Aflatoxin B1-exposed hepatocyte-derived extracellular vesicles: Initiating hepatic stellate cell-mediated liver fibrosis through a p53-Parkin-dependent mitophagy pathway.

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

DRAC 2022: A public benchmark for diabetic retinopathy analysis on ultra-wide optical coherence tomography angiography images.

We described a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). Within this challenge, we provided the DRAC datset, an ultra-wide optical coherence tomography angiography (UW-OCTA) dataset (1,103 images), addressing three primary clinical tasks: diabetic retinopathy (DR) lesion segmentation, image quality assessment, and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams submitting different solutions for these three tasks, respectively. This paper presents a concise summary and analysis of the top-performing solutions and results across all challenge tasks. These solutions could provide practical guidance for developing accurate classification and segmentation models for image quality assessment and DR diagnosis using UW-OCTA images, potentially improving the diagnostic capabilities of healthcare professionals. The dataset has been released to support the development of computer-aided diagnostic systems for DR evaluation.

The relationship between right atrial wall inflammation and poor prognosis of atrial fibrillation based on 18F-FDG positron emission tomography/computed tomography.

Background: Atrial fibrillation (AF) has been identified to increase stroke risk, even after oral anticoagulants (OACs), and the recurrence rate is high after radiofrequency catheter ablation (RFCA). Inflammation is an essential factor in the occurrence and persistence of AF. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an established molecular imaging modality to detect local inflammation. We aimed to investigate the relationship between atrial inflammatory activity and poor prognosis of AF based on 18F-FDG PET/CT. Methods: A total of 204 AF patients including 75 with paroxysmal AF (ParAF) and 129 with persistent AF (PerAF) who underwent PET/CT before treatment were enrolled in this prospective cohort study. Clinical data, electrocardiograph (ECG), echocardiography, and cardiac 18F-FDG uptake were collected. Follow-up information was obtained from patient clinical case notes or telephone reviews, with the starting point being the time of PET/CT scan. The follow-up deadline was either the date of AF recurrence after RFCA, new-onset stroke, or May 2023. Cox proportional hazards regression models were used to identify predictors of poor prognosis and hazard ratios (HRs) with 95% confidence intervals (CIs) was calculated. Results: Median follow-up time was 29 months [interquartile range (IQR), 22-36 months]. Poor prognosis occurred in 52 patients (25.5%), including 34 new-onset stroke patients and 18 recrudescence after RFCA. The poor prognosis group had higher congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (TIA) or thromboembolism (doubled), vascular disease, age 65-74 years, sex category (female) (CHA2DS2-VASc) score [3.0 (IQR, 1.0-3.75) vs. 2.0 (IQR, 1.0-3.0), P=0.01], right atrial (RA) wall maximum standardized uptake value (SUVmax) (4.13±1.82 vs. 3.74±1.58, P=0.04), higher percentage of PerAF [39 (75.0%) vs. 90 (59.2%), P=0.04], left atrial (LA) enlargement [45 (86.5%) vs. 104 (68.4%), P=0.01], and RA wall positive FDG uptake [40 (76.9%) vs. 79 (52.0%), P=0.002] compared with the non-poor prognosis group. Univariate and multivariate Cox proportional hazard regression analysis concluded that only CHA2DS2-VASc score (HR, 1.29; 95% CI: 1.06-1.57; P=0.01) and RA wall positive FDG uptake (HR, 2.68; 95% CI: 1.10-6.50; P=0.03) were significantly associated with poor prognosis. Conclusions: RA wall FDG positive uptake based on PET/CT is tightly related to AF recurrence after RFCA or new-onset stroke after antiarrhythmic and anticoagulation treatment.

Interventing mitochondrial PD-L1 suppressed IFN-γ-induced cancer stemness in hepatocellular carcinoma by sensitizing sorafenib-induced ferroptosis.

Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.

A pan-cancer analysis of anti-proliferative protein family genes for therapeutic targets in cancer.

The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and BTG4. The APRO family is reportedly associated with the initiation and progression of cancers. This study aims to undertake a comprehensive investigation of the APRO family of proteins as a prognostic biomarker in various human tumors. We performed a pan-cancer analysis of the APRO family based on The Cancer Genome Atlas (TCGA). With the bioinformatics methods, we explored the prognostic value of the APRO family and the correlation between APRO family expression and tumor mutation burden (TMB), microsatellite instability (MSI), drug sensitivity, and immunotherapy in numerous cancers. Our results show that the APRO family was primarily down-regulated in cancer samples. The expression of APRO family members was linked with patient prognosis. In addition, APRO family genes showed significant association with immune infiltrate subtypes, tumor microenvironment, and tumor cell stemness. Finally, our study also demonstrated the relationship between APRO family genes and drug sensitivity. This study provides comprehensive information to understand the APRO family's role as an oncogene and predictor of survival in some tumor types.

Right atrial wall inflammation detected by 18F-FDG PET/CT may be significantly associated with persistent atrial fibrillation: a prospective case-control study.

AIM: Atrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT. METHODS: Thirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared. RESULTS: PerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P < 0.001; SUVmax: 4.10(3.20-4.90) VS. 2.60(2.40-3.10), P < 0.001]. Multivariate logistic regression analyses demonstrated that RA wall SUVmax was the independent influencing factor of PerAF (OR = 1.80, 95%CI 1.02-3.18, P = 0.04). In 22 AF patients with RA wall positive FDG uptake (HFLC+Fast), the "HFLC+Fast+Heparin" method did not significantly change RA wall FDG uptake evaluated by either quantitative analysis or visual analysis. High CHA2DS2-VASc score group had higher RA wall 18F-FDG uptake [3.35 (2.70, 4.50) vs, 2.8 (2.4, 3.1) P = 0.01]. CONCLUSIONS: RA wall FDG positive uptake was present mainly in PerAF. A higher RA wall 18F-FDG uptake was an independent influencing factor of PerAF. RA wall FDG uptake based on 18F-FDG PET/CT may indicate pathological inflammation. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR2000038288.

Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.

BACKGROUND: T cell factor-1 (TCF-1) + stem-like tumor-infiltrating lymphocytes (stem-like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF-1+ TILs and their prognostic significance in patients with surgically resected LUADs. METHODS: Expression of TCF-1, CD8, and ICs including programmed death-1 (PD-1), lymphocyte activating-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF-1 expressions and clinicopathological characteristics of patient prognoses were analyzed. RESULTS: Positive TCF-1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM-3 expression, LAG-3 expression, and PD-1 expression. TCF-1 positivity was significantly associated with a better recurrence-free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF-1+/CD8+ group had the best RFS and OS, while the TCF-1-/CD8- group had the worst RFS and OS. Similarly, patients with TCF-1 + PD-1- had the best prognoses and patients with TCF-1-PD-1+ had the worst prognoses. CONCLUSION: TCF-1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF-1+ TILs were related to CD8 density, TIM-3 expression, LAG-3 expression, and PD-1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF-1 and CD8 densities or PD-1 expression further stratified patients into different groups with distinct prognoses.

Protein phosphatase 2A-B55ß mediated mitochondrial p-GPX4 dephosphorylation promoted sorafenib-induced ferroptosis in hepatocellular carcinoma via regulating p53 retrograde signaling.

Rationale: As a key endogenous negative regulator of ferroptosis, glutathione peroxidase 4 (GPX4) can regulate its antioxidant function through multiple post-translational modification pathways. However, the effects of the phosphorylation/dephosphorylation status of GPX4 on the regulation of inducible ferroptosis in hepatocellular carcinoma (HCC) remain unclear. Methods: To investigate the effects and molecular mechanism of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells. Sorafenib (Sora) was used to establish the ferroptosis model in HCC cells in vitro. Using the site-directed mutagenesis method, we generated the mimic GPX4 phosphorylation or dephosphorylation HCC cell lines at specific serine sites of GPX4. The effects of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells were examined. The interrelationships among GPX4, p53, and protein phosphatase 2A-B55ß subunit (PP2A-B55ß) were also explored. To explore the synergistic anti-tumor effects of PP2A activation on Sora-administered HCC, we established PP2A-B55ß overexpression xenograft tumors in a nude mice model in vivo. Results: In the Sora-induced ferroptosis model of HCC in vitro, decreased levels of cytoplasmic and mitochondrial GPX4, mitochondrial dysfunction, and enhanced p53 retrograde signaling occurred under Sora treatment. Further, we found that mitochondrial p53 retrograded remarkably into the nucleus and aggravated Sora-induced ferroptosis. The phosphorylation status of GPX4 at the serine 2 site (GPX4Ser2) revealed that mitochondrial p-GPX4Ser2 dephosphorylation was positively associated with ferroptosis, and the mechanism might be related to mitochondrial p53 retrograding into the nucleus. In HCC cells overexpressing PP2A-B55ß, it was found that PP2A-B55ß directly interacted with mitochondrial GPX4 and promoted Sora-induced ferroptosis in HCC. Further, PP2A-B55ß reduced the interaction between mitochondrial GPX4 and p53, leading to mitochondrial p53 retrograding into the nucleus. Moreover, it was confirmed that PP2A-B55ß enhanced the ferroptosis-mediated tumor growth inhibition and mitochondrial p53 retrograde signaling in the Sora-treated HCC xenograft tumors. Conclusion: Our data uncovered that the PP2A-B55ß/p-GPX4Ser2/p53 axis was a novel regulatory pathway of Sora-induced ferroptosis. Mitochondrial p-GPX4Ser2 dephosphorylation triggered ferroptosis via inducing mitochondrial p53 retrograding into the nucleus, and PP2A-B55ß was an upstream signal modulator responsible for mitochondrial p-GPX4Ser2 dephosphorylation. Our findings might serve as a potential theranostic strategy to enhance the efficacy of Sora in HCC treatment through the targeted intervention of p-GPX4 dephosphorylation via PP2A-B55ß activation.

Emission and purification of evaporated-condensed oil droplets affected by condensation nuclei during machining.

Fine oil droplets emitted by evaporation-condensation during machining are typical indoor air contaminants. Airborne particles can act as condensation nuclei, facilitating the condensation of oil vapor. The physical properties of these resultant droplets significantly affect their purification efficiency. Herein, this study aimed to elucidate the emission characteristics of oil droplets formed by evaporation-condensation affected by condensation nuclei and the purification efficiency of intense field dielectric (IFD) technology for the droplets under varying airflow velocities. Results show that the removal of condensation nuclei can effectively reduce the mass of evaporated-condensed oil droplets, and the increment in the mass of oil droplets reached 1.7 times the increment in the mass of condensation nuclei. It was more effective to reduce the mass of oil droplets by removing large condensation nuclei and decreasing the amount of evaporated soluble oil, as compared to removing smaller condensation nuclei or using straight oil. Condensation nuclei mainly contributed to the generation of oil droplets below 5 µm. For droplet diameters of 0.3-5.0 µm and airflow velocities of 0.5-2.0 m/s, the purification efficiency was within the 84-96% range. The purification efficiency of the IFD purifier for oil droplets could be improved either by increasing the size of the oil droplets or by reducing the airflow velocity.

Suppurative Temporomandibular Arthritis Caused by Chronic Suppurative Otitis Media: A Case Report.

The clinical diagnosis and treatment, including information such as age, history, clinical symptoms, signs, audiology, imaging examination, mode of operation, and postoperative follow-up, of a patient with suppurative temporomandibular arthritis caused by chronic suppurative otitis media were analyzed. As conservative drug treatment and drainage surgery were ineffective, the patient was treated with microscopic open radical mastoidectomy, tympanoplasty, the plasty of the cavity of auricular concha, facial nerve decompression, coarctation of the mastoid cavity combined with otoendoscpic resection of the lower temporomandibular lesions, and standard anti-inflammatory treatment after surgery. The patient appeared to be cured at the 3-month follow-up. The ear canal was dry, without any preauricular swelling, purulent ear discharge, otalgia, limitation of mouth opening, or other symptoms. A clear diagnosis by defining the scope of the lesions, analysis of the transmission route of the lesions, and standard conservative treatment, local drainage, and surgical resection, if necessary, are recommended for patients with suppurative temporomandibular arthritis.

Application of Ag@Cu Water-Based Nanomaterial Conductive Ink in 3D Printing.

Copper (Cu) nanoparticles are considered a promising alternative to silver (Ag) and gold (Au) for printed electronics applications. Because Cu has higher electrical conductivity, it is significantly cheaper than Ag and Au. To study the applicability of electronic printing, we prepared Ag@Cu conductive ink by using a stepwise feeding method to disperse nano Ag and nano Cu in ethanol and water. The ink has the advantages of nontoxic, low content, and low cost. A three-dimensional (3D) model was designed, and a conductive pattern was printed on the photo paper substrate using extrusion 3D printing technology. The influence of waterborne resin on the adhesion of conductive patterns is discussed. The printed conductive pattern can maintain the stability of conductivity after 100 bending cycles. The conductive pattern has good thermal stability. It can be tested 10 times under 2 conditions of 85°C and room temperature to maintain good conductivity. This shows that Ag@Cu conductive ink printed flexible electronic products are competitive.

Multi-omics analysis reveals BDE47 induces depression-like behaviors in mice by interfering with the 2-arachidonoyl glycerol-associated microbiota-gut-brain axis.

2,2',4,4'-tetrabromodiphenyl ether (BDE47) is a foodborne environmental risk factor for depression, but the pathogenic mechanism has yet to be fully characterized. In this study, we clarified the effect of BDE47 on depression in mice. The abnormal regulation of the microbiome-gut-brain axis is evidenced closely associated with the development of depression. Using RNA sequencing, metabolomics, and 16s rDNA amplicon sequencing, the role of the microbiome-gut-brain axis in depression was also explored. The results showed that BDE47 exposure increased depression-like behaviors in mice but inhibited the learning memory ability of mice. The RNA sequencing analysis showed that BDE47 exposure disrupted dopamine transmission in the brain of mice. Meanwhile, BDE47 exposure reduced protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT), activated astrocytes and microglia cells, and increased protein levels of NLRP3, IL-6, IL-1ß, and TNF-α in the brain of mice. The 16 s rDNA sequencing analysis showed that BDE47 exposure disrupted microbiota communities in the intestinal contents of mice, and faecalibaculum was the most increased genus. Moreover, BDE47 exposure increased the levels of IL-6, IL-1ß, and TNF-α in the colon and serum of mice but decreased the levels of tight junction protein ZO-1 and Occludin in the colon and brain of mice. In addition, the metabolomic analysis revealed that BDE47 exposure induced metabolic disorders of arachidonic acid and neurotransmitter 2-Arachidonoyl glycerol (2-AG) was one of the most decreased metabolites. Correlation analysis further revealed gut microbial dysbiosis, particularly faecalibaculum, is associated with altered gut metabolites and serum cytokines in response to BDE47 exposure. Our results suggest that BDE47 might induce depression-like behavior in mice through gut microbial dysbiosis. The mechanism might be associated with the inhibited 2-AG signaling and increased inflammatory signaling in the gut-brain axis.

Timing of Percutaneous Balloon Kyphoplasty for Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Percutaneous balloon kyphoplasty (PKP) is widely used to treat osteoporotic vertebral compression fractures (OVCFs). In addition to rapid and effective pain relief, the ability to recover the lost height of fractured vertebral bodies and reduce the risk for complications are believed to be the main advantages of this procedure. However, there is no consensus on the appropriate surgical timing for PKP. OBJECTIVES: This study systematically evaluated the relationship between the surgical timing of PKP and clinical outcomes to provide more evidence for clinicians to choose the intervention timing. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched for relevant randomized controlled trials and prospective, and retrospective cohort trials published up to November 13, 2022. All included studies explored the influence of PKP intervention timing for OVCFs. Data regarding clinical and radiographic outcomes and complications were extracted and analyzed. RESULTS: Thirteen studies involving 930 patients with symptomatic OVCFs were included. Most patients with symptomatic OVCFs achieved rapid and effective pain relief after PKP. In comparison to delayed PKP intervention, early PKP intervention was associated with similar or better outcomes in terms of pain relief, improvement of function, restoration of vertebral height, and correction of kyphosis deformity. The meta-analysis results showed there was no significant difference in cement leakage rate between early PKP and late PKP (odds ratio [OR] = 1.60, 95% CI, 0.97-2.64, P = 0.07), whereas delayed PKP had a higher risk for adjacent vertebral fractures (AVFs) than early PKP (OR = 0.31, 95% CI: 0.13-0.76, P = 0.01). LIMITATIONS: The number of included studies was small, and the overall quality of the evidence was very low. CONCLUSIONS: PKP is an effective treatment for symptomatic OVCFs. Early PKP may achieve similar or better clinical and radiographic outcomes for treating OVCFs than delayed PKP. Furthermore, early PKP intervention had a lower incidence of AVFs and a similar rate of cement leakage compared with delayed PKP. Based on current evidence, early PKP intervention might be more beneficial to patients.

Clinical relevance of serum lipids in the carcinogenesis of oral squamous cell carcinoma.

BACKGROUND: Dyslipidaemia is associated with cancers. However, the specific expression of serum lipids in oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) remains unclear, and it remains unknown whether serum lipids are associated with the development of OPMD and OSCC. This study investigated the serum lipid profiles of OPMD and OSCC patients, and the association of serum lipids with the occurrence of OPMD and OSCC. METHODS: A total of 532 patients were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Serum lipid parameters including total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo-A), apolipoprotein B (Apo-B), and lipoprotein (a) (Lpa) were analysed, and clinicopathological data were collected for further analysis. Furthermore, a regression model was used to evaluate the relationship between serum lipids and the occurrence of OSCC and OPMD. RESULTS: After adjusting for age and sex, no significant differences were observed in serum lipid or body mass index (BMI) between OSCC patients and controls (P > 0.05). HDL-C, Apo-A, and Apo-B levels were lower in OSCC patients than in OPMD patients (P < 0.05); HDL-C and Apo-A levels were higher in OPMD patients than in controls (P < 0.05). Furthermore, female OSCC patients had higher Apo-A and BMI values than males. The HDL-C level was lower in patients under 60 years of age than in elders (P < 0.05); and age was related to a higher risk of developing OSCC. Female patients with OPMD had higher TC, HDL-C, and Apo-A levels than males (P < 0.05); OPMD patients over 60 years of age had higher HDL-C than youngers (P < 0.05), whereas the LDL-C level was lower in elders (P < 0.05). The HDL-C and BMI values of the patients with oral leukoplakia (OLK) with dysplasia were more elevated than those of the oral lichen planus group, and the LDL-C, and Apo-A levels in patients with OLK with dysplasia were decreased (P < 0.05). Sex, high HDL-C and Apo-A values were associated with the development of OPMD. CONCLUSION: Serum lipids exhibited certain differences according to the occurrence and development of OSCC; high levels of HDL-C and Apo-A might be markers for predicting OPMD.

Construction of a novel anoikis-related prognostic model and analysis of its correlation with infiltration of immune cells in neuroblastoma.

Background: Anoikis resistance (AR) plays an important role in the process of metastasis, which is an important factor affecting the risk stage of neuroblastoma (NB). This study aims to construct an anoikis-related prognostic model and analyze the characteristics of hub genes, important pathways and tumor microenvironment of anoikis-related subtypes of NB, so as to provide help for the clinical diagnosis, treatment and research of NB. Methods: We combined transcriptome data of GSE49710 and E-MTAB-8248, screened anoikis-related genes (Args) closely related to the prognosis of NB by univariate cox regression analysis, and divided the samples into anoikis-related subtypes by consistent cluster analysis. WGCNA was used to screen hub genes, GSVA and GSEA were used to analyze the differentially enriched pathways between anoikis-related subtypes. We analyzed the infiltration levels of immune cells between different groups by SsGSEA and CIBERSORT. Lasso and multivariate regression analyses were used to construct a prognostic model. Finally, we analyzed drug sensitivity through the GDSC database. Results: 721 cases and 283 Args were included in this study. All samples were grouped into two subtypes with different prognoses. The analyses of WGCNA, GSVA and GSEA suggested the existence of differentially expressed hub genes and important pathways in the two subtypes. We further constructed an anoikis-related prognostic model, in which 15 Args participated. This model had more advantages in evaluating the prognoses of NB than other commonly used clinical indicators. The infiltration levels of 9 immune cells were significantly different between different risk groups, and 13 Args involved in the model construction were correlated with the infiltration levels of immune cells. There was a relationship between the infiltration levels of 6 immune cells and riskscores. Finally, we screened 15 drugs with more obvious effects on NB in high-risk group. Conclusion: There are two anoikis-related subtypes with different prognoses in the population of NB. The anoikis-related prognostic model constructed in this study can accurately predict the prognoses of children with NB, and has a good guiding significance for clinical diagnosis, treatment and research of NB.

An international analysis of stem cell research in intervertebral disc degeneration.

Stem cell therapy has been increasingly investigated as a promising strategy for intervertebral disc degeneration (IDD). However, no international analysis of stem cell research has yet been conducted. This study aimed to analyze the major characteristics of published reports of stem cell use for IDD and to present a global insight into stem cell research. The study period spanned from the inception of the Web of Science database to 2021. A search strategy using specific keywords was implemented to retrieve relevant publications. The numbers of documents, citations, countries, journals, article types, and stem cell types were evaluated. A total of 1170 papers were retrieved. The analysis showed a significant increase in the number of papers over time (p < 0.001). High-income economies accounted for the majority of papers (758, 64.79 %). China produced the most articles (378, 32.31 %), followed by the United States (259, 22.14 %), Switzerland (69, 5.90 %), United Kingdom (54, 4.62 %), and Japan (47, 4.02 %). The United States ranked first in terms of the number of citations (10,346), followed by China (9177) and Japan (3522). Japan ranked first in terms of the number of citations per paper (74.94), followed by United Kingdom (58.54) and Canada (53.74). When standardized by population, Switzerland ranked first, followed by Ireland and Sweden. When gross domestic product was considered, Switzerland ranked first, followed by Portugal and Ireland. The number of papers was positively correlated with gross domestic product (p < 0.001, r = 0.673); however, there was no significant correlation with population (p = 0.062, r = 0.294). Mesenchymal stem cells were the most investigated stem cells, followed by nucleus pulposus-derived stem cells and adipose-derived stem cells. A sharp increase in stem cell research was observed in the field of IDD. China produced the most, although several European countries were more productive relative to their populations and economies.

Identification of risk and prognostic factors for intrahepatic vascular invasion in patients with hepatocellular carcinoma: a population-based study.

Background: The aim of this study was to develop nomograms to predict the risk of intrahepatic vascular invasion (IVI) of hepatocellular carcinoma (HCC) patients and estimate the overall survival (OS) and cancer-specific survival (CSS) of HCC patients with IVI. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with HCC from 2010 to 2015. Ultimately, 1,287 HCC patients with IVI were included in this study and randomly divided into training (n=901) and validation (n=386) cohorts. Multivariate logistic regression analysis and multivariate Cox proportional hazards regression analysis were performed to construct nomograms to visually quantify the risk of IVI in patients with HCC and predict the prognosis. The prediction effect of nomograms was evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA), respectively. Results: The C-index of the nomogram for risk prediction was 0.730. The C-indices based on the nomogram were 0.762 [95% confidence interval (CI): 0.745-0.779] and 0.770 (95% CI: 0.753-0.787) for OS and CSS prediction in the training cohort, respectively. In the validation cohort, the C-indices were 0.779 (95% CI: 0.752-0.806) and 0.795 (95% CI: 0.768-0.822) for OS prediction and CSS prediction, respectively. Overall, the ROC curve, calibration plots, and DCA indicated the good performance of nomograms. Conclusions: We identified the relevant risk and prognostic factors for IVI in patients with HCC. The nomograms performed well on validation and may help to facilitate clinical decision-making.

Monitoring of organophosphorus pesticide residues in plant and vegetable tissues by a novel silver nanocluster probe.

More and more attention has been paid to the problem of pesticide residues, especially in plants and vegetables, due to their close relationship with human health and food safety. Compared to conventional detecting techniques, the fluorescence sensing method has achieved good results for pesticides detection. However, most of the reported fluorescent probes needed two or more steps to achieve the detection of pesticide residues, which greatly limited their application for in vivo imaging and in situ analysis of agricultural residues in plants and vegetables. In this paper, an Ag nanoclusters (AgNCs) based fluorescent probe is developed for one-step detection of pesticide residues. The novel nanoprobe displayed impressive advantages, such as a selective response to glyphosate pesticide, rapid response within 1 min and an ultralow detection limit of 21 nM. The sensing mechanism is attributed to the unique coordination interaction between AgNCs and glyphosate, which not only increased the size of AgNCs to form big Ag particles, but also caused the fluorescence quenching of AgNCs system. Due to its favorable properties, the probe has been successfully applied to imaging the organophosphorus pesticide of glyphosate in the leave tissues of Arabidopsis thaliana and the root tip cells of lettuce for the first time.

Breathable, antifreezing, mechanically skin-like hydrogel textile wound dressings with dual antibacterial mechanisms.

Hydrogels are emerging as the most promising dressings due to their excellent biocompatibility, extracellular matrix mimicking structure, and drug loading ability. However, existing hydrogel dressings exhibit limited breathability, poor environmental adaptability, potential drug resistance, and limited drug options, which extremely restrict their therapeutic effect and working scenarios. Here, the current research introduces the first paradigm of hydrogel textile dressings based on novel gelatin glycerin hydrogel (glyhydrogel) fibers fabricated by the Hofmeister effect based wet spinning. Benefiting from the unique knitted structure, the textile dressing features excellent breathability (1800 times that of the commercially available 3 M dressing) and stretchability (535.51 ± 38.66%). Furthermore, the glyhydrogel textile dressing can also withstand the extreme temperature of -80 °C, showing the potential for application in subzero environments. Moreover, the introduction of glycerin endows the textile dressing with remarkable antibacterial property and expands the selection of loaded drugs (e.g., clindamycin). The prepared glyhydrogel textile dressing shows an excellent infected wound healing effect with a complete rat skin closure within 14 days. All these functions have not been achievable by traditional hydrogel dressings and provide a new approach for the development of hydrogel dressings.