Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.

Osteosarcoma is the most common malignant bone tumor. It has a poor prognosis because of a lack of therapeutic targets and strategies. The SET domain-containing lysine-specific methyltransferase, SET7/9, has various functions in different cancer types in tissue-type and signaling context-dependent manners. The role of SET7/9 in osteosarcoma cells is currently controversial and its potential as a therapeutic candidate in osteosarcoma is unknown. In the present study, SET7/9 inhibition or ablation suppressed osteosarcoma cell proliferation by causing G1 arrest. Mechanistically, SET7/9 inhibition disrupted the interaction between cyclin-dependent kinase 4 (CDK4) and cyclin D1, which affected CDK4-cyclin D1 complex function, leading to decreased phosphorylation of retinoblastoma protein. CDK4 was overexpressed in osteosarcoma tissues and was closely related to a poor prognosis in patients with osteosarcoma. We therefore hypothesized that SET7/9 inhibition might increase the sensitivity of osteosarcoma cells to CDK4 inhibitors, potentially decreasing the risk of adverse effects of CDK4 inhibitors. The combination of SET7/9 and CDK4 inhibition enabled dose reductions of both inhibitors and had a synergistic effect against osteosarcoma growth in vivo. Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.

Transformational Modulation of Fluorescence to Room Temperature Phosphorescence in Metal-Organic Frameworks with Flexible C-S-C Bonds.

Photoluminescent metal-organic frameworks (MOFs) have been a subject of considerable interest for many years. However, the regulation of excited states of MOFs at the single crystal level remains restricted due to a lack of control methods. The singlet-triplet emissive property can be significantly influenced by crystal conformational distortions. This review introduces an intelligent responsive MOF material, denoted as LIFM-SHL-3a, characterized by flexible C-S-C bonds. LIFM-SHL-3a integrates elastic structural dynamics with fluorescence and room temperature phosphorescence (RTP) modulation under heating conditions. The deformable carbon-sulfur bond essentially propels the distortion of molecular conformation and alters the stacking mode, as illustrated by single-crystal-to-single-crystal transformation detection. The deformation of flexible C-S-C bonds leads to different noncovalent interactions in the crystal system, thereby achieving modulation of the fluorescence (F) and RTP bands. In the final state structure, the ratio of fluorescence is 66.7%, and the ratio of RTP is 32.6%. This stands as a successful demonstration of modulating F/RTP within the dynamic MOF, unlocking potential applications in optical sensing and beyond. Especially, a PL thermometer with a relative sensitivity of 0.096-0.104%·K-1 in the range of 300-380 K and a H2S probe with a remarkably low LOD of 125.80 nM can be obtained using this responsive MOF material of LIFM-SHL-3a.

Hydraulic-driven adaptable morphing active-cooling elastomer with bioinspired bicontinuous phases.

The active-cooling elastomer concept, originating from vascular thermoregulation for soft biological tissue, is expected to develop an effective heat dissipation method for human skin, flexible electronics, and soft robots due to the desired interface mechanical compliance. However, its low thermal conduction and poor adaptation limit its cooling effects. Inspired by the bone structure, this work reports a simple yet versatile method of fabricating arbitrary-geometry liquid metal skeleton-based elastomer with bicontinuous Gyroid-shaped phases, exhibiting high thermal conductivity (up to 27.1 W/mK) and stretchability (strain limit >600%). Enlightened by the vasodilation principle for blood flow regulation, we also establish a hydraulic-driven conformal morphing strategy for better thermoregulation by modulating the hydraulic pressure of channels to adapt the complicated shape with large surface roughness (even a concave body). The liquid metal active-cooling elastomer, integrated with the flexible thermoelectric device, is demonstrated with various applications in the soft gripper, thermal-energy harvesting, and head thermoregulation.

Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Hub gene identification and molecular subtype construction for Helicobacter pylori in gastric cancer via machine learning methods and NMF algorithm.

Helicobacter pylori (HP) is a gram-negative and spiral-shaped bacterium colonizing the human stomach and has been recognized as the risk factor of gastritis, peptic ulcer disease, and gastric cancer (GC). Moreover, it was recently identified as a class I carcinogen, which affects the occurrence and progression of GC via inducing various oncogenic pathways. Therefore, identifying the HP-related key genes is crucial for understanding the oncogenic mechanisms and improving the outcomes of GC patients. We retrieved the list of HP-related gene sets from the Molecular Signatures Database. Based on the HP-related genes, unsupervised non-negative matrix factorization (NMF) clustering method was conducted to stratify TCGA-STAD, GSE15459, GSE84433 samples into two clusters with distinct clinical outcomes and immune infiltration characterization. Subsequently, two machine learning (ML) strategies, including support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), were employed to determine twelve hub HP-related genes. Beyond that, receiver operating characteristic and Kaplan-Meier curves further confirmed the diagnostic value and prognostic significance of hub genes. Finally, expression of HP-related hub genes was tested by qRT-PCR array and immunohistochemical images. Additionally, functional pathway enrichment analysis indicated that these hub genes were implicated in the genesis and progression of GC by activating or inhibiting the classical cancer-associated pathways, such as epithelial-mesenchymal transition, cell cycle, apoptosis, RAS/MAPK, etc. In the present study, we constructed a novel HP-related tumor classification in different datasets, and screened out twelve hub genes via performing the ML algorithms, which may contribute to the molecular diagnosis and personalized therapy of GC.

One/Two-Photon-Excited ESIPT-Attributed Coordination Polymers with Wide Temperature Range and Color-Tunable Long Persistent Luminescence.

The multiple metastable excited states provided by excited-state intramolecular proton transfer (ESIPT) molecules are beneficial to bring temperature-dependent and color-tunable long persistent luminescence (LPL). Meanwhile, ESIPT molecules are intrinsically suitable to be modulated as D-π-A structure to obtain both one/two-photon excitation and LPL emission simultaneously. Herein, we report the rational design of a dynamic CdII coordination polymer (LIFM-106) from ESIPT ligand to achieve the above goals. By comparing LIFM-106 with the counterparts, we established a temperature-regulated competitive relationship between singlet excimer and triplet LPL emission. The optimization of ligand aggregation mode effectively boost the competitiveness of the latter. In result, LIFM-106 shows outstanding one/two-photon excited LPL performance with wide temperature range (100-380 K) and tunable color (green to red). The multichannel radiation process was further elucidated by transient absorption and theoretical calculations, benefiting for the application in anti-counterfeiting systems.

Effects of theta burst stimulation on the coherence of local field potential during working memory task in rats.

Theta burst stimulation (TBS), a highly efficient repetitive transcranial magnetic stimulation (rTMS) paradigm, has been widely used to modulate the working memory (WM) ability in experimental and clinical study. However, the underly neuroelectrophysiological mechanism remains unclear. The aim of this study was to compare the effect of iTBS, cTBS and rTMS on WM and explore the neural oscillatory communication changes in PFC involved in spatial WM task. 18 rats were treated by iTBS, cTBS and rTMS respectively (n = 6 each), while the rats in control group (n = 6) received no stimulation. T-maze WM task was used to assess the rats' performance of WM after stimulation. Local field potentials (LFPs) were recorded from a microelectrode array implanted in the medial prefrontal cortex (mPFC) while the rats were performing the WM task. Functional connectivity (FC) strength was assessed by LFP-LFP coherence calculations. The results showed that the rats from the rTMS group and iTBS group are able to reach criteria in less time than the control group's duration of the T-maze task. The power and the coherence value of rTMS and iTBS groups show a significant increase in the theta-band and gamma-band activity, wheras there are no significant differences of the energy and the coherence value between the cTBS group and the control group in theta-band. Furthermore, significantly positive correlations were observed between changes of memory performance during the WM task and the changes of the coherence value of the LFPs. In conclusion, these results indicate that rTMS and iTBS may improve the ability of WM by modulating the neural activity and connectivity in PFC.

Development and validation of nomograms predicting overall and cancer-specific survival for non-metastatic primary malignant bone tumor of spine patients.

At present, no study has established a survival prediction model for non-metastatic primary malignant bone tumors of the spine (PMBS) patients. The clinical features and prognostic limitations of PMBS patients still require further exploration. Data on patients with non-metastatic PBMS from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression analysis using Cox, Best-subset and Lasso regression methods was performed to identify the best combination of independent predictors. Then two nomograms were structured based on these factors for overall survival (OS) and cancer-specific survival (CSS). The accuracy and applicability of the nomograms were assessed by area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Results: The C-index indicated that the nomograms of OS (C-index 0.753) and CSS (C-index 0.812) had good discriminative power. The calibration curve displays a great match between the model's predictions and actual observations. DCA curves show our models for OS (range: 0.09-0.741) and CSS (range: 0.075-0.580) have clinical value within a specific threshold probability range compared with the two extreme cases. Two nomograms and web-based survival calculators based on established clinical characteristics was developed for OS and CSS. These can provide a reference for clinicians to formulate treatment plans for patients.

Surgical treatment versus observation in moderate intermittent exotropia (SOMIX): study protocol for a randomized controlled trial.

BACKGROUND: Intermittent exotropia (IXT) is the most common type of strabismus in China, but the best treatment and optimal timing of intervention for IXT remain controversial, particularly for children with moderate IXT who manifest obvious exodeviation frequently but with only partial impairment of binocular single vision. The lack of randomized controlled trial (RCT) evidence means that the true effectiveness of the surgical treatment in curing moderate IXT is still unknown. The SOMIX (surgical treatment versus observation in moderate intermittent exotropia) study has been designed to determine the long-term effectiveness of surgery for the treatment and the natural history of IXT among patients aged 5 to 18 years old. METHODS/DESIGN: A total of 280 patients between 5 and 18 years of age with moderate IXT will be enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. After initial clinical assessment, all participants will be randomized to receive surgical treatment or observation, and then be followed up for 5 years. The primary objective is to compare the cure rate of IXT between the surgical treatment and observation group. The secondary objectives are to identify the predictive factors affecting long-term outcomes in each group and to observe the natural course of IXT. DISCUSSION: The SOMIX trial will provide important guidance regarding the moderate IXT and its managements and modify the treatment strategies of IXT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02736526 . Registered April 13, 2016.

Echinacoside from Cistanche tubulosa ameliorates alcohol-induced liver injury and oxidative stress by targeting Nrf2.

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong-Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti-inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2-related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML-12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase-3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol-induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.

Verbenalin attenuates hepatic damage and mitochondrial dysfunction in alcohol-associated steatohepatitis by regulating MDMX/PPARα-mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbenalin is a major compound in Verbena officinalis L. Verbena officinalis L was first recorded in the 'Supplementary Records of Famous Physicians.' Verbenalin (VE) is its active constituent and has been found to have many biological effects, including anti-obesity, anti-inflammatory, and antioxidant activities, removing jaundice, and treating malaria. It could treat lump accumulation, dysmenorrhea, throat obstruction, edema, jaundice, and malaria. Palmitic acid (PA), oleic acid (OA), ethanol, and acetaminophen liver injuries have been proven to benefit from verbenalin. AIM OF THE STUDY: To study the effects of verbenalin on the prevention of alcoholic steatohepatitis (ASH) through the regulation of oxidative stress and mitochondrial dysfunction by regulating MDMX (Murine double minute X)/PPARα (Peroxisome proliferator-activated receptor alpha)-mediated ferroptosis. MATERIAL AND METHODS: C57BL/6 mice treated with alcohol followed by the Gao-Binge protocol were administered verbenalin by gavage simultaneously. The mitochondrial mass and morphology were visualized using TEM. AML-12 cells were stimulated with ethanol to mimic ASH in vitro. Western blotting, co-immunoprecipitation, and kit determination were simultaneously performed. The target protein of verbenalin was identified by molecular docking, and cellular thermal shift assay (CETSA) further confirmed its interactions. RESULTS: Verbenalin alleviates oxidative stress and ferroptosis in alcohol-associated steatohepatitis. To elucidate the molecular mechanism by which verbenalin inhibits abnormal mitochondrial dysfunction, molecular docking was performed, and MDMX was identified as the target protein of verbenalin. CETSA assays revealed a specific interaction between MDMX and verbenalin. Co-immunoprecipitation demonstrated that PPARα played a critical role in promoting the ability of MDMX to affect ferroptosis. Verbenalin regulates MDMX/PPARα-mediated ferroptosis in AML-12 cells. CONCLUSION: Verbenalin regulates ferroptosis and highlights the therapeutic potential of verbenalin and ferroptosis inhibition in reducing alcoholic steatohepatitis.

A bibliometric and visual analysis of publications on artificial intelligence in colorectal cancer (2002-2022).

Background: Colorectal cancer (CRC) has the third-highest incidence and second-highest mortality rate of all cancers worldwide. Early diagnosis and screening of CRC have been the focus of research in this field. With the continuous development of artificial intelligence (AI) technology, AI has advantages in many aspects of CRC, such as adenoma screening, genetic testing, and prediction of tumor metastasis. Objective: This study uses bibliometrics to analyze research in AI in CRC, summarize the field's history and current status of research, and predict future research directions. Method: We searched the SCIE database for all literature on CRC and AI. The documents span the period 2002-2022. we used bibliometrics to analyze the data of these papers, such as authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analysis were the main methods of analysis. Citespace, VOSviewer, and SCImago Graphica were used to visualize the results. Result: This study selected 1,531 articles on AI in CRC. China has published a maximum number of 580 such articles in this field. The U.S. had the most quality publications, boasting an average citation per article of 46.13. Mori Y and Ding K were the two authors with the highest number of articles. Scientific Reports, Cancers, and Frontiers in Oncology are this field's most widely published journals. Institutions from China occupy the top 9 positions among the most published institutions. We found that research on AI in this field mainly focuses on colonoscopy-assisted diagnosis, imaging histology, and pathology examination. Conclusion: AI in CRC is currently in the development stage with good prospects. AI is currently widely used in colonoscopy, imageomics, and pathology. However, the scope of AI applications is still limited, and there is a lack of inter-institutional collaboration. The pervasiveness of AI technology is the main direction of future housing development in this field.

Clinical characteristics and risk factors of acute acquired concomitant esotropia in last 5 years: a retrospective case-control study.

OBJECTIVES: A remarkable increase in the number and proportion of surgical patients with acute acquired concomitant esotropia (AACE) has been noted in our hospital in recent years. We aimed to analyse the clinical characteristics and associated risk factors of this increasing number of strabismus in last 5 years. METHODS: Medical information was obtained in 62 AACE patients and 73 orthotropic patients as control group completed questionnaires and examination items from March 2017 to May 2020. Data included age at onset, refractive error, angle of deviation, binocular vision, eye care habits, and optical quality of spectacles. RESULTS: Of the 62 AACE patients, the mean ± standard deviation age at onset was 25.3 ± 8.5 years, with 47 (75.8%) cases showing myopia, 9 (14.5%) showing emmetropia, and 6 (9.7%) showing hypermetropia. Among the AACE patients, 35 (56.5%) performed >8 h of close work daily and 36 (58.1%) reported late-night use of digital devices. When compared with the control group, the risk factors identified for AACE included long durations of close work (odds ratio [OR], 11.72; 95% confidence interval [CI], 3.53-38.91; P < 0.001) and immoderate late-night use of digital devices (OR, 14.29; 95% CI, 4.10-49.72; P < 0.001). CONCLUSION: Our study demonstrated that young adults accounted for the majority of the growing number of individuals affected by AACE in last 5 years, and excessive close visual activities and immoderate late-night use of digital devices were found to be associated with the onset of AACE.

Multiomics characteristics and immunotherapeutic potential of EZH2 in pan-cancer.

Enhancer of zeste homolog 2 (EZH2) is a significant epigenetic regulator that plays a critical role in the development and progression of cancer. However, the multiomics features and immunological effects of EZH2 in pan-cancer remain unclear. Transcriptome and clinical raw data of pan-cancer samples were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and subsequent data analyses were conducted by using R software (version 4.1.0). Furthermore, numerous bioinformatics analysis databases also reapplied to comprehensively explore and elucidate the oncogenic mechanism and therapeutic potential of EZH2 from pan-cancer insight. Finally, quantitative reverse transcription polymerase chain reaction and immunohistochemical assays were performed to verify the differential expression of EZH2 gene in various cancers at the mRNA and protein levels. EZH2 was widely expressed in multiple normal and tumor tissues, predominantly located in the nucleoplasm. Compared with matched normal tissues, EZH2 was aberrantly expressed in most cancers either at the mRNA or protein level, which might be caused by genetic mutations, DNA methylation, and protein phosphorylation. Additionally, EZH2 expression was correlated with clinical prognosis, and its up-regulation usually indicated poor survival outcomes in cancer patients. Subsequent analysis revealed that EZH2 could promote tumor immune evasion through T-cell dysfunction and T-cell exclusion. Furthermore, expression of EZH2 exhibited a strong correlation with several immunotherapy-associated responses (i.e., immune checkpoint molecules, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) status, and neoantigens), suggesting that EZH2 appeared to be a novel target for evaluating the therapeutic efficacy of immunotherapy.

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia.

Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey ( Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral, neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging (MRI), behavioral tasks, flash visual evoked potentials (FVEP), electroretinogram (ERG), optical coherence tomography (OCT), and whole-genome sequencing (WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway. Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion, natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system, especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.

Downregulating PDPK1 and taking phillyrin as PDPK1-targeting drug protect hepatocytes from alcoholic steatohepatitis by promoting autophagy.

The health risk stemming from drinking alcohol is serious, sometimes even life-threatening. Alcoholic steatohepatitis (ASH) is a critical stage leading to cirrhosis and end-stage liver disease. However, its pathogenesis is still far from clearly understood, and a treatment that is widely recognised as effective has not been discovered. Interestingly, PDPK1,3-phosphoinositide-dependent protein kinase 1, also known as PDK1, was observed to be obviously increased in the ASH model by our researchers. We also investigated the protective role of autophagy in ASH. Here, we studied the function of PDPK1 and found an efficient treatment to alleviate symptoms by targeting PDPK1 in ASH. In our study, PDPK1 affected hepatocyte self-healing by inhibiting autophagy. Both inhibiting PDPK1 and the phosphorylation of PDPK1 (ser241) could protect hepatocytes from suffering heavy alcoholic hepatitis.

An Earthquake Emergency Web Data Cleaning and Classification Method Based on Word Frequency and Position Weighting.

The speed of earthquake emergency web document data cleaning is one of the key factors affecting emergency rescue decision-making. Data classification is the core process of data cleaning, and the efficiency of data classification determines the speed of data cleaning. This article is based on earthquake emergency Web document data and HTML structural features, combined with TF-IDF Algorithm and information calculation model, improves the word frequency factor and location factor parameters, and proposes the weighted frequency algorithm P-TF-IDF for earthquake emergency Web documents. To filter out less frequent words and optimize the FastText model, N-gram Feature word vectors effectively improve the efficiency of Web document data classification; for text classification data, use missing data recognition rules, data classification rules, and data repair rules to design an artificial intelligence-based earthquake emergency network information data cleaning framework to detect invalid data sets value, complete data comparison and redundancy judgment, clean up data conflicts and data errors, and generate a complete data set without duplication. The data cleaning framework not only completes the fusion of earthquake emergency network information but also provides a data foundation for the visualization of earthquake emergency data.

A digital mask to safeguard patient privacy.

The storage of facial images in medical records poses privacy risks due to the sensitive nature of the personal biometric information that can be extracted from such images. To minimize these risks, we developed a new technology, called the digital mask (DM), which is based on three-dimensional reconstruction and deep-learning algorithms to irreversibly erase identifiable features, while retaining disease-relevant features needed for diagnosis. In a prospective clinical study to evaluate the technology for diagnosis of ocular conditions, we found very high diagnostic consistency between the use of original and reconstructed facial videos (κ ≥ 0.845 for strabismus, ptosis and nystagmus, and κ = 0.801 for thyroid-associated orbitopathy) and comparable diagnostic accuracy (P ≥ 0.131 for all ocular conditions tested) was observed. Identity removal validation using multiple-choice questions showed that compared to image cropping, the DM could much more effectively remove identity attributes from facial images. We further confirmed the ability of the DM to evade recognition systems using artificial intelligence-powered re-identification algorithms. Moreover, use of the DM increased the willingness of patients with ocular conditions to provide their facial images as health information during medical treatment. These results indicate the potential of the DM algorithm to protect the privacy of patients' facial images in an era of rapid adoption of digital health technologies.

Regional Downregulation of Dopamine Receptor D1 in Bilateral Dorsal Lateral Geniculate Nucleus of Monocular Form-Deprived Amblyopia Models.

Amblyopia is a common eye disease characterized by impaired best-corrected visual acuity. It starts in early childhood and leads to permanent vision reduction if left untreated. Even though many young patients with amblyopia are well treated in clinical practice, the underlying mechanism remains to be elucidated, which limits not only our understanding of this disease but also the therapeutic approach. To investigate the molecular mechanism of amblyopia, primate and rodent models of monocular-deprived amblyopia were created for mRNA screening and confirmation. We obtained 818 differentially expressed genes from the dorsal lateral geniculate nucleus (dLGN) of a primate model of amblyopia. After Gene Ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the main enriched pathways were related to neural development. Interestingly, a particular neurotransmitter pathway, the dopaminergic pathway, was identified. The downregulation of dopamine receptor D1 (DRD1) was confirmed in both monkey and mouse samples. Furthermore, the immunofluorescence staining indicated that DRD1 expression was downregulated in both ventrolateral region of the contralateral dLGN and the dorsomedial region of the ipsilateral dLGN in the mouse model. The regions with downregulated expression of DRD1 were the downstream targets of the visual projection from the amblyopic eye. This study suggested that the downregulation of DRD1 in the LGN may be a cause for amblyopia. This may also be a reason for the failure of some clinical cases of levodopa combined with carbidopa applied to amblyopes.