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Rong Hong,1,2,* Xiaoxia Ping,2,3,* Yuanying Liu,2 Feiwen Feng,2 Su Hu,2,3 Chunhong Hu2,3 1Department of Radiology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215100, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhong Hu; Su Hu, Department of Radiology, The First Affiliated Hospital of Soochow University; Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, People’s Republic of China, Email sdhuchunhong@sina.com; husu@suda.edu.cnPurpose: The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model.Methods: In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models’ performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility.Results: Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664– 0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781– 0.906) and 0.836 (95% CI: 0.732– 0.940) in the training and testing cohorts, respectively.Conclusion: The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.Keywords: computed tomography, invasive mucinous adenocarcinoma, radiomics, machine learning

Linhua Wu,1 Jian Li,1 Xiaowei Ruan,2 Jialiang Ren,3 Xuejun Ping,4 Bing Chen1 1Department of Radiology, General Hosipital of Ningxia Medical University, YinChuan, Ningxia Hui Autonomous Region, People’s Republic of China; 2Department of Radiology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of China; 3Department of Pharmaceuticals Diagnosis, GE Healthcare, Beijing, People’s Republic of China; 4Department of Clinical Medical Faculty, Medical University of Ningxia, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of ChinaCorrespondence: Xuejun Ping, Department of Clinical Medical Faculty, Medical University of Ningxia, No. 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia Hui Autonomous Region, People’s Republic of China, Tel +8613709516402, Email 627898331@qq.comBackground: Energy spectrum CT is an effective method to evaluate the biological behavior of lung cancer. Radiomics is a non-invasive technology to obtain histological information related to lung cancer.Purpose: To investigate the value of the radiomics models on the bases of enhanced spectral CT images of peripheral lung cancer to predict the expression of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).Material and Methods: This study retrospectively analyzed 73 patients with peripheral lung cancer confirmed by postoperative pathology. All patients underwent dual-phase enhanced spectral CT scans before surgery. Regions of interest (ROI) were delineated in the arterial phase and venous phase. Key radiomics features were extracted and models were established to predict the expression of VEGF and EGFR, respectively. All models were established based on the expression levels of VEGF and EGFR in tissues detected by immunohistochemical staining as reference standards. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of each model, and decision curve analysis (DCA) was used to evaluate the clinical utility of the models.Results: In predicting the expression level of VEGF, the combined (COMB) model composed of one spectral feature and two radiomics features achieved the best performance with area under ROC (AUC) 0.867 (95% CI: 0.767– 0.966), accuracy of 0.812, sensitivity of 0.879, and specificity of 0.667. According to the expression level of EGFR, three importance radiomics features were retained in the arterial and venous phases to establish the multiphase phase model which has the best performance with AUC of 0.950 (95% confidence interval: 0.89– 1.00), accuracy of 0.896, sensitivity of 0.868, and specificity of 1.Conclusion: The radiomics model of enhanced spectral CT images of peripheral lung cancer can predict the expression of EGFR and VEGF.Keywords: peripheral lung cancer, radiomics, energy spectrum CT, VEGF, EGFR

We have developed an integrated, project-oriented curriculum for undergraduate molecular biology and biochemistry laboratory courses spanning two semesters that is organized around the "ldhA" gene from the yogurt-fermenting bacterium "Lactobacillus bulgaricus," which encodes the enzyme d-lactate dehydrogenase. The molecular biology module, which consists of nine experiments carried out over eleven sessions, begins with the isolation of genomic DNA from "L. bulgaricus" in yogurt and guides students through the process of cloning the "ldhA" gene into a prokaryotic expression vector, followed by mRNA isolation and characterization of recombinant gene expression levels using RT-PCR. The biochemistry module, which consists of nine experiments carried out over eight sessions, begins with overexpression of the cloned ldhA gene and guides students through the process of affinity purification, biochemical characterization of the purified "LdhA" protein, and analysis of enzyme kinetics using various substrates and an inhibitor, concluding with a guided inquiry investigation of structure-function relationships in the three-dimensional structure of "LdhA" using molecular visualization software. Students conclude by writing a paper describing their work on the project, formatted as a manuscript to be submitted for publication in a scientific journal. Overall, this curriculum, with its emphasis on experiential learning, provides hands-on training with a variety of common laboratory techniques in molecular biology and biochemistry and builds experience with the process of scientific reasoning, along with reinforcement of essential transferrable skills such as critical thinking, information literacy, and written communication, all within the framework of an extended project having the look and feel of a research experience.

Abstract Purpose To investigate the value and age- and gender-specific threshold values of bone mineral density (BMD) by quantitative computed tomography (QCT) for the prediction of spontaneous thoracolumbar vertebral fractures and thoracolumbar junction fractures accompanying distant vertebral fractures. Methods Among the 556 patients included, 68 patients had thoracolumbar vertebral fractures (12 patients with distant vertebral fractures, 56 patients without distant vertebral fractures) and 488 patients had no vertebral fractures. All patients were grouped by gender and age. According to the principle of Youden index, the threshold values were calculated from receiver operating characteristic (ROC) curves. Results The threshold values for predicting thoracolumbar vertebral fractures were 89.8 mg/cm3 for all subjects, 90.1 mg/cm3 for men, and 88.6 mg/cm3 for women. The threshold values for men aged

Abstract As one of the main occupational hazards, welding fumes can cause oxidative damage and induce series of diseases, such as COPD or asthma. To clarify the effects of the metal fume ultrafine particulates (MF-UFPs) of welding fumes on oxidative damage, UFPs were collected by melt inert gas (MIG) and manual metal arc (MMA) welding, and the composition was confirmed. Human bronchial epithelial 16HBE cells were treated with 0–1000 µg/cm2 MF-UFPs to analyse the cytotoxicity, oxidative stress and cytokines. The protein and mRNA expression of Keap1-Nrf-2/antioxidant response elements (AREs) signalling pathway components were also analysed. After 4 h of treatment, the cell viability decreased 25% after 33.85 and 32.81 µg/cm2 MIG/MMA-UFPs treated. The intracellular ATP concentrations were also decreased significantly, while LDH leakage was increased. The decreased mitochondrial membrane potential and increased ROS suggested the occurrence of oxidative damage, and the results of proteome profiling arrays also showed a significant increase in IL-6 and IL-8. The expression of AREs which related to antioxidant and anti-inflammatory were also increased. These results indicate that the MF-UFPs can cause oxidative stress in 16HBE cells and activate the Nrf-2/ARE signalling pathway to against oxidative damage.

Abstract Fluid management remains a critical challenge in the treatment of septic shock, with individualized approaches lacking. This study aims to develop a statistical model based on transcriptomics to identify subgroups of septic shock patients with varied responses to fluid strategy. The study encompasses 494 septic shock patients. A benefit score is derived from the transcriptome space, with higher values indicating greater benefits from restrictive fluid strategy. Adherence to the recommended strategy is associated with a hazard ratio of 0.82 (95% confidence interval: 0.64–0.92). When applied to the baseline hospital mortality rate of 16%, adherence to the recommended fluid strategy could potentially lower this rate to 13%. A proteomic signature comprising six proteins is developed to predict the benefit score, yielding an area under the curve of 0.802 (95% confidence interval: 0.752–0.846) in classifying patients who may benefit from a restrictive strategy. In this work, we develop a proteomic signature with potential utility in guiding fluid strategy for septic shock patients.

Introduction: Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China. Methods: We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022 to January 8, 2023. The non-contrast enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient's clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality. Results: This study included a total of 858 hemodialysis patients, of which 660 were infected with COVID-19. The mean age was (55.61±14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level and calcium were independent risk factors for disease severity, while platelets, urea nitrogen and creatinine were identified as independent protective factors. Furthermore, total iron- binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p < 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes. Conclusion: The majority of HD patients are susceptible to COVID-19. Demographic, clinical features and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. Case presentation We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. Conclusions When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn’t be missed in the evaluation of embolic sources.

Abstract Background Whey, which has high biochemical oxygen demand and chemical oxygen demand, is mass-produced as a major by-product of the dairying industry. Microbial fermentation using whey as the carbon source may convert this potential pollutant into value-added products. This study investigated the potential of using whey powder to produce α-ketoisovalerate, an important platform chemical. Results Klebsiella oxytoca VKO-9, an efficient L-valine producing strain belonging to Risk Group 1 organism, was selected for the production of α-ketoisovalerate. The leucine dehydrogenase and branched-chain α-keto acid dehydrogenase, which catalyzed the reductive amination and oxidative decarboxylation of α-ketoisovalerate, respectively, were inactivated to enhance the accumulation of α-ketoisovalerate. The production of α-ketoisovalerate was also improved through overexpressing α-acetolactate synthase responsible for pyruvate polymerization and mutant acetohydroxyacid isomeroreductase related to α-acetolactate reduction. The obtained strain K. oxytoca KIV-7 produced 37.3 g/L of α-ketoisovalerate from lactose, the major utilizable carbohydrate in whey. In addition, K. oxytoca KIV-7 also produced α-ketoisovalerate from whey powder with a concentration of 40.7 g/L and a yield of 0.418 g/g. Conclusion The process introduced in this study enabled efficient α-ketoisovalerate production from low-cost substrate whey powder. Since the key genes for α-ketoisovalerate generation were integrated in genome of K. oxytoca KIV-7 and constitutively expressed, this strain is promising in stable α-ketoisovalerate fermentation and can be used as a chassis strain for α-ketoisovalerate derivatives production.

Abstract. Background:. Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. Methods:. We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. Results:. This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. Conclusion:. This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

The branches and leaves of 8 varieties of Lonicera japonica as materials, a high-performance liquid chromatography detection method for 8 phenolic acid components was established to determine the content characteristics of phenolic acids in the samples. The content determination results were evaluated by multivariate statistical methods such as cluster analysis, factor comprehensive analysis, and partial least squares discriminant analysis (PLS-DA). The results indicated that the established method for determining the content of 8 phenolic acids in the branches and leaves of L. japonica was stable, reliable and simple. The variation range of phenolic acids total content in the branches and leaves of 8 varieties of L. japonica was 19.4162~33.6684 mg·g−1, and 40.9900~80.3068 mg·g−1, respectively. The total content of phenolic acids varied greatly among different varieties, with 'Beihua No.1' had the highest total content in both branches and leaves, and 'Juhua No.1' had the lowest total content. Cluster analysis found that among the branches of 'Beihua No.1' was clustered separately into one group, with higher content of each component than other varieties. Factor comprehensive analysis showed that the comprehensive score of 'Beihua No.1' was >1. PLS-DA analysis identified isochlorogenic acid A, isochlorogenic acid C, ferulic acid and chlorogenic acid as the main components that might cause differences in phenolic acid content in branches. Among leaves, 'Beihua No.1' and 'Jiufeng No.1' were clustered into one category, and their comprehensive factor analysis scores were both greater than 1. PLS-DA analysis identified chlorogenic acid, caffeic acid and ferulic acid as the main components that might cause differences in phenolic acid content in leaves. In summary, there were differences in the main phenolic acid composition characteristics of different varieties. In terms of phenolic acid content, the branches and leaves of 'Beihua No.1' and 'Jiufeng No.1' have more advantages. This study provides a scientific basis for the utilization of L. japonica branches and leaves.

Abstract Background Central venous catheters (CVC) are used for dialysis in end-stage renal disease patients, presenting a significant risk for Catheter-Related Bloodstream Infections (CRBSI). While Lean Six Sigma has been effective in reducing CRBSI, its efficacy outside intensive care units (ICU) remains less explored. This study aims to evaluate the effectiveness of Lean Six Sigma in mitigating CRBSI risks among non-ICU hemodialysis patients. Methods The study was conducted in a nephrology department, focusing on patients undergoing hemodialysis with temporary CVC from February to December 2021. The Lean Six Sigma method, using Define-Measure-Analyze-Improve-Control (DMAIC) methodology, was implemented in 2022 to reduce CRBSI incidence. The 2021 CRBSI rate served as the benchmark, with a goal to reduce it by the end of 2022. Value-stream mapping, Fishbone Diagrams, and Root Cause Analysis identified potential CRBSI causes. After implementing targeted improvements, CRBSI rates before and after the intervention were compared. Results The Lean Six Sigma method significantly decreased CRBSI incidence from 12.79 to 2.32 per 1,000 catheter-days following the implementation of targeted interventions ( $$\:{\chi\:}^{2}$$ =4.60, P = 0.05). This improvement was observed comparing February-December 2021 with January-December 2022. Conclusion The findings demonstrate the effectiveness of the Lean Six Sigma method in non-ICU settings, suggesting broader applicability in hemodialysis patient care.

Abstract Background This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. Methods Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. Results The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. Conclusions The expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Background: The anterolateral thigh (ALT) flap plays a crucial role in reconstructive surgeries, providing versatile and reliable soft-tissue coverage. Flap thickness is a critical determinant of tissue volume and quality. Vascular factors, including the vascular diameter of the perforators and the length of the vascular pedicle, significantly influence flap viability and postrepair outcomes. To enhance preoperative assessment, this study integrated gender and body mass index (BMI) to analyze the anatomical characteristics of ALT flaps. Methods: This study used somatic penetrating ultrasonography to examine bilateral ALT flaps in patients. This study analyzed the relationship between gender and ALT flap thickness, vascular diameter of the perforators, and vascular pedicle length. Chi-square test was used to assess variations in age and gender. Multiple t-tests compared flap thickness, vascular diameter, and pedicle length between men and women in different BMI groups. Results: A total of 158 patients were included in this study from January 2018 to December 2022. In BMI < 24 and BMI ≥ 24.0 groups, males had lower ALT flap thickness than females (p < 0.0001 in each subgroup). Similarly, the vascular diameter of the perforators followed the same trend, with females having larger vascular diameters than males in BMI < 24 and BMI ≥ 24.0 groups. In terms of vascular pedicle length, males had longer pedicle length than females in both BMI < 24 and BMI ≥ 24.0 groups (p < 0.05 in each subgroup). Conclusions: Females demonstrate greater ALT flap thickness and larger vascular diameter of the perforators than males, whereas males have a longer length of the vascular pedicle.

New psychoactive substances (NPS) have become a global health and social problem. Their structures are variable and can be easily modified to produce new compounds. Traditional analytical techniques mostly rely on standard substances and mass spectrometry databases. The increased structural diversity of NPS makes the mass spectrometry databases be unable to comprehensively cover the mass spectra of all possible NPS, which in turn makes it difficult to perform structural identification of completely unknown compounds. Advances in machine learning have emerged as a potential solution to this dilemma. In this study, the k-nearestneighbor (KNN), support vector machine (SVM), random forests (RF) and artificial neural network (ANN) algorithms were constructed based on a dataset of mass spectra of 871 compounds. The four algorithmic models for identifying new psychoactive substances were used for structural classification prediction. The training and test sets were divided according to the ratio of 7:3, and the fit method was invoked on the training set to construct the model and train the parameters of the model, and the generalization ability of the model was evaluated on the test set. A grid search with 5-fold cross-validation was used to optimize the hyperparameters of the models. The performance of the four classification prediction models was evaluated by using the confusion matrix, accuracy, precision, recall and f-scores for each of the four models for characterizing 261 samples from the test set. Overall, the RF prediction model has the best classification prediction for the seven NPS as well as negative samples, with an overall accuracy of 89.27%, which is higher than the other three classification prediction models. The overall accuracies of the KNN, SVM, and ANN models are 79.31%, 83.14%, and 83.52%, respectively. In addition, the RF prediction model also has high accuracy for the NPS prediction of specific classes, and the accuracies for synthetic cathinones, fentanyl, synthetic cannabinoids, and benzodiazepines are 100%, 93%, 95%, and 100%, respectively, which can warrant good prediction for the structural classes of unknown compounds. In conclusion, this study develops a strategy for rapid analysis of new psychoactive substances using machine learning algorithms based on mass spectral datasets, realizing the classification prediction of structural classes of unknown compounds, thus providing a basis for the structural identification of unknown psychoactive compounds.

Fusarium graminearum is the main pathogenic fungus causing wheat head blight. It not only causes severe crop yield reduction, but also produces fungal toxins such as deoxynivalenol (DON) and 15-acetyl deoxynivalenol (15-ADON), which are dangerous food pollutants to people and livestock. For the genetic functional study of Fusarium graminearum, it is often necessary to culture mycelium on LTB medium in the laboratory to investigate its regulatory effect on DON and 15-ADON synthesis. However, the detection of DON and 15-ADON in the mycelium is focused on extracellular, with less focus on the detection of intracellular. Simultaneous detection of intracellular and extracellular DON and 15-ADON can provide more in-depth information of fungal toxin production and secretion functions. In the study, a method based on gas chromatography-mass spectrometry (GC-MS) for simultaneous detection of DON and 15-ADON was developed. The solvents for extracting DON and 15-ADON can be completely separated and the calibration curves of each extract show good linear relationship within a certain range. The mass spectrometric characteristic scan shows high ionization efficiency for both DON and 15-ADON. The retention time of DON and 15-ADON in chromatogram are 6.98 and 7.68 min, respectively. Qualitative analysis of DON was performed using m/z 295, 235, and 193 under single ion monitor (SIM) mode, while m/z 392, 235, and 193 were used for 15-ADON. The highest intensity ion m/z 235 was selected for the quantification of DON, and m/z 193 for the quantification of 15-ADON. This method was used to detect the intracellular and extracellular levels of DON and 15-ADON in wild-type PH-1 and tri5 mutant with DON biosynthesis deficiency. The intracellular DON and 15-ADON levels in PH-1 are determined to be (149.13±9.15) μg/g and (1833.31±185.33) μg/g, extracellular levels are (5910.35±468.23) μg/g and (45222.12±2726.81) μg/g, respectively. The study identified a mutant strain with the deletion of the first enzyme involved in the synthesis pathway of DON and 15-ADON，both DON and 15-ADON are not detected in the extracellular and intracellular of the tri5 mutant. Additionally, this research confirms that after 7 days of cultivation in LTB medium, the wild-type strain exhibits higher levels of 15-ADON in both intracellular and extracellular compared to DON, with extracellular levels of DON and 15-ADON being higher than intracellular levels. This method can provide a methodological reference for the functional study of toxin synthesis in Fusarium graminearum.

Abstract Background Motor neuron disease (MND) is a chronic and progressive neurodegenerative disorder with an unknown cause. The development of amyotrophic lateral sclerosis (ALS) is believed to be linked to an immune response. Monocytes/macrophages and T cells are key players in the disease’s advancement. Monitoring levels of cytokines in the blood can help forecast patient outcomes, while immunotherapy shows promise in alleviating symptoms for certain individuals. Case presentation A 56-year-old male patient was admitted to the hospital due to progressive limb weakness persisting for eight months. The neurological examination revealed impairments in both upper and lower motor neurons, as well as sensory anomalies, without corresponding signs. Electrophysiological examination results indicated extensive neuronal damage and multiple peripheral nerve impairments, thereby the diagnosis was ALS. One month ago, the patient began experiencing symptoms of dry mouth and a bitter taste. Following tests for rheumatic immune-related antibodies and a lip gland biopsy, a diagnosis of Sjögren’s syndrome (SS) was proposed. Despite treatment with medications such as hormones (methylprednisolone), immunosuppressants (hydroxychloroquine sulfate), and riluzole, the symptoms did not significantly improve, but also did not worsen. Conclusion It is recommended to include screening for SS in the standard assessment of ALS. Furthermore, research should focus on understanding the immune mechanisms involved in ALS, providing new insights for the diagnosis and treatment of ALS in conjunction with SS.

Abstract Background Fritillaria ussuriensis is an endangered medicinal plant known for its notable therapeutic properties. Unfortunately, its population has drastically declined due to the destruction of forest habitats. Thus, effectively protecting F. ussuriensis from extinction poses a significant challenge. A profound understanding of its genetic foundation is crucial. To date, research on the complete mitochondrial genome of F. ussuriensis has not yet been reported. Results The complete mitochondrial genome of F. ussuriensis was sequenced and assembled by integrating PacBio and Illumina sequencing technologies, revealing 13 circular chromosomes totaling 737,569 bp with an average GC content of 45.41%. A total of 55 genes were annotated in this mitogenome, including 2 rRNA genes, 12 tRNA genes, and 41 PCGs. The mitochondrial genome of F. ussuriensis contained 192 SSRs and 4,027 dispersed repeats. In the PCGs of F. ussuriensis mitogenome, 90.00% of the RSCU values exceeding 1 exhibited a preference for A-ended or U-ended codons. In addition, 505 RNA editing sites were predicted across these PCGs. Selective pressure analysis suggested negative selection on most PCGs to preserve mitochondrial functionality, as the notable exception of the gene nad3 showed positive selection. Comparison between the mitochondrial and chloroplast genomes of F. ussuriensis revealed 20 homologous fragments totaling 8,954 bp. Nucleotide diversity analysis revealed the variation among genes, and gene atp9 was the most notable. Despite the conservation of GC content, mitogenome sizes varied significantly among six closely related species, and colinear analysis confirmed the lack of conservation in their genomic structures. Phylogenetic analysis indicated a close relationship between F. ussuriensis and Lilium tsingtauense. Conclusions In this study, we sequenced and annotated the mitogenome of F. ussuriensis and compared it with the mitogenomes of other closely related species. In addition to genomic features and evolutionary position, this study also provides valuable genomic resources to further understand and utilize this medicinal plant.

Abstract Mental fatigue during long-term motor imagery (MI) may affect intention recognition in MI applications. However, the current research lacks the monitoring of mental fatigue during MI and the definition of robust biomarkers. The present study aims to reveal the effects of mental fatigue on motor imagery recognition at the brain region level and explore biomarkers of mental fatigue. To achieve this, we recruited 10 healthy participants and asked them to complete a long-term motor imagery task involving both right- and left-handed movements. During the experiment, we recorded 32-channel EEG data and carried out a fatigue questionnaire for each participant. As a result, we found that mental fatigue significantly decreased the subjects’ motor imagery recognition rate during MI. Additionally the theta power of frontal, central, parietal, and occipital clusters significantly increased after the presence of mental fatigue. Furthermore, the phase synchronization between the central cluster and the frontal and occipital lobes was significantly weakened. To summarize, the theta bands of frontal, central, and parieto–occipital clusters may serve as powerful biomarkers for monitoring mental fatigue during motor imagery. Additionally, changes in functional connectivity between the central cluster and the prefrontal and occipital lobes during motor imagery could be investigated as potential biomarkers.

To enhance the energy absorption characteristics of the energy-absorbing structure in metal alloy 3D printing, various heat treatment conditions were studied on the 3D printed hourglass multi-cellular energy-absorbing structure (HTMEAS). The results reveal that as the annealing temperature rises, the structural morphology of the α-Al+Si phase in AlSi10Mg alloy undergoes alterations, particularly when the annealing temperature remains below 300°C. After heat treatment, the HTMEAS can contract layer by layer along the gradient and undergo controllable and orderly deformation. The maximum energy absorption, displacement, and peak force reached 758 J, 30 mm, and 30 kN, respectively.These values represent a significant enhancement of 146.8 %, 157.8 %, and 50 % compared to those without heat treatment, showcasing commendable mechanical properties. This advancement establishes a solid theoretical framework and assurance for the future development and refinement of 3D printing energy-absorbing structures.

Carbon fibre reinforced silicon carbide (C/C-SiC) composite materials have attracted increasing attention in brake system of high-speed trains, due to their low density, high specific strength, thermal stability, and frictional wear performance. This study aims to explore the mechanical properties of the 2.5D C/C-SiC composites, in order to characterise its potential application to the friction braking system of high-speed trains. To comprehensively evaluate the mechanical performance of the 2.5D C/C-SiC composites, the chemical vapor infiltration (CVI) method was adopted to prepare novel samples with high densification and low content of residual Si. The mechanical properties and failure mechanisms of the composites were investigated under various loading conditions, including tension, compression, bending, and shear tests. The experimental results indicated that the 2.5D C/C-SiC composites exhibited superior mechanical properties, with average in-plane tensile strength, compressive strength, bending strength, and interlaminar shear strength reaching 127.67 MPa, 326.92 MPa, 355.74 MPa, and 9.77 MPa, respectively, which are 2–8 times higher than the mechanical properties of C/C-SiC composites in existing publications. Under different loading conditions, the composites demonstrated characteristics of ductile fracture, pseudo-plastic compression fracture, pseudo-plastic bending fracture, and brittle shear fracture. Both high fibre content and the formation of SiC structure were advantageous for enhancing the load-bearing performance of C/C-SiC composites. The outstanding mechanical properties of the 2.5D C/C-SiC composite render the brake disc highly resistant to deformation and cracking under high stress, thereby enhancing its durability and establishing it as the ideal material for the next generation of high-speed train brake discs.

G protein-coupled receptors (GPCRs) play a pivotal role in fundamental biological processes and disease development. GPCR isoforms, derived from alternative splicing, can exhibit distinct signaling patterns. Some highly-truncated isoforms can impact functional performance of full-length receptors, suggesting their intriguing regulatory roles. However, how these truncated isoforms interact with full-length counterparts remains largely unexplored. Here, we computationally investigated the interaction patterns of three human GPCRs from three different classes, ADORA1 (Class A), mGlu2 (Class C) and SMO (Class F) with their respective truncated isoforms because their homodimer structures have been experimentally determined, and they have truncated isoforms deposited and identified at protein level in Uniprot database. Combining the neural network-based AlphaFold2 and two physics-based protein-protein docking tools, we generated multiple complex structures and assessed the binding affinity in the context of atomistic molecular dynamics simulations. Our computational results suggested all the four studied truncated isoforms showed potent binding to their counterparts and overlapping interfaces with homodimers, indicating their strong potential to block homodimerization of their counterparts. Our study offers insights into functional significance of GPCR truncated isoforms and supports the ubiquity of their regulatory roles.

Abstract The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08–2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08–2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08–2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction.

Abstract Background Arterial blood gas analysis (ABGA) plays a vital role in emergency and intensive care, which is affected by many factors, such as different instrumentation, temperature, and testing time. However, there are still no relevant reports on the difference in discarding different blood volumes on ABGA values. Methods We enrolled 54 patients who underwent thoracoscopic surgery and analysed differences in blood gas analysis results when different blood volumes were discarded from the front line of the arterial heparin blood collector. A paired t test was used to compare the results of the same patient with different volumes of blood discarded from the samples. The difference was corrected by Bonferroni correction. Results Our results demonstrated that the PaO2, PaCO2, and THbc were more stable in the 4th ml (PaO2 = 231.3600 ± 68.4878 mmHg, PaCO2 = 41.9232 ± 7.4490 mmHg) and 5th ml (PaO2 = 223.7600 ± 12.9895 mmHg, PaCO2 = 42.5679 ± 7.6410 mmHg) blood sample than in the 3rd ml (PaO2 = 234.1000 ± 99.7570 mmHg, PaCO2 = 40.6179 ± 7.2040 mmHg). Conclusion It may be more appropriate to discard the first 3 ml of blood sample in the analysis of blood gas results without wasting blood samples.

Abstract Background K. pneumoniae liver abscess (KPLA) mostly involves the right lobe. We present a case of K. pneumoniae caudate liver abscess with invasive liver abscess syndrome (ILAS) was rarely identified. Case presentation A 53-year-old man with elevated glycated hemoglobin with chills, rigors and a fever of five days. The patient presented with tachycardia and fever. Physical examination revealed tenderness over the right abdomen was elicited. In particular, the inflammatory markers were markedly elevated, and computerized tomography (CT) showed pulmonary abscess, pulmonary embolism and caudate liver abscess. The patient’s sequential organ failure assessment (SOFA) score was 10 points. Klebsiella pneumoniae was isolated from sputum, urine and blood. With the suspicion of liver abscesses, ILAS and sepsis. The patient was successfully treated with antibiotics. He returned to close to his premorbid function. Conclusion K. pneumoniae caudate liver abscess was rare. This is the first detailed report of K. pneumoniae caudate liver abscess with invasive liver abscess syndrome. Patients with cryptogenic K. pneumoniae liver abscess are advised to undergo an examination of intestinal barrier function. The study indicates that in patients with K. pneumoniae liver abscess, a caudate liver abscess size of ≤ 9.86 cm² may be characteristic of those suitable for conservative treatment of invasive liver abscess syndrome.

Abstract Freshwater scarcity and microplastics (MPs) pollution are two concerning and intertwined global challenges. In this work, we propose a “one stone kills two birds” strategy by employing an interfacial solar evaporation platform (ISEP) combined with a MPs adsorbent. This strategy aims to produce clean water and simultaneously enhance MPs removal. Unlike traditional predecessors, our ISEP generates condensed water free from MPs contamination. Additionally, the photothermally driven interfacial separation process significantly improves the MPs removal performance. We observed a removal ratio increase of up to 5.5 times compared to previously reported MPs adsorbents. Thus, our rationally-designed ISEP holds promising potential to not only mitigate the existing water scarcity issue but also remediate MPs pollution in natural water environments.

The metro tunnel settlement would directly affect the normal train operation and the comfort of passengers; severe uneven settlement can easily cause tunnel structural diseases. The relevant studies mainly focused on long-term settlement prediction and single factor impact analysis; it is necessary to analyze the multiple factors that influence the tunnel foundation settlement. A three-dimensional finite element numerical model of one shield tunnel section of Zhengzhou metro 1st line was constructed and the vertical load of metro train was simulated as artificial excitation force to extract the dynamic stress and static deviator stress data. Introducing the cumulative plastic strain calculation formula under cyclic load, the layered summation method was used to calculate the tunnel foundation settlement. The influences of factors, such as the properties of soil where the tunnel is buried, the depth of track bed void, and metro operation velocity, on the tunnel foundation settlement were further analyzed. The results show that the numerical simulated foundation settlement and development law are consistent with on-site measured results, which verifies the accuracy of finite element simulation. The tunnel foundation settlement decreases with the increase of sand content in the surrounding soil layer; the size of the track bed void would exacerbate the stress concentration and vibration amplification in the tunnel and track bed slab, and then increase the dynamic deviatoric stress of soil layer under the tunnel and foundation settlement. Increasing the metro train velocity would increase the lateral influence range of foundation settlement. The sensitivity of tunnel settlement to various factors is obtained with orthogonal experimental method, range analysis method, and variance analysis method. The descending order of sensitivity is soil layer properties, train velocity, and track bed void, in which, soil layer property has a highly significant level and vehicle speed a has significant level. This study can provide basic information for the deformation monitoring, safety assessment, and reinforcement treatment of operating metro tunnels.

BackgroundNatural pyrethrins have long been widely used in the fields of environmental and household hygiene. Studies have reported that natural pyrethrins have potential liver toxicity, but their specific mechanisms are still unclear yet. ObjectiveTo explore the effect of natural pyrethrins on DNA damage in human liver cells. MethodsThis study used human liver cell QSG7701 as an in vitro testing model. After exposure to DMSO and a series of concentrations of natural pyrethrins (5, 10, 20, and 40 μg·mL−1) for 6 and 24 h, reactive oxygen species (ROS) was detected by fluorescence microscopy using a fluorescence probe, thiobarbituric acid reactive substance (TBARS) by colorimetric method using a microplate reader, DNA damage by comet assay through observing DNA fragment migration under microscope, and phospho H2AX (γH2AX) and 8-oxoguanine (8-oxoG) by immunofluorescence assay using a laser confocal microscope. ResultsAs the exposure concentration of natural pyrethrins increased, the fluorescence intensity of ROS significantly increased in a concentration-dependent manner. The differences in ROS between the 10 μg·mL−1 and above groups and the control group were statistically significant (P

Abstract Background Tyrosine phosphorylation of intracellular proteins is a post‐translational modification that plays a regulatory role in signal transduction during cellular events. Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases (PTPs) contributed their role as a convergent node to mediate cross‐talk between signaling pathways. In the context of cancer, PTP‐mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy. This is achieved by the promotion of constitutive activation of growth‐stimulatory signaling pathways or modulation of the immune‐suppressive tumor microenvironment. Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors, reversing drug resistance that was responsible for clinical failures during cancer therapy. Areas covered This review aimed to elaborate recent insights that supported the involvement of PTP‐mediated pathways in the development of resistance to targeted therapy and immune‐checkpoint therapy. Expert opinion This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long‐term tumor regression. Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced‐stage tumors.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Abstract Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Abstract Background Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. Methods A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. Results This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. Conclusion This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography–tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements. HIGHLIGHT Etomidate (ET) use has spread rapidly, and it is now one of the most seriously abused substances in China. Our study first developed a simple, fast, and sensitive direct injection method for the quantitative determination of ET and etomidate acid in wastewater. After optimizing the UPLC–MS/MS and sample pretreatment conditions, the method was applied to authentic wastewater samples (n = 245) from several WWTPs in China.;

Abstract This study aims to research on the mechanical and frost resistance properties of pressed concrete blocks mixed with the polymeric aluminum chloride (PAC) waste residue. Experimental studies on the activity index of volcanic ash, mechanical property, frost resistance and microstructure of pressed concrete blocks mixed with PAC waste residue were carried out. The results show that the activity index of volcanic ash of PAC waste residue reaches 74.96% at a particle size of 0.075 mm or less and a curing age of 28 days. Based on results of mechanical property tests, the optimum dosage of PAC waste residue is 15%, at which time the compressive and bending strength only decreases by 14.57% and 15.84%. Based on results of frost resistance tests, the optimum dosage of PAC waste residue for pressed concrete blocks is 10%. After 50 freeze–thaw cycles, when the dosage of PAC waste residue is 10%, the strength loss rate is only 3.04%. XRD and SEM tests show that PAC waste residue participates in chemical reactions. With a small amount of PAC waste residue, the structure of the specimen remains dense and therefore the strength decreases less.

Abstract Background It is well established that hypercholesterolemia increases the risk of atherosclerosis, especially because it reduces the availability of nitric oxide (NO). However, the relationship between hypercholesterolemia and NO in regulating colorectal cancer development and progression remains unknown. Methods We conducted bioinformatics analysis, qRT-PCR, ChIP-qPCR assays, luciferase report assays, clonogenic survival assays, and multiple mouse models to investigate the function and mechanism of hypercholesterolemia in regulating NO signaling. Additionally, NOS inhibitors were used to evaluate the potential of therapeutic strategy in anti-tumor response. Results Here, we show that oxidized low-density lipoprotein (oxLDL) cholesterol and its receptor LOX-1 are essential for hypercholesterolemia-induced colorectal tumorigenesis. Mechanically, the oxLDL promotes the oxidant stress-dependent induction of hypoxia signaling to transcriptionally up-regulate NO synthase (NOS) especially NOS1 expression in colorectal cancer (CRC) cells. More importantly, our results suggested that selective inhibition of NOS1 with its specific inhibitor Nω-Propyl-L-arginine is a suitable therapeutic strategy for hypercholesterolemia-related CRC with both efficacy and toxicity reduction. Conclusions Our findings established that hypercholesterolemia induces the oxidant stress-dependent induction of hypoxia signaling to transcriptionally up-regulate NOS1 expression in CRC cells, and the clinically applicable NOS1 inhibitor Nω-Propyl-L-arginine represents an effective therapeutic strategy for hypercholesterolemia-related CRC.

Abstract Objective Myocardial infarction (MI) -induced cardiac dysfunction can be attenuated by aerobic exercises. This study explored the mechanism of interval training (IT) regulating cardiac function in MI rats, providing some theoretical basis for clarifying MI pathogenesis and new ideas for clinically treating MI. Methods Rats were subjected to MI modeling, IT intervention, and treatments of the Transforming growth factor-β1 (TGF-β1) pathway or the nod-like receptor protein 3 (NLRP3) activators. Cardiac function and hemodynamic indicator alterations were observed. Myocardial pathological damage and fibrosis, reactive oxygen species (ROS) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, MDA content, inflammasome-associated protein levels, and inflammatory factor levels were assessed. The binding between TGF-β1 and receptor was detected. Results MI rats exhibited decreased left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS), left ventricular systolic pressure (LVSP), positive and negative derivates max/min (dP/dt max/min) and increased left ventricular end-systolic pressure (LVEDP), a large number of scar areas in myocardium, disordered cell arrangement and extensive fibrotic lesions, increased TGF-β1 and receptor binding, elevated ROS level and MDA content and weakened SOD, CAT and GSH-Px activities, and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and cleaved-caspase-1 levels, while IT intervention caused ameliorated cardiac function. IT inactivated the TGF-β1 pathway to decrease oxidative stress in myocardial tissues of MI rats and inhibit NLRP3 inflammasome activation. Activating NLRP3 partially reversed IT-mediated improvement on cardiac function in MI rats. Conclusion IT diminished oxidative stress in myocardial tissues and suppressed NLRP3 inflammasome activation via inactivating the TGF-β1 pathway, thus improving the cardiac function of MI rats.

Abstract Hair is an advantageous biological sample due to its recordable, collectable, and storable nature. Hair's primary components are keratin and keratin-associated proteins. Owing to its abundance of cystine, keratin possesses impressive mechanical strength and chemical stability, formed by creating disulfide bonds as crosslinks within the protein peptide chain. Furthermore, keratin is cross-linked with keratin-associated proteins to create a complex network structure that provides the hair with strength and rigidity. Protein extraction serves as the foundation for hair analysis research. Bleaching hair causes damage to the structure between keratin and keratin-associated proteins, resulting in texture issues and hair breakage. This article outlines various physical treatment methods and lysate analysis that enhance the efficiency of hair protein extraction. The PLEE method achieves a three-fold increase in hair protein extraction efficiency when using a lysis solution containing SDS and combining high temperatures with intense shaking, compared to previous methods found in literature. We utilized the PLEE method to extract hair from both normal and damaged groups. Normal samples identified 156–157 proteins, including 51 keratin and keratin-associated proteins. The damaged group consisted of 155–158 identified proteins, of which 48–50 were keratin and keratin-associated proteins. Bleaching did not cause any notable difference in the protein identification of hair. However, it did reduce coverage of keratin and keratin-associated proteins significantly. Our hair protein extraction method provides extensive coverage of the hair proteome. Our findings indicate that bleaching damage results in subpar hair quality due to reduced coverage of protein primary sequences in keratin and keratin-associated proteins.

Abstract Background A large number of psychological consequences including sleep health emerged during the 2019 Coronavirus disease (COVID-19) pandemic. Sleep patterns in toddlers are vulnerable to negative environmental exposures, however, very few studies on this topic have been published so far. Objectives In this paper, we aimed to investigate the sleep patterns and associated factors in toddlers from China confined at home in the context of COVID-19 pandemic. Methods From April to November 2021, a convenience sample of 493 parents of young children aged (12–35 months) were surveyed from Fuzhou, Sanming, Quanzhou, Nanping, and Longyan cities in the Fujian Province, China. A cross-sectional survey was conducted via Electronic questionnaires to collect parent and child social-demographic characteristics. The Brief Infant Sleep Questionnaire (BISQ) was used to collect data on sleep practices, sleep duration and patterns, as well as the number of nocturnal awaking . Results The mean age of toddlers was 2.11 years old, and 52.54% (259/493) were males. Among the 493 toddlers’ sleep patterns, 331(67.1%) initiated sleep accompanied by parents, 67(13.6%) slept independently, 59 (12.0%) were breast fed/bottle fed to initiate sleep, 27 (5.5%) were held and 9 (1.8%) rocked. The clear longitudinal association between the duration of night-time sleep, the frequency of nighttime awakenings, and various sleep patterns remains clear (p

Planktonic microorganisms have been recognized as important components in biogeochemical cycling in lakes. However, research into the impact of phyllosphere microorganisms, particularly those involved in carbon cycling, on CO2 fluxes in macrophyte-dominated lakes within the context of global environmental changes remains scarce. Here, by employing high-throughput sequencing techniques, we experimentally tested how nutrient enrichment, top-down effects of fish and increases in dissolved organic carbon (DOC) affect CO2 exchange flux at the water-air interface by altering the community structure and functioning of phyllosphere bacteria on macrophytes. We found that our mesocosm ecosystems exhibited a net absorption of CO2, but nutrient enrichment significantly decreased the absorption ability. Mantel tests and multiple regression modeling also showed that eutrophication-associated parameters (total nitrogen, total phosphorus and ammonium nitrogen), pH, and extinction coefficient were the key drivers influencing abundance of phyllosphere functional microorganisms. In addition, these experimental treatments significantly altered the composition, diversity and co-occurrence networks of carbon cycling-associated phyllosphere microorganisms, which impacted the CO2 flux. Structural equation models and linear regression further showed that the Shannon Index of phyllosphere functional microorganisms related to carbon cycling (rather than plant volume inhabited - PVI) had a significant positive impact on CO2 fixation. This means that environmental changes—especially eutrophication—may hinder carbon sequestration by decreasing the diversity of phyllosphere microorganisms rather than reducing the abundance of submerged macrophytes. This study increases our understanding of carbon cycling processes in aquatic environments from a management perspective by emphasizing the importance of protecting the diversity of phyllosphere microorganisms in macrophyte-dominated lakes.

ABSTRACT Enzymatic therapy with nicotine-degrading enzyme is a new strategy in treating nicotine addiction, which can reduce nicotine concentrations and weaken withdrawal in the rat model. However, when O2 is used as the electron acceptor, no satisfactory performance has been achieved with one of the most commonly studied and efficient nicotine-catabolizing enzymes, NicA2. To obtain more efficient nicotine-degrading enzyme, we rationally designed and engineered a flavoenzyme Pnao, which shares high structural similarity with NicA2 (RMSD = 1.143 Å) and efficiently catalyze pseudooxynicotine into 3-succinoyl-semialdehyde pyridine using O2. Through amino acid alterations with NicA2, five Pnao mutants were generated, which can degrade nicotine in Tris-HCl buffer and retain catabolic activity on its natural substrate. Nicotine-1′-N-oxide was identified as one of the reaction products. Four of the derivative mutants showed activity in rat serum and Trp220 and Asn224 were found critical for enzyme specificity. Our findings offer a novel avenue for research into aerobic nicotine catabolism and provide a promising method of generating additional nicotine-catalytic enzymes.IMPORTANCENicotine, the main active substance in tobacco, results in cigarette addiction and various diseases. There have been some attempts at using nicotine oxidoreductase, NicA2, as a therapeutic for nicotine cessation. However, it uses cytochrome c as it is electron acceptor, which is impractical for therapeutic use compared with using O2 as an oxidant. Thus, amino acid alteration was performed on Pnao using NicA2 as model. Five of the mutants generated degraded nicotine at a rate similar to NicA2, and one of the catabolic compounds was identified as nicotine-1′-N-oxide. Our research highlights a new direction in developing enzymes that efficiently catabolize nicotine without co-enzymes and suggests that structure-similar human original MAOA (or B) may assist with nicotine cessation after being engineered.

ObjectiveApproximately 10%–70% of patients may develop diaphragmatic dysfunction after cardiac surgery, which may lead to delayed weaning from mechanical ventilation, increased ICU stays, postoperative hospitalization stays, and respiratory complications. However, its impact on prognosis and risk factors remain controversy. Therefore, we conducted a retrospective cohort study in which we evaluated diaphragmatic dysfunction in patients who underwent cardiac surgery via bedside diaphragm ultrasound to investigate its prognosis and possible risk factors.MethodsData from the electronic medical records system included case records and ultrasound images of the diaphragm for 177 consecutive patients admitted to the ICU following cardiac thoracotomy surgeries performed between June and September 2020. Diaphragmatic dysfunction was defined as a diaphragmatic excursion of less than 9 mm in women and less than 10 mm in men at rest, with an average thickening fraction of less than 20%. SPSS 25.0 software was used to analyse the relationships between patients' general information, intraoperative and postoperative factors and diaphragmatic dysfunction, as well as the impact on patients' hospitalization days, mechanical ventilation time and respiratory system complications.ResultsThe incidence of early postoperative diaphragmatic dysfunction after cardiac surgery was 40.7%. Patients with diaphragmatic insufficiency were more likely to sequentially use noninvasive ventilation within 24 h after weaning off mechanical ventilation (3.8% vs. 12.5%, P = 0.029) and to require more oxygen support (23.8% vs. 40.3%, P = 0.019). Although there was no significant difference, the diaphragmatic dysfunction group tended to have longer ICU stays and postoperative hospital stays than did the normal diaphragmatic function group (P = 0.119, P = 0.073). Univariate and multivariate logistic regression analyses both revealed that chest tube drainage placed during surgery accompanied by bloody drainage fluid was an independent risk factor for diaphragmatic dysfunction (univariate analysis: 95% CI: 1.126–4.137, P = 0.021; multivariate analysis: 95% CI: 1.036–3.897, P = 0.039).ConclusionEearly diaphragmatic dysfunction after cardiac surgery increased the proportion of patients who underwent sequential noninvasive ventilation after weaning from mechanical ventilation and who required more oxygen. Chest tube drainage placed during surgery accompanied by bloody drainage fluid was an independent risk factor for diaphragmatic dysfunction, providing evidence-based guidance for respiratory rehabilitation after cardiac surgery.

Lung cancer, which is a leading cause of cancer-related deaths worldwide, frequently metastasizes to the bones, significantly diminishing patients’ quality of life and complicating treatment strategies. This study aims to develop an advanced 3D Mask R-CNN model, enhanced with the ConvNeXt-V2 backbone, for the automatic segmentation of bone tumors and identification of lung cancer metastasis to support personalized treatment planning. Data were collected from two hospitals: Center A (106 patients) and Center B (265 patients). The data from Center B were used for training, while Center A’s dataset served as an independent external validation set. High-resolution CT scans with 1 mm slice thickness and no inter-slice gaps were utilized, and the regions of interest (ROIs) were manually segmented and validated by two experienced radiologists. The 3D Mask R-CNN model achieved a Dice Similarity Coefficient (DSC) of 0.856, a sensitivity of 0.921, and a specificity of 0.961 on the training set. On the test set, it achieved a DSC of 0.849, a sensitivity of 0.911, and a specificity of 0.931. For the classification task, the model attained an AUC of 0.865, an accuracy of 0.866, a sensitivity of 0.875, and a specificity of 0.835 on the training set, while achieving an AUC of 0.842, an accuracy of 0.836, a sensitivity of 0.847, and a specificity of 0.819 on the test set. These results highlight the model’s potential in improving the accuracy of bone tumor segmentation and lung cancer metastasis detection, paving the way for enhanced diagnostic workflows and personalized treatment strategies in clinical oncology.