High Sensitivity Triboelectric Based Flexible Self-Powered Tactile Sensor with Bionic Fingerprint Ring Structure.

Flexible self-powered tactile sensors, with applications spanning wearable electronics, human-machine interaction, prosthetics, and soft robotics, offer real-time feedback on tactile interactions in diverse environments. Despite advances in their structural development, challenges persist in sensitivity and robustness, particularly when additional functionalities, such as high transparency and stretchability. In this study, we present a novel approach integrating a bionic fingerprint ring structure with a PVDF-HFP/AgNWs composite fiber electrode membrane, fabricated via 3D printing technology and electrospinning, respectively, yielding a triboelectric nanogenerator (TENG)-based self-powered tactile sensor. The sensor demonstrates high sensitivity (5.84 V/kPa in the 0-10 kPa range) and rapid response time (10 ms), attributed to the microring texture on its surface, and exhibits exceptional robustness, maintaining electrical output integrity even after 24,000 cycles of loading. These findings highlight the potential of the microring structures in addressing critical challenges in flexible sensor technology.

Targeting macrophagic RasGRP1 with catechin hydrate ameliorates sepsis-induced multiorgan dysfunction.

BACKGROUND: The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research. PURPOSE: This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis. STUDY DESIGN AND METHODS: Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments. RESULTS: Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis. CONCLUSION: This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1.

Whole-genome analysis of Escherichia coli isolated from wild Amur tiger (Panthera tigris altaica) and North China leopard (Panthera pardus japonensis).

Background: Escherichia coli is an important intestinal flora, of which pathogenic E. coli is capable of causing many enteric and extra-intestinal diseases. Antibiotics are essential for the treatment of bacterial infections caused by pathogenic E. coli; however, with the widespread use of antibiotics, drug resistance in E. coli has become particularly serious, posing a global threat to human, animal, and environmental health. While the drug resistance and pathogenicity of E. coli carried by tigers and leopards in captivity have been studied intensively in recent years, there is an extreme lack of information on E. coli in these top predators in the wild environment. Methods: Whole genome sequencing data of 32 E. coli strains collected from the feces of wild Amur tiger (Panthera tigris altaica, n = 24) and North China leopard (Panthera pardus japonensis, n = 8) were analyzed in this article. The multi-locus sequence types, serotypes, virulence and resistance genotypes, plasmid replicon types, and core genomic SNPs phylogeny of these isolates were studied. Additionally, antimicrobial susceptibility testing (AST) was performed on these E. coli isolates. Results: Among the E. coli isolates studied, 18 different sequence types were identified, with ST939 (21.9%), ST10 (15.6%), and ST3246 (9.4%) being the most prevalent. A total of 111 virulence genes were detected, averaging about 54 virulence genes per sample. They contribute to invasion, adherence, immune evasion, efflux pump, toxin, motility, stress adaption, and other virulence-related functions of E. coli. Sixty-eight AMR genes and point mutations were identified. Among the detected resistance genes, those belonging to the efflux pump family were the most abundant. Thirty-two E. coli isolates showed the highest rate of resistance to tetracycline (14/32; 43.8%), followed by imipenem (4/32; 12.5%), ciprofloxacin (3/32; 9.4%), doxycycline (2/32; 6.3%), and norfloxacin (1/32; 3.1%). Conclusions: Our results suggest that E. coli isolates carried by wild Amur tigers and North China leopards have potential pathogenicity and drug resistance.

Antiferromagnetic magnonic charge current generation via ultrafast optical excitation.

Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

A SARS-CoV-2 Mpro fluorescent sensor for exploring pharmacodynamic substances from traditional Chinese medicine.

The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL-1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.

PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.

OBJECTIVE: This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways. METHOD: Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation. RESULTS: Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention. CONCLUSIONS: PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

The effects of the traffic signs information volume on the visual characteristics and workload of novice and experienced drivers.

BACKGROUND: The effects of traffic sign information volume (TSIV) on the visual characteristics and workload of novice and experienced drivers were investigated in this study. TSIV plays a crucial role in road traffic safety, and understanding its impact on drivers is essential for designing effective traffic sign systems. OBJECTIVE: This research aimed to compare the visual characteristics and workload of novice and experienced drivers under varying TSIV doses through simulated driving tests. The objective was to provide insights for optimizing the design of road TSIV. METHODS: Six TSIV levels were considered: S0, S1, S2, S3, S4, and S5, representing different workload levels. Participants, including both novice and experienced drivers, were involved in simulated driving scenarios with varying TSIV levels. Eye movement data was collected using an eye tracker device. The study was conducted in China, and appropriate driving simulators and equipment were utilized. RESULTS: The findings revealed several valuable results. Experienced drivers exhibited a higher proportion of saccade behavior in the 30-90 ms time period and did not show rapid saccade behavior during the 0-30 ms period, indicating superior visual search strategies. Both novice and experienced drivers demonstrated improved visual cognitive abilities at the S3 level of TSIV, which corresponds to normal and safe driving conditions. Furthermore, a majority of both groups had saccade amplitudes in the range of 0°-4°, with experienced drivers showing a slightly higher proportion. About 82% of experienced drivers had saccade behavior within the range of 0°-2°, compared to 75% of novice drivers. CONCLUSIONS: The study concludes that the S3 level of TSIV, corresponding to 30 bits/km, is optimal for both novice and experienced drivers. This level promotes better visual performance and reduces visual workload, indicating that drivers' information acquisition capacity and visual search strategies are maximized while keeping the workload associated with driving at a minimum. These findings have significant implications for enhancing driving safety.

Predicting rectal cancer tumor budding grading based on MRI and CT with multimodal deep transfer learning: A dual-center study.

Objective: To investigate the effectiveness of a multimodal deep learning model in predicting tumor budding (TB) grading in rectal cancer (RC) patients. Materials and methods: A retrospective analysis was conducted on 355 patients with rectal adenocarcinoma from two different hospitals. Among them, 289 patients from our institution were randomly divided into an internal training cohort (n = 202) and an internal validation cohort (n = 87) in a 7:3 ratio, while an additional 66 patients from another hospital constituted an external validation cohort. Various deep learning models were constructed and compared for their performance using T1CE and CT-enhanced images, and the optimal models were selected for the creation of a multimodal fusion model. Based on single and multiple factor logistic regression, clinical N staging and fecal occult blood were identified as independent risk factors and used to construct the clinical model. A decision-level fusion was employed to integrate these two models to create an ensemble model. The predictive performance of each model was evaluated using the area under the curve (AUC), DeLong's test, calibration curve, and decision curve analysis (DCA). Model visualization Gradient-weighted Class Activation Mapping (Grad-CAM) was performed for model interpretation. Results: The multimodal fusion model demonstrated superior performance compared to single-modal models, with AUC values of 0.869 (95% CI: 0.761-0.976) for the internal validation cohort and 0.848 (95% CI: 0.721-0.975) for the external validation cohort. N-stage and fecal occult blood were identified as clinically independent risk factors through single and multivariable logistic regression analysis. The final ensemble model exhibited the best performance, with AUC values of 0.898 (95% CI: 0.820-0.975) for the internal validation cohort and 0.868 (95% CI: 0.768-0.968) for the external validation cohort. Conclusion: Multimodal deep learning models can effectively and non-invasively provide individualized predictions for TB grading in RC patients, offering valuable guidance for treatment selection and prognosis assessment.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

Evaluation of eye-catching effect in highway tunnel entrance area based on saccade behavior.

OBJECTIVE: This study aimed to investigate the effects of visual attraction in the entrance areas of highway tunnels on drivers' saccade behavior and driving safety, with the objective of providing insights for tunnel entrance design and driver education. METHODS: Fifty participants were recruited for the naturalistic driving experiment. Four different visually attractive driving scenarios (baseline, landscape-style architecture, tip slogan, and billboard) were selected. Eye-tracking technology was utilized to record and analyze the scanning behavior of participating drivers. Various metrics, including saccade duration, frequency, amplitude, velocity, and the peak-to-average ratio of saccade velocity (PARSV), were measured and compared across different scenarios. RESULTS: The results revealed different patterns of visual scanning dynamics among the four experimental scenarios, reflecting the different levels of visual-cognitive demands and situation awareness of drivers. The visual attraction in the tunnel entrance area resulted in prolonged saccade duration, increased saccade amplitude, reduced saccade frequency, and slower, less stable saccade velocity. Among these, drivers exhibited the most intricate and unstable scanning behavior, accompanied by the lowest level of situational awareness, particularly under the influence of visual attraction of tip slogan. CONCLUSIONS: The findings highlight the importance of considering visual attraction in tunnel entrance design. Minimizing unnecessary visual attraction can help reduce distractions and maintain driver attention, ultimately enhancing driving safety. Driver education programs should emphasize the significance of adapting to visual attraction at tunnel entrances to promote safer driving practices. Overall, this study contributes valuable insights into the effects of visual attraction on driver scanning behavior, facilitating the development of strategies to improve tunnel design and driver education.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging.

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

Social comparison and aggression: The mediating role of relative deprivation and moderating role of covert narcissism.

Social comparison is a universal social phenomenon that profoundly influences aggressive behaviours among young adults. Based on the general aggression model, this study investigated the relationship between social comparison and aggression, and the mediating role of relative deprivation. To further explore the mechanism underlying this influence, covert narcissism was examined as a moderator in this relationship, based on relative deprivation theory. The results from the current study using a total of 726 Chinese college students showed that social comparison was positively correlated with aggression, which was mediated by relative deprivation. Specifically, more frequent social comparison was associated with higher relative deprivation, which was, in turn, associated with higher aggression. Covert narcissism acted as a moderator in this model. Covert narcissism exacerbated the relationships between social comparison and relative deprivation and relative deprivation and aggression. Specifically, compared to individuals with low levels of covert narcissism, those with high levels of covert narcissism exhibited greater relative deprivation when subjected to the same social comparisons, subsequently displaying increased levels of aggression. This study deepens the understanding of the relationship between social comparison and aggression and provides an intervention direction and a theoretical basis for effectively preventing aggression in young adults.

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling.

The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1ß, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Unraveling the impact of fog on driver behavior in highway tunnel entrances: A field experiment.

OBJECTIVES: This research aims to (1) study the visual and psychological characteristics of drivers in foggy tunnel entrances, (2) compare driver behavior inside and outside foggy tunnels, and (3) propose improvement ideas based on the study results. METHODS: A realistic vehicle trial was conducted. Eight participants completed trials in both foggy and clear zones on the same roadway. Drivers' physiological and psychological properties were analyzed using gaze, saccade, pupil, and heart rate as primary indicators. Pupil area change rate and heart rate variability (HRV) were used as secondary indicators. RESULTS: Visibility and tunnel area had a significant impact on drivers' visual and psychological traits. For instance, drivers in the foggy zone exhibited longer fixation duration, larger pupil area, faster heart rate, and greater HRV. Moreover, the foggy zone inside the tunnel heightened drivers' visual discomfort and psychological tension. CONCLUSION: The study suggests a high risk associated with driving in the entrance area of highway tunnels during foggy conditions, particularly after entering the tunnel. This situation significantly increases drivers' visual and psychological load. Furthermore, the effectiveness of retro-reflective facilities diminishes. Therefore, employing more self-illuminated or actively illuminated visual guiding facilities is recommended to aid drivers in acquiring traffic information.

The Influence of Emodin Succinyl Ethyl Ester on Non-alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

Expression characteristics and potential function of non-coding RNA in mouse cortical cells.

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

ecGBMsub: an integrative stacking ensemble model framework based on eccDNA molecular profiling for improving IDH wild-type glioblastoma molecular subtype classification.

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named "XGBoost.Enet-stacking-Enet" was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.