Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Causal associations of cognition, intelligence, education, health and lifestyle factors with cervical spondylosis: a mendelian randomization study.

Background: Education, cognition, and intelligence are phenotypically and genetically related. Education has been shown to have a protective effect on the risk of developing cervical spondylosis. However, it is unclear whether cognition and intelligence have independent causal effects on cervical spondylosis, and whether health and lifestyle factors influence this association. Methods: We first assessed the independent effects of education, cognition, and intelligence on cervical spondylosis by two-sample Mendelian randomization and multivariable Mendelian randomization analysis, and evaluated 26 potential association mediators using two-step Mendelian randomization, and calculated the median proportion. Results: The results showed that only education had an independent causal effect on cervical spondylosis, and had a protective effect on the risk of cervical spondylosis (ß: 0.3395; se: 0.166; p < 0.05; OR:0.71; [95%CI: 0.481-0.943]. Of the 26 potential associated mediators, a factor was identified: SHBG (mediated proportion: 2.5%). Univariable Mendelian randomization results showed that the risk factors for cervical spondylosis were time spent watching TV (OR:1.96; [95%CI: 1.39-2.76]), smoking (OR:2.56; [95%CI: 1.061-1.486]), body mass index (OR:1.26; [95%CI: 1.124-1.418]), percentage of body fat (OR:1.32; [95%CI: 1.097-1.593]), major depression (OR:1.27; [95%CI: 1.017-1.587]) and sitting height (OR:1.15; [95%CI: 1.025-1.291]). Protective factors include computer using (OR:0.65; [95%CI: 0.418-0.995]), sex hormone binding globulin (OR:0.87; [95%CI: 0.7955-0.951]) and high-density lipoprotein (OR:0.90; [95%CI: 0.826-0.990]). Conclusion: Our findings demonstrate the causal and independent effects of education on cervical spondylosis and suggest that lifestyle media may be a priority target for the prevention of cervical spondylosis due to low educational attainment.

Knockdown of vitellogenin receptor based on minute insect RNA interference methods affects the initial mature egg load in the pest natural enemy Trichogramma dendrolimi.

Vitellogenin receptor (VgR) plays a crucial role in oogenesis by mediating endocytosis of vitellogenin and a portion of the yolk proteins in many insect species. However, the function of VgR in minute parasitoid wasps is largely unknown. Here, we applied Trichogramma dendrolimi, a minute egg parasitoid, as a study model to investigate the function of VgR in parasitoids. We developed RNA interference (RNAi) methods based on microinjection of prepupae in T. dendrolimi. RNAi employs nanomaterial branched amphipathic peptide capsules (BAPC) as a carrier for double-stranded RNA (dsRNA), significantly enhancing delivery efficiency. Also, artificial hosts without medium were used to culture the injected prepupae in vitro. Utilizing these methods, we found that ovarian growth was disrupted after knockdown of TdVgR, as manifested by the suppressed development of the ovariole and the inhibition of nurse cell internalization by oocytes. Also, the initial mature egg load in the ovary was significantly reduced. Notably, the parasitic capacity of the female adult with ovarian dysplasia was significantly decreased, possibly resulting from the low availability of mature eggs. Moreover, ovarian dysplasia in T. dendrolimi caused by VgR deficiency are conserved despite feeding on different hosts. The results confirmed a critical role of TdVgR in the reproductive ability of T. dendrolimi and provided a reference for gene functional studies in minute insects.

Research Progress on Active Ingredients and Product Development of Lycium ruthenicum Murray.

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.

Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Three-Dimensional Structure Light Robot-Assisted Frameless Stereotactic Brain Biopsy.

BACKGROUND AND OBJECTIVES: To assess the feasibility, accuracy, and safety of 3-dimensional (3D) structure light robot-assisted frameless stereotactic brain biopsy. METHODS: Five consecutive patients (3 males, 2 females) were included in this study. The patients' clinical, imaging, and histological data were analyzed, and all patients received a 3D structure light robot-assisted frameless stereotactic brain biopsy. The raw and/or analyzed data of the study are available from the corresponding author. RESULTS: The statistical results showed a mean age of 59.6 years (range 40-70 years), a mean target depth of 60.9 mm (range 53.5-65.8 mm), a mean radial error of 1.2 ± 0.7 mm (mean ± SD), a mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 0.6 mm. The calculated Pearson product-moment correlation coefficient (r = 0.23) revealed no correlation between target depth and absolute tip error. All biopsy needles were placed in line with the planned trajectory successfully, and diagnostic specimens were harvested in all cases. Histopathological analysis revealed lymphoma (2 cases), lung adenocarcinoma (1 case), glioblastoma multiforme (1 case), and oligodendroglioma (1 case). CONCLUSION: Surface registration using the 3D structure light technique is fast and precise because of the achievable million-scale point cloud data of the head and face. 3D structure light robot-assisted frameless stereotactic brain biopsy is feasible, accurate, and safe.

A hydrodynamic-based dual-function microfluidic chip for high throughput discriminating tumor cells.

A hydrodynamic-based microfluidic chip consisted of two function units that could not only separate tumor cells (TCs) from whole blood but also remove residual blood cells was designed. The separation of TCs was achieved by a straight contraction-expansion array (CEA) microchannel on the front end of the chip. The addition of contractive structure brought a micro-vortex like Dean vortex that promoted cell focusing in the channel, while when cells entered the dilated region, the wall-induced lift force generated by the channel wall gave cells a push away from the wall. As the wall-induced lift force is proportional to the third power of the cell diameter, TCs with larger diameter will have a larger lateral migration under the wall-induced lift force, realizing the separation of TCs from blood sample. Fluorescent particles with diameters of 19.3 µm and 4.5 µm were used to simulate TCs and red blood cells, respectively, to verify the separation capacity of the proposed CEA microchannel for particles with different diameter. And a separation efficiency 98.7% for 19.3 µm particles and a removal rate 96.2% for 4.5 µm particles was observed at sample flow rate of 10 µL min-1 and sheath flow rate of 190 µL min-1. In addition, a separation efficiency about 96.1% for MCF-7 cells (stained with DiI) and removal rates of 96.2% for red blood cells (RBCs) and 98.7% for white blood cells (WBCs) were also obtained under the same condition. However, on account of the large number of blood cells in the blood, there will be a large number of blood cells remained in the isolated TCs, so a purification unit based on hydrodynamic filtration (HDF) was added after the separation microchannel. The purification channel is a size-dictated cell filter that can remove residual blood cells but retain TCs, thus achieving the purification of TCs. Combined the CEA microchannel and the purifier, the microchip facilitates sorting of MCF-7 cells from whole blood with a separation rate about 95.3% and a removal rate over 99.99% for blood cells at a sample flow rate of 10 µL min-1, sheath flow rate of 190 µL min-1 and washing flow rate of 63 µL min-1.

Prognosis of LSPD versus TIPS for the treatment of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: This study aimed to compare postoperative complications in patients with esophagogastric variceal bleeding (EVB) who underwent laparoscopic splenectomy combined with pericardial devascularization (LSPD) versus transjugular intrahepatic portosystemic shunt (TIPS) procedures. METHODS: A retrospective collection of medical records was conducted from January 2014 to May 2020 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The study included patients from the departments of trauma surgery, interventional radiology, and general surgery who were diagnosed with EVB caused by portal hypertension and treated with LSPD or TIPS. Follow-up data were obtained to assess the occurrence of postoperative complications in both groups. RESULTS: A total of 201 patients were included in the study, with 104 cases in the LSPD group and 97 cases in the TIPS group. There was no significant difference in the 1-year and 3-year post-surgery survival rates between the TIPS and LSPD groups (P = 0.669, 0.066). The 3-year survival rate of Child-Pugh B patients in the LSPD group was higher than TIPS group (P = 0.041). The LSPD group also had a significantly higher rate of freedom from rebleeding at 3-year post-surgery compared to the TIPS group (P = 0.038). Stratified analysis showed no statistically significant difference in the rebleeding rate between the two groups. Furthermore, the LSPD group had a higher rate of freedom from overt hepatic encephalopathy at 1-year and 3-year post-surgery compared to the TIPS group (P = 0.007, < 0.001). The LSPD group also had a lower rate of severe complications at 3-year post-surgery compared to the TIPS group (P = 0.020). CONCLUSION: Compared to TIPS, LSPD does not increase the risk of mortality and rebleeding, while demonstrating fewer complications. In patients classified as Child-Pugh A and B, the use of LSPD for treating EVB is both safe and effective.

Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study.

BACKGROUND: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS. METHOD: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities. RESULT: Based on 10,993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, we developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios. CONCLUSIONS: We successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment.

Effects of polypropylene microplastics on carbon dioxide dynamics in intertidal mangrove sediments.

Microplastics (MPs) in soil can influence CO2 dynamics by altering organic carbon (OC) and microbial composition. Nevertheless, the fluctuation of CO2 response attributed to MPs in mangrove sediments is unclear. This study explores the impact of micro-sized polypropylene (mPP) particles on the carbon dynamics of intertidal mangrove sediments. In the high-tide level sediment, after 28 days, the cumulative CO2 levels for varying mPP dosages were as follows: 496.86 ± 2.07, 430.38 ± 3.84 and 447.09 ± 1.72 mg kg-1 for 0.1%, 1% and 10% (w/w) mPP, respectively. The CO2 emissions were found to be increased with a 0.1% (w/w) mPP level and decreased with 1% and 10% (w/w) mPP at high-tide level sediment, suggesting a tide level-specific dose dependence of the CO2 emission pattern in mangrove sediments. Overall, results indicated that the presence of mPP in mangrove sediments would potentially affect intertidal total CO2 storage under given experimental conditions.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BACKGROUND: Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. METHODS: This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. RESULTS: (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. CONCLUSIONS: Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides an aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides a new aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define novel molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides a new aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define novel molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

Characteristics of Epicoccum latusicollum as revealed by genomic and metabolic phenomic analysis, the causal agent of tobacco Epicoccus leaf spot.

Epicoccum latusicollum is a fungus that causes a severe foliar disease on flue-cured tobacco in southwest China, resulting in significant losses in tobacco yield and quality. To better understand the organism, researchers investigated its optimal growth conditions and metabolic versatility using a combination of traditional methods and the Biolog Phenotype MicroArray technique. The study found that E. latusicollum exhibited impressive metabolic versatility, being able to metabolize a majority of carbon, nitrogen, sulfur, and phosphorus sources tested, as well as adapt to different environmental conditions, including broad pH ranges and various osmolytes. The optimal medium for mycelial growth was alkyl ester agar medium, while oatmeal agar medium was optimal for sporulation, and the optimum temperature for mycelial growth was 25°C. The lethal temperature was 40°C. The study also identified arbutin and amygdalin as optimal carbon sources and Ala-Asp and Ala-Glu as optimal nitrogen sources for E. latusicollum. Furthermore, the genome of E. latusicollum strain T41 was sequenced using Illumina HiSeq and Pacific Biosciences technologies, with 10,821 genes predicted using Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. Analysis of the metabolic functions of phyllosphere microorganisms on diseased tobacco leaves affected by E. latusicollum using the Biolog Eco microplate revealed an inability to efficiently metabolize a total of 29 carbon sources, with only tween 40 showing some metabolizing ability. The study provides new insights into the structure and function of phyllosphere microbiota and highlights important challenges for future research, as well as a theoretical basis for the integrated control and breeding for disease resistance of tobacco Epicoccus leaf spot. This information can be useful in developing new strategies for disease control and management, as well as enhancing crop productivity and quality.

Effect of laser shock peening on microstructure and mechanical properties of laser cladding 30CrMnSiNi2A high-strength steel.

The effect of laser shock peening (LSP) on the microhardness and tensile properties of laser cladding (LC) 30CrMnSiNi2A high-strength steel was studied. After LSP, the microhardness of the cladding zone reached approximately 800 HV0.2, which was 25% higher than that of the substrate, while the cladding zone without LSP had an approximately 18% increase in its microhardness. Two strengthening processes were designed: groove LSP + LC + surface LSP versus LC + surface LSP. The former's tensile strength and yield strength were less than 10% weaker than those of forged materials, which is the best mechanical property recovery found in LC samples. The microstructural characteristics of the LC samples were analysed by scanning electron microscopy (SEM) and electron backscatter diffraction. Under the action of the laser-induced shock wave, the grain size of the LC sample surface was refined, the low-angle grain boundaries on the surface layer increased significantly, and the austenite grain length was reduced from 30-40 µm in the deep layer to 4-8 µm in the surface layer. In addition, LSP modulated the residual stress field, hence preventing the weakening effect of the LC process's thermal stress on the components' mechanical properties.

[Latest Findings on Polyketides/Non-ribosomal Peptides That Are Secondary Metabolites of Streptococcus mutans].

Dental caries is a chronic infectious disease that occurs in the hard tissue of teeth under the influence of multiple factors, among which bacteria being a key factor. Streptococcus mutans ( S. mutans) is considered a major pathogen that causes caries. Secondary metabolites, including bacteriocins and polyketides/non-ribosomal peptides, are a class of small-molecule compounds synthesized by S. mutans. To date, polyketides/non-ribosomal peptides identified in S. mutans include mutanobactin, mutanocyclin, and mutanofactin, which are synthesized by the mub, muc, and muf biosynthetic gene clusters, respectively. These polyketides/non-ribosomal peptides play important roles in bacterial inter-species competition, oxidative stress, and biofilm formation. In this review, we provided an overview of the synthesis, function and regulation of three polyketides/non-ribosomal peptides of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin, aiming to provide new insights into the cariogenic mechanism of S. mutans and to promote the better management of dental caries.

Machine learning for prediction of delirium in patients with extensive burns after surgery.

AIMS: Machine learning-based identification of key variables and prediction of postoperative delirium in patients with extensive burns. METHODS: Five hundred and eighteen patients with extensive burns who underwent surgery were included and randomly divided into a training set, a validation set, and a testing set. Multifactorial logistic regression analysis was used to screen for significant variables. Nine prediction models were constructed in the training and validation sets (80% of dataset). The testing set (20% of dataset) was used to further evaluate the model. The area under the receiver operating curve (AUROC) was used to compare model performance. SHapley Additive exPlanations (SHAP) was used to interpret the best one and to externally validate it in another large tertiary hospital. RESULTS: Seven variables were used in the development of nine prediction models: physical restraint, diabetes, sex, preoperative hemoglobin, acute physiological and chronic health assessment, time in the Burn Intensive Care Unit and total body surface area. Random Forest (RF) outperformed the other eight models in terms of predictive performance (ROC:84.00%) When external validation was performed, RF performed well (accuracy: 77.12%, sensitivity: 67.74% and specificity: 80.46%). CONCLUSION: The first machine learning-based delirium prediction model for patients with extensive burns was successfully developed and validated. High-risk patients for delirium can be effectively identified and targeted interventions can be made to reduce the incidence of delirium.

Evaluating the Correlation of Hedgehog Pathway with Claudin-1 Expression in Invasive Breast Cancer.

Being a heterogeneous disease, breast cancer illustrates different biological and phenotypic features which make its diagnosis and treatment challenging. This study aimed to evaluate the expression levels of crucial components of the Hedgehog signaling pathway, the correlation between the signal transducer Smo, and clinicopathologic features (lymph node metastasis and metastasis stage) in invasive breast carcinoma. Besides, the inverse correlation was considered between expression levels of Smo and Claudin-1. For this purpose, in a case-control study, we evaluated 72 tumor and adjacent normal tissue specimens obtained from invasive ductal breast cancer patients. The expression levels of Hedgehog signaling components (Smo, Gli1, and Ptch), Claudin-1, E-cadherin, and MMP2 were measured by qRT-PCR. The correlations between Smo expressions with some clinicopathologic parameters were also analyzed. Compared to normal adjacent tissues, the results showed up-regulation of Hedgehog signaling in invasive breast carcinoma samples. Upregulation of the signal transducer Smo correlated with tumor stages and lymph node metastasis of the breast tumors. This correlation was affected by the expression of Her2. A significant correlation existed between expression levels of the signal transducer Smo and Claudin-1, E-cadherin as an epithelial cell marker, and MMP2 as a metastasis-related gene in advanced metastatic tumor samples. Based on the obtained results, a new layer of molecular complexity was found, which should be considered in managing patients with invasive breast carcinoma. The results suggested a key role for Hedgehog signaling in invasive breast carcinoma. In terms of the inverse correlation between expression levels of Claudin-1 and Hedgehog signaling, Claudin-1 could serve as a candidate gene in diagnostic studies. Thus, its clinical significance should be further clarified.

Spatial distribution characteristics and risk assessment of soil heavy metal pollution around typical coal gangue hill located in Fengfeng Mining area.

The pollution of heavy metals in soil caused by exposed coal gangue and its prevention and control has become a hot issue restricting the green mining of coal in China. Nemerow integrated pollution index (NIPI), potential ecological risk index (RI) and human health risk assessment model were used to evaluate the pollution and risk of heavy metals (Cu, Cr, As, Pb) in the soil around the typical coal gangue hill in Fengfeng mining area of China. The results show that: firstly, the accumulation of coal gangue leads to the enrichment of four heavy metals in the surrounding shallow soil, and NIPI and RI were 1.0-4.4 and 21.63-91.28, respectively. The comprehensive pollution level of heavy metals in soil reached the warning line and above, and the potential ecological risk level reached slightly and above. When the horizontal distance exceeded 300 m, 300 m and 200 m, respectively, the influence of coal gangue hill on the heavy metal content in shallow soil, the comprehensive pollution level of heavy metals and the potential ecological risk level basically disappeared. In addition, based on the potential ecological risk assessment results and main risk factors, the ecological risk configuration of the study area was divided into five categories: "strong ecological risk + As," "intermediate ecological risk + As + Cu," "intermediate ecological risk + As + Cu or Pb," "minor ecological risk + As + Cu" and "minor ecological risk + As + Cu or Pb." The hazard index (HI) and total carcinogenic risk (TCR) of shallow soil polluted by heavy metals in the study area were 0.24-1.07 and 0.41 × 10-4-1.78 × 10-4, respectively, which posed non-carcinogenic and carcinogenic risks to children, but the risks were controllable. This study will help to take strategic measures to accurately control and repair the heavy metal pollution in the soil around the coal gangue hill and provide a scientific basis for solving the safe use of agricultural land and realizing the construction of ecological civilization.