset (CN‐N), which provides annual nitrogen rates for rice, wheat and maize in China at a 1‐km spatial resolution from 2004 to 2016. This dataset was developed by harmonizing county‐level and provincial agricultural nitrogen statistics with gridded crop distribution maps, resulting in 13 years of nitrogen rate maps for each crop covering 2004–2016. Validation against farmers' surveys by crop indicates CN‐N reliably quantifies average nitrogen rates and trends for each crop over 2004–2016, demonstrating improved spatial heterogeneity compared to previous datasets rasterized using only provincial statistics. Our study provides a crop‐specific, temporally consistent, gridded nitrogen rate dataset based on the finest‐scale county‐level agricultural nitrogen statistics. This can support future process‐based modelling for sustainable agricultural nitrogen management strategies.

Abstract C–H bond activation enables the facile synthesis of new chemicals. While C–H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C–H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C–C coupling mediated by 2D TMDCs to promote C–H activation and carbon dots synthesis. Our results shed light on 2D materials for C–H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

Abstract The introduction of flows within sessile droplets is highly effective for many lab-on-a-chip chemical and biomedical applications. However, generating such flows is difficult due to the typically small droplet volumes. Here, we present a simple, non-contact strategy to generate internal flows in sessile droplets for enhancing mixing and mass transport. The flows are driven by actuating a rigid substrate into oscillation with certain amplitude distributions without relying on the resonance of the droplet itself. Substrate oscillation characteristics and corresponding flow patterns are documented herein. Mixing indices and mass transfer coefficients of sessile droplets on the substrate surface are measured using optical and electrochemical methods. They demonstrate complete mixing within the droplets in 1.35 s and increases in mass transfer rates of more than seven times static values. Proof of concept was conducted with experiments of silver nanoparticle synthesis and with heavy metal ion sensing employing the sessile droplet as a microreactor for synthesis and an electrochemical cell for sensing. The degrees of enhancement of synthesis efficiency and detection sensitivity attributed to the internal flows are experimentally documented.

ObjectiveThe aim of this study was to conduct a systematic review and meta-analysis of the incidence of inflammatory bowel disease-associated bronchiectasis (IBD-BE) and to explore the possible risk factors for IBD-BE, which could help to understand the pulmonary involvement in patients with IBD and to determine the global incidence of the disease.MethodsWe searched PubMed and EMBASE databases to identify information on the prevalence of IBD-BE among IBD patients in the published literature. Information was extracted on study design, country, year, IBD-BE testing method, IBD characteristics, number of IBD-BE cases and total number of IBD patients, and factors associated with IBD-BE. We conducted meta-analyses using random-effects or fixed-effects models to estimate the prevalence of IBD-BE among IBD patients.ResultsOut of a total of 682 studies, we identified 16 studies that reported prevalence. These studies used a heterogeneous approach to identify IBD-BE. In these 16 studies, there were 92,191 patients with IBD, of whom 372 cases of IBD-BE were identified. The results of the meta-analysis showed that the overall prevalence of IBD-BE in IBD derived from the use of a random effects model was 5.0% (95% CI 2.0–12.0%). In contrast, the prevalence of IBD-BE in studies using high-resolution chest computed tomography (HRCT) imaging was 12% (95% CI 4–39%) using a random-effects model. When only retrospective studies with sample sizes greater than 100 (n = 6) were considered, the prevalence was 1% (95% CI 0–1%). However, when only retrospective studies with sample sizes less than 100 were included (n = 4), the prevalence was 29% (95% CI 6–100%); in prospective studies (n = 6), the combined prevalence was 11% (95% CI 4–29%). we performed a subgroup analysis of the differences in the incidence of IBD-BE between the different studies, each of which we subgrouped by type of study, type of disease, duration of disease, and diagnostic modality, and the results showed no significance. Future studies should standardize methods to identify IBD-BE cases and investigate the natural history and clinical course given the relatively high prevalence among IBD.ConclusionIn this systematic review and meta-analysis, the prevalence of IBD-BE was 12% among studies with HRCT imaging, suggesting that bronchiectasis may be an underestimated common extraintestinal manifestation of IBD. Asymptomatic patients with IBD-BE may present with abnormalities on HRCT or pulmonary function tests. Future studies should standardize methods to identify IBD-BE cases and investigate the natural history and clinical course given the relatively high prevalence among IBD.

Abstract Peritendinous adhesion that forms after tendon injury substantially limits daily life. The pathology of adhesion involves inflammation and the associated proliferation. However, the current studies on this condition are lacking, previous studies reveal that cyclooxygenase‐2 (COX2) gene inhibitors have anti‐adhesion effects through reducing prostaglandin E2 (PGE2) and the proliferation of fibroblasts, are contrary to the failure in anti‐adhesion through deletion of EP4 (prostaglandin E receptor 4) gene in fibroblasts in mice of another study. In this study, single‐cell RNA sequencing analysis of human and mouse specimens are combined with eight types of conditional knockout mice and further reveal that deletion of COX2 in myeloid cells and deletion of EP4 gene in sensory nerves decrease adhesion and impair the biomechanical properties of repaired tendons. Furthermore, the COX2 inhibitor parecoxib reduces PGE2 but impairs the biomechanical properties of repaired tendons. Interestingly, PGE2 local treatment improves the biomechanical properties of the repaired tendons. These findings clarify the complex role of PGE2 in peritendinous adhesion formation (PAF) and tendon repair.

BackgroundThe COVID-19 pandemic has profoundly affected the care practices of total joint arthroplasty (TJA) throughout the world. However, the impact of the pandemic on TJA care practices has not yet been studied in China.MethodsThis retrospective multicenter cohort included patients aged 18 years or older who underwent TJA between January 2019 and December 2019 (prepandemic period) and January 2020 to December 2021 (pandemic period). Data were obtained from the medical records of 17 Chinese hospitals. Interrupted time series (ITS) analysis was used to estimate differences in monthly TJA volume, hospitalization proportion of TJA, preoperative characteristics, postoperative complications, 30-day readmissions, length of stay (LOS), and costs in inpatients undergoing TJA between the prepandemic and pandemic periods. Multivariate regression and propensity score matching (PSM) analyses were used to assess the impact of the COVID-19 pandemic on hospital complications, readmissions at 30 days, LOS, and costs at the patient level.ResultsA total of 752,477 inpatients undergoing TJA in the prepandemic period, 1,291,248 in the pandemic period, with an average 13.1% yearly decrease in the volume of TJA during the pandemic. No significant changes were observed in the proportion of hospitalizations for TJA. ITS analyses showed increases in the proportion of comorbidities (8.5%, 95% CI: 3.4–14.0%) and the number of comorbidities (15.6%, 95% CI: 7.7–24.1%) in TJA cases during the pandemic, without increasing LOS, costs, complications, and readmission rates. Multivariate and PSM analyses showed 6% and 26% reductions in costs and readmission rates during the pandemic, respectively.ConclusionsThe COVID-19 pandemic was associated with more severe preoperative conditions and decreased volume, costs, and readmission rates in patients undergoing TJA in China. These findings demonstrate that the COVID-19 pandemic did not have a dramatic impact on the TJA care pattern in China, which may have resulted from active and strict strategies in combating COVID-19 as well as a rapid response in hospital management.

Summary: PsbS protein is essential for the rapid induction of non-photochemical quenching (NPQ) under low night temperatures (LNTs), but its stability is often affected by adverse environmental conditions. However, the regulatory mechanism for the stability of PsbS or chloroplast proteins remains to be fully characterized. We show that LNT decreases NPQ levels and SlPsbS protein abundance in tomato leaves. LNT-activated chloroplast vesicles (SlCVs) targeting the chloroplasts induce the formation of CV-containing vesicles (CCVs) containing SlPsbS, exported from the chloroplasts. Subsequently, SlCV and SlPsbS contact COP9 signalosome subunit 5A (SlCSN5A) in the cytosol and are ubiquitinated and degraded. Genetic evidence demonstrates that the overexpression of SlCV aggravates SlPsbS protein degradation, whereas silencing of SlCSN5 and SlCV delays LNT-induced NPQ reduction and SlPsbS protein turnover. This study reveals a ubiquitin-dependent degradation pathway of chloroplast proteins co-mediated by CV and CSN5A, thereby providing a basic reference for the regulation of chloroplast protein stability under stress conditions.

IntroductionPRV infection in swine can cause devastating disease and pose a potential threat to humans. Advancing the interplay between PRV and host is essential to elucidate the pathogenic mechanism of PRV and identify novel anti-PRV targets.MethodsPARP11-KO PK-15 cells were firstly constructed by CRISPR/Cas9 technology. Next, the effect of PARP11-KO on PRV infection was determined by RT-qPCR, TCID50 assay, RNA-seq, and western blot.Results and discussionIn this study, we identified PARP11 as a host factor that can significantly affect PRV infection. Inhibition of PARP11 and knockout of PARP11 can significantly promoted PRV infection. Subsequently, we further found that PARP11 knockout upregulated the transcription of NXF1 and CRM1, resulting in enhanced transcription of viral genes. Furthermore, we also found that PARP11 knockout could activate the autophagy pathway and suppress the mTOR pathway during PRV infection. These findings could provide insight into the mechanism in which PARP11 participated during PRV infection and offer a potential target to develop anti-PRV therapies.

Abstract Apart from simulating biological synapses, memristors can also be used in the secure encryption by exploiting their inherent random resistive switching (RS) properties. In this work, nonvolatile Ta/BiFeO3/ZrO2/Pt memristor is fabricated with 2 nm inserting BiFeO3 layer. At a high compliance current of 10 mA, it presents gradual RS characteristics during the set process, which resulting in 30 conductance states. Synaptic behavior can be successfully mimicked by precise conductance modulating under pulse electrical stimulation. Whereas under a low compliance current of 500 µA, it exhibits abrupt RS behavior, and the set voltage ranged from 0.3–0.8 V, which can be effectively as an entropy source for true random number generator (TRNG). Due to its Shannon entropy of 300 bits is 0.99987, Hamming weights and intra‐Hamming distances tend to be 50%. Furthermore, the software simulation of encryption and decryption of cat image is achieved by combining the key generated by TRNG. The controllable electrical properties of the Ta/BiFeO3/ZrO2/Pt device can be modulated by the compliance current, thus meeting the computing or safety requirements, which provides a solid foundation for the development of integrating computation and security at the hardware level.

Abstract Background Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. Results We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. Conclusion Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.

Abstract Background Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. Methods The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. Results XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. Conclusions XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1.

Abstract Understanding how climate variability affects oilseed yields is crucial for ensuring a stable oil supply in regions such as China, where self‐sufficiency in edible vegetable oils is low. Here, we found coherent patterns in the interannual variability of Sea Surface Temperature (SST) anomalies and percent crop yield anomalies in the three ocean basins, and then quantified the contribution of these SST modes to oilseed crop yield anomalies. Our analysis revealed that, at the national level, the six tropical SST modes collectively accounted for 51% of soybean, 52% of rapeseed, and 33% of peanut yield anomalies in China. Tropical Indian Ocean variability exerts the greatest impact on soybean and peanut yield variability, whereas the most significant impact on rapeseed yield anomalies is attributed to El Niño‐Southern Oscillation. Finally, this study examined the specific ways in which changes in SST modes can affect oilseed crop yields using changes in local meteorological variables. Our findings revealed the relationship between tropical SST variability and oilseed crop yields, providing a detailed understanding of the diverse connections between SST modes and oilseed crop yield. This study deepens our knowledge of the influence of climate variability on agriculture, offering valuable insights for devising strategies to mitigate the adverse effects of climate variability on oilseed crop production in China.

During infection, positive-stranded RNA causes a rearrangement of the host cell membrane, resulting in specialized membrane structure formation aiding viral genome replication. Double-membrane vesicles (DMVs), typical structures produced by virus-induced membrane rearrangements, are platforms for viral replication. Nidoviruses, one of the most complex positive-strand RNA viruses, have the ability to infect not only mammals and a few birds but also invertebrates. Nidoviruses possess a distinctive replication mechanism, wherein their nonstructural proteins (nsps) play a crucial role in DMV biogenesis. With the participation of host factors related to autophagy and lipid synthesis pathways, several viral nsps hijack the membrane rearrangement process of host endoplasmic reticulum (ER), Golgi apparatus, and other organelles to induce DMV formation. An understanding of the mechanisms of DMV formation and its structure and function in the infectious cycle of nidovirus may be essential for the development of new and effective antiviral strategies in the future.

The Microphthalmia-associated Transcription Factor (MITF) governs numerous cellular and developmental processes. In mice, it promotes specification and differentiation of the retinal pigmented epithelium (RPE), and in humans, some mutations in MITF induce congenital eye malformations. Herein, we explore the function and regulation of Mitf in Drosophila eye development and uncover two roles. We find that knockdown of Mitf results in retinal displacement (RDis), a phenotype associated with abnormal eye formation. Mitf functions in the peripodial epithelium (PE), a retinal support tissue akin to the RPE, to suppress RDis, via the Hippo pathway effector Yorkie (Yki). Yki physically interacts with Mitf and can modify its transcriptional activity in vitro. Severe loss of Mitf, instead, results in the de-repression of retinogenesis in the PE, precluding its development. This activity of Mitf requires the protein phosphatase 2 A holoenzyme STRIPAK-PP2A, but not Yki; Mitf transcriptional activity is potentiated by STRIPAK-PP2A in vitro and in vivo. Knockdown of STRIPAK-PP2A results in cytoplasmic retention of Mitf in vivo and in its decreased stability in vitro, highlighting two potential mechanisms for the control of Mitf function by STRIPAK-PP2A. Thus, Mitf functions in a context-dependent manner as a key determinant of form and fate in the Drosophila eye progenitor epithelium.

Background: Given the preventable nature of most healthcare-associated infections (HAIs), it is crucial to understand their characteristics and temporal patterns to reduce their occurrence. Methods: A retrospective analysis of medical record cover pages from a Chinese hospital information system was conducted for surgery inpatients from 2010 to 2019. Association rules mining (ARM) was employed to explore the association between disease, procedure, and HAIs. Joinpoint models were used to estimate the annual HAI trend. The time series of each type of HAI was decomposed to analyze the temporal patterns of HAIs. Results: The study included data from 623,290 surgery inpatients over 10 years, and a significant decline in the HAI rate was observed. Compared with patients without HAIs, those with HAIs had a longer length of stay (29 days vs. 9 days), higher medical costs (96226.57 CNY vs. 22351.98 CNY), and an increased risk of death (6.42% vs. 0.18%). The most common diseases for each type of HAI differed, although bone marrow and spleen operations were the most frequent procedures for most HAI types. ARM detected that some uncommon diagnoses could strongly associate with HAIs. The time series pattern varied for each type of HAI, with the peak occurring in January for respiratory system infections, and in August and July for surgical site and bloodstream infections, respectively. Conclusions: Our findings demonstrate that HAIs impose a significant burden on surgery patients. The differing time series patterns for each type of HAI highlight the importance of tailored surveillance strategies for specific types of HAI.

The Kezhayi to Gongnaisi section of the Duku expressway is predominantly characterized by alpine landforms, with steep terrain cutting that provides conducive conditions for avalanche development. The study on the evaluation of snow avalanche susceptibility in this area is a crucial prerequisite for the safety construction and operation of the Duku expressway. The 149 snow avalanche points were collected by employing remote sensing interpretation and field investigations. Through correlation analysis of these factors, 10 evaluation factors were selected, forming the avalanche evaluation factor system. Subsequently, the non-avalanche points and original avalanche points were extracted using the K-means clustering method and random method to create a sample set. Machine learning techniques, including multilayer perceptron (MLP) and support vector machine (SVM) algorithms, were utilized to assess avalanche susceptibility in the study area. The results show that the sample datasets extracted by the random and K-means clustering methods were used for training, the Kappa coefficient of the R-SVM, R-MLP, K-SVM, and K-MLP models were greater than 0.6. These four sets of models exhibited a high degree of consistency between the predicted results and actual values of the validation dataset. The AUC (area under curve) value trained by MLP increased from 0.762 to 0.983, while the AUC value trained by SVM increased from 0.724 to 0.951. Based on the K-MLP model partition with the highest evaluation accuracy, the snow avalanche development in the research area has a relatively minor impact on the proposed route but may pose a threat to tunnel entrances. This study provides theoretical support and methodological references for the construction, operation and mitigation of sonw avalanche disasters for the Duku expressway.

Abstract Ubiquitination, catalyzed usually by a three-enzyme cascade (E1, E2, E3), regulates various eukaryotic cellular processes. E3 ligases are the most critical components of this catalytic cascade, determining both substrate specificity and polyubiquitination linkage specificity. Here, we reveal the mechanism of a naturally occurring E3-independent ubiquitination reaction of a unique human E2 enzyme UBE2E1 by solving the structure of UBE2E1 in complex with substrate SETDB1-derived peptide. Guided by this peptide sequence-dependent ubiquitination mechanism, we developed an E3-free enzymatic strategy SUE1 (sequence-dependent ubiquitination using UBE2E1) to efficiently generate ubiquitinated proteins with customized ubiquitinated sites, ubiquitin chain linkages and lengths. Notably, this strategy can also be used to generate site-specific branched ubiquitin chains or even NEDD8-modified proteins. Our work not only deepens the understanding of how an E3-free substrate ubiquitination reaction occurs in human cells, but also provides a practical approach for obtaining ubiquitinated proteins to dissect the biochemical functions of ubiquitination.

The Simultaneous Localization and Mapping (SLAM) environment is evolving from static to dynamic. However, traditional SLAM methods struggle to eliminate the influence of dynamic objects, leading to significant deviations in pose estimation. Addressing these challenges in dynamic environments, this paper introduces a semantic-assisted LIDAR tightly coupled SLAM method. Specifically, to mitigate interference from dynamic objects, a scheme for calculating static semantic probability is proposed. This enables the segmentation of static and dynamic points while eliminating both stationary dynamic objects and moving environmental blocking objects. Additionally, in point cloud feature extraction and matching processes, we incorporate constraint conditions based on semantic information to enhance accuracy and improve pose estimation precision. Furthermore, a semantic similarity constraint is included within the closed-loop factor module to significantly enhance positioning accuracy and facilitate the construction of maps with higher global consistency. Experimental results from KITTI and M2DGR datasets demonstrate that our method exhibits generalization ability towards unknown data while effectively mitigating dynamic interference in real-world environments. Compared with current state-of-the-art methods, our approach achieves notable improvements in both accuracy and robustness.

Frequency stepping is a widely used technique for ultrahigh-resolution synthetic aperture radar (SAR). Although reducing the burden of hardware, this technique increases the complexity of imaging algorithms due to the intersubband time offsets and intersubband errors of delay, amplitude, and phase. To address the above problems, an improved ultrahigh-resolution stepped-frequency spaceborne SAR imaging algorithm is proposed in this article. By generating subband images individually, performing intersubband error estimation based on primary points, and then synthesizing the subband images in the imaging domain, the proposed algorithm effectively avoids the problem of time offsets and significantly improves intersubband error compensation accuracy benefiting from the high SNR in the imaging domain. Besides, considering the characteristics of nonideal factors in frequency-stepped SAR, a series of error compensation methods aiming at stop-and-go approximation, ionospheric error, and tropospheric delay are integrated to the proposed algorithm. The effectiveness of the proposed algorithms is verified via computer simulations, and real data experiments are also conducted based on both an X-band spaceborne SAR system, Taijing 4-01, and a Ka-band spaceborne SAR system, Luojia 2-01.

Abstract Blue light using flavin (BLUF) photoreceptors respond to light via one of nature’s smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial. Here, we incorporate site-specific fluorinated Trp into three BLUF proteins, i.e., AppA, OaPAC and SyPixD, and characterize the percentages for the Wout, WinNHin and WinNHout conformations using 19F nuclear magnetic resonance spectroscopy. Using femtosecond spectroscopy, we identify that one key WinNHin conformation can introduce a branching one-step proton transfer in AppA and a two-step proton transfer in OaPAC and SyPixD. Correlating the flavin quenching dynamics with the active-site structural heterogeneity, we conclude that the quenching rate is determined by the percentage of WinNHin, which encodes a Tyr-Gln configuration that is not conducive to proton transfer.

Abstract We investigated aging-related changes in nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the spinal cord of aged dogs. At all levels of the spinal cord examined, NADPH-d activities were observed in neurons and fibers in the superficial dorsal horn (DH), dorsal gray commissure (DGC) and around the central canal (CC). A significant number of NADPH-d positive macro-diameter fibers, termed megaloneurites, were discovered in the sacral spinal cord (S1–S3) segments of aged dogs. The distribution of megaloneurites was characterized from the dorsal root entry zone (DREZ) into the superficial dorsal horn, along the lateral collateral pathway (LCP) to the region of sacral parasympathetic nucleus (SPN), DGC and around the CC, but not in the cervical, thoracic and lumbar segments. Double staining of NADPH-d histochemistry and immunofluorescence showed that NADPH-d positive megaloneurites co-localized with vasoactive intestinal peptide (VIP) immunoreactivity. We believed that megaloneurites may in part represent visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.

Abstract Background The Chinese central government launched the third phase of health system reforms in 2009. After a decade since the initiation of the reform, the health system has witnessed noteworthy gains. However, there is no concurrent improvement in public satisfaction with the health system. This study analysed various factors that influence public satisfaction with the system and examined whether perceived quality of care affects public satisfaction. Methods A longitudinal nationally representative survey was used for this study. We used five waves of China Family Panel Studies (CFPS) survey data. The final sample consisted of 145 843 observations. A two-way fixed-effects ordered logistic model was used for the analysis. Results The results indicate that perceived good quality of care was positively associated with public satisfaction in health system regardless of rural–urban residence. Older adults and individuals with more than 3 years of college education were less likely to be satisfied with the system in rural areas. Personal income and the density of medical professionals in the geographic area tend to improve public satisfaction in rural areas. Having medical insurance coverage and fair or good self-rated health improved the probability of reporting public satisfaction in urban areas. Married people and individuals who lived in the West region were less likely to be satisfied with the health system in urban areas. Conclusions Knowledge and skills of healthcare providers or physical quality of facilities are not sufficient in improving public satisfaction in the health system. Policymakers need to identify options to influence the important factors that affect public perception of the system. This analysis identified several policy-amenable factors to improve public perception of the health system in rural and urban China.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-023-11221-6.

This paper introduces WaterGPT, a language model designed for complex multimodal tasks in hydrology. WaterGPT is applied in three main areas: (1) processing and analyzing data such as images and text in water resources, (2) supporting intelligent decision-making for hydrological tasks, and (3) enabling interdisciplinary information integration and knowledge-based Q&A. The model has achieved promising results. One core aspect of WaterGPT involves the meticulous segmentation of training data for the supervised fine-tuning phase, sourced from real-world data and annotated with high quality using both manual methods and GPT-series model annotations. These data are carefully categorized into four types: knowledge-based, task-oriented, negative samples, and multi-turn dialogues. Additionally, another key component is the development of a multi-agent framework called Water_Agent, which enables WaterGPT to intelligently invoke various tools to solve complex tasks in the field of water resources. This framework handles multimodal data, including text and images, allowing for deep understanding and analysis of complex hydrological environments. Based on this framework, WaterGPT has achieved over a 90% success rate in tasks such as object detection and waterbody extraction. For the waterbody extraction task, using Dice and mIoU metrics, WaterGPT’s performance on high-resolution images from 2013 to 2022 has remained stable, with accuracy exceeding 90%. Moreover, we have constructed a high-quality water resources evaluation dataset, EvalWater, which covers 21 categories and approximately 10,000 questions. Using this dataset, WaterGPT achieved the highest accuracy to date in the field of water resources, reaching 83.09%, which is about 17.83 points higher than GPT-4.

In the process of driving, the steering, braking, and driving conditions and different road conditions affect the vibration characteristics of the vehicle in the vertical, roll, and pitch directions. These factors greatly impact the riding comfort of the vehicle. Among them, the uneven distribution of vertical load between the left and right or the front and rear suspension is one of the important factors affecting the performance indicators of the vehicle’s roll angle acceleration and pitch angle acceleration. In order to improve the ride comfort of the vehicle in vertical, roll, and pitch motion, the inerter is introduced in this paper to form a new type of suspension structure with the “spring-damping” base element, inertial suspension. It breaks away from the traditional “spring-damping” base element of the inherent suspension structure. In this paper, the mechatronic inerter is taken as the actual controlled object, and the inertial suspension structure is considered as the controlled model based on the dynamic surface control theory and the pseudo-inverse matrix principle. Thus, the coordinated control of the inertial suspension can be achieved. Under random road input, compared with passive suspension, the ride comfort performance indicators of the vehicle with inertial suspension based on dynamic surface control are significantly improved. Finally, a Hardware-in-the-Loop (HiL) test of the controller based on dynamic surface control is carried out to verify that the performance of the vehicle inertial suspension using the dynamic surface control algorithm had improved in terms of vehicle ride comfort. The error between the experimental results and the simulation results is about 8%, which verifies the real-time performance and effectiveness of the dynamic surface controller in the real controller.

In order to solve the problem of complex coupling characteristics between multivariate load sequences and the difficulty in accurate multiple load forecasting for integrated renewable energy systems (IRESs), which include low-carbon emission renewable energy sources, in this paper, the TCN-FECAM-Informer multivariate load forecasting model is proposed. First, the maximum information coefficient (MIC) is used to correlate the multivariate loads with the weather factors to filter the appropriate features. Then, effective information of the screened features is extracted and the frequency sequence is constructed using the frequency-enhanced channel attention mechanism (FECAM)-improved temporal convolutional network (TCN). Finally, the processed feature sequences are sent to the Informer network for multivariate load forecasting. Experiments are conducted with measured load data from the IRES of Arizona State University, and the experimental results show that the TCN and FECAM can greatly improve the multivariate load prediction accuracy and, at the same time, demonstrate the superiority of the Informer network, which is dominated by the attentional mechanism, compared with recurrent neural networks in multivariate load prediction.

The Multidrug and Toxic Compound Extrusion (MATE) proteins serve as pivotal transporters responsible for the extrusion of metabolites, thereby playing a significant role in both plant development and the detoxification of toxins. The MATE gene family within the Brachypodium distachyon, which is an important model organism of the Poaceae family, remains largely unexplored. Here, a comprehensive identification and analysis of MATE genes that complement B. distachyon were conducted. The BdMATE genes were systematically categorized into five distinct groups, predicated on an assessment of their phylogenetic affinities and protein structure. Furthermore, our investigation revealed that dispersed duplication has significantly contributed to the expansion of the BdMATE genes, with tandem and segmental duplications showing important roles, suggesting that the MATE genes in Poaceae species have embarked on divergent evolutionary trajectories. Examination of ω values demonstrated that BdMATE genes underwent purifying selection throughout the evolutionary process. Furthermore, collinearity analysis has confirmed a high conservation of MATE genes between B. distachyon and rice. The cis-regulatory elements analysis within BdMATEs promoters, coupled with expression patterns, suggests that BdMATEs play important roles during plant development and in response to phytohormones. Collectively, the findings presented establish a foundational basis for the subsequent detailed characterization of the MATE gene family members in B. distachyon.

This paper introduces a semiconductor optical amplifier (SOA) with high power and narrow linewidth broadening achieved through active region mode control. By integrating mode control with broad-spectrum epitaxial material design, the device achieves high gain, high power, and wide band output. At a wavelength of 1550 nm and an ambient temperature of 20 °C, the output power reaches 757 mW when the input power is 25 mW, and the gain is 21.92 dB when the input power is 4 mW. The 3 dB gain bandwidth is 88 nm, and the linewidth expansion of the input laser after amplification through the SOA is only 1.031 times. The device strikes a balance between high gain and high power, offering a new amplifier option for long-range light detection and ranging (LiDAR).

(1) Background: Discarded young fig fruits (DYFFs) result in a waste of resources, such as sparse fruits and residual fruits, and there has been no research on the relationship between phenolic compounds and biological activity in DYFFs (2) Methods: Different deep eutectic solvents (DESs) and 80% ethanol were used to prepare DYFF extracts, and polyphenol extraction efficiency and bioactivities in the DYFFs extracts were compared. (3) Results: More than 1700 phytochemicals were identified in DYFFs, and thirteen of these typical phenolic compounds were analyzed quantitatively; chlorogenic acid, rutin, luteolin 8-C-glucoside, and epicatechin are the main polyphenols in DYFFs, especially chlorogenic acid with 2720–7980 mg/kg. Ferulic acid, caffeic acid, epicatechin, (+)-catechin, luteolin 8-C-glucoside, rutin, hesperetin, and chlorogenic acid showed different degrees of correlation with in vitro antioxidant activity. Moreover, the highest total phenol content found in the extracts of ChCl-Ethylene glycol (Choline chloride:Ethylene glycol = 1:2) was 8.88 mg GAE/g DW, and all quantitatively analyzed phenolic compounds had high levels in various DESs and 80% ethanol. The 80% ethanol and Choline chloride (ChCl) solvent system showed the greatest antioxidant properties, and the Choline chloride-Urea (Choline chloride: Urea = 1:2) extract of DYFFs exhibited the highest inhibitory activity. (4) Conclusions: DESs have demonstrated potential as promising green solvents, especially the ChCl solvent system, which facilitates the extraction of polyphenols.

AimsIn the year 2021, human brucellosis ranked fifth in terms of the number of cases among all statutorily notifiable infectious diseases in China, thus remaining a significant concern for public health. This study aims to provide insights into the financial burden of human brucellosis by examining hospital stays and associated costs for affected individuals.MethodsIn this retrospective study, we gathered updated data from 467 inpatient cases primarily diagnosed with human brucellosis at eight major tertiary hospitals in Beijing, China, spanning from 2013 to 2023. To comprehensively explore the economic impact on individuals, we not only analyzed the duration of hospital stays and total costs but also examined various charge types, including drug, lab test, medical imaging, medical treatment, surgical procedures, medical supplies and consumables, inpatient bed care, nursing services, and other services costs. Statistical analysis was employed to compare differences among gender, age, ethnicity, type of health insurance, condition at admission, comorbidity index, the performance of surgery, and the site of infection.ResultsBoth the length of stay and total cost exhibited significant variations among insurance, surgery, and infection site groups. Utilization categories demonstrated significant differences between patients who underwent surgery and those who did not, as well as across different infection sites. Furthermore, multiple linear regression analysis revealed that the condition at admission, Elixhauser comorbidity index, infection site, and surgery influenced both hospital stay and total cost. In addition, age and insurance type were associated with total costs.ConclusionBy delving into various utilization categories, we have addressed a significant gap in the literature. Our findings provide valuable insights for optimizing the allocation and management of health resources based on the influencing factors identified in this study.

Objective: The ultrasonic cardiac output monitor (USCOM), an instrument that monitors the evolution of a patient's hemodynamic status and determines the type of shock, has become an important tool for assessing cardiac pathology and predicting changes in disease, but there are some variations in the instrumental findings for different physical conditions of patients. This article examines whether there are differences in the quality of USCOM waveforms measured in different types of critically ill patients based on clinical characteristics and test parameters. Methods: Baseline data, diagnoses, echocardiograms, ventilation patterns, and USCOM results were retrospectively collected from patients in the emergency intensive care unit. Waveform quality was quantified using the Fremantle score to determine the extent to which age, body mass index (BMI), chronic obstructive pulmonary disease (COPD), respiratory failure, cardiac enlargement, valvular heart disease, and ventilation pattern influenced USCOM waveform quality. Results: Age, body mass index, chronic obstructive pulmonary disease, respiratory failure, right and left heart enlargement, aortic valve disease (excluding aortic stenosis), and ventilation mode did not have a significant effect on USCOM waveform quality in critically ill patients (P > 0.05). Conclusions: Various physical conditions of critically ill patients may have limited effect on the quality of the USCOM waveform, potentially rendering USCOM suitable for early assessment of hemodynamic status during ICU admission.

Abstract Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor‐bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single‐cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect. In addition, in vivo assays are performed to investigate combination therapy strategies for enhancing the abscopal effect. The results showed that RT significantly inhibited localized tumor and lung metastasis progression and improved the TME. Mechanistically, RT promoted the release of tumor‐derived exosomes carrying circPIK3R3, which is taken up by macrophages. circPIK3R3 promoted Type I interferon (I‐IFN) secretion and M1 polarization via the miR‐872‐3p/IRF7 axis. Secreted I‐IFN activated the JAK/STAT signaling pathway in CD8+ T cells, and promoted IFN‐γ and GZMB secretion. Together, the study shows that tumor‐derived exosomes promote I‐IFN secretion via the circPIK3R3/miR‐872‐3p/IRF7 axis in macrophages and enhance the anti‐tumor immune response of CD8+ T cells.

Background and purposeIrregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics.Materials and methodsFourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter’s absolute change and relative rates of change during the cardiac cycle.ResultsSeven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms (< 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased (p = 0.035), but the relative rates of change in aneurysm size (p = 0.013), height (p = 0.014), width (p = 0.008), height-to-width ratio (p = 0.009), dome-to-neck ratio (p = 0.019) and bottleneck factor (p = 0.012) decreased.ConclusionAlthough the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-of-concept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs.

Objective: This review aims to conduct a comprehensive study of the diagnostic accuracy of interleukin-6 (IL-6) for multiple diseases by utilizing existing systematic reviews and meta-analyses. Methods: We performed a thorough search of Embase, Web of Science, PubMed, and Cochrane Database of Systematic Reviews up to April 2023 to gather meta-analyses that investigate the diagnostic accuracy of IL-6. To assess the methodological quality of the studies, we employed the Assessing the Methodological Quality of Systematic Reviews-2 and Grading of Recommendations, Assessment, Development and Evaluation criteria. Results: We included 34 meta-analyses out of the 3024 articles retrieved from the search. These meta-analyses covered 9 categories of diseases of the International Classification of Diseases-11. Studies rated as ''Critically Low'' or ''Very Low'' in the quality assessment process were excluded, resulting in a total of 6 meta-analyses that encompassed sepsis, colorectal cancer, tuberculous pleural effusion (TPE), endometriosis, among others. Among these diseases, IL-6 demonstrated a relatively high diagnostic potential in accurately identifying TPE and endometriosis. Conclusions: IL-6 exhibited favorable diagnostic accuracy across multiple diseases, suggesting its potential as a reliable diagnostic biomarker in the near future. Substantial evidence supported its high diagnostic accuracy, particularly in the cases of TPE and endometriosis.

Abstract Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors. This was a retrospective, observational cohort study of adult patients admitted to an ICU ≥ 72 h between 10/1/2015 and 10/31/2020 with available fluid balance data. Models to predict fluid overload (a positive fluid balance ≥ 10% of the admission body weight) in the 48–72 h after ICU admission were created. Potential patient and medication fluid overload predictor variables (n = 28) were collected at either baseline or 24 h after ICU admission. The optimal traditional logistic regression model was created using backward selection. Supervised, classification-based ML models were trained and optimized, including a meta-modeling approach. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared between the traditional and ML fluid prediction models. A total of 49 of the 391 (12.5%) patients developed fluid overload. Among the ML models, the XGBoost model had the highest performance (AUROC 0.78, PPV 0.27, NPV 0.94) for fluid overload prediction. The XGBoost model performed similarly to the final traditional logistic regression model (AUROC 0.70; PPV 0.20, NPV 0.94). Feature importance analysis revealed severity of illness scores and medication-related data were the most important predictors of fluid overload. In the context of our study, ML and traditional models appear to perform similarly to predict fluid overload in the ICU. Baseline severity of illness and ICU medication regimen complexity are important predictors of fluid overload.

Abstract Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics.

Abstract Background Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. Results Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. Conclusion The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity. Graphical abstract

Abstract Seawater electrolysis is a viable method for producing hydrogen on a large scale and low-cost. However, the catalyst activity during the seawater splitting process will dramatically degrade as salt concentrations increasing. Herein, CoP is discovered that could reject chloride ions far from catalyst in electrolyte based on molecular dynamic simulation. Thus, a binder-free electrode is designed and constructed by in-situ growth of homogeneous CoP on rGO nanosheets wrapped around the surface of Ti fiber felt for seawater splitting. As expected, the as-obtained CoP/rGO@Ti electrode exhibits good catalytic activity and stability in alkaline electrolyte. Especially, benefitting from the highly effective repulsive Cl− intrinsic characteristic of CoP, the catalyst maintains good catalytic performance with saturated salt concentration, and the overpotential increasing is less than 28 mV at 10 mA cm−2 from 0 M to saturated NaCl in electrolyte. Furthermore, the catalyst for seawater splitting performs superior corrosion-resistance with a low solubility of 0.04%. This work sheds fresh light into the development of efficient HER catalysts for salinity tolerance hydrogen evolution.

Abstract Background It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied. Aim To evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF). Methods We performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications. Results The ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (

Abstract Background Melanoma is the deadliest form of skin tumor, and G protein-coupled receptors (GPCRs) play crucial roles in its carcinogenesis. Furthermore, the tumor microenvironment (TME) affects the overall survival (OS) and the response to immunotherapy. The combination of GPCRs and TME from a multi-omics perspective may help to predict the survival of the melanoma patients and their response to immunotherapy. Methods Bulk-seq, single-cell RNA sequencing (scRNA-seq), gene mutations, immunotherapy responses, and clinicopathologic feature data were downloaded from public databases, and prognostic GPCRs and immune cells were screened using multiple machine learning algorithms. The expression levels of GPCRs were detected using real-time quantitative polymerase chain reaction (qPCR) in A375 and HaCaT cell lines. The GPCR–TME classifier was constructed and verified using different cohorts and multi-omics. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and tracking tumor immunophenotype (TIP) were used to identify the key biological pathways among the GPCR–TME subgroups. Then, tumor mutational burden (TMB), vital mutant genes, antigen presentation genes, and immune checkpoints were compared among the subgroups. Finally, the differences in immunotherapy response rates among the GPCR–TME subgroups were investigated. Results A total of 12 GPCRs and five immune cell types were screened to establish the GPCR–TME classifier. No significant differences in the expression levels of the 12 GPCRs were found in the two cell lines. Patients with high GPCR score or low TME score had a poor OS; thus, the GPCRlow/TMEhigh subgroup had the most favorable OS. The scRNA-seq result revealed that immune cells had a higher GPCR score than tumor and stromal cells. The GPCR–TME classifier acted as an independent prognostic factor for melanoma. GSEA, WGCNA, and TIP demonstrated that the GPCRlow/TMEhigh subgroup was related to the activation and recruitment of anti-tumor immune cells and the positive regulation of the immune response. From a genomic perspective, the GPCRlow/TMEhigh subgroup had higher TMB, and different mutant genes. Ultimately, higher expression levels of antigen presentation genes and immune checkpoints were observed in the GPCRlow/TMEhigh subgroup, and the melanoma immunotherapy cohorts confirmed that the response rate was highest in the GPCRlow/TMEhigh cohort. Conclusions We have developed a GPCR–TME classifier that could predict the OS and immunotherapy response of patients with melanoma highly effectively based on multi-omics analysis.

PANoptosis pathway gene sets encompassing pyroptosis, apoptosis, and necroptosis were identified from the MSigDB database. We analyzed the perturbations and crosstalk in the PANoptosis pathway in prostate adenocarcinoma (PRAD), including gene mutation, transcription, methylation, and clinical features. By constructing a PANoptosis signature, we accurately predicted the prognosis and immunotherapeutic response of PRAD patients. We further explored the molecular features and immunological roles of the signature, dividing patients into high- and low-score groups. Notably, the high-score group correlated with better survival outcomes and immunotherapeutic responses, as well as a higher mutation frequency and enrichment score in the PANoptosis and HALLMARK pathways. The PANoptosis signature also enhanced overall antitumor immunity, promoted immune cell infiltration, upregulated immune checkpoint regulators, and revealed the cold tumor characteristics of PRAD. We also identified potential drug targets based on the PANoptosis signature. These findings lead the way in identifying novel prognostic markers and therapeutic targets for patients with PRAD.