[Evaluation of augmented reality technology in the recognizing of oral and maxillofacial anatomy].

OBJECTIVE: To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy. METHODS: This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy. The image data were selected according to the experiment content, and the important blood vessels and bone tissue structures, such as upper and lower jaws, neck arteries and veins were reconstructed in 3D(3-dimensional) by digital software to generate experiment models, and the reconstructed models were encrypted and stored in the cloud. The QR (quick response) code corresponding to the 3D model was scanned by a networked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing. Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively. Subjects' feedback was collected in the form of a post-class questionnaire to evaluate the effectiveness of augmented reality technology-assisted recognizing. RESULTS: In the study, 83 undergraduate students were included as subjects in this study. Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy. All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud, and zoom in/out/rotate the model on the mobile. Augmented reality technology could provide personalized 3D model, based on learners' needs and abilities. The results of likert scale showed that augmented reality technology was highly recognized by the students (9.19 points), and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning (9.01 and 8.85 points respectively). CONCLUSION: Augmented reality technology can realize the three-dimensional visualization of important structures of oral and maxillofacial anatomy and stimulate students' enthusiasm for learning. Besides, it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area. The application of augmented reality technology achieves favorable effect in the recognizing of oral and maxillofacial anatomy.

Embryo injected with Ochratoxin A induced jejunum injury in ducklings by activating the TLR4 signaling pathway: Involvement of intestinal microbiota.

Ochratoxin A (OTA) is a common mycotoxin that causes intestinal injury in humans and various animal species. OTA may lead to intestinal injury in offspring due to the maternal effect. The aim of this study was to investigate the mechanism of embryo injected with OTA induced jejunum injury in ducklings. The results showed that OTA disrupted the jejunum tight junctions in hatching ducklings, and promoted the secretion of inflammatory cytokines. And this inflammatory response was caused by the activation of the TLR4 signaling pathway. Moreover, embryo injected with OTA could cause damage to the intestinal barrier in 21-day-old ducks, characterized by shortened villi, crypt hyperplasia, disrupted intestinal tight junctions, increased level of LPS in the jejunum, activation of the TLR4 signaling pathway, and increased levels of pro-inflammatory cytokines. Meanwhile, OTA induced oxidative stress in the jejunum. And dysbiosis of gut microbiota was mainly characterized by an increased the relative abundance of Bacteroides, Megamonas, Fournierella, and decreased the relative abundance of Alistipes and Weissella. Interestingly, embryo injected with OTA did not induce these changes in the jejunum of antibiotics-treated 21-day-old ducks. In conclusion, embryo injected with OTA induced jejunum injury in ducklings by activating the TLR4 signaling pathway, which involvement of intestinal microbiota.

Eliminating Hole Extraction Barrier in 1D/3D Perovskite Heterojunction for Efficient and Stable Carbon-Based CsPbI3 Solar Cells with a Record Efficiency.

Carbon-based perovskite solar cells (C-PSCs) have the advantages of low-cost and high-stability, but their photovoltaic performance is limited by severe defect-induced recombination and low hole extraction efficiency. One-dimensional (1D) perovskite has been proven to effectively passivate the defects on the perovskite surface, therefore reducing non-radiative recombination loss. However, the unsuitable energy level of most 1D perovskite renders an undesired downward band bending for three-dimensional (3D) perovskite, resulting in a high hole extraction barrier and reduced hole extraction efficiency. Therefore, rational design and selection of 1D perovskites as the modifiers are essential in balancing defect passivation and hole extraction. In this work, based on simulation calculations, thiocholine iodide (TchI) is selected to prepare 1D perovskite with high work function, and then constructs TchPbI3/CsPbI3 1D/3D perovskite heterojunction. Experimental results show that this strategy eliminates the hole extraction barrier at perovskite/carbon interface, which improves the hole extraction efficiency of corresponding devices. Meanwhile, the strong interaction between the thiol group and Pb suppresses defect-induced recombination effectively and improves the stability of CsPbI3. The assembled C-PSCs exhibit a champion efficiency of 19.08% and a certified efficiency of 18.7%. To the best of our knowledge, this is a new efficiency record for inorganic C-PSCs. This article is protected by copyright. All rights reserved.

Differential lncRNA profiles of blood plasma-derived exosomes from systemic lupus erythematosus.

INTRODUCTION: Long non-coding RNAs (lncRNAs) dysregulation is key in the pathogenesis of systemic lupus erythematosus (SLE), but the role of exosomal lncRNAs in SLE has not been well studied. We elucidated the profiles of plasma exosomal lncRNAs expression in patients with SLE and predictd their potential clinical significance in SLE. METHODS: In the screening stage, six newly diagnosed and untreated patients with SLE and six healthy controls were examined by high-throughput sequencing technology, and differential exosomal lncRNA profiles were constructed. In the validation phase, two differentially selected exosomal lncRNAs from 20 patients each with active and stable SLE and 20 healthy controls were verified with RT-qPCR. The correlation between the selected exosomal lncRNAs and SLE clinical indicators was examined. The diagnostic value of the selected exosomal lncRNAs in SLE was analyzed by the receiver operator characteristic (ROC) curve. RESULTS: Exosomes were successfully extracted from the patients and controls. Sequencing-phase sequencing demonstrated 528 upregulated lncRNAs and 7491 downregulated lncRNAs. In the validation stage, exosomal LINC00667 and DANCR were significantly upregulated in the patients, and positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Exosomal DANCR expression between the active and stable SLE patients was different. The area under the curve(AUC) of exosomal LINC00667 and DANCR for SLE diagnosis was 0.815 and 0.759, respectively. CONCLUSIONS: Exosomal LINC00667 and DANCR were upregulated in SLE, and might be new biomarkers thereof. Exosomal DANCR was associated with SLE activity.

Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.

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

Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning.

Background: Non-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide and G protein-coupled receptor 146 (GPR146) in diabetes and its sequelae. However, the specific mechanisms through which GPR146 modulates immune responses remain poorly understood. Furthermore, the utility of GPR146 as a diagnostic or prognostic marker for NSOI has not been conclusively demonstrated. Methods: We adopted a comprehensive analytical strategy, merging differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) datasets GSE58331 and GSE105149 with immune-related genes from the ImmPort database. Our methodology combined LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) for feature selection, followed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore gene sets co-expressed with GPR146, identifying a significant enrichment in immune-related pathways. The tumor microenvironment's immune composition was quantified using the CIBERSORT algorithm and the ESTIMATE method, which confirmed a positive correlation between GPR146 expression and immune cell infiltration. Validation of GPR146 expression was performed using the GSE58331 dataset. Results: Analysis identified 113 DEGs associated with GPR146, with a significant subset showing distinct expression patterns. Using LASSO and SVM-RFE, we pinpointed 15 key hub genes. Functionally, these genes and GPR146 were predominantly linked to receptor ligand activity, immune receptor activity, and cytokine-mediated signaling. Specific immune cells, such as memory B cells, M2 macrophages, resting mast cells, monocytes, activated NK cells, plasma cells, and CD8+ T cells, were positively associated with GPR146 expression. In contrast, M0 macrophages, naive B cells, M1 macrophages, activated mast cells, activated memory CD4+ T cells, naive CD4+ T cells, and gamma delta T cells showed inverse correlations. Notably, our findings underscore the potential diagnostic relevance of GPR146 in distinguishing NSOI. Conclusion: Our study elucidates the immunological signatures associated with GPR146 in the context of NSOI, highlighting its prognostic and diagnostic potential. These insights pave the way for GPR146 to be a novel biomarker for monitoring the progression of NSOI, providing a foundation for future therapeutic strategies targeting immune-metabolic pathways.

The roles of IRF8 in nonspecific orbital inflammation: an integrated analysis by bioinformatics and machine learning.

BACKGROUND: Nonspecific Orbital Inflammation (NSOI) represents a persistent and idiopathic proliferative inflammatory disorder, characterized by polymorphous lymphoid infiltration within the orbit. The transcription factor Interferon Regulatory Factor 8 (IRF8), integral to the IRF protein family, was initially identified as a pivotal element for the commitment and differentiation of myeloid cell lineage. Serving as a central regulator of innate immune receptor signaling, IRF8 orchestrates a myriad of functions in hematopoietic cell development. However, the intricate mechanisms underlying IRF8 production remain to be elucidated, and its potential role as a biomarker for NSOI is yet to be resolved. METHODS: IRF8 was extracted from the intersection analysis of common DEGs of GSE58331 and GSE105149 from the GEO and immune- related gene lists in the ImmPort database using The Lasso regression and SVM-RFE analysis. We performed GSEA and GSVA with gene sets coexpressed with IRF8, and observed that gene sets positively related to IRF8 were enriched in immune-related pathways. To further explore the correlation between IRF8 and immune-related biological process, the CIBERSORT algorithm and ESTIMATE method were employed to evaluate TME characteristics of each sample and confirmed that high IRF8 expression might give rise to high immune cell infiltration. Finally, the GSE58331 was utilized to confirm the levels of expression of IRF8. RESULTS: Among the 314 differentially expressed genes (DEGs), some DEGs were found to be significantly different. With LASSO and SVM-RFE algorithms, we obtained 15 hub genes. For biological function analysis in IRF8, leukocyte mediated immunity, leukocyte cell-cell adhesion, negative regulation of immune system process were emphasized. B cells naive, Macrophages M0, Macrophages M1, T cells CD4 memory activated, T cells CD4 memory resting, T cells CD4 naive, and T cells gamma delta were shown to be positively associated with IRF8. While, Mast cells resting, Monocytes, NK cells activated, Plasma cells, T cells CD8, and T cells regulatory (Tregs) were shown to be negatively linked with IRF8. The diagnostic ability of the IRF8 in differentiating NSOI exhibited a good value. CONCLUSIONS: This study discovered IRF8 that are linked to NSOI. IRF8 shed light on potential new biomarkers for NSOI and tracking its progression.

Analysis of physical and mechanical behaviors and microscopic mineral characteristics of thermally damaged granite.

Temperature's influence on the physical and mechanical properties of rocks is a crucial concern for the rational design of deep rock engineering structures and the assurance of their long-term stability. To systematically comprehend the impact of the evolution of mineral composition and micro characteristics on the physical and mechanical behavior of thermally damaged granite, we observed the microscopic structural defects inside the rocks with a polarizing microscope and revealed the thermal damage mechanism of granite from a microscopic perspective by combining ultrasound detection and XRD phase characteristic analysis. The results show that the physical properties of the specimens changed significantly at three characteristic temperature points: 400 °C, 800 °C, and 1000 °C. Under high temperature conditions, the diffraction intensity of all minerals in granite, except for quartz, generally decreased, and stable minerals decomposed. Albite and potash feldspar decomposed to form anorthoclase, thereby reducing the structural stability of the rock material. In addition, the peak width of various minerals decreased to varying degrees with increasing temperature. The increase in mineral volume further damaged the internal structure of the rock material while promoting the transformation from grain boundary to intergranular cracks and from intragranular cracks to transgranular cracks, ultimately forming a interconnected crack network. Thermal damage significantly reduced the longitudinal wave velocity, uniaxial compressive strength, and elastic modulus of the specimens, while the stress-strain curve relationship indicated that the specimens underwent two opposite processes of transformation from brittleness to ductility and then from ductility to brittleness. The thermal damage threshold of granite in this study was 600 °C.

[Research progress of diagnostic and therapeutic value of carbon dioxide-derived indicators in patients with sepsis].

Effectively assessing oxygen delivery and demand is one of the key targets for fluid resuscitation in sepsis. Clinical signs and symptoms, blood lactic acid levels, and mixed venous oxygen saturation (SvO2) or central venous oxygen saturation (ScvO2) all have their limitations. In recent years, these limitations have been overcome through the use of derived indicators from carbon dioxide (CO2) such as mixed veno-arterial carbon dioxide partial pressure difference (Pv-aCO2, PCO2 gap, or ΔPCO2), the ratio of mixed veno-arterial carbon dioxide partial pressure difference to arterial-mixed venous oxygen content difference (Pv-aCO2/Ca-vO2). Pv-aCO2, PCO2 gap or ΔPCO2 is not a purely anaerobic metabolism indicator as it is influenced by oxygen consumption. However, it reliably indicates whether blood flow is sufficient to carry CO2 from peripheral tissues to the lungs for clearance, thus reflecting the adequacy of cardiac output and metabolism. The Pv-aCO2/Ca-vO2 may serve as a marker of hypoxia. SvO2 and ScvO2 represent venous oxygen saturation, reflecting tissue oxygen utilization. When oxygen delivery decreases but tissues still require more oxygen, oxygen extraction rate usually increases to meet tissue demands, resulting in decreased SvO2 and ScvO2. But in some cases, even if the oxygen delivery rate and tissue utilization rate of oxygen are reduced, it may still lead to a decrease in SvO2 and ScvO2. Sepsis is a classic example where tissue oxygen utilization decreases due to factors such as microcirculatory dysfunction, even when oxygen delivery is sufficient, leading to decrease in SvO2 and ScvO2. Additionally, the solubility of CO2 in plasma is approximately 20 times that of oxygen. Therefore, during sepsis or septic shock, derived variables of CO2 may serve as sensitive markers for monitoring tissue perfusion and microcirculatory hemodynamics. Its main advantage over blood lactic acid is its ability to rapidly change and provide real-time monitoring of tissue hypoxia. This review aims to demonstrate the principles of CO2-derived variables in sepsis, assess the available techniques for evaluating CO2-derived variables during the sepsis process, and discuss their clinical relevance.

Caffeine improves mitochondrial dysfunction in the white matter of neonatal rats with hypoxia-ischemia through deacetylation: a proteomic analysis of lysine acetylation.

Aims: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. Main methods: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Key findings: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Significance: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.

Intravoxel incoherent motion diffusion-weighted imaging and dynamic contrast-enhanced MRI for predicting parametrial invasion in cervical cancer.

PURPOSE: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients. METHODS: A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters. RESULTS: Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78-27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49-29.10; P = 0.01), f (OR 5.12; 95% CI 1.23-21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19-17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25-19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%. CONCLUSION: The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.

Molecular mechanisms of Tetrastigma hemsleyanum Diels&Gilg against lung squamous cell carcinoma: From computational biology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum （T. hemsleyanum）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. AIM OF THE STUDY: To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. MATERIALS AND METHODS: The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI-H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum. RESULTS: We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI-H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum, such as procyanidin B1, catechin, quercetin, and kaempferol, etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7, respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. CONCLUSION: In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum, which further consolidated the claim of its traditional uses.

Normal Values for Atrial Deformation Measured by Feature-Tracking Cardiac MRI: A Meta-Analysis.

BACKGROUND: A consensus on normal atrial deformation measurements by feature-tracking cardiac MRI remained absent. PURPOSE: Provide reference ranges for atrial strain parameters in normal subjects, evaluating the influence of field strength and analysis software on the measurements. STUDY TYPE: Meta-analysis. POPULATION: 2708 subjects from 42 studies undergoing cardiac MRI. ASSESSMENT: A systematic search was conducted from database (PubMed, Web of Science, ScienceDirect, and EMBASE) inception through August 2023. The random-effects model was used to pool the means of biatrial strain parameters. Heterogeneity and clinical variable effects were assessed. Strain measurements among different field strengths and analysis software were compared. STATISTICAL TESTS: The inverse-variance method, Cochrane Q statistic, and I2 value, meta-regression analysis, and ANOVA were used; P < 0.05 was considered statistically significant. RESULTS: The pooled means of left atrial (LA) total strain (εs), passive strain (εe), and active strain (εa) were 37.46%, 22.73%, and 16.24%, respectively, and the pooled means of LA total strain rate (SRs), passive strain rate (SRe), and active strain rate (SRa) were 1.66, -1.95, and -1.83, indicating significant heterogeneity. The pooled means of right atrial (RA) εs, εe, and εa were 44.87%, 26.05%, and 18.83%. RA SRs, SRe, and SRa were 1.66, -1.95, and -1.83, respectively. The meta-regression identified age as significantly associated with LA εs, εe and SRe, field strength was associated with LA SRa (all P < 0.05). ANOVA revealed differences in LA εa and SRa among different analysis software and in LA εs and all LA strain rates (all P < 0.05) among field strengths. No significant differences were identified in RA strain across analysis software (RA strain: P = 0.145-0.749; RA strain rates: P = 0.073-0.744) and field strengths (RA strain: P = 0.641-0.794; RA strain rates: P = 0.204-0.458). DATA CONCLUSION: This study demonstrated the pooled reference values of biatrial strain. Age, analysis software, and field strength were attributed to differences in LA strain, whereas RA strain showed consistency across different field strengths and analysis software. Limited study subjects may account for the absence of influence on RA strain. TECHNICAL EFFICACY: Stage 5.

Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Association of fetal fraction and cell-free fetal DNA with adverse pregnancy outcomes: A systematic review.

BACKGROUND: Adverse pregnancy outcomes, which can be caused by multiple factors, present a significant threat to the health of mothers and their babies. Cell-free fetal DNA (cffDNA) from placental trophoblast cells might be able to reflect placental and fetal status. Previous studies have yielded controversial results regarding the association of FF or cffDNA with various adverse pregnancy outcomes. A previous study has attempted to systematically assess the association between low fetal fraction (FF) and adverse pregnancy outcomes, but it failed to perform quantitative analyses due to the few studies included. In the present study, we attempted to quantitatively assess the association of FF (or cffDNA) with adverse pregnancy outcomes and further analyze the causes of heterogeneity. OBJECTIVES: To investigate the association of high/low FF or cffDNA with adverse pregnancy outcomes. SEARCH STRATEGY: We searched the databases of PubMed, Embase, Cochrane, and Web of Science from January 1, 1990, to June 15, 2022 in this meta-analysis. SELECTION CRITERIA: Studies on the relationships of adverse pregnancy outcomes in women with FF or cell free DNA were included. Non-English literature was excluded. DATA COLLECTION AND ANALYSIS: Data about pregnancy outcomes and cell free DNA were extracted and meta-analyzed. Subgroup analysis was performed by different outcomes. MAIN RESULTS: There were 11 studies included involving 8280 participants. No significant heterogeneity was observed among the studies (I2 = 27%, 25%), and a fixed-effect model was used for weighted quantitative analysis. The results revealed that the FF or cffDNA during pregnancy was significantly associated with adverse pregnancy outcomes in pregnant women (OR = 1.57, 95% CI [1.24, 1.99], P = 0.233). The overall incidence of the maternal adverse outcomes was 8% (95% CI: 5-13). Subgroup analysis of different outcomes showed an evident association between low FF or cffDNA and hypertensive disorders of pregnancy (HDP) (OR = 1.76, 95% CI [1.36, 2.27], P = 0.581). There was no evidence that the occurrence of spontaneous preterm birth (sPTB) and placental abnormality was associated with FF or cffDNA. No association was observed between low FF or cffDNA during pregnancy and adverse outcomes in fetuses (OR = 1.39, 95% CI [0.99, 1.94], P = 0.242). The overall incidence of adverse outcomes in fetuses was 8% (95% CI: 6-11). There were controversies over the association between high FF or cffDNA and HDP, and sPTB and small for gestational age infant, among different studies. CONCLUSIONS: Pregnant women with low FF or cffDNA during the first or second trimester of pregnancy have an overall increased risk of adverse pregnancy outcomes, especially HDP. However, the association between FF and various pregnancy outcomes needs to be further explored by more prospective studies.

The efficacy of clinicopathological and imaging features in differentiating benign from malignant parotid micro- and minitumors: a retrospective analysis.

OBJECTIVE: To compare clinicopathological and imaging features of micro- and minitumors of the parotid gland and provide a reference for preoperative prediction of benign vs malignant status. STUDY DESIGN: Patients with parotid gland tumors treated surgically were selected. Relevant clinicopathological and imaging data were collected for patients with maximum tumor diameters ≤20 mm on preoperative computed tomography (CT). The lesions were divided into 2 groups, microtumors and minitumors, based on maximum tumor diameter. CT imaging features of benign and malignant tumors were compared through binary logistic regression analysis. RESULTS: Microtumors and minitumors were categorized by maximum diameters <10 mm (n = 74) and 10-20 mm (n = 611), respectively. Benign and malignant minitumors exhibited significant differences in boundary, tumor density, margin morphology, spiculation margin, and CT values in the plain and arterial phase (P ≤ .027), resembling those found in typical malignant parotid gland tumors. However, no significant differences were observed between benign and malignant microtumors. Logistic regression analysis identified boundary, margin morphology, and spiculation margin as independent predictors of malignancy. The prediction model excelled in identifying benign lesions but was less successful in identifying malignancies. CONCLUSION: Parotid gland minitumors had imaging features similar to typical larger malignant tumors. Active exclusion of the malignant risk and early surgical treatment is recommended for these tumors.

Revealing the Hypoglycemic Effect of Red Yeast Rice: Perspectives from the Inhibition of α-Glucosidase and the Anti-Glycation Capability by Ankaflavin and Monascin.

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC50 of 126.5 ± 2.5 and 302.6 ± 2.5 µM, respectively, compared with acarbose (IC50 = 341.3 ± 13.6 µM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL-1, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes.

From tissue lesions to neurotoxicity: The devastating effects of small-sized nanoplastics on red drum Sciaenops ocellatus.

Nanoplastic pollution typically exhibits more biotoxicity to marine organisms than microplastic pollution. Limited research exists on the toxic effects of small-sized nanoplastics on marine fish, especially regarding their post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to small-sized polystyrene nanoplastics (30 nm, PS-NPs) for 7 days for the exposure experiments, followed by 14 days of recovery experiments. Histologically, hepatic lipid droplets and branchial epithelial liftings were the primary lesions induced by PS-NPs during both exposure and recovery periods. The inhibition of total superoxide dismutase activity and the accumulation of malondialdehyde content throughout the exposure and recovery periods. Transcriptional and metabolic regulation revealed that PS-NPs induced lipid metabolism disorders and DNA damage during the initial 1-2 days of exposure periods, followed by immune responses and neurotoxicity in the later stages (4-7 days). During the early recovery stages (2-7 days), lipid metabolism and cell cycle were activated, while in the later recovery stage (14 days), the emphasis shifted to lipid metabolism and energy metabolism. Persistent histological lesions, changes in antioxidant capacity, and fluctuations in gene and metabolite expression were observed even after 14 days of recovery periods, highlighting the severe biotoxicity of small-sized PS-NPs to marine fish. In summary, small-sized PS-NPs have severe biotoxicity, causing tissue lesions, oxidative damage, lipid metabolism disorders, DNA damage, immune responses, and neurotoxicity in red drum. This study offers valuable insights into the toxic effects and resilience of small-sized nanoplastics on marine fish.

Molecular spectra and docking simulations investigated the binding mechanisms of tetracycline onto E. coli extracellular polymeric substances.

Extracellular polymeric substances (EPS), which were an important fraction of natural organic matter (NOM), played an important role in various environmental processes. However, the heterogeneity, complexity, and dynamics of EPS make their interactions with antibiotics elusive. Using advanced multispectral technology, this study examined how EPS interacts with different concentrations of tetracycline (TC) in the soil system. Our results demonstrated that protein-like (C1), fulvic-like (C2), and humic-like (C3) fractions were identified from EPS. Two-dimensional synchronous correlation spectroscopy (2D-SF-COS) indicated that the protein-like fraction gave faster responses than the fulvic-like fraction during the TC binding process. The sequence of structural changes in EPS due to TC binding was revealed by two-dimensional Fourier Transformation Infrared correlation spectroscopy (2D-FTIR-COS) as follows: 1550 > 1660 > 1395 > 1240 > 1087 cm-1. It is noteworthy that the sensitivity of the amide group to TC has been preserved, with its intensity gradually increasing to become the primary binding site for TC. The integration of hetero-2DCOS maps with moving window 2D correlation spectroscopy (MW2DCOS) provided a unique insight into understanding the correlation between EPS fractions and functional groups during the TC binding process. Moreover, molecular docking (MD) discovered that the extracellular proteins would provide plenty of binding sites with TC through salt bridges, hydrogen bonds, and π-π base-stacking forces. With these results, systematic investigations of the dynamic changes in EPS components under different concentrations of antibiotic exposure demonstrated the advanced capabilities of multispectral technology in examining intricate interactions with EPS in the soil environment.