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Abstract Color is one of the most important indicators to characteristic the quality of tobacco, which is strongly related to the variations of chemical components. In order to clarify the relationship between the changes of tobacco color and chemical components, here we established several prediction models of chemical components with the color values of tobacco based on machine learning algorithms. The results of correlation analysis showed that tobacco moisture content was highly significantly correlated with the parameters such as a*, H* and H°, the reducing sugar and total sugar content of tobacco was significantly correlated with the color values, and the starch content was highly significantly correlated with the color values except for b* and C*. The random forest models performed best in predicting tobacco moisture, reducing sugar, total sugar and starch constructed with the R 2 of the model validation set was higher than 0.90, and the RPD value was greater than 2.0. The consistent between the predictions and measurements verified the availability and feasibility using color values to predict some chemical components of the tobacco leaves with high accuracy, and which has distinct advantages and potential application to realize the real-time monitoring of some chemical components in the tobacco curing process.

Abstract Background Although low-dose computed tomography (LDCT) screening effectively reduces LC mortality in high-risk individuals with a history of smoking in China, the feasibility and efficacy of lung cancer screening (LCS) in individuals who never smoked versus individuals who smoked remains unclear. Methods We conducted a retrospective analysis of prospective cohort studies at the National Cancer Center (NCC) in China from January 2006 to December 2022. A comprehensive LCS initiative was undertaken, involving 30,468 participants (54.5% male). Participants underwent LCS using LDCT. Potential malignancies were managed through joint consensus between patients and their physicians. Epidemiology, screening eligibility criteria, and LC detection rates and survival outcomes were compared between individuals who smoked and individuals who never smoked. Results Among 30,468 participants, 339 LCs were pathologically confirmed in 289 patients. The LC detection rate was 0.9% (289/30,468) overall, 0.8% in individuals who smoked (71/9,042), and 1.0% in individuals who never smoked (218/21,426). In individuals who smoked, LC detection rates were 0.5% (21/4516) and 1.1% (50/4526) in the

Recent autonomous driving systems heavily rely on 3D point cloud data collected from multiple sensors for environmental awareness and decision-making. However, it is unrealistic to expect the autonomous driving system to recognize all road environments and handle every traffic situation. Models for autonomous driving need to be updated in real time in order for the system to adapt to more situations. This is where online continual learning becomes crucial. Online continual learning is an important method in the field of autonomous driving, as it enables models to update their parameters with streaming input data for adapting to new environments and conditions. Online continual learning in the field of autonomous driving faces several challenges: inefficient data fusion, catastrophic forgetting, insufficient computational resources, violation of road privacy and categories imbalance. To tackle these challenges, we propose an Analytic Online Continual Learning method for 3D Point Cloud Classification (3D-AOCL). This approach utilizes Analytic Learning to update parameters and integrates a feature fusion module along with a category balancer to address the above issues. It is capable of fusing data in feature level, balancing samples across various categories and updating parameters by calculating the analytical solution. We have validated our method on the vehicle side, the infrastructure side, and vehicle-infrastructure cooperative data on the V2X-Seq dataset. The experimental results demonstrate that our model effectively addresses key issues in online continual learning for autonomous driving systems, outperforming other models by approximately 4.00% to 6.00% in AMCA scores while only keeping 0.75% trainable parameters.

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Abstract Neutrophil infiltration plays a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, pertinent mechanisms remain poorly elucidated. Here, we obtained the data from gene expression omnibus (GEO) and gene set enrichment analysis (GSEA) to identify and validate neutrophil-associated hub genes in CRSwNP. We found that four neutrophil-associated hub genes, namely ICAM1, IL-1β, TYROBP, and BCL2A1, were markedly upregulated and positively correlated with neutrophil infiltration levels in patients with CRSwNP. Subsequently, this was confirmed by real-time quantitative PCR. In conclusion, we identified the role of neutrophil infiltration in the pathophysiology of CRSwNP, which may be the potential targets for the diagnosis and treatment of CRSwNP.

Abstract Oil reservoirs, being one of the significant subsurface repositories of energy and carbon, host diverse microbial communities affecting energy production and carbon emissions. Viruses play crucial roles in the ecology of microbiomes, however, their distribution and ecological significance in oil reservoirs remain undetermined. Here, we assemble a catalogue encompassing viral and prokaryotic genomes sourced from oil reservoirs. The catalogue comprises 7229 prokaryotic genomes and 3,886 viral Operational Taxonomic Units (vOTUs) from 182 oil reservoir metagenomes. The results show that viruses are widely distributed in oil reservoirs, and 85% vOTUs in oil reservoir are detected in less than 10% of the samples, highlighting the heterogeneous nature of viral communities within oil reservoirs. Through combined microcosm enrichment experiments and bioinformatics analysis, we validate the ecological roles of viruses in regulating the community structure of sulfate reducing microorganisms, primarily through a virulent lifestyle. Taken together, this study uncovers a rich diversity of viruses and their ecological functions within oil reservoirs, offering a comprehensive understanding of the role of viral communities in the biogeochemical cycles of the deep biosphere.

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract The practice of oil and gas exploration has confirmed the existence of recoverable shale oil resources in the Permian Lucaogou Formation on the northern edge of the Bogda Mountains. However, previous research on the development characteristics and main controlling factors of shale oil resources in this area is relatively limited. In order to elucidate the development characteristics and principal controlling factors of the shale deposit in the Lucaogou Formation, the characteristics, physical properties, diagenesis, and influencing factors of the shale ore were investigated utilising data derived from outcrop, drilling, seismic, and geochemical analysis. The findings indicate that the shale of the Lucaogou Formation is prevalent and extensive. The deposit’s lithology is predominantly composed of dark grey and grey-black mud shale, interspersed with thin layers of dark grey and grey-black sandy mud shale and dolomite mud shale. The most prevalent minerals are carbonate minerals, followed by feldspar and quartz, with a notable proportion of brittle minerals. The deposit is primarily composed of dissolution pores, bedding fractures, and structural fractures, with a porosity of 1.23–3.26% and permeability of 0.012–0.076 mD, which are characteristic of ultra-low porosity and ultra-low permeability deposits. Among the three deposit types, the sandstone type exhibits the most favourable physical properties, followed by the dolomite type and the shale type, which displays the least favourable properties. The shale of the Lucaogou Formation is currently in the middle diagenetic phase, which is characterised by compaction, cementation (carbonate cementation, mudstone cementation, pebble cementation), and dissolution. The destructive effect of compaction and cementation on the physical properties is counterbalanced by the constructive effect of dissolution. The diagenetic environment has gradually changed from an alkaline environment to a slightly alkaline, slightly acidic stage.

Background Maintenance hemodialysis (MHD) and peritoneal dialysis (PD) are main treatment methods for uremic patients. It remains an important content of clinical research on better developing treatment protocols to address overhydration (OH) in dialysis patients, and the effect of applying body composition monitor (BCM) on the prognosis of dialysis patients treated with different dialysis models is still controversial. Objective To explore the relationship between OH parameters of BCM and prognosis in patients treated with MHD and PD. Methods From October 2017 to March 2022, 334 patients on maintenance dialysis in Beijing Jishuitan Hospital affiliated to Capital Medical Medical University, Beijing Boai Hospital, Aviation General Hospital, Beijing Changping District Hospital and Beijing Changping Hospital of Integrated Traditional Chinese and Western Medicine were included as the study objects and divided into MHD group (n=188) and PD group (n=146) according to their renal replacement therapy mode. The general data of and BCM related parameters were collected through the electronic medical record system. Patients included in the study were followed up, dialysis treatment parameters, body weight, systolic blood pressure and diastolic blood pressure were recorded, and the average of multiple follow-up results were calculated. Endpoint events were recorded during follow-up period, with the primary endpoint event as all-cause death (ACM), secondary endpoint events as cardiovascular events (CVE), combined adverse events (CAE), surgery or fracture (SOF). Spearman rank correlation analysis was used to explore the correlation between endpoint events and BCM parameters, and stepwise multiple Logistic regression analysis was used to explore the influencing factors of secondary endpoint events in patients. The ACM survival curve was plotted by Kaplan-Meier method, and the difference of survival curve between the two groups was compared by Log-rank test. Multivariate Cox regression analysis was used to explore the influencing factors of ACM. Results A total of 311 patients completed follow-up, with a median follow-up time of 29.9 (18.0, 36.0) months, including 176 patients in MHD group and 135 patients in PD group. Dialysis age, body weight, target body weight, adipose tissue content and adipose tissue index in MHD group were higher than those in PD group, and OH was lower than that in PD group (P

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets epithelial cells in the respiratory tract, triggering an acute proinflammatory response and chronic lung inflammation. Probiotic supplementation has shown promise in reducing the nasopharyngeal SARS-CoV-2 viral load, diminishing symptom frequency and duration, and mitigating inflammation; thus, it is a potential strategy for treating coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. In this study, we evaluated the effects of the oral administration of the Lactobacillus plantarum GUANKE strain, a gram-positive bacterium originally isolated from a healthy individual, on SARS-CoV-2 infection in a human ACE2 transgenic mouse model. We found that GUANKE significantly reduced inflammatory cell infiltration and pulmonary interstitial exudation in mice. The transcription of CCL2, TNFA, IL1B, IL6, and IL17C in the lungs was reduced. The protein levels of TNF-α, IL-1β, IL-6, and IL-17 in the lungs were significantly lower in GUANKE-treated mice than in control mice. The viral load in GUANKE-treated mice was lower than that in saline-treated mice, although this difference did not reach statistical significance. L. plantarum GUANKE can decrease SARS-CoV-2-induced lung inflammation in mice, suggesting its potential for use as an agent for treating SARS-CoV-2 infection.IMPORTANCEMost otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel L. plantarum GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. L. plantarum GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

A thorough understanding of the thermophysical properties of phase change materials and the natural convection effect during the phase transition process is crucial for the accurate modeling and designing latent heat storage systems. However, research findings on the thermophysical properties of n-octadecane and the natural convection effect during the solidification process remain insufficient. In this study, the thermophysical properties of n-octadecane, including latent heat, thermal conductivity, density, thermal expansion coefficient and dynamic viscosity, were systematically measured under varying temperature conditions. Subsequently, a comprehensive solidification experiment of n-octadecane in a spherical capsule was conducted to assess the temporal and spatial temperature distribution characteristics and the evolution patterns of the solidification front. Finally, numerical techniques were employed to quantify the impact of natural convection. The results indicate that, the relationship between solidification mass fraction and time follows a quartic polynomial pattern. Based on the temperature curve at the central point, the solidification process of n-octadecane can be divided into four distinct stages. The first two stages account for 98.2 % of the total heat release, with natural convection primarily concentrated in the sensible heat release stage of liquid phase, contributing only 2.3 % to the entire solidification process, making its effect essentially negligible.

Understanding the thermodynamics of interfacial interactions between oil and kerogen is imperative for developing technologies aimed at improving hydrocarbon recovery in reservoirs, especially in unconventional shale, which retains abundant hydrocarbons in a non-porous medium. The temperature effect on the interactions of a light oil molecular cluster with kerogen was investigated using molecular dynamics simulation. Non-polar and polar light oil droplets were modeled with clusters of 30 octane molecules and 30 octanethiol molecules in water, respectively. Kerogen was modeled with a molecular fragment from a mature type II kerogen. The potential of mean force calculations was performed at constant volume and temperature via umbrella sampling at temperatures in 300–500 K range, comparable to the reservoir temperatures of common shale plays. The results show that the free energy of desorption of oil droplets scales linearly with temperature and has a strong negative temperature dependence, suggesting a significant entropic contribution to the free energy and underscoring the fundamental basis of the thermal stimulation technique for improved oil recovery. The simulations suggest that single molecules cannot represent the interactions of an oil droplet with the kerogen surface. The internal dynamics within the droplets play an important role in the strong temperature dependence of the free energy. The calculated free energy, contact angle, and surface tension of oil droplets are comparable with observations and provide an improved understanding of the interfacial interactions between the multicomponent fluid and kerogen. Such agreement demonstrates the reliability of the method and molecular models for modeling the complex interfacial interaction system. The results present a thermodynamic understanding and molecular details of the temperature effect on the oil interactions with kerogen, providing valuable insight into strategies for unconventional oil recovery.

Although thyroid cancer is an indolent tumor with a favorable prognosis, lymph node metastasis (LNM) serves as a major concern for many patients. Because LNM is strongly correlated with recurrence, distant metastasis, and shortened survival, a precise and timely diagnosis and following appropriate management for LNM are necessary. However, significant challenges still exist in the diagnosis of small LNs (

Background: Outpatient hysteroscopic surgery requires patients to be anaesthetised and recover quickly, and the drugs used must be safe and effective. Remifentanil is typically co-administered with propofol as total intravenous anaesthesia (TIVA) for hysteroscopy because of its favourable pharmacokinetic and pharmacodynamic properties. However, the optimal dose of remifentanil when co-administered with propofol without neuromuscular blocking agents (NMBAs) has not been established. Objectives: In this sequential dose-finding study, the 90% effective dose (ED90) of remifentanil effect-site concentration (Ce) combined with propofol without NMBAs during outpatient hysteroscopy was calculated to minimise the side effects of using higher doses. Design: This sequential dose-finding study was conducted in August 2022. Methods: Forty patients who underwent outpatient hysteroscopy under TIVA were included in the study. With a biased coin up-and-down design, the initial remifentanil Ce was established at 2 ng/mL, and the subsequent remifentanil dosage was determined based on the reaction of the previous patient. The primary outcome was a remifentanil Ce that resulted in successful TIVA by maintaining a Narcotrend index

Background: To enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions. Purpose: To investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules. Materials and methods: This retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists. Results: The training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729–0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750–0.755) and a specificity of 0.761 (95%CI: 0.758–0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543–0.691, p

Abstract The recent experimental confirmation of perovskite monolayers has sparked ongoing efforts in their prediction and synthesis, showcasing their flexible tunable band gap and potential in advanced functional devices. Although large-scale computational designs have been successfully performed for inorganic perovskite monolayers, the complexity introduced by organic cations hinders the same approaches applied to the hybrid halide perovskite monolayers. To address this challenge, we have proposed a high-throughput first-principles computational workflow that automates the design of hybrid halide perovskite monolayers. We strategically reduce the complexity of the configurations by analyzing the orientation of cations and the structural symmetry. Over 400 hybrid halide perovskite monolayers have been designed, and their structures and fundamental properties are stored in the database. Correlation analyses show a strong correlation between band gaps and metal-halogen-metal bond angles or metal-halogen bond lengths, consistent with prior studies for bulk and layered perovskites. The underlying physics that the band gap is modulated by the antibonding in the metal-halogen bond makes band gap engineering of hybrid halide perovskite monolayers feasible. Accordingly, initial research on lateral heterojunctions and solar cells has been conducted to explore the potential practical applications of the designed hybrid halide perovskite monolayers. Our study lays the foundation for further exploration of hybrid halide perovskite monolayers and highlights promising opportunities for their potential applications in electronic and optical devices.

Abstract Background Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. Methods Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). Results Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45–49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35–39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P

Abstract Low damping characteristics have always been a key sticking points in the development of gas bearings. The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearings. This paper proposed a novel hermetic diaphragm squeeze film damper (HDSFD) for oil-free turbomachinery supported by gas lubricated bearings. Several types of HDSFDs with symmetrical structure were proposed for good damping performance. By considering the compressibility of the damper fluid, based on hydraulic fluid mechanics theory, a dynamic model of HDSFDs under medium is proposed, which successfully reflects the frequency dependence of force coefficients. Based on the dynamic model, the effects of damper fluid viscosity, bulk modulus of damper fluid, thickness of damper fluid film and plunger thickness on the dynamic stiffness and damping of HDSFDs were analyzed. An experimental test rig was assembled and series of experimental studies on HDSFDs were conducted. The damper fluid transverse flow is added to the existing HDSFD concept, which aims to make the dynamic force coefficients independent of frequency. Although the force coefficient is still frequency dependent, the damping coefficient at high frequency excitation with damper fluid supply twice as that without damper fluid supply. The results serve as a benchmark for the calibration of analytical tools under development.

Abstract Background Gastric cancer is one of the most common tumors worldwide, and most patients are deprived of treatment options when diagnosed at advanced stages. PRDM14 has carcinogenic potential in breast and non-small cell lung cancer. however, its role in gastric cancer has not been elucidated. Methods We aimed to elucidate the expression of PRDM14 using pan-cancer analysis. We monitored the expression of PRDM14 in cells and patients using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. We observed that cell phenotypes and regulatory genes were influenced by PRDM14 by silencing PRDM14. We evaluated and validated the value of the PRDM14-derived prognostic model. Finally, we predicted the relationship between PRDM14 and small-molecule drug responses using the Connectivity Map and The Genomics of Drug Sensitivity in Cancer databases. Results PRDM14 was significantly overexpressed in gastric cancer, which identified in cell lines and patients’ tissues. Silencing the expression of PRDM14 resulted in apoptosis promotion, cell cycle arrest, and inhibition of the growth and migration of GC cells. Functional analysis revealed that PRDM14 acts in epigenetic regulation and modulates multiple DNA methyltransferases or transcription factors. The PRDM14-derived differentially expressed gene prognostic model was validated to reliably predict the patient prognosis. Nomograms (age, sex, and PRDM14-risk score) were used to quantify the probability of survival. PRDM14 was positively correlated with sensitivity to small-molecule drugs such as TPCA-1, PF-56,227, mirin, and linsitinib. Conclusions Collectively, our findings suggest that PRDM14 is a positive regulator of gastric cancer progression. Therefore, it may be a potential therapeutic target for gastric cancer.

In the process of constructional backfilling coal mining (CBCM), the demand for the strength of cemented gangue backfill (CGB) samples varies with different backfill rates. It is planned to adjust the strength of CGB samples by changing the proportion of fly ash in the dosage of cement-fly ash binary cementitious material (hereinafter referred to as the proportion of fly ash), and conduct uniaxial compression tests on CGB samples with different proportions of fly ash (0−90%) to explore the range of strength control of CGB samples, and analyze the failure morphology of the samples using digital image correlation technology, and analyze the brittle ductile failure mode of the samples using AE events. The strength of coal gangue and the strength of cement-fly ash binary cementitious material with different fly ash proportions are measured using the pressure cylinder method and uniaxial compression test, respectively, and the mechanism of strength formation of CGB samples is revealed based on the relationship between the strength of coal gangue and the strength of cement-fly ash binary cementitious material. The research results indicate that the strength of CGB decreases with the increase of proportion of fly ash, achieving a larger range of strength control for CGB: 1.77−30.04 MPa. The failure morphology and the brittle ductile failure mode of samples with different replacement rates of CGB samples are different, and the corresponding strength range of the samples is also different, Material properties have undergone fundamental changes. As the proportion of fly ash increases, in terms of the failure morphology, CGB samples transition from shear failure (0−50% proportion of fly ash) to tensile shear composite failure (60%−80% proportion of fly ash) and then to tensile failure (90% proportion of fly ash), corresponding to the strength ranges are 20.8−30.04 MPa, 5.63−12.35 MPa, and 1.77 MPa; In terms of the brittle ductile failure mode, the samples transition from brittle-ductile failure (0−40% proportion of fly ash) to ductile failure (50%−90% proportion of fly ash), corresponding to the strength ranges are 24.64−30.04 MPa and 1.77−20.8 MPa. The strength of CGB is determined by the strength of the cement-fly ash binary cementitious material (1.43−55.5 MPa) and the strength of coal gangue (with an average strength of 4.43 MPa). Cement-fly ash binary cementitious material contributes significantly to the strength of CGB, while coal gangue limits the strength of CGB. The obtained experimental results provide a certain reference for the strength selection of filling materials in CBCM.

Abstract To analyze the clinical characteristics and to improve clinicians’ understanding of multiple pulmonary sclerosing pneumocytoma (PSP) patients. A total of 36 PSP patients with multiple tumor characteristics were identified from the literature search. They were compared with 43 solitary PSP patients diagnosed and treated in our hospital in the past 5 years. Thus, the pathogenesis, clinical symptoms, diagnosis methods, treatment strategies, and prognosis of pulmonary sclerosing pneumocytoma (PSP) patients with multiple tumors were explored. Patients with multiple PSP are mostly distributed in Asia (88.89%) and are females (83.33%). PSP can be located in any one lobe (19.44%), or grow across ipsilateral lobes (44.44%), or even, bilateral lobes (36.11%). It can be accompanied by metastasis (9.09%) and is prone to misdiagnosis (27.78%). Compared with solitary PSP, the occurrence age of multiple PSP was younger (mean ± standard deviation [SD]: 40.36 ± 18.12: 51.28 ± 12.74 years), but there was no significant difference in sex, tumor size (mean ± SD: 43.54 ± 46.18: 30.56 ± 17.62 mm), or symptoms. Individualized surgical resection is required for treatment, including pneumonectomy (17.65%), lobectomy (23.53%), subpulmonary lobectomy (38.24%), or combined lobectomy (5.88%). Multiple PSP is relatively rare. Surgical resection within a limited time should be the main treatment for such patients. The prognosis of patients with multiple PSP is generally good, but inappropriate diagnosis and treatment plans may lead to poor prognosis.

Abstract Background Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Abstract SETD3 is an essential host factor for the replication of a variety of enteroviruses that specifically interacts with viral protease 2A. However, the interaction between SETD3 and the 2A protease has not been fully characterized. Here, we use X-ray crystallography and cryo-electron microscopy to determine the structures of SETD3 complexed with the 2A protease of EV71 to 3.5 Å and 3.1 Å resolution, respectively. We find that the 2A protease occupies the V-shaped central cleft of SETD3 through two discrete sites. The relative positions of the two proteins vary in the crystal and cryo-EM structures, showing dynamic binding. A biolayer interferometry assay shows that the EV71 2A protease outcompetes actin for SETD3 binding. We identify key 2A residues involved in SETD3 binding and demonstrate that 2A’s ability to bind SETD3 correlates with EV71 production in cells. Coimmunoprecipitation experiments in EV71 infected and 2A expressing cells indicate that 2A interferes with the SETD3-actin complex, and the disruption of this complex reduces enterovirus replication. Together, these results reveal the molecular mechanism underlying the interplay between SETD3, actin, and viral 2A during virus replication.

Abstract Objective To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). Methods Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion. Results Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p

Abstract Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5′ UTR, were specifically recognized by the m6A “reader” protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

Immune checkpoint inhibitors (ICIs) become integral in clinical practice, yet their application in cancer therapy is constrained by low overall response rates and the primary resistance of cancers to ICIs. Herein, this study proposes aggregation-induced emission (AIE)-based nanoparticles (NPs) for a more effective and synergistic approach combining immunotherapy and photodynamic therapy (PDT) to achieve higher responses than anti-PD-L1 monotherapy. The TBP@aPD-L1 NPs are constructed by functionalizing azide group-modified TBP-2 (TBP-N3) with anti-PD-L1 antibodies via the DBCO-S-S-PEG2000-COOH linker. The anti-PD-L1 target the tumor cells and promote the TBP-N3 accumulation in tumors for enhanced PDT. Notably, the TBP-N3, featuring aggregation-induced emission, boosts reactive oxygen species (ROS) generation through both type I and type II processes for enhanced PDT. The TBP@aPD-L1-mediated PDT induces more powerful effects of direct tumor cell-killing and further elicits effective immunogenic cell death (ICD), which exerts anti-tumor immunity by activating T cells for ICI treatment and reshapes the tumor immune microenvironment (TIME), thereby enhancing the efficacy of PD-L1 blockade of anti-PD-L1. Consequently, TBP@aPD-L1 NPs demonstrated significantly enhanced inhibition of tumor growth in the mouse model of malignant melanoma (MM). Our NPs act as a facile and effective drug delivery platform for enhanced immunotherapy combined with enhanced PDT in treating MM.

Abstract Background Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Methods Demographic information, tissue and blood cells, endoscopic scores, Lund‐Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Results Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control‐related symptoms at follow‐up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Conclusions Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.

ObjectiveWe conducted this meta-analysis to comprehensively explore the prognostic value of the preoperative plasma fibrinogen in Asian patients diagnosed with urothelial cancer (UC).MethodsAfter a systematic search of Web of Science, PubMed, and Embase before May 2024, we included 10 studies in our meta-analysis. The hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression free survival (PFS) were estimated using fixed effect model.ResultsThis meta-analysis included a total of 2875 patients. UC patients with an elevated preoperative plasma fibrinogen had worse OS (pooled HR: 2.13, 95% CI: 1.81-2.51; P

ABSTRACT Background The aim of this study is to investigate the radiological features of primary pulmonary invasive mucinous adenocarcinoma (IMA) in a relatively large population to help improve its further understanding and its accuracy of initial diagnosis. Methods This retrospective study included consecutive patients with pathologically confirmed primary pulmonary IMA from January 2019 to December 2021. According to tumor morphology, IMAs were divided into regular nodule/mass, irregular, and large consolidative types. According to tumor density, IMAs were divided into solid, halo, part‐solid, pure ground‐glass, and cystic types. ANOVA, chi‐square, or Fisher exact tests were used to analyze the differences in radiological and clinicopathological characteristics of IMA according to morphological and density subtypes. Results We analyzed 312 patients. Pulmonary IMA tended to occur in the elderly, with a slightly higher number of women than men. IMA showed a predominance in the lower lobe and adjacent to pleura. IMA of regular nodule/mass, irregular, and large consolidative types accounted for 80.8% (252/312), 13.8% (43/312), and 5.4% (17/312), respectively. Solid, halo, part‐solid, pure ground‐glass, and cystic IMAs accounted for 55.8% (174/312), 28.2% (88/312), 11.2% (35/312), 1.3% (4/312), and 3.5% (11/312), respectively. The lobulated (76.9%), spiculated (63.5%), and air bronchogram (56.7%) signs were common in IMA. Dead branch sign (88.2%), angiogram sign (88.2%), and satellite nodules/skipping lesions (47.1%) were common in large‐consolidative‐type IMA. Kirsten rat sarcoma viral oncogene mutations were common (56.1%), whereas epidermal growth factor receptor mutations were relatively rare (2.3%). Conclusions Pulmonary IMA of regular nodule/mass type and solid type were the most common at the initial diagnosis. Detailed radiological features can aid in the differential diagnosis of IMA.

Background Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored.Methods To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1).Results In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy.Conclusions Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.

Abstract Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing.

Abstract Background Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. Materials and methods With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. Results Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1β), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-β1 (TGF-β1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. Conclusion IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice. Graphical Abstract

Abstract Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Abstract Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Abstract Background Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated. Material and methods The silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting. Results The use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN). Conclusion By regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of "external and internal reshaping".

Abstract Background Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. Results Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. Conclusions ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neurostimulation approach for emotion regulation. This research aimed to clarify the underlying neural basis responsible for taVNS’s impact on emotional regulation related brain regions. Thirty-two healthy volunteers were allocated into a taVNS group, which received electrical stimulation at the concha area of the ear, and a sham group, which received earlobe stimulation. Resting-state functional magnetic resonance imaging data were collected from both the taVNS and sham groups pre- and post-stimulation. To evaluate the alterations in neural activity and connectivity resulting from auricular electrical stimulation, degree centrality and functional connectivity analyses were used. The results indicated that taVNS modulated the neural activity of several brain regions, including the bilateral precuneus, temporal gyrus, precentral gyrus, and postcentral gyrus, whereas earlobe stimulation did not produce such effects. taVNS may improve emotion regulation by modulating neural activation and functional connectivity in key brain regions, then facilitating the integration of emotional responses, memories, and experiences. Thus, these brain regions may serve as potential therapeutic targets for taVNS in treating disorders associated with emotional dysregulation. These findings provide insight into the neural basis through which taVNS influences emotion regulation and hold potential for the development of neuromodulation-based therapeutic strategies for emotional disorders.

Abstract Background We aimed to develop a combined model based on radiomics and computed tomography (CT) imaging features for use in differential diagnosis of benign and malignant subcentimeter (≤ 10 mm) solid pulmonary nodules (SSPNs). Methods A total of 324 patients with SSPNs were analyzed retrospectively between May 2016 and June 2022. Malignant nodules (n = 158) were confirmed by pathology, and benign nodules (n = 166) were confirmed by follow-up or pathology. SSPNs were divided into training (n = 226) and testing (n = 98) cohorts. A total of 2107 radiomics features were extracted from contrast-enhanced CT. The clinical and CT characteristics retained after univariate and multivariable logistic regression analyses were used to develop the clinical model. The combined model was established by associating radiomics features with CT imaging features using logistic regression. The performance of each model was evaluated using the area under the receiver-operating characteristic curve (AUC). Results Six CT imaging features were independent predictors of SSPNs, and four radiomics features were selected after a dimensionality reduction. The combined model constructed by the logistic regression method had the best performance in differentiating malignant from benign SSPNs, with an AUC of 0.942 (95% confidence interval 0.918–0.966) in the training group and an AUC of 0.930 (0.902–0.957) in the testing group. The decision curve analysis showed that the combined model had clinical application value. Conclusions The combined model incorporating radiomics and CT imaging features had excellent discriminative ability and can potentially aid radiologists in diagnosing malignant from benign SSPNs. Relevance statement The model combined radiomics features and clinical features achieved good efficiency in predicting malignant from benign SSPNs, having the potential to assist in early diagnosis of lung cancer and improving follow-up strategies in clinical work. Key points • We developed a pulmonary nodule diagnostic model including radiomics and CT features. • The model yielded the best performance in differentiating malignant from benign nodules. • The combined model had clinical application value and excellent discriminative ability. • The model can assist radiologists in diagnosing malignant from benign pulmonary nodules. Graphical Abstract