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Traditional Chinese medicine (TCM), both a longstanding medical practice in Asia and an increasingly utilized supplement or alternative medicine in Western countries, has become a focal point within the life sciences in recent years. TCM formulations represent a cornerstone of treatment, with their chemical composition serving as the fundamental basis for their pharmacological effects. However, the intricate nature of chemical composition, low abundance of various constituents, and presence of numerous isomeric compounds, alongside interactions among different medicinal substances, render the effective separation and identification of the components in TCM herbs challenging by using traditional analytical methods. In this study, an analytical method of ultra-high-performance liquid chromatography-quadrupole/Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) was developed for identifying the chemical components in the traditional Chinese medicine formula of Jiuwei decoction. The sample pretreatment method involved ultrasonic/microwave-assisted extraction, ensuring comprehensive extraction of the active components in Jiuwei decoction. Parameters of this extraction included a microwave power at 300 W, ultrasonic power at 340 W, temperature at 45 ℃, and an extraction duration of 30 min. Subsequent to extraction, chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 column (150 mm×2.1 mm, 1.7 µm) at 30 ℃, with an injection volume of 2 μL per run. The mobile phase consisted of water with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.3 mL/min. Before entering the quadrupole/Orbitrap high-resolution mass spectrometer for detection, samples underwent ionization under both positive and negative ion modes. Data acquisition was then conducted in full MS scan/data-dependent MS/MS scan (Full MS/dd-MS2) acquisition mode. Following data collection, chromatographic peak alignment and extraction were performed using the Xcalibur 4.1 software. Accurate mass information of precursor ions and fragment ions was meticulously compared with various databases, including the Orbitrap Traditional Chinese Medicine Library (OTCML), as well as other online databases such as TCMSP, ChemSpider, PubChem, PubMed, and Web of Science, in addition to a self-curated database for identification purposes. A total of 144 compounds are successfully identified, encompassing 24 flavonoids, 30 alkaloids, 12 terpenes, 23 phenylpropanoids, 26 phenols, 10 amino acids, 7 organic acids, 5 steroids, and 7 other types of compounds. Among these compounds, alkaloids such as sinomenine, phellodendrine, magnoflorine, isocorydine, and corydinematrine exhibit notably high contents and mass spectrometric responses, whereas flavonoids and saponins display comparatively lower MS responses. The herbal sources of these compounds were identified, and the fragmentation patterns of representative compounds were thoroughly analyzed. This study provides a precise identification of the chemical constituents in Jiuwei decoction, thus furnishing a robust scientific foundation for further exploration into its pharmacological effects and mechanisms of action. Moreover, this study serves as an invaluable reference for the analysis of the chemical composition of TCM formulations. Nonetheless, it is crucial to acknowledge the inherent limitations and scopes of various analytical methods and instruments. Therefore, in the pursuit of analyzing active components in TCMs, it is advisable to delve deeper into separation and identification through the utilization of diverse techniques such as nuclear magnetic resonance spectroscopy, ultraviolet/infrared spectroscopy, and capillary electrophoresis-mass spectrometry.

Abstract Objectives To describe and analyze the clinical characteristics and outcomes of Lanmaoa asiatica poisoning cases. Methods We conducted a retrospective study of Lanmaoa asiatica poisoning cases admitted to the emergency department of the First People's Hospital of Yunnan Province from January 2023 to December 2023. Results A total of 81 patients were admitted, with ages ranging from 14 to 84 years and a median age of 42.5 ± 14.6, predominantly female (72.8%). The peak poisoning cases were observed in July (n = 55, 67.9%). The commonest clinical presentation was the mixed neuropsychiatric and gastroenteritic type (64.2%), while 24.7% of patients presented with neuropsychiatric symptoms only and 11.1% of patients presented with pure gastroenteritic symptoms. The most common first symptom was visual hallucination (n = 56, 69.1%), followed by gastrointestinal symptoms such as nausea (n = 44, 54.3%) and vomiting (n = 36, 44.4%). Around 69.4% of patients had delayed onset of neuropsychiatric symptoms of 12–24 h after mushroom intake and 78.7% of patients had onset of gastroenteritic symptoms within 6 h after ingestion. Laboratory tests showed normal blood routine, liver function, kidney function, cardiac enzymes, and coagulation function. The median length of stay was 3 days, and no fatalities were reported. Conclusions Lanmaoa asiatica poisoning peaked in July. The commonest clinical presentation was the mixed neuropsychiatric and gastroenteritic type. The most common first symptom was visual hallucination. The incubation period for gastrointestinal symptoms was shorter than neuropsychiatric symptoms. Short hospitalization and absence of organ function damage was observed in Lanmaoa asiatica poisoning.

Abstract Background The optimal treatment of complicated type B aortic dissection (cTBAD) involving arch anomalies remain unclear. Methods We consecutively enrolled patients with cTBAD involving arch anomalies who underwent endovascular repair using a single-branched stent graft (SBSG) at our medical center between January 2020 and January 2023. The demographics, clinical manifestation, operation detail, and follow-up outcomes of these patients were retrospectively collected and analyzed. Results A total of 16 patients (14 men; 55.8 ± 11.7 years) were enrolled, including isolated left vertebral artery (ILVA) (n = 6), aberrant right subclavian artery (ARSA) (n = 7), and right aortic arch and aberrant left subclavian artery (ALSA) with Kommerell’s diverticulum (KD) (n = 3). Among them, six patients with multi-branched arch anomalies. The endovascular management strategies of patients were diverse based on their aortic morphology. The early outcome demonstrated that one patient experienced an immediate intraoperative type Ia endoleak, which was resolved by balloon dilation, and two patients exhibited bird-beak configuration. After a median of follow-up of 910 (743–1023) days, the long-term outcome revealed that two patients developed endoleak. No death, retrograde type A aortic dissection (RTAD), paraplegia, stent graft-induced new entry tear (SINE), or branch section stenosis of SBSG were observed during the follow-up. Conclusion Our limited experience suggests that endovascular repair with a SBSG appears to be a relatively safe, feasible, and effective treatment option for patients with cTBAD and arch anomalies.

Abstract Trastuzumab (Tra)-induced cardiotoxicity (TIC) is a serious side effect of cancer chemotherapy, which can seriously harm the health of cancer patients. However, there is currently a lack of effective and reliable biomarkers for the early diagnosis of TIC in clinical practice. Therefore, we screened the TIC candidate diagnostic gene solute carrier family 6 member 6 (SLC6A6) by combining multi-machine learning algorithm based on bioinformatics. In addition, cross-validation showed that SLC6A6 had a consistent expression trend in multi-data-sets. To further explore the diagnostic capability of SLC6A6 in TIC, we constructed a nomogram diagnostic model based on SLC6A6 expression level, and receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis proved that SLC6A6 had good diagnostic capability. In order to further verify the TIC expression of SLC6A6 in the real world, we have constructed cell and animal models. Animal experiments showed that left ventricular ejection fraction (LVEF) was significantly decreased (from 65.01 ± 3.30% and 351.32 ± 3.51%, p

Abstract Maximum drift ratio (MDR), one of the engineering demand parameters (EDPs), provides fundamental physical value for predicting building damage. Existing machine learning based prediction models mainly rely on numerical simulation data or structural experiments and are not appropriate for prediction of seismic response of real structures. The New Earthquake Data (NDE1.0) is the most comprehensive publicly available dataset of actual structural seismic response observations. Currently the prediction models using NDE1.0 are mainly based on linear or log-linear regression. In this study, based on the NDE1.0 flatfile, we develop a full-feature support vector regression (SVR) based MDR prediction model (SVR-MDR), treating all the available 41 characteristic parameters including structural information as input feature. To improve the model’s efficiency and practical applicability, we also establish a reduced-feature SVR model (RSVR-MDR) by selecting 10 fundamental parameters based on SHapley Additive exPlanations (SHAP) values and the accessibility of features. Our results demonstrate that SVR-MDR model outperform other machine learning models such as kernel ridge regression and decision tree models, and SVR-MDR and RSVR-MDR models outperform conventional loglinear regression and multinomial models, because SVR can map the complex nonlinear function of multiple variables and consider the available information of buildings especially the fundamental frequency. The proposed RSVR-MDR model have promising potential application for post-event seismic damage assessment and post-event emergency response in near real time.

Recently, a significant breakthrough in natural gas exploration was achieved in well Qiatan-1 in the Permian carbonate strata of the Western Tianshan thrust belt in the piedmont depression of southwestern Tarim Basin, marking the discovery of a new exploration layer in the area. However, this region is characterized by multiple sets of source rocks and extremely complex sedimentary and structural features. Research on the genesis and source of the natural gas in well Qiatan-1 is insufficient, restricting its further natural gas exploration. Therefore, the study systematically investigated the genesis and source of the natural gas in well Qiatan-1 based on regional geological background, geochemical characteristics of the gas, and potential source rock features. The measured results showed that the natural gas in well Qiatan-1 was mainly composed of methane (83.53%), with a gas dryness coefficient (C1/C1-5) of 0.992, and contained relatively high levels of N2 (8.36%), CO2 (7.28%), and He (0.110%). The carbon isotope values of methane, ethane, propane, and CO2 in the gas were -27.8‰, -20.2‰, -18.4‰, and 1.7‰, respectively. Based on the natural gas composition and alkane carbon/hydrogen isotope composition, the natural gas in well Qiatan-1 was determined to be coal-type gas in the high to over-mature stage. Considering the distribution, organic matter abundance, type, thermal maturity of its potential source rocks, the gas in this well was mainly sourced from Permian source rocks in the Permian Qipan Formation, and may also be mixed with a small amount of carbon isotopes, forming heavier inorganic hydrocarbon gases. In addition, the components and isotopic evidence of non-hydrocarbon gases such as N2, CO2, and He showed that a certain proportion of inorganic gas had mixed into the natural gas in well Qiatan-1. The helium isotopic composition suggested that the proportion of mantle-derived helium was about 14.6%, and the He content had reached the standard for helium-rich natural gas (He ≥ 0.100%).

Abstract To have effective water resource management, the distributed hydrological models are commonly applied for supporting the decision‐making processes. Among different inputs, the spatial distributed rainfall plays significant role in those model simulations. Many interpolation methods have been developed for generating distributed rainfall based on measurement samples. However, depending on the catchment characteristics and data availability, the suitable interpolation algorithm is case‐dependent. This paper presents one operational approach for determining the resonable interpolation algorithm in a complex large catchment (Var catchment, France). Based on the daily rainfall data (2008–2014) collected from 16 stations in the Var catchment, six different interpolation approaches including: inverse distance weight (IDW), spline, kriging with linear and spherical semi‐variogram models and geographically weighted regression considering elevation effects and the combined impacts of elevation and distance to the sea were tested. Integrated the results of statistical and modeling assessments, the 400 m resolution distributed rainfall generated by IDW algorithm shows high preference in generating distributed rainfall in the Var catchment. Moreover, the strategy described in the article also shows promising acceptability for other catchments.

Abstract Currently, the diagnosis of delirium is solely based on clinical observation, lacking objective diagnostic tools, and the regulatory networks and pathological mechanisms behind it are not yet fully understood. Exosomes have garnered considerable interest as potential biomarkers for a variety of illnesses. This research aimed to delineate both the proteomic and metabolomic landscapes inherent to exosomes, assessing their diagnostic utility in postoperative delirium (POD) and understanding the underlying pathophysiological frameworks. Integrated analyses of proteomics and metabolomics were conducted on exosomes derived from plasma of individuals from both the non-postoperative delirium (NPOD) control group and the POD group. Subsequently, the study utilized the Connectivity Map (CMap) methodology for the identification of promising small-molecule drugs and carried out molecular docking assessments to explore the binding affinities with the enzyme MMP9 of these identified molecules. We identified significant differences in exosomal metabolites and proteins between the POD and control groups, highlighting pathways related to neuroinflammation and blood-brain barrier (BBB) integrity. Our CMap analysis identified potential small-molecule therapeutics, and molecular docking studies revealed two compounds with high affinity to MMP9, suggesting a new therapeutic avenue for POD. This study highlights MMP9, TLR2, ICAM1, S100B, and glutamate as key biomarkers in the pathophysiology of POD, emphasizing the roles of neuroinflammation and BBB integrity. Notably, molecular docking suggests mirin and orantinib as potential inhibitors targeting MMP9, providing new therapeutic avenues. The findings broaden our understanding of POD mechanisms and suggest targeted strategies for its management, reinforcing the importance of multidimensional biomarker analysis and molecular targeting in POD intervention.

Abstract The preparation of sintered NdFeB magnets is complex, time-consuming, and costly. Data-driven machine learning methods can enhance the efficiency of material synthesis and performance optimization. Traditional machine learning models based on mathematical and statistical principles are effective for structured data and offer high interpretability. However, as the scale and dimensionality of the data increase, the computational complexity of models rises dramatically, making hyperparameter tuning more challenging. By contrast, neural network models possess strong nonlinear modeling capabilities for handling large-scale data, but their decision-making and inferential processes remain opaque. To enhance interpretability of neural network, we collected 1,200 high-quality experimental data points and developed a multi-head attention regression model by integrating an attention mechanism into the neural network. The model enables parallel data processing, accelerates both training and inference speed, and reduces reliance on feature engineering and hyperparameter tuning. The coefficients of determination for remanence and coercivity are 0.97 and 0.84, respectively. This study offers new insights into machine learning-based modeling of structure-property relationships in materials and has potential to advance the research of multimodal NdFeB magnet models.

Ground freeze‒thaw processes have significant impacts on infiltration, runoff and evapotranspiration. However, there are still critical knowledge gaps in understanding of hydrological processes in permafrost regions, especially of the interactions among permafrost, ecology, and hydrology. In this study, an alpine permafrost basin on the northeastern Qinghai‒Tibet Plateau was selected to conduct hydrological and meteorological observations. We analyzed the annual variations in runoff, precipitation, evapotranspiration, and changes in water storage, as well as the mechanisms for runoff generation in the basin from May 2014 to December 2015. The annual flow curve in the basin exhibited peaks both in spring and autumn floods. The high ratio of evapotranspiration to annual precipitation (>1.0) in the investigated wetland is mainly due to the considerably underestimated ‘observed’ precipitation caused by the wind-induced instrumental error and the neglect of snow sublimation. The stream flow from early May to late October probably came from the lateral discharge of subsurface flow in alpine wetlands. This study can provide data support and validation for hydrological model simulation and prediction, as well as water resource assessment, in the upper Yellow River Basin, especially for the headwater area. The results also provide case support for permafrost hydrology modeling in ungauged or poorly gauged watersheds in the High Mountain Asia.

Abstract The human brain’s distinctive folding pattern has attracted the attention of researchers from different fields. Neuroscientists have provided insights into the role of four fundamental cell types crucial during embryonic development: radial glial cells, intermediate progenitor cells, outer radial glial cells, and neurons. Understanding the mechanisms by which these cell types influence the number of cortical neurons and the emerging cortical folding pattern necessitates accounting for the mechanical forces that drive the cortical folding process. Our research aims to explore the correlation between biological processes and mechanical forces through computational modeling. We introduce cell-density fields, characterized by a system of advection-diffusion equations, designed to replicate the characteristic behaviors of various cell types in the developing brain. Concurrently, we adopt the theory of finite growth to describe cortex expansion driven by increasing cell density. Our model serves as an adjustable tool for understanding how the behavior of individual cell types reflects normal and abnormal folding patterns. Through comparison with magnetic resonance images of the fetal brain, we explore the correlation between morphological changes and underlying cellular mechanisms. Moreover, our model sheds light on the spatiotemporal relationships among different cell types in the human brain and enables cellular deconvolution of histological sections.

The development of Si–HfO2/Yb2Si2O7/Yb2SiO5 environmental barrier coatings (EBCs) aims to improve the operational temperature and longevity of ceramic matrix composites (CMCs) in turbine environments. Nevertheless, several critical questions remain unanswered, including the oxidation mechanism of Si–HfO2 bond coating, the compatibility of its mixed thermally grown oxide (m-TGO) with adjacent layers during thermal cycling, and the evolution pattern of vertical mud-cracks that impact the overall performance in service. Using plasma spraying physical vapor deposition (PS-PVD), we fabricated these EBCs on a CMC substrate, and thermal cycling tests at 1400, 1450, and 1500 °C revealed that their durability reached 200 h. m-TGO growth followed a parabolic model, with the oxygen diffusion activation energy being 133.69 kJ/mol between 1400 and 1450 °C and 101.47 kJ/mol from 1450 to 1500 °C, emphasizing that the transport of molecular oxygen is key to controlling the oxidation of m-TGO in this EBC system. Although residual stresses and stored elastic strain energy build up between m-TGO and adjacent layers, especially around the cristobalite phase transition temperature, causing interlaminar crack formation in later thermal cycles, the stored elastic strain energy remains lower than that of the silicon oxide–thermally grown oxide (SiO2–TGO) formed in Si bond coating system. In addition to [110] dislocations, (001) twinning and interaction zones between twinning and dislocations were discovered for the first time, driving the bifurcation of mud cracks. Notably, controlling the mud-crack density is vital for protection of Yb2SiO5 layer, as bifurcated mud-crack tips may converge with adjacent mud-cracks.

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1β-mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F+/CD206+, emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F+/CD206+ subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1β. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F+/CD206+ KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions.

Metasurfaces, composed of planar arrays of intricately designed meta-atom structures, possess remarkable capabilities in controlling electromagnetic waves in various ways. A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation, amplitude modulation, and polarization conversion. Conventional design processes often involve extensive parameter sweeping, a laborious and computationally intensive task heavily reliant on designer expertise and judgement. Here, we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics, which is compatible to both single- and multi-objective device design tasks. We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80% in the visible spectrum. We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator. The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination, with associated generation efficiencies surpassing 88%. Finally, we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength, with efficiencies over 50%. Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization, empowering designers to create diverse high-performance and multifunctional metasurface optics.

BackgroundIn vitro biomechanical testing is crucial for the preclinical assessment of novel implant designs. Given the constraints of limited supply and high costs associated with human specimens, calf spines are frequently employed as surrogates for human spines in both in vivo and in vitro biomechanical studies.MethodsThis study selected 60 spinal vertebrae from calves aged between 12 and 18 weeks. The specimens were randomly assigned to two treatment groups, A and B, each comprising 30 specimens. Group A served as the control without decalcification, while Group B underwent decalcification using an 18.3% ethylene diamine tetraacetic acid solution. The impact of decalcification was assessed through histological, imaging, and biomechanical analyses.FindingsDecalcification took approximately 2 months, resulting in osteoporotic vertebrae with a bone mineral density reduction of approximately 50.89% compared to pre-decalcification levels. The bone microstructure was significantly altered, characterized by a decrease in trabecular thickness and number and an increase in trabecular separation. Additionally, the trabecular bone pattern factor (TBPf) and Structure Model Index (SMI) increased. The modulus of elasticity, yield stress, and ultimate stress of the vertebral bodies were all reduced in correlation with the decrease in bone mineral density, demonstrating a strong correlation between these parameters.InterpretationThe data from this study indicate that the decalcification method is effective and capable of rapidly establishing an osteoporotic model suitable for biomechanical testing of clinical devices. This method offers the benefits of ease of operation, reliability, and a controllable degree of osteoporosis.

Summary: Parkinson’s disease (PD) is a common neurodegenerative disease and is difficult to treat due to its elusive mechanisms. Recent studies have identified a striking association between oligodendrocytes and PD progression, yet how oligodendrocytes regulate the pathogenesis of PD is still unknown. Here, we show that G-protein-coupled receptor 37 (GPR37) is upregulated in oligodendrocytes of the substantia nigra and that prosaposin (PSAP) secretion is increased in parkinsonian mice. The released PSAP can induce interleukin (IL)-6 upregulation and secretion from oligodendrocytes via a GPR37-dependent pathway, resulting in enhanced neuroinflammation, dopamine neuron degeneration, and behavioral deficits. GPR37 deficiency in oligodendrocytes prevents neurodegeneration in multiple PD models. Finally, the hallmarks of the PSAP-GPR37-IL-6 axis are observed in patients with PD. Thus, our results reveal that dopaminergic neurons interact with oligodendrocytes via secreted PSAP, and our findings identify the PSAP-GPR37-IL-6 axis as a driver of PD pathogenesis and a potential therapeutic target that might alleviate PD progression in patients.

This study was to investigate the in vitro antimicrobial activity of fish protein hydrolysate (FPH) against Vibrio harveyi, V. anguillarum, and V. scophthalmi, as well as the nonspecific immunity, intestinal microbiota, and disease resistance to V. harveyi in turbot. FPH was prepared from Pollock. The antibacterial activity of FPH was measured by the agar well diffusion, turbidometric assay, and plate count. The feeding trial was performed to study the effect of FPH on the resistance against V. harveyi in turbot after feeding three diets containing a high level of fish meal (FM), a high level of soybean meal (SM), and 100 g/kg FPH. Agar well diffusion showed the clearest inhibition zone of FPH was observed against V. harveyi, followed by V. scophthalmi. The bacterial growth curve and plate count showed a slight antibacterial effect of FPH against V. anguillarum. Results of the feeding trial showed that FPH enhanced antioxidant and immune responses before V. harveyi challenge as modulating immunoglobulin M (IgM), catalase (CAT), and myeloperoxidase (MPO) activities in serum, as well as the number of goblet cells in the intestine. Meanwhile, the expression of some pro-inflammatory cytokines (interleukin-1β [il-1β], il-6, and il-8) was downregulated in the FPH group after the V. harveyi challenge. Survival probability in the FPH group increased after challenging to V. harveyi based on the Kaplan–Meier analysis. Results of intestinal microbiota showed the relative abundance of Vibrio in the SM group was the highest, followed by the FPH and control groups. Similarly, the relative abundance of distal intestinal V. harveyi was significantly reduced in the FPH group by analyzing the vhhp2 gene. In conclusion, the present FPH against Vibrio strains was species-specific, with stronger antibacterial activity to V. harveyi. Dietary FPH enhanced the nonspecific immunity and antibacterial activity of turbot, increasing the resistance to V. harveyi.

Background: Fixed drug eruption (FDE) is a drug hypersensitivity reaction caused by antibiotics and non-steroidal anti-inflammatory drugs primarily. Antondine injection is a drug used to reduce fever, mainly composed of aminopyrine, antipyrine and barbiturate, and its adverse reactions include anaphylactic shock, epidermolysis, rash, agranulocytosis, etc. FDE caused by Antondine injection is an uncommon phenomenon, and the drug eruption caused by these ingredients has been reported in the current case report. However, the fatal severe fixed drug eruption caused by it has not been reported. Here, we report a case of severe PDE after treatment with Antondine, highlighting it’s necessary to avoid these medications with this ingredient when using antipyretic medications.

Intravascular large B-cell lymphoma (IVLBCL) is a highly aggressive type of non-Hodgkin’s lymphoma. The clinical manifestations and imaging of this disease are nonspecific, making diagnosis challenging. We report a case of a patient with recurrent stroke-like symptoms, primarily characterized by hemiplegia, vertigo, ataxia, and proteinuria. Brain MRI revealed multiple cerebral infarctions, microbleeds, and meningeal enhancement. Ultimately, the patient was diagnosed with IVLBCL through a brain tissue biopsy, and involvement of the kidneys was suspected. We suggest considering IVLBCL in patients who present with recurrent stroke-like symptoms, fluctuating neurological deficits, the aforementioned MRI findings, and involvement of other organs. Additionally, central nervous system vasculitis(CNSV) may represent a transitional manifestation of the disease. Pathological biopsy is the gold standard for diagnosis. We hope that through this case, doctors can gain a deeper understanding of IVLBCL, enabling early diagnosis and timely treatment to improve prognosis.

Changes in brain tissue stiffness are closely linked to the development and diseases of the nervous system. Endoplasmic reticulum (ER) stress plays a role in various pathological processes related to epilepsy. However, the relationship between stiffness changes, ER stress, and epilepsy remains unclear. This study aimed to investigate the impact of Best1 upregulation on alleviating ER stress and the underlying mechanism. Additionally, we proposed a protective strategy to prevent cell death resulting from ER stress in epilepsy. This study investigated the expression levels of ER stress-related proteins in epileptic tissues of varying stiffness. Atomic force microscopy revealed differences in stiffness across various lesion regions in patients with epilepsy. The expression levels of ECM and ER stress-related proteins were elevated in tissues with higher stiffness. Polypropionamide hydrogels were used to simulate extracellular matrix (ECM) with varying stiffness levels. Basal ER stress increased in the stiffer hydrogel substrates. Furthermore, the calcium-activated anion channel Bestrophin 1 (Best1) mitigated ER stress induced by both the stiffer substrate and thapsigargin. The loss-of-function mutations in Best1 inhibited this activity. The underlying mechanism involves the upregulation of the endosomal sorting complex required for the transport (ESCRT) components by Best1, which helps mitigate ER stress. These findings suggest that increased stiffness of the cellular microenvironment may contribute to neuronal death during epileptogenesis. Additionally, Best1 upregulation may serve as a protective strategy against excessive ER stress-induced neuronal damage in epilepsy.

IntroductionFritillaria taipaiensis P. Y. Li is a plant used to treat respiratory diseases such as pneumonia, bronchitis, and influenza. Its wild resources have become increasingly scarce, and the demand for efficient artificial cultivation has increased significantly in recent years. Phosphorus-solubilizing fungi can promote the dissolution of insoluble phosphate complex, which benefits plant nutrition. Another strategy for efficiently cultivating traditional Chinese medicine plants is to combine the soil with phosphorus-solubilizing fungi to provide nutrients and other desired features. This study aimed to investigate the effects of different phosphorus-solubilizing fungi and their combinations on photosynthesis, physiological and biochemical characteristics, and expression of protective enzyme system–related genes, and to find a reference strain suitable for the artificial cultivation and industrial development of F. taipaiensis P. Y. Li. In this study, the phosphorus-solubilizing fungi isolated from the rhizosphere soil of F. taipaiensis P. Y. Li were applied to the cultivation of F. taipaiensis P. Y. Li for the first time.MethodsIn this study, seven treatment groups (S1-S7) and one control group were set up using indoor pots as follows: S1 (inoculation with Aspergillus tubingensis), S2 (inoculation with A. niger), S3 (inoculation with Aspergillus nigerfunigatus) and S4 (inoculation with A. tubingensis and A. niger), S5 (inoculation with A. tubingensis and A. nigerfunigatus), S6 (inoculation with A. niger and A. nigerfunigatus), S7 (inoculation with A. tubingensis, A. niger, and A. nigerfunigatus), and CK (control group). These strains were inoculated into pots containing F. taipaiensis P. Y. Li bulbs,and the effects of different phosphorus-solubilizing fungi and combinations on the photosynthetic characteristics, basic physiological and biochemical indicators, and differential gene expression of protective enzyme systems in F. taipaiensis P. Y. Li leaves were determined.ResultsMost growth indexes showed significant differences in the fungal treatment groups compared with the CK group (P < 0.05). The stem diameter and plant height in the S5 group were the highest, which were 58.23% and 62.49% higher than those in the CK group, respectively. The leaf area in the S7 group was the largest, which increased by 141.34% compared with that in the CK group. Except for intercellular CO2 concentration (Ci), the contents of photosynthetic pigments, photosynthetic parameters, and amounts of osmoregulatory substances increased to varying degrees in the fungal treatment groups (P < 0.05). Among these, the S5 group had the highest stomatal conductance index and soluble sugar and free proline contents, whereas S6 had the highest chlorophyll a and soluble protein contents. In addition, the malondialdehyde (MDA) content in all inoculation groups was lower than that in the CK group. The MDA content was the lowest in S7, about 44.83% of that in the CK group. The activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) were higher in all inoculation groups than those in the CK group; the changes in SOD and CAT activities were significant (P < 0.05). The expression levels of FtSOD, FtPOD, and FtCAT in the S5 group were the highest, which were 8.67, 7.65, and 6.08 times of those in the CK group, respectively.ConclusionVarious combinations of phosphorus-solubilizing fungi exhibit differential capacities to enhance plant growth indices (including leaf area, plant height, and stem diameter), promote the accumulation of photosynthetic pigments, regulate osmotic pressure, and elevate antioxidant activity. Notably, The three fungal combinations (S7) were prone to cause a certain degree of antagonism, leading to suboptimal performances in certain biochemical indicators, such as free proline and POD levels. Our study pointed out that the S5 group inoculated with A. tubingensis and A. niger had the best overall effect. These experimental results provided a theoretical basis for the selection and development of artificial cultivation of F. taipaiensis P. Y. Li.

Abstract The emergence of monkeypox has become a global health threat after the COVID‐19 pandemic. Due to the lack of available specifically treatment against MPV, developing an available vaccine is thus the most prospective and urgent strategy. Herein, a programmable macrophage vesicle based bionic self‐adjuvanting vaccine (AM@AEvs‐PB) is first developed for defending against monkeypox virus (MPV). Based on MPV‐related antigen‐stimulated macrophage‐derived vesicles, the nanovaccine is constructed by loading the mature virion (MV)‐related intracellular protein (A29L/M1R) and simultaneously modifying with the enveloped virion (EV) antigen (B6R), enabling them to effectively promote antigen presentation and enhance adaptive immune through self‐adjuvant strategy. Owing to the synergistic properties of bionic vaccine coloaded MV and EV protein in defensing MPV, the activation ratio of antigen‐presenting cells is nearly four times than that of single antigen in the same dose, resulting in stronger immunity in host. Notably, intramuscular injection uptake of AM@AEvs‐PB demonstrated vigorous immune‐protective effects in the mouse challenge attempt, offering a promising strategy for pre‐clinical monkeypox vaccine development.

Lycopi herba, a traditional Chinese medicinal plant, has long been valued for its aerial parts. however, its roots, which are often discarded as non-medicinal waste, actually contain flavonoid compounds that possess potential medicinal values such as anti-inflammatory, antioxidant, and anti-tumor activities. Despite this, studies on the extraction, purification, and biological activity assessment of total flavonoids from L. herba roots (TFLHR) remain inadequate. Our study aimed to optimize the extraction and purification processes for TFLHR and evaluate their anti-proliferative effects on human fibroblast-like synoviocytes (HFLS-RA), which are key pathological cells in rheumatoid arthritis. By utilizing ultrasound-assisted extraction combined with response surface methodology (RSM), we optimized the extraction conditions, achieving a total flavonoid content of 90.484 ± 0.974 mg/g under the optimal settings: a liquid–solid ratio of 48:1 mL/g, 13 min of ultrasound treatment, 70 % ethanol, and an extraction temperature of 43°C. Subsequently, macroporous resin chromatography was employed for flavonoid purification, with AB-8 resin exhibiting the highest performance, achieving adsorption and desorption rates of 79.64 ± 1.51 % and 88.61 ± 1.02 %, respectively. By further refining the purification conditions through RSM, the purity of flavonoids was increased to 63.9 ± 1.86 %. Through ultra performance liquid chromatography tandem-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) analysis, 74 flavonoid compounds across 15 categories were identified. Further activity studies demonstrated that purified TFLHR exhibited significant concentration-dependent anti-proliferative effects on HFLS-RA cells. This study not only provides a scientific basis for the comprehensive utilization of L. herba root resources but also highlights the potential medicinal value of TFLHR in the treatment of rheumatoid arthritis, laying a foundation for future research into its specific mechanisms and clinical applications.

BackgroundDetecting programmed death ligand 1 (PD-L1) expression based on immunohistochemical (IHC) staining is an important guide for the treatment of lung cancer with immune checkpoint inhibitors. However, this method has problems such as high staining costs, tumor heterogeneity, and subjective differences among pathologists. Therefore, the application of deep learning models to segment and quantitatively predict PD-L1 expression in digital sections of Hematoxylin and eosin (H&E) stained lung squamous cell carcinoma is of great significance.MethodsWe constructed a dataset comprising H&E-stained digital sections of lung squamous cell carcinoma and used a Transformer Unet (TransUnet) deep learning network with an encoder-decoder design to segment PD-L1 negative and positive regions and quantitatively predict the tumor cell positive score (TPS).ResultsThe results showed that the dice similarity coefficient (DSC) and intersection overunion (IoU) of deep learning for PD-L1 expression segmentation of H&E-stained digital slides of lung squamous cell carcinoma were 80 and 72%, respectively, which were better than the other seven cutting-edge segmentation models. The root mean square error (RMSE) of quantitative prediction TPS was 26.8, and the intra-group correlation coefficients with the gold standard was 0.92 (95% CI: 0.90–0.93), which was better than the consistency between the results of five pathologists and the gold standard.ConclusionThe deep learning model is capable of segmenting and quantitatively predicting PD-L1 expression in H&E-stained digital sections of lung squamous cell carcinoma, which has significant implications for the application and guidance of immune checkpoint inhibitor treatments. And the link to the code is https://github.com/Baron-Huang/PD-L1-prediction-via-HE-image.

Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.

Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan–Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4–exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P

Abstract Background Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. Methods To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT–qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT–qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1’s regulation of autophagy in GC. Results Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. Conclusion PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC. Graphical Abstract

Abstract Background Pulmonary hypertension (PH) is a long-term disease that impacts approximately 1% of the world’s population. Currently, levosimendan (Lev) is proposed for PH treatment. However, the mechanism of Lev in the treatment of PH is unknown. Methods We used hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) to establish a PH cell model. A number of cell biology methods were performed to assay alterations in cell proliferation, migration and apoptosis after Lev treatment. qRT-PCR and WB were performed to test the levels of circUSP34 and miR-1298, and BMP/Smad protein respectively. In addition, the regulatory relationship between circUSP34 or BMPR2 with miR-1298 was verified through the use of double luciferase as well as RIP assay. In addition, we explored the regulatory effect of Lev on the circUSP34/miR-1298/BMP/Smad axis using a rat PH model. Results Our results demonstrate that Lev inhibited PASMCs cell proliferation, migration and promoted apoptosis exposed to hypoxia. In hypoxia-treated PASMCs, circUSP34 expression got downregulated while miR-1298 upregulated, whereas the addition with Lev resulted in upregulation of circUSP34 expression and downregulation of miR-1298 expression, indicating that circUSP34 can target and regulate miR-1298. In addition, miR-1298 targets and regulates the expression of BMPR2. In a rat PH model induced by hypoxia combined with SU5416, Lev upregulated circUSP34 targeting miR-1298-mediated BMP/Smad axis to alleviate the PH phenotype. Conclusion We have shown that Lev can be used as a therapeutic drug for PH patients, which works through the circUSP34/miR-1298/BMP/Smad axis to alleviate PH symptoms.

This paper utilizes data on the records of damage to expressways and main roads caused by precipitation in Liaoning Province from 2017 to 2021. It analyzes the temporal and spatial characteristics of damage accidents, calculates the effective rainfall before the occurrence of accidents, and establishes a probability fitting model for road water damage. The results show that precipitation-induced road damage events in Liaoning Province generally occur from May to October, with a peak in July and August. The occurrence of road water damage follows a pattern of gradually delaying from northwest to southeast, and the number of accidents is highly correlated with precipitation. The eastern and western parts of Liaoning are high-incidence areas, with Dandong, Chaoyang, Huludao, and Benxi being the high-incidence areas within the province. Among various methods compared, the fitting effect of the road water damage probability conforms to the Gaussian distribution probability density function. The critical rainfall threshold for disaster in the eastern and southern parts of Liaoning is higher than that in the central and northern parts. Under the same effective rainfall conditions, the risk of road water damage in plain areas is higher than in mountainous and hilly areas. The road water damage situation during a flooding process in Liaoning in 2022 is used for verification, indicating a strong role in flood control guidance.

Abstract The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

Abstract Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment. NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1β, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses. Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers. Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy.

To achieve rapid and accurate identification of valuable wood products, an analytical method was developed by combining electric soldering iron cauterization with soft ionization by chemical reaction in transfer-mass spectrometry (SICRIT-MS). SICRIT is a flow-through dielectric barrier discharge ionization technique pioneered by Zenobi et al. in 2016. The electric soldering iron cauterization-SICRIT-MS method requires no sample pretreatment, easy operation and a single analysis in less than 5 s, meeting the demands of rapid analysis. Operating parameters for the soldering iron and SICRIT ion source were optimized to achieve maximum total ion current intensity under soldering iron temperature of 450 ℃, ion source AC voltage amplitude of 2 000 V, and sample transfer line temperature of 150 ℃. With the optimized parameters, the SICRIT-MS method was applied to analyze valuable wood samples, including 29 certified standard wood samples and 6 online-purchased real samples, resulting in a dataset of 210 sets of mass spectral fingerprint data. Based on the mass spectral fingerprint data acquired under positive ion mode, a predictive model was trained using the random forest algorithm. The random forest model underwent optimization for the number of decision trees, max feature algorithm, and feature selection criteria, was evaluated through out-of-bag and 10-fold cross-validation. The results showed the error rates of out-of-bag and 10-fold cross-validation are 4.76% and 4.74%, respectively. The established random forest model can accurately distinguish wood samples from the genera Dalbergia, Guibourtia, and Pterocarpus with a classification accuracy of larger than 95%. The importance of features in distinguishing the three wood genera was investigated through binary classification modeling, revealing features 269.1, 270.1, 255.1, 159.0, 182.1, 102.1 and 83.1 as crucial in classification. These features may correspond to characteristic compounds in different wood species or differences in the content of the same compound across species. The predictive model was successfully applied to rapid identification of genera in valuable wood products sold online. Three purchased Guibourtia samples are confirmed as authentic, while the other three are not identified as the claimed genera. This method provides a scientific basis and experimental reference for authenticity identification and quality evaluation.

This study presents a detailed investigation into the soil arching effects within deep foundation pits (DFPs), focusing on their mechanical behavior and implications for structural design. Through rigorous 3D finite element modeling and parameter sensitivity analyses, the research explores the formation, geometric characteristics, and spatial distribution of soil arching phenomena. The investigation encompasses the influence of key parameters such as elastic modulus, cohesion, and internal friction angle on the soil arching effect. The findings reveal that soil arching within DFPs exhibits distinct spatial characteristics, with the prominent arch axis shifting as excavation depth progresses. Optimal soil arching is observed when the pile spacing approximates three times the pile diameter, enhancing soil retention and minimizing deformation risks. Sensitivity analyses highlight the significant impact of soil parameters on soil arching behavior, underscoring the critical role of cohesive forces and internal friction angles in shaping arching characteristics. By elucidating the interplay between soil parameters and soil arching effects, the research provides insights for optimizing pile spacing and structural stability.

Abstract Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780 to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.

Abstract Objective This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated. Methods A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda. Results In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include “skepticism about the accuracy of the model”, “delay in early prediction by the indicator of length of neuro-ICU stay”, and “lack of a proper protocol for clinical application”. Conclusions We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.

The wave spectrum describes the distribution of wave energy across frequency and direction. Obtaining wave spectrum information with high accuracy is of great value for oceanographic research and disaster prevention and reduction. Currently, wave spectral data can be obtained from remote sensing observations, global meteorological and climate reanalysis products, and in-situ observations, which exhibit different advantages and limitations in terms of spatio-temporal resolution, accuracy, and data coverage. Fusing these diverse spectral data to complement the advantage of improving the accuracy of wave spectrum is very promising. However, there is still no simple and effective method to fuse the above spectral data. In this study, a multi-source spectral fusion method is developed based on BU-NET, which realizes the integration of ERA5 spectra and SWIM spectra, with buoy spectra as the reference. The results of the systematic evaluation indicate that the fusion spectra alleviate parasitic peaks, address the issue of larger mean energy, and compensate for energy loss due to the cutoff frequency in the SWIM spectra. The fusion spectra also alleviate energy underestimation during high sea states in the ERA5 spectra. Furthermore, the accuracy of the significant wave height, mean wave period, dominant wave period, and dominant wave direction obtained from the fusion spectra is improved. The root mean square errors between these parameters from the fusion spectra and those from buoy spectra are 0.217 m, 0.378 s, 1.599 s, and 33.094°, respectively.

ABSTRACT Purpose Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T‐cell receptor (TCR) diversity in UTUC and UCB. Materials and Methods Targeted next‐generation sequencing or whole‐exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle‐invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes of MIBC. Results Chromatin regulatory genes were frequently mutated in both UTUC and UCB. Rapid relapse and progression of non‐MIBC are correlated with alterations of KMT2C and EP300. Frequency of alterations in chromatin regulatory genes is higher in UTUC patients with SBS22 and SBS2 signatures and lower in UCB patients with SBS2 and SBS6 signatures. GATA3 and CK5 double‐positive patients with higher frequencies of SMARCA4, ARID1A, and EP300 mutations have better prognoses than patients with basal subtypes. Although UTUC and UCB in the same patient can be either clonally related or developed independently, mutated genes in chromatin pathway were enriched in the related clones. Compared to UTUC, UCB had more deleterious mutations in DNA damage repair (DDR) genes, higher levels of tumor mutation burden (TMB) and copy number variations (CNVs), as well as higher TCR clonality and lower TCR diversity. Conclusions Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.

Cholesterol is an important component of fresh biological baits and essential precursor to synthesize steroid hormones for crustacean. However, the cholesterol demand in Pacific white shrimp broodstock and its roles on ovary development and reproductive capacity are unknown. In the present study, female Pacific white shrimp broodstock (initial weight 51.3 ± 0.5 g) were fed with three diets contained 0.5 %, 1 % or 1.5 % cholesterol for 45 days. The results found that dietary cholesterol levels did not affect survival rate, weight gain, egg-laying number, vitellogenin content and vitellogenin receptor gene expression in the hepatopancreas. However, the hepatosomatic index, gonadosomatic index, egg diameter, vitellogenin level in the ovary and fertilized egg, C22:6n-3 (DHA) level in the fertilized egg, total protein, triglyceride and cholesterol contents were all increased in the 1.0 % and 1.5 % cholesterol groups than those in the 0.5 % cholesterol group. Moreover, compared with the 0.5 % and 1.0 % cholesterol groups, the 1.5 % cholesterol group had significantly higher gonad maturation number, mating rate, estradiol level in the hemolymph, steroid hormones synthesis related genes (HMGCR, StAR, 17βHSD and 1vMFBP) expression in the ovary and hepatopancreas. In conclusion, dietary 1.5 % cholesterol could promote ovary development and reproductive capacity in female Litopenaeus vannamei broodstock by improving nutrients accumulation and steroid hormones synthesis pathway. Our results provide guidance for design of artificial compound feed and healthy development of shrimp broodstock farm.

The shallow sea underwater acoustic channel exhibits a significant sparse multipath structure. The temporally multiple sparse Bayesian learning (TMSBL) algorithm can effectively estimate this sparse multipath channel. However, the complexity of the algorithm is high, the signal-to-noise ratio (SNR) of shallow-sea underwater acoustic communication is low, and the estimation performance of the TMSBL algorithm is greatly affected by noise. To address this problem, an improved TMSBL underwater acoustic channel estimation method based on a dictionary learning noise reduction algorithm is proposed. Firstly, the K-Singular Value Decomposition (K-SVD) dictionary learning method is used to reduce the noise of the received pilot matrix, reducing the influence of noise on the signal. Then, the Generalized Orthogonal Matching Pursuit (GOMP) channel estimation method is combined to obtain a priori information such as the perceptual matrix and hyperparameter matrix for TMSBL channel estimation; and the noise variance is obtained by using the null subcarrier calculation instead of iteratively updating the noise variance in the TMSBL, to improve the estimation accuracy and reduce the algorithmic complexity. Finally, the TMSBL channel estimation method is used to estimate the underwater acoustic channels of different symbols jointly. The simulation results show that the normalized mean square error of the channel estimation of the improved TMSBL method is reduced by about 92.2% compared with the TMSBL algorithm, obtaining higher estimation accuracy; running time is reduced by about 45.6%, and there is also better performance in terms of the running speed, which provides a reference for underwater acoustic channel estimation.

Abstract Objective This study aims to assess the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a potential indicator for predicting the probability of developing pulmonary arterial hypertension (PAH) in hyperthyroidism patients. A nomogram model will be developed based on our findings, as well as the receiver operating characteristic (ROC) curve. Methods The study involved 166 hyperthyroid patients treated at Yijishan Hospital, and the period covered August 2021 to August 2022. Patients were divided into two groups according to pulmonary artery systolic pressure ≥35 mmHg. Univariate and multivariate logistic analyses were performed on the two groups' demographic and laboratory data to identify potential diagnostic markers. These parameters were evaluated using ROC curves to determine their precision in forecasting PAH. The findings were validated by plotting a calibration curve based on a line chart model. Results In the study, eventually, 80 patients were enrolled: 30 in the PAH group and 50 in the No PAH group. Multipleistic regression analysis predicted the occurrence risk of developing PAH. When paired with other conventional echocardiographic parameters (such as TAPSE, MPI, and SV) and serological markers (such as FT3 and FT4), the developed model demonstrated outstanding predictive performance with an area under the ROC curve of 0.985, a Youden index of 0.971, a sensitivity of 100%, and a specificity of 97.1%. Conclusions The nomogram model constructed by combining the TAPSE/PASP ratio with FT3 and FT4 serum markers, as well as conventional ultrasound parameters SV and MPI in hyperthyroidism patients, demonstrates robust discriminatory ability and consistency.

Abstract Background The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. Methods Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. Results In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. Conclusion This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Abstract Background Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. Methods We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. Results We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. Conclusions Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC. Graphical abstract The mechanism of circ0003692 in suppressing metastasis of GC. FNDC3B-267aa encoded by circ0003692 interacted with c-Myc and promoted the proteasomal degradation of c-Myc, thereby down-regulated c-Myc-Snail/Slug axis and EMT pathway.