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Abstract Great progress has been made in utilizing immune checkpoint blockade (ICB) for the treatment of non-small-cell lung cancer (NSCLC). Therapies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, expressed on tumor cells, have demonstrated potential in improving patient survival rates. An unresolved issue involves immune suppression induced by exosomal PD-L1 within the tumor microenvironment (TME), particularly regarding CD8+ T cells. Our study unveiled the crucial involvement of LAMTOR1 in suppressing the exosomes of PD-L1 and promoting CD8+ T cell infiltration in NSCLC. Through its interaction with HRS, LAMTOR1 facilitates PD-L1 lysosomal degradation, thereby reducing exosomal PD-L1 release. Notably, the ability of LAMTOR1 to promote PD-L1 lysosomal degradation relies on a specific ubiquitination site and an HRS binding sequence. The findings suggest that employing LAMTOR1 to construct peptides could serve as a promising strategy for bolstering the efficacy of immunotherapy in NSCLC. The discovery and comprehension of how LAMTOR1 inhibits the release of exosomal PD-L1 offer insights into potential therapeutic strategies for improving immunotherapy. It is imperative to conduct further research and clinical trials to investigate the feasibility and efficacy of targeting LAMTOR1 in NSCLC treatment.

Abstract To evaluate the efficacy of neuronavigation-assisted stereotactic drilling drainage compared with that of craniotomy in the treatment of massive intracerebral haemorrhage (ICH) in elderly patients. This was a randomized, controlled, blind endpoint clinical study. Elderly patients with massive ICH treated at our neurosurgery department, without the formation of brain herniation preoperatively, all underwent neurosurgical intervention. Patients were randomly assigned to two groups: the minimally invasive surgery (MIS) group, which received neuronavigation-assisted stereotactic drilling drainage, and the craniotomy haematoma removal surgery (CHRS) group. Patient characteristics, surgical anaesthesia methods, surgery duration, intraoperative bleeding volume, duration of ICU stay duration of hospital stay, complications, and modified Rankin scale (mRS) scores at 90 days posttreatment were compared between the two groups. Statistical analysis was performed on the collected data. A total of 67 patients were randomly assigned, with 33 (49.25%) in the MIS group and 34 (50.75%) in the CHRS group. Compared with the CHRS group, the MIS group had advantages, including the use of local anaesthesia, shorter surgery duration, less intraoperative bleeding, shorter ICU stay, and fewer complications (P 0.05). For elderly patients with massive ICH without brain herniation, stereotactic drilling drainage is a simple surgical procedure that can be performed under local anaesthesia. Patients treated with this approach seem to have better outcomes than those treated with craniotomy. In clinical practice, neuronavigation-assisted stereotactic drilling drainage is recommended for surgical treatment in elderly patients with massive ICH without brain herniation. Clinical trial registration number: NCT04686877

Abstract China faces challenges in reaching its carbon neutrality goal by the year 2060 to meet the Paris Agreement and improving air quality simultaneously. Dramatic nitrogen emission reductions will be brought by this ambitious target, yet their impact on the natural ecosystem is not clear. Here, by combining two atmospheric chemistry models and two process-based terrestrial ecosystem models constrained using nationwide measurements, we show that atmospheric nitrogen deposition in China’s terrestrial land will decrease by 44–57% following two emission control scenarios including one aiming at carbon neutrality. They consequently result in a pronounced shrinkage in terrestrial net ecosystem production, by 11–20% depending on models and emission scenarios. Our results indicate that the nitrogen emission reductions accompanying decarbonization would undermine natural carbon sinks and in turn set back progress toward carbon neutrality. This unintended impact calls for great concern about the trade-offs between nitrogen management and carbon neutrality.

Olfaction, the sense of smell, is crucial for animal survival, especially in localizing prey or food. However, little is known about the fish behavioral responses to specific food odors and which olfactory receptor might be activated by the food odors. Here, we examined the evolutionary relationships and classified the subfamilies of olfactory receptors (ORs), and conducted behavioral and gene expression analysis in grass carp (Ctenopharyngodon idellus). We identified 196 intact ORs in the grass carp genome and classified them into 8 subfamilies: β, δ, ε, η, γ, κ, θ, and ζ. 12 representative ORs (4 β, 4 δ, and 4 ε) were highly expressed in the olfactory epithelium (OE) of 24-month-old grass carp. Behavioral exploration found that grass carp showed different behaviors to different food odors at a series of concentrations. Specifically, 0.01 μmol/L amino acid mixtures and 0.005 × Hydrilla verticillata extracts strongly changed the preference index and swimming trajectories in 6-month-old grass carp. In addition, the two food odors stimulation differentially induced ORs expression in three tissues, especially strong in the olfactory bulb and brain. Altogether, our results suggest that olfaction plays an important role in the regulation of fish feeding behavior and provide a basis for further studies on the function and specific recognition of olfactory receptors in fish.

Complex equipment refers to special equipment that differs from general equipment. The collaborative development work of complex equipment in the military-civilian integration context involves numerous suppliers. We consider a two-tier supply network composed of different suppliers that participate in the development work to assemble complex equipment that cooperate with a main-manufacturer regarding spare parts. However, in terms of spare parts, a substitution relationship exists in assembly work for complex equipment. Hence, selecting a suitable supplier from the matching process between suppliers and spare parts under a military-civilian integration background is essential. This study considers three main analyses to obtain a suitable supplier for the development work of complex equipment. First, we construct a two-stage model to acquire the necessary evaluation dimension for subsequent processes. Second, we examine the evaluated attributes for the matching process based on entropy-group-DEMATEL analysis. Third, we perform information aggregation for the uncertain preference information between spare parts and suppliers using a Bonferroni mean operator. Finally, an illustrative example is presented to demonstrate the whole efficiency. Through the aforementioned analysis, we can select a suitable supplier that could participate in complex equipment military-civilian collaborative development work.

Abstract Background Sleep disorders have a significant impact on asthma. The aim of this study was to explore the association between nocturnal bedtime and asthma among adults in the United States. Methods This study was a cross-sectional analysis involving 11,475 participants from the National Health and Nutrition Examination Survey (NHANES) during the period of 2015–2018. Nocturnal bedtime was categorized into three distinct groups: 2100 h or earlier, between 2100 h and 2300 h, and 2300 h or later. The association between night bedtime and asthma was detected using multivariable logistic regression analyses. Additionally, subgroup analyses were conducted to assess the impact of subgroups. Results After adjustment for confounders, a positive association was revealed between later bedtime (after 2300 h) and the prevalence of asthma (OR = 1.20, 95%CI: 1.01–1.43). In the subgroup analysis, the following factors were associated with increased risk: 18–39 years (OR = 1.23, 95%CI: 1.02–1.48); female sex (OR = 1.30, 95%CI: 1.01–1.68); Hispanic patients (OR = 1.66, 95%CI: 1.17–2.37); heavy drinkers (OR = 1.52, 95%CI: 1.17–1.96); Body Mass Index (BMI) (

Abstract Superwetting aerogel is a promising alternative for the remediation of emulsified oily wastewater for its high porosity combined with extreme wettability enabled high separation performances to emulsion wastewater. However, it remains challenging for superwetting aerogels to accomplish high-performance dual separation to surfactant-stabilized oil-in-water (O/W) and water-in-oil (W/O) emulsions with high stability. Herein, an environmentally benign superamphiphilic composite aerogel was prepared by a green synthesis route that relied on the utilization of natural amphiphilic biomass. Collagen fibers (CFs) were utilized to construct the three-dimensional (3D) supramolecular skeleton of aerogel to provide high storage capacity of water/oil and outstanding capillary effect to boost the mass transfer. The two-dimensional (2D) lamellar structure of gelatin (Gel) was further grown on the skeleton of CFs aerogel to play the role for simultaneously enhanced demulsifying capability and spreading of emulsions. The as-prepared superamphiphilic aerogel enabled the separation of highly stable surfactant-stabilized O/W and W/O emulsions with high separation efficiency and flux. Excellent recycling performances and anti-fouling performance were also confirmed. Our investigations therefore demonstrated that the structural engineering of superamphiphilic aerogel is a promising way to realize high-performance dual separation of surfactant-stabilized O/W and W/O emulsion wastewater. Graphical Abstract

Objective: Endoscopic injection is one of the simplest minimally invasive methods for the treatment of gastroesophageal diseases. However, the safety of injection material limits its clinical application. We investigated the feasibility, safety and efficacy of endoscopic autogenous fat transplantation (EAFT) in the lower part of esophagus in the treatment of gastroesophageal reflux disease in New Zealand albino rabbits. Methods: Eight New Zealand albino rabbits were used for autogenous fat transplantation. The dynamic pH value of the lower esophagus was monitored before and one week after fat transplantation in two rabbits. The local retention of fat was observed by endoscopy, and the pathological analysis was made at the junction of esophagus and stomach after two weeks of fat transplantation in six albino rabbits. During the experiment, the weight, dietary habit and infection of albino rabbits were monitored. Results: Endoscopic autogenous fat transplantation of the lower esophagus was successfully performed in 8 albino rabbits. The average pH value of the esophagus increased from 5.6 to 7.5 and 7.4 to 7.9, respectively in two rabbits one week after transplantation. The fat barrier of the lower esophagus was remained locally and observed by endoscopy two weeks after transplantation in six rabbits. Pathology showed that the adipocytes survived in the submucosa with neovascularization. No complications of bleeding, perforation and infection occurred. All albino rabbits kept normal dietary habit. No significant changes in weight were observed. Conclusion: Endoscopic autogenous fat transplantation in lower esophagus is considered as a safe and feasible method by preliminary animal experiments, which can provide a new option in the treatment of gastroesophageal reflux disease (GERD) and is worth further study.

Abstract Aim Recent imaging studies have found significant abnormalities in the brain’s functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. Methods We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. Results In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P

Abstract Having an accurate understanding of the scale effect of surface morphology characteristics is crucial to examining the mechanical behavior of rock structural plane. At present, the quantification and sampling methods of surface morphology show diversity, which is the potential reason for the inconsistent research conclusions on scale effect. Firstly, based on mathematical statistics and correlation analysis, the most representative parameter is proposed from hundreds of morphological parameters. Then, the previous scale effect sampling methods are analyzed. In order to ensure that the selected samples are representative, a novel sampling method, considering all morphological information, is proposed. By means of the novel quantification and sampling methods, the size effect characteristics are systematically analyzed. Under the conditions of different rock types, shear directions and sampling locations, etc., discontinuity roughness does not change significantly with sampling scale. As sampling scale increases, the distribution range of representative samples is gradually concentrated, the total amount decreases, and the proportion increases. However, the distribution of representative samples on the initial structural plane does not show obvious regularity. These findings would provide theoretical support for the deformation control and stability analysis of rock mass in engineering.

Abstract Background Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. Materials and methods This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. Results The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1. Conclusions Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Abstract Background The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). Methods This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. Results Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p

Abstract Microorganisms are essential in the decomposition of corpses and play a significant role in forensic science. However, previous studies have primarily focused on animal remains, specifically the gut, skin, and burial environment. Insufficient research has been conducted on the microbiota of human cadavers, especially in cases of advanced decomposition and additional tissues, resulting in a lack of relevant reference data. In this study, the microbiota of eight cadavers at different stages of decomposition were detected using 16S rRNA, metagenomic sequencing and 2bRAD-M sequencing. Nine different sites, including oral and nasal cavities, heart, liver, spleen, lung, kidney, muscle and gut, were analysed and the efficacy of these methods was evaluated. The results showed that 16S rRNA sequencing was the most cost-effective method for the study of cadavers in the early stages of decomposition, whereas for cadaveric tissues in the late stages of decomposition, 2bRAD-M could overcome host contamination more effectively than metagenomic sequencing. This paves the way for new opportunities in data retrieval and promotes in-depth investigations into the microbiota.

Objective Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re‐rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS‐PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. Methods This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS‐PSAT at our institution and were followed up for 8–48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle‐Hindfoot Scale (AOFAS‐AHS), associated with local complications and isokinetic tests. Results None of the patients had infection, necrosis, or sural nerve injury. Re‐rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS‐AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). Conclusion The MIS‐PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re‐rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

ABSTRACT: Noncovalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals and hydrogen bonding for GA, and hydrophobic forces for others. Conformation of LF was affected at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, whereas RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(2-ethylbenzothiazoline-6-sulfonate) (ABTS), and ferric reducing antioxidant power (FRAP) models. Caffeic acid, CGA, and RA significantly decreased the emulsifying stability index and improved foam ability of LF, and the effect of CA and RA was the most remarkable, respectively.

Shipwreck salvage is a risky, time-consuming, and expensive process. Although there are many sunken ships along coastlines and in the open seas, the salvage process of a sunken ship has rarely been reported. The integrated salvage of the “Yangtze River Estuary II” shipwreck used a novel method with 22 closely locked curved rectangular pipes to form a watertight base that wrapped the shipwreck inside. The basing was lifted out of the water using a powerful crane situated on an engineering ship. For the first time, the tunneling method was used in a shipwreck salvage project, significantly reducing the disturbance to the shipwreck and its stowage, thereby preserving the original state and integrity of the shipwreck to the greatest extent. In this study, the basic concepts of the salvage method and process are explained. Solutions to critical issues in the new salvage method are provided, including jacking force prediction and major considerations for the structural design of the salvage system. The design of the salvage system and salvage process of the “Yangtze River Estuary II” shipwreck are introduced. The monitored jacking force, pipe deformation, and observed water-tightness verified that the proposed method was effective and efficient. Other possible application scenarios for the proposed method are presented at the end.

Based on the best-track dataset from the Shanghai Typhoon Institute/China Meteorological Administration, the paper provides a comprehensive summary and analysis of tropical cyclone (TC) activities in the Western North Pacific (WNP) and the South China Sea (SCS) for 2022. Using the historical climatology from 1951 to 2020, the anomalous conditions during 2022 in TC frequency, origin locations, tracks, intensity, and duration for the entire ocean basin as well as landfall events in China are examined. Results show that the overall TC frequency is slightly lower than normal, but the multiple TC events have a very high frequency of occurrence. Origin locations of TCs, which mark the starting points of their paths, show a large westward and northward deviation from climatology. Around 40% of the named TCs exhibit a shift in their direction of movement from westerly to easterly. Additionally, comparisons of the means, medians, upper and lower quartiles all indicate that the intensity of TCs in 2022 is generally lower than the climatology, with the duration of TCs at tropical storm intensity or above being shorter than usual. A notable observation is the fewer incidence of TC landfalls in China, but with a geographical concentration in Guangdong Province. These anomalous annual TC activities are influenced by related atmospheric and oceanic environmental conditions modulated by multi-scale climate variability. The findings provide useful information for enhancing disaster mitigation strategies in the Asia-Pacific region.

The corrosion features of 20# carbon steel, the base material of sour water stripper, in NH4Cl solution were examined in this research. The anatomical samples of the corroded parts were characterized by an X-ray diffractometer and other analytical tools. It was found to be a localized perforation caused by pitting, and the corrosion product was FeCl2. 20# steel was subjected to electrochemical testing using Tafel polarization and Electrochemical impedance spectroscopy. The studies showed that the 20# steel’s cathodic depolarization reaction rate speeds as density rises, and that the concentration polarization gets more marked as temperature rises. The corrosion rate of 20# steel is the fastest when temperature hits its highest point of 80°C, measuring 4.7142 mm/a. When density rose from 5 to 20%, corrosion rate grew from 1.6378 to 7.2430 mm/a.

Abstract Background Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Abstract Background Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long‐term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. Methods In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4‐week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Results Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2‐year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12‐month progression‐free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2‐55.6), with an 18‐month PFS rate of 37.8% (95% CI, 22.7‐52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3‐36.9), and the 24‐month OS rate was 47.8% (95% CI, 31.7‐62.3). Age > 50 years, programmed death‐ligand 1 (PD‐L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. Conclusion Long‐term survival follow‐up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first‐line platinum‐based chemotherapy. No new safety signals were noted with long‐term treatment.

Abstract Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract

Abstract Background The neutrophil percentage-to-albumin ratio (NPAR), which is defined as the percentage of neutrophils divided by the concentration of albumin, is a cost-effective and readily available biomarker of inflammation. This study aimed to evaluate the association between the NPAR and the severity of coronary atherosclerosis in patients with chronic kidney disease (CKD). Methods A total of 280 CKD patients who underwent coronary angiography were retrospectively enrolled in this study. The severity of coronary atherosclerosis was evaluated using the Gensini score (GS). Patients were divided into low-, medium- and high-NPAR groups according to the tertiles of the NPAR values. Logistic regression analysis was conducted to analyze the relationship between the NPAR and the GS. The cutoff points for the sensitivity and specificity of the NPAR in predicting the GS were estimated via receiver operating characteristic (ROC) analysis. Results There was a higher prevalence of coronary artery disease (CAD) among CKD patients with higher NPARs (P =0.041). More patients in the high-NPAR group had complex CAD (triple-vessel disease and/or left main coronary artery stenosis) and chronic total occlusion lesions, and more of these patients required revascularization therapy (P60) in CKD patients was 1.91 (sensitivity 0.495, specificity 0.749), with an area under the curve (AUC) of 0.650 (95% CI 0.581-0.719, P

Abstract Porous materials with ultrahigh specific strength are highly desirable for aerospace, automotive and construction applications. However, because of the harsh processing of metal foams and intrinsic low strength of polymer foams, both are difficult to meet the demand for scalable development of structural foams. Herein, we present a supramolecular metallic foam (SMF) enabled by core-shell nanostructured liquid metals connected with high-density metal-ligand coordination and hydrogen bonding interactions, which maintain fluid to avoid stress concentration during foam processing at subzero temperatures. The resulted SMFs exhibit ultrahigh specific strength of 489.68 kN m kg−1 (about 5 times and 56 times higher than aluminum foams and polyurethane foams) and specific modulus of 281.23 kN m kg−1 to withstand the repeated loading of a car, overturning the previous understanding of the difficulty to achieve ultrahigh mechanical properties in traditional polymeric or organic foams. More importantly, end-of-life SMFs can be reprocessed into value-added products (e.g., fibers and films) by facile water reprocessing due to the high-density interfacial supramolecular bonding. We envisage this work will not only pave the way for porous structural materials design but also show the sustainable solution to plastic environmental risks.

Abstract Background Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. Methods This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. Results The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI

Abstract Killer cell lectin-like receptor B1 (KLRB1) is implicated in cancer progression and immunity. In this study, we aimed to evaluate the expression levels of KLRB1 in lung adenocarcinoma (LUAD) and analyze the relationship between KLRB1 expression levels, LUAD progression, and the tumor immune microenvironment. KLRB1 levels in LUAD were analyzed using data from the TCGA and XENA databases. Additionally, the diagnostic values of KLRB1 were analyzed in patients with LUAD. Survival and meta-analyses were employed to investigate the relationship between KLRB1 levels and other prognostic factors in patients with LUAD. Bioinformatics and cellular experiments were used to understand the functions and mechanisms of KLRB1. In addition, correlation analysis was used to investigate the relationship between KLRB1 levels and the immune microenvironment in LUAD. Reduced KLRB1 expression in LUAD was found to positively correlate with tumor size, distant metastasis, pathological stage, age, overall survival, diagnostic value, and disease-specific survival in patients with LUAD (P

Abstract Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.

The ginsenoside isomers were analyzed and distinguished by using inlet ionization-high resolution mass spectrometry technology under positive and negative ion modes with optimum inlet temperatures. The results showed that under the full scanning mode of positive and negative ion modes with the optimum experimental temperature, different types of ions were formed according to the characteristics of different numbers of polymers formed by isomeric monomers of ginsenoside, and the identification of ginsenoside isomers was realized. For the identification of ginsenoside CK and Rh2, there was no obvious difference in their MS spectra under positive ion mode. However, under negative ion mode with the inlet temperature of 200 ℃, ginsenoside CK tended to form polymers of [M+Cl]－, Rh2 tended to form polymers of [M+COOH]－, and the number of polymers of CK was significantly higher than that of Rh2. For the identification of ginsenoside Rb2 and Rc, under positive ion mode with the inlet temperature of 200 ℃, ginsenoside Rb2 and Rc could produce polymers of [M+Na]+, but the polymers peak intensity of Rb2 was significantly higher than that of Rc. Under negative ion mode with the inlet temperature of 200 ℃, Rb2 tended to form polymers of [M+Cl]－, and Rc tended to form polymers of [M+COOH]－. For the identification of ginsenoside Rg1 and Rf, there was no obvious difference in their MS spectra under the positive ion mode. Under negative ion mode with the inlet temperature of 200 ℃, Rg1 and Rf tended to form polymers of [M+Cl]－ and [M−H]−, respectively. In this study, the three pairs of isomers in ginsenosides were basically identified by using the full MS scanning method and the control of the mass spectrometry inlet temperature. The experimental method is simple, fast, and has the characteristics of low consumption. This study confirms that the entrance ionization mass spectrometry technique can provide a theoretical reference for the rapid discrimination and identification of ginsenoside isomers.

Abstract The design and implementation of virtual museums have evolved over decades, broadening the scope of traditional museum exhibitions and serving as an effective complement to physical museums. However, virtual visual effects have consistently fallen short of replicating the authentic exhibition experience and cannot substitute for physical museums. In this paper, we report a dual-mode mixed visualization system combining computational photography and binocular stereo vision techniques, and introduce an innovative virtual museum for Sanxingdui bronzes. This approach enables visitors to engage with the artifacts in a multifaceted manner-allowing for navigation, interaction, auditory guidance, and the examination of textural details as if handling the artifacts directly. Further analysis of participant responses in terms of visual cognition and aesthetic appreciation across different settings demonstrates that this dual-mode mixed visualization delivers not only a spatiotemporal experience consistent with the real world but also surreal visual effects. This immersive experience allows audiences to experience Sanxingdui art intimately, offering both high-resolution visuals and cost-effectiveness.

Abstract Ambient air temperature is a key factor affecting human health. Female reproductive disorders are representative health risk events under low temperature. However, the mechanism involving in cold-induced female reproductive disorders remains largely unknown. Female mice were intermittently exposed to cold conditions (4 °C) to address the health risk of low temperature on female reproductive system. Primary granulosa cells (GCs) were prepared and cultured under low temperature (35 °C) or exposed to β3-adrenoreceptor agonist, isoproterenol, to mimic the condition of cold exposure. Western-blot, RT-PCR, co-IP, ELISA, pharmacological inhibition or siRNA-mediated knockdown of target gene were performed to investigate the possible role of hormones, gap conjunction proteins, and ER stress sensor protein in regulating female reproductive disorders under cold exposure. Cold exposure induced estrous cycle disorder and follicular dysplasia in female mice, accompanying with abnormal upregulation of progesterone and its synthetic rate-limiting enzyme, StAR, in the ovarian granulosa cells. Under the same conditions, an increase in connexin 43 (CX43) expressions in the GCs was also observed, which contributed to elevated progesterone levels in the ovary. Moreover, ER stress sensor protein, PERK, was activated in the ovarian GCs after cold exposure, leading to the upregulation of downstream NRF2-dependent CX43 transcription and aberrant increase in progesterone synthesis. Most importantly, blocking PERK expression in vivo significantly inhibited NRF2/CX43/StAR/progesterone pathway activation in the ovary and efficiently rescued the prolongation of estrous cycle and the increase in follicular atresia of the female mice induced by cold stress. We have elucidated the mechanism of ovarian PERK/NRF2/CX43/StAR/progesterone pathway activation in mediating female reproductive disorder under cold exposure. Targeting PERK might be helpful for maintaining female reproductive health under cold conditions.

Abstract Background Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. Methods Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1β, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. Results NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. Conclusions NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.

Abstract Background Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously. Methods Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse. Results Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P

Abstract The problem of bearing current is common in wind power generation system, which leads to the attenuation of generator life and great economic losses. Bearing voltage of a 5.5 MW wind‐turbine permanent magnet synchronous generator is studied. The bearing voltage equivalent circuit is modelled by studying the internal system structure of the generator, and an extraction method of cable parameters, generator winding parameters and stray capacitance parameters based on experiments is proposed to simulate the system. A system test platform is built to test the common mode voltage, common mode current and bearing voltage, and the test results are compared with the simulation results in time domain and frequency domain. The result indicate that the common mode equivalent model can accurately simulate the actual bearing voltage. Finally, rotor flange insulation is adopted to suppress bearing voltage. The relationship between the design of rotor flange insulation with suppressing effect is discussed. Finally, an optimisation design method is presented for the proposed suppression scheme.

Abstract The modelling and analysis of high‐frequency bearing voltage are of great significance to the assessment and mitigation of the electrical erosion risk in wind power systems. However, the dual‐winding permanent magnet synchronous generator (DW‐PMSG), as one of the mainstream models in wind power industry, has not been specifically analysed for its bearing voltage modelling method in the existing research. The high frequency common mode equivalent circuit model of DW‐PMSG is established, and the effect of parasitic parameters between two sets of winding on bearing voltage is analysed. A model parameters extraction method based on differential evolution algorithm is proposed, and the range of parameters is estimated by finite element simulation and test results, which improves the search efficiency and solution accuracy. The accuracy of the proposed model is verified by the comparison of simulation and experimental results. On this basis, it is possible to conduct more in‐depth research on the bearing voltage and bearing currents of DW‐PMSG, and provide theoretical basis and simulation means for the design of suppression schemes.

ABSTRACTWith the development of dynamic acquisition technology for satellite video data, significant progress in target tracking has been made in recent years. This progress plays an important role in monitoring rapidly changing events. Different from targets in ordinary videos, targets in satellite videos usually demonstrate the phenomenon of a small size occupation pattern (small) and weak feature capture (dim) due to occlusion, illumination variation, and confusion with the surroundings. To the best of our knowledge, while some review work has been proposed for satellite videos object tracking, it has primarily concentrated on new datasets or has simply applied target tracking algorithms designed for ordinary videos directly to satellite videos for review. There is a lack of a comprehensive overview of satellite videos data sources and previous satellite video target tracking algorithms. Hence, there is a need for a systematic summary and in-depth exploration of the theory and the present state of satellite video object tracking. We provide an overview as well as a meta-analysis of satellite video targets, data sources, performance metrics, state-of-art models, and the trend of the target-specific comparative methods. To identify emerging research trends and opportunities, we classify established and emerging algorithms into three main categories and evaluate their performance on typical satellite videos. By providing comprehensive comparisons from both experimental (qualitative and quantitative) and theoretical perspectives, we demonstrate the tracking effects of several popular methods in various situations to show their strengths and weaknesses. In addition, this paper also collects the latest open-source datasets and predicts promising future research directions. Our collections of satellite videos benchmark datasets are available at: https://zenodo.org/record/8425369.

ObjectivesYao syndrome (YAOS, OMIM# 617321) is a kind of systemic autoinflammatory diseases (SAIDs) linked to the nucleotide-binding oligomerization domain containing 2 (NOD2). Clinical reports of YAOS in China are sparse. Herein, we reported the largest YAOS cohort of Chinese patients to expand the understanding of its phenotype, genotype, and therapeutic responses.MethodsThis study enrolled 15 adult patients diagnosed with YAOS at Peking Union Medical College Hospital from April 2015 to May 2024. Whole-exome sequencing was performed on all patients. Clinical data, genetic variations, and treatment responses were documented and compared with a Caucasian cohort.ResultsThe mean age of disease onset was 35 ± 17 years old. The most common clinical manifestations included recurrent high-grade fever (100%), gastrointestinal symptoms (73.3%), arthralgia/arthritis, fatigue, myalgia, and lower extremity swelling (46.7%). All patients exhibited elevated acute-phase reactants during episodes. 12 heterozygous NOD2 variants were identified, with Q902K in 4 patients, R471C in 3, and variants c.-14C>T, A110T, S127L, R311W, A432V, Y514H, R541P, A661P, K818Q, A886V each found in individual patients. 90% of the patients responded well to glucocorticoids, and 55.6% to sulfasalazine. 66.7% of patients who received TNF inhibitors achieved complete resolution of symptoms. Additionally, one patient each responded favorably to canakinumab and tocilizumab. Compared to the Caucasian cohort, our cohort exhibited a more balanced gender ratio and a higher proportion of recurrent fever, proteinuria/hematuria as well as more frequent leukocytosis, elevated acute phase reactants, and anemia. Lower proportions of arthralgia/arthritis, skin rashes, headaches, and sicca-like symptoms were noted in our cohort. Moreover, a higher proportion of patients in our cohort showed a good response to TNF inhibitors.ConclusionChinese patients with YAOS had more pronounced inflammatory manifestations compared to the Caucasian cohort. Variants c.-14C>T, A110T, S127L, A661P, K818Q, A886V, R471C, and A432V were identified as novel NOD2 variants in YAOS. TNF, IL-6, and IL-1 inhibitors are the promising treatment options. These findings expand the clinical spectrum, genetic profile, and treatment efficacy of YAOS, underscoring the need for heightened awareness of this disease in diverse populations.

BackgroundLipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the association between Lp(a) and adverse outcomes in patients with ischemic heart failure (IHF) remains unclear. This study aimed to investigate the relationship between serum Lp(a) levels and the incidence of major adverse cardiovascular events (MACE) in IHF patients.MethodsIn this single-center, retrospective cohort study, 1,168 IHF patients who underwent elective percutaneous coronary intervention (PCI) were enrolled. Patients were divided into four groups based on Lp(a) quartiles. The primary endpoint was MACE, defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. Cox proportional hazards models were used to evaluate the association between Lp(a) quartiles and adverse outcomes. Restricted cubic spline (RCS) curve were constructed to explore the nonlinear relationship between Lp(a) levels and MACE risk. Subgroup analyses were performed to investigate the association in different subgroups.ResultsThe incidence of MACE increased significantly across Lp(a) quartiles (Quartile 4 vs. Quartile 1: 46.4% vs. 22.9%, P

The study of spatial conflicts of land use (SCLU) is an important breakthrough to reveal the evolution mechanism of regional human-land relationship. Accurate identification of SCLU and scientific exploration of its spatio-temporal characteristics of their driving factors are pivotal for regional sustainable development. However, the basic theoretical system of SCLU still needs to be improved, and the spatio-temporal characteristics of SCLU at different spatial scales and landforms as well as the spatio-temporal correlation effects of its driving factors need to be further studied. This study utilizes theoretical models for the identification of SCLU. Employing a comprehensive index approach involving ArcGIS, FRAGSTATS landscape pattern analysis, and the multi-scale geographically weighted regression model, the spatio-temporal characteristics of SCLU are analyzed across different administrative scales and Macro-landforms. The investigation unveils the intrinsic mechanisms of spatio-temporal differentiation driven by various factors from 2000 to 2020 in the arid and semiarid region of Xinjiang, China. Results indicated that: (1) SCLU is a sensitive indicator of human-land interaction, measurable using conflict risk and effect; (2) The SCLU in Xinjiang presents a spatial pattern of “severe conflict around the three mountains and mild conflict around the two basins” and the SCLU transitioned from an outbreak to a relief stage over the past two decades; (3) SCLU varies significantly among landform types, with conflict intensity in Plain > Mountains > Platform > Hill areas; (4) Elevation and slope in natural environmental factors, human footprint and distance of patches from water, from roads, and from railroads in social activity factors have inhibitory effects on SCLU, and GDP, population density, and human impact index in economic development factors have positive effects on SCLU, and focusing on controlling potentially high-conflict risk areas and enhancing the upgrading of ecological quality are key to mitigating SCLU. The results validate the proposed theoretical framework and provide theoretical and practical references for accurately identifying SCLU and optimizing national territory spatial patterns.

Abstract Siberian wildfire is of paramount importance in the carbon cycle and climate change as it is a major disturbance in the pan‐Arctic ecosystems. In recent decades, the Siberian wildfire regime has been shifting; however, less is known about its process‐based feedback mechanisms. By integrating in‐situ and satellite observational data sets as well as chemistry‐climate coupled modeling, we find that central Siberia has featured the most prominent wildfire escalation during the past two decades, which is closely related to hydrological drought with decreasing rainfall and drying soil under a fast‐warming Arctic. Furthermore, fire‐emitted aerosols compound the increasing wildfires via serving as cloud condensation nuclei and suppressing precipitation, forming self‐amplifying feedback. As the Arctic warming is projected to continue, wildfires are estimated to more than double by the end of this century. This work highlights the great importance of fire risk management based on a fundamental scientific understanding of the complex climate system.

BackgroundThyroid-associated ophthalmopathy (TAO) is a prevalent autoimmune disease characterized by ocular symptoms like eyelid retraction and exophthalmos. Prior neuroimaging studies have revealed structural and functional brain abnormalities in TAO patients, along with central nervous system symptoms such as cognitive deficits. Nonetheless, the changes in the static and dynamic functional network connectivity of the brain in TAO patients are currently unknown. This study delved into the modifications in static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) among thyroid-associated ophthalmopathy patients using independent component analysis (ICA).MethodsThirty-two patients diagnosed with thyroid-associated ophthalmopathy and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. ICA method was utilized to extract the sFNC and dFNC changes of both groups.ResultsIn comparison to the HC group, the TAO group exhibited significantly increased intra-network functional connectivity (FC) in the right inferior temporal gyrus of the executive control network (ECN) and the visual network (VN), along with significantly decreased intra-network FC in the dorsal attentional network (DAN), the default mode network (DMN), and the left middle cingulum of the ECN. On the other hand, FNC analysis revealed substantially reduced connectivity intra- VN and inter- cerebellum network (CN) and high-level cognitive networks (DAN, DMN, and ECN) in the TAO group compared to the HC group. Regarding dFNC, TAO patients displayed abnormal connectivity across all five states, characterized by notably reduced intra-VN connectivity and CN connectivity with high-level cognitive networks (DAN, DMN, and ECN), alongside compensatory increased connectivity between DMN and low-level perceptual networks (VN and basal ganglia network). No significant differences were observed between the two groups for the three dynamic temporal metrics. Furthermore, excluding the classification outcomes of FC within VN (with an accuracy of 51.61% and area under the curve of 0.35208), the FC-based support vector machine (SVM) model demonstrated improved performance in distinguishing between TAO and HC, achieving accuracies ranging from 69.35 to 77.42% and areas under the curve from 0.68229 to 0.81667. The FNC-based SVM classification yielded an accuracy of 61.29% and an area under the curve of 0.57292.ConclusionIn summary, our study revealed that significant alterations in the visual network and high-level cognitive networks. These discoveries contribute to our understanding of the neural mechanisms in individuals with TAO, offering a valuable target for exploring future central nervous system changes in thyroid-associated eye diseases.

N6-Methyladenosine (m6A) RNA modification plays an essential role in many biological processes. To investigate the regulatory role of m6A on the skeletal muscle development in Hu sheep, this study took newborn Hu sheep (b_B Group) and six-month-old Hu sheep (s_B Group) as the objects. MeRIP-seq and RNA-Seq analysis techniques were used to detect differentially methylated genes (DMGs) and differentially expressed genes (DEGs) in the longissimus dorsi muscle of Hu sheep at different months of age. Then, conjoint analysis was further employed to screen for key genes involved in skeletal muscle development that are modified by m6A and expressed by mRNA. According to the results of the MeRIP-seq analysis, there were 285 m6A differentially methylated peaks (DMPs) in total between b_B Group and s_B Group, with 192 significant upregulated peaks and 93 significant downregulated peaks. GO and KEGG analysis revealed that DMGs are mainly enriched in actin-binding, cellular transport, and metabolic pathways. According to the results of the RNA-seq analysis, there were 4,349 DEGs in total between b_B Group and s_B Group, with 2010 upregulated genes and 2,339 downregulated genes. DEGs are found to be mainly enriched in the regulation of actin cytoskeleton tissue, AMPK and FoxO signaling pathways, etc. The conjoint analysis demonstrated that 283 genes were both modified by m6A and expressed by mRNA. Among them, three genes relevant to muscle growth (RGMB, MAPK8IP3, and RSPO3) were selected as candidates for quantitative validation, and the results were in line with the sequencing results. The results mentioned above all suggest that m6A plays a certain role in the skeletal muscle development in Hu sheep.

Background: Breast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. Method: We conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. Results: Between March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. Conclusion: Patients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Intestinal obstruction, a rare manifestation of immunotherapy-related gastrointestinal adverse events, can be severe and even life-threatening with intestinal perforation. We present a 64-year-old man with HCC and currently under the therapy with Pembrolizumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After conservative treatment, the patient underwent colonoscopy where no cause of ileus was discovered. The patient received high-dose prednisone due to the side effects of immune checkpoint inhibitor therapy. This resulted in a gradual improvement of symptoms.

BackgroundPeriodontitis is a chronic inflammatory disease potentially associated with obesity and type 2 diabetes (T2D). Sleeve gastrectomy (SG) has shown substantial effect on weight loss and treatment of T2D. However, there is no direct evidence comparing the impact of SG on the periodontal status of patients with and without T2D.ObjectivesTo determine the impact of SG on the periodontal status of patients with and without T2D in a real-world setting.MethodsIn a prospective and two-armed cohort design, participants who were scheduled for SG at an affiliated hospital between April 2022 and December 2022 were approached for eligibility. After a clinical evaluation and oral examination, those with periodontitis were included and further divided into the DM group (diabetic) and the Control group (non-diabetic) with a 1-year follow-up after surgery. The primary outcome was the periodontal status of patients at 12 months after SG. The secondary outcomes included weight loss, diabetes remission, and alterations in inflammatory markers for up to 1 year after SG.ResultsFifty-seven and 49 patients were included in the DM and the Control group, respectively. Before surgery, patients in the DM group had further worsened periodontal condition compared with those in the Control group. Accompanied by weight loss and glucose reduction, patients in both groups demonstrated significant decreases in plaque index (PLI) and bleeding index (BI) with no alterations in probing depth or clinical attachment loss for up to 1 year after SG. Even patients in the DM group achieved less TWL% (32.79 ± 6.20% vs. 37.95 ± 8.34, P

Abstract PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

Background Metabolic syndrome (MetS) has been shown to have a negative impact on prostate cancer (PCa). However, there is limited research on the effects of MetS on testosterone levels in metastatic prostate cancer (mPCa). Objective This study aims to investigate the influence of MetS, its individual components, and composite metabolic score on the prognosis of mPCa patients, as well as the impact on testosterone levels. Additionally, it seeks to identify MetS-related risk factors that could impact the time of decline in testosterone levels among mPCa patients. Methods A total of 212 patients with mPCa were included in the study. The study included 94 patients in the Non-MetS group and 118 patients in the combined MetS group. To analyze the relationship between MetS and testosterone levels in patients with mPCa. Additionally, the study aimed to identify independent risk factors that affect the time for testosterone levels decline through multifactor logistic regression analysis. Survival curves were plotted by the Kaplan-Meier method. Results Compared to the Non-MetS group, the combined MetS group had a higher proportion of patients with high tumor burden, T stage ≥ 4, and Gleason score ≥ 8 points (P < 0.05). Patients in the combined MetS group also had higher lowest testosterone values and it took longer for their testosterone to reach the lowest level (P < 0.05). The median progression-free survival (PFS) time for patients in the Non-MetS group was 21 months, while for those in the combined MetS group it was 18 months (P = 0.001). Additionally, the median overall survival (OS) time for the Non-MetS group was 62 months, whereas for the combined MetS group it was 38 months (P < 0.001). The median PFS for patients with a composite metabolic score of 0–2 points was 21 months, 3 points was 18 months, and 4–5 points was 15 months (P = 0.002). The median OS was 62 months, 42 months, and 29 months respectively (P < 0.001). MetS was found to be an independent risk factor for testosterone levels falling to the lowest value for more than 6 months. The risk of testosterone levels falling to the lowest value for more than 6 months in patients with MetS was 2.157 times higher than that of patients with Non-MetS group (P = 0.031). Patients with hyperglycemia had a significantly higher lowest values of testosterone (P = 0.015). Additionally, patients with a BMI ≥ 25 kg/m2 exhibited lower initial testosterone levels (P = 0.007). Furthermore, patients with TG ≥ 1.7 mmol/L experienced a longer time for testosterone levels to drop to the nadir (P = 0.023). The lowest value of testosterone in the group with a composite metabolic score of 3 or 4–5 was higher than that in the 0–2 group, and the time required for testosterone levels to decrease to the lowest value was also longer (P < 0.05). Conclusion When monitoring testosterone levels in mPCa patients, it is important to consider the impact of MetS and its components, and make timely adjustments to individualized treatment strategies.

Background: The role of Mast cells has not been thoroughly explored in the context of prostate cancer's (PCA) unpredictable prognosis and mixed immunotherapy outcomes. Our research aims to employs a comprehensive computational methodology to evaluate Mast cell marker gene signatures (MCMGS) derived from a global cohort of 1091 PCA patients. This approach is designed to identify a robust biomarker to assist in prognosis and predicting responses to immunotherapy. Methods: This study initially identified mast cell-associated biomarkers from prostate adenocarcinoma (PRAD) patients across six international cohorts. We employed a variety of machine learning techniques, including Random Forest, Support Vector Machine (SVM), Lasso regression, and the Cox Proportional Hazards Model, to develop an effective MCMGS from candidate genes. Subsequently, an immunological assessment of MCMGS was conducted to provide new insights into the evaluation of immunotherapy responses and prognostic assessments. Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and pathway analysis to explore the biological pathways and mechanisms associated with MCMGS. Results: MCMGS incorporated 13 marker genes and was successful in segregating patients into distinct high- and low-risk categories. Prognostic efficacy was confirmed by survival analysis incorporating MCMGS scores, alongside clinical parameters such as age, T stage, and Gleason scores. High MCMGS scores were correlated with upregulated pathways in fatty acid metabolism and β-alanine metabolism, while low scores correlated with DNA repair mechanisms, homologous recombination, and cell cycle progression. Patients classified as low-risk displayed increased sensitivity to drugs, indicating the utility of MCMGS in forecasting responses to immune checkpoint inhibitors. Conclusion: The combination of MCMGS with a robust machine learning methodology demonstrates considerable promise in guiding personalized risk stratification and informing therapeutic decisions for patients with PCA.

BackgroundToxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, life-threatening immunologic reactions. Previous relevant literature has provided limited information regarding this disease’s genetic susceptibility and management principles.ObjectivesThis study aimed to describe a phenobarbital-induced TEN case report with HLA-B*15:02 and HLA-B*58:01 negative, CYP2C19*1/*2. In addition, we revised the existing literature on phenobarbital-induced SJS/TEN to explore its clinical characteristics.MethodsWe describe a woman undergoing treatment with Phenobarbital for status epilepticus who developed classic cutaneous findings of TEN. A systematic search was conducted in the PubMed, Medline, WanFang, and CNKI databases from 1995 to 2023. The search terms used were “Stevens-Johnson Syndrome,” “Toxic Epidermal Necrolysis,” and “Phenobarbital.”ResultsWe report a case of TEN resulting from phenobarbital; it tested negative for the HLA-B*15:02 and HLA-B*58:01 allele and CYP2C19*1/*2 intermediate metabolism. Supportive treatment with steroids and antihistamines resulted in complete resolution of the skin lesions and improvement in clinical symptoms after 14 days. Physicians and clinical pharmacists should be aware of these potential phenobarbital-related adverse events and closely monitor patients with first-time use of phenobarbital. Among 19 cases were identified in the literature, with 11 (57.9%) cases of SJS, 6 (31.6%) cases of TEN, and 2 (7.2%) cases of SJS-TEN/DRESS overlap. A total of 5 (26.3%) did not survive, of which 4 (21.1%) were under 12 years old and 1 (5.3%) was over 12 years old.ConclusionPhenobarbital-induced SJS/TEN may still occur in patients who test negative for HLA-B*15:02 and HLA-B*58:01, CYP2C19*1/*2. Most cutaneous adverse events occur early in the course of Phenobarbital therapy and should be closely monitored early in the course of treatment. In addition, Phenobarbital should be used with caution in patients with a history of asthma and allergy to antipyretics and analgesics.

Humidification–dehumidification is well-suited for solar-powered operation. Packed bed humidifier is an essential system component for water evaporation. Computational fluid dynamics (CFD) simulation of the packed bed humidifier is a challenging multiscale task. The simultaneous capture of micro flow properties and macro transfer performance by existing CFD models is inadequate. This paper presents a novel CFD model for a structured packed bed humidifier. The Eulerian method is applied to the multiphase flow and several simplified models are proposed to evaluate the influence of the microstructure on the transfer properties. The model can predict the overall transfer performance and partially reflect the micro flow characteristics. It is found that the air temperature increases rapidly when the packing height is 1.65 m or

Abstract Ferroptosis plays important roles both in normal physiology and multiple human diseases. It is well known that selenoprotein named glutathione peroxidase 4 (GPX4) is a crucial regulator for ferroptosis. However, it remains unknown whether other selenoproteins responsible for the regulation of ferroptosis, particularly in gut diseases. In this study, it is observed that Selenoprotein I (Selenoi) prevents ferroptosis by maintaining ether lipids homeostasis. Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. Mechanistically, Selenoi deficiency causes a remarkable decrease in ether‐linked phosphatidylethanolamine (ePE) and a marked increase in ether‐linked phosphatidylcholine (ePC). The imbalance of ePE and ePC results in the upregulation of phospholipase A2, group IIA (Pla2g2a) and group V (Pla2g5), as well as arachidonate‐15‐lipoxygenase (Alox15), which give rise to excessive lipid peroxidation. Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI. Strikingly, GPX4 overexpression cannot rescue the ferroptosis phenotypes of SELENOI‐knockdown cells, while SELENOI overexpression can partially rescue GPX4‐knockdown‐induced ferroptosis. It suggests that SELENOI prevents ferroptosis independent of GPX4. Taken together, these findings strongly support the notion that SELENOI functions as a novel suppressor of ferroptosis during colitis and colon tumorigenesis.

Objectives: Our objective was to compare the effectiveness of Traditional Chinese herbal Kampo medicine Goreisan in improving recurrence in patients with chronic subdural hematoma (CSDH).Methods: Eligible randomized controlled trials prospective trials, and retrospective cohort studies were systematically identified through searches of PubMed, Cochrane Library, and CNKI from inception to March 2024. Following the application of predetermined inclusion and exclusion criteria to screen the available studies, main outcome measures were rigorously extracted. RevMan v5.4 software was utilized to evaluate the overall recurrence rate, employing a random-effects model to calculate pooled odds ratios with the Mantel-Haenszel estimation method. Inter-study heterogeneity was assessed using the Cochran Q (Chi-square) test and I2 statistics. Funnel plots were used to evaluate publication bias.Results: Among the 48 articles initially screened for citation, eight were ultimately selected for inclusion in the study. The results of our network meta-analysis indicate that patients with newly diagnosed Chronic subdural hematoma experienced a significantly reduced recurrence rate when treated with Goreisan compared to standard neurosurgical treatment (OR: 0.72; 95% CI 0.61–0.86; p = 0.00003). There was no statistically significant difference in the incidence rates of complications, including general fatigue, allergic reactions, hepatic dysfunction, and interstitial pneumonia (OR: 7.21; 95% CI 0.37–141.29; p = 0.19).Conclusion: Traditional medicine Goreisan was effective in reducing CDSH recurrence rates. For clinical treatment, it provides a high level of evidence-based medicine. It is also necessary to conduct multicenter randomized controlled trials with dose adjustments to determine whether Goreisan interventions improve neurological function or prognosis.