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Abstract Background Xanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluorescein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. Results In this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endogenous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial respiratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mutant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthrocolins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was responsible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biological active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also appeared in the rat blood. Conclusion Our findings provide a mechanistic insight into in vivo synthesis of complex and condensed arthrocolins induced by simple phenols and exploits a quinol based method to generate endogenous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes.

Background The emergence of the green supply chain represents a natural evolution from the traditional model. However, this transition has created trust concerns in operational processes. Fortunately, blockchain technology offers a promising solution to address this issue and help businesses overcome related obstacles. As artificial intelligence and blockchain continue to advance, enterprises are increasingly exploring opportunities for green innovation investments, although the optimal timing for successful product innovation can be difficult to predict. Methods The effects of successful innovation on eco-friendly supply chains are analyzed through various factors such as optimal investment strategy, level of blockchain technology, and overall system profit. Differential game theory is used to determine the most effective approach across three alliance modes: horizontal cooperative, non-cooperative, and vertical cooperative. Additionally, the impact of innovation uncertainty on member strategies and alliance selection is thoroughly examined. Results According to the results, predicting the likelihood of innovation realization can influence decision makers to prioritize current profits. Both horizontal and vertical cooperative alliance models can lead to Pareto improvements in total system profit, both before and after innovation success. However, the vertical cooperative alliance model proves to be more effective, especially at higher realization rates. Green suppliers stand to benefit from the vertical cooperative alliance model, as it can enhance their innovative investment strategy, while platform cooperation does not significantly affect their strategy. Platforms, on the other hand, can benefit from the vertical cooperative alliance model, as it can promote their innovative investment strategy and level of blockchain technology.

With the growth of people’s demand for loans, banks and other financial institutions put forward higher requirements for customer credit risk level classification, the purpose is to make better loan decisions and loan amount allocation and reduce the pre-loan risk. This article proposes a Multi-Level Classification based Ensemble and Feature Extractor (MLCEFE) that incorporates the strengths of sampling, feature extraction, and ensemble classification. MLCEFE uses SMOTE + Tomek links to solve the problem of data imbalance and then uses a deep neural network (DNN), auto-encoder (AE), and principal component analysis (PCA) to transform the original variables into higher-level abstract features for feature extraction. Finally, it combined multiple ensemble learners to improve the effect of personal credit risk multi-classification. During performance evaluation, MLCEFE has shown remarkable results in the multi-classification of personal credit risk compared with other classification methods.

In order to maximize personal interests, enterprises have a tendency to choose environmental pollution in exchange for corporate profits, resulting in negative externalities; the Civil Code of the People’s Republic of China imposes legal regulations on the environmental infringement of enterprises in order to achieve the maximization of the use of the allocation of social resources and promote the sustainable development of society. Subsequent judicial interpretations have set a two-fold cap on the amount of punitive damages. However, in cases of extremely serious environmental damage, the two-fold cap on punitive damages for environmental infringement will create the possibility of insufficient compensation. Based on this, this paper analyzes the legal text of China’s punitive damages provisions for environmental infringement and analyzes the interrelationships between enterprises and between enterprises and potential environmental infringement victims in a game analysis. The results of the analysis show that as the amount of punitive damages for environmental infringement increases, the probability of the infringed person filing a lawsuit and that of the enterprise reducing its environmental infringement behavior also increase. In order to promote the cause of China’s sustainable development, this paper puts forward relevant suggestions for the improvement of China’s environmental legal regulation: first, the upper limit of the amount of punitive damages for environmental infringement should be canceled; second, the amount of reasonable punitive damages should be set on the basis of the damages caused by environmental infringement on human beings and the environment; lastly, in the baseline setting of the amount of punitive damages, additional factors need to be taken into account, and the amount of punitive damages should be set for the enterprises with a high degree of maliciousness. Finally, additional factors need to be considered in setting the benchmark for the amount of punitive damages, which should penalize the enterprises causing environmental infringement with a high degree of malice with heavier penalties and, at the same time, penalize the enterprises with a smaller scale of operation and economic strength with lighter penalties.

Abstract Postural abnormalities are common disabling motor complications affecting patients with Parkinson’s disease (PD). We proposed a summary index for postural abnormalities (IPA) based on Kinect depth camera and explored the clinical value of this indicator. Seventy individuals with PD and thirty age-matched healthy controls (HCs) were enrolled. All participants were tested using a Kinect-based system with IPA automatically obtained by algorithms. Significant correlations were detected between IPA and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (r s = 0.369, p = 0.002), MDS-UPDRS-III total score (r s = 0.431, p

Background and purpose: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, 10%-30% of NSCLC patients with EGFR sensitive mutation still have primary drug resistance when receiving TKI targeted therapy. Therefore, to study the clinical efficacy of EGFR-TKI and find out its prognostic predictors has important significance for the treatment of advanced NSCLC patients with EGFR sensitive mutation. The purpose of this research was to evaluate the efficacy of icotinib as first-line treatment in patients with EGFR-mutant advanced NSCLC and investigate the prognostic predictors. Methods: A total of 258 stage ⅢB-Ⅳ NSCLC patients with EGFR mutation who were admitted to Fujian Cancer Hospital from January 2016 to November 2017 were selected. One hundred and eighteen advanced NSCLC patients with EGFR mutation were enrolled, and baseline circulating tumor DNA (ctDNA) EGFR-mutant status was determined using the plasma test. All these patients received icotinib 125mg three times a day. The χ2 test was used to compare the differences in clinicopathological characteristics between different EGFR mutation groups. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier survival curve. The log-rank test was used for univariate analysis, and the COX regression model was used for multivariate analysis. Results: The objective response rate (ORR) of 118 patients was 62.7% (95% CI: 53.9%-71.6%), the disease control rate (DCR) was 92.4% (95% CI: 87.5%-97.2%), and the median PFS was 11.3months (95% CI: 9.1-13.5 months), and the median OS was 32.0 months (95% CI: 26.9-37.1 months). No statistically significant difference was found in the clinicopathological characteristics between different EGFR expression types (P>0.05), while the best efficacy between different EGFR mutation groups was significantly different (P=0.040). Univariate analysis showed that EGFR mutation status in plasma ctDNA test was not correlated with PFS and OS of patients (P>0.05). Multivariate analysis showed that baseline lactate dehydrogenase (LDH) expression level, EGFR types, pleural effusion and the best curative effect might be independent factors of PFS. The patient’s N stage, bone metastasis, time to PFS and presence of EGFR T790M mutation might be independent predictors of OS. Conclusion: Icotinib as first-line treatment was effective in EGFR-mutant advanced NSCLC patients. The EGFR mutation status in plasma ctDNA test was not correlated with the clinical efficacy of patients. Bone metastasis was found to be an independent factor of worse prognosis.

Objective To quantify bradykinesia in Parkinson's disease (PD) with a Kinect depth camera-based motion analysis system and to compare PD and healthy control (HC) subjects. Methods Fifty PD patients and twenty-five HCs were recruited. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was used to evaluate the motor symptoms of PD. Kinematic features of five bradykinesia-related motor tasks were collected using Kinect depth camera. Then, kinematic features were correlated with the clinical scales and compared between groups. Results Significant correlations were found between kinematic features and clinical scales ( P

In the original publication [...]

BackgroundDecreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson’s disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well.PurposeTo evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD).MethodsThirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios.ResultsThe combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively.Conclusion131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

ObjectivesThis study analyzed the clinical and imaging characteristics of patients with cancer-related cryptogenic stroke (CCS) involving the bilateral anterior and the posterior circulations (three circulations) and evaluate the diagnostic value of clinical and imaging features for patients with cryptogenic stroke involving three circulations (CST).MethodsOf the 12,580 patients with acute ischemic stroke, 148 patients with CST from May 2017 to November 2021 were divided into the cancer group (n = 81) and the non-cancer group (n = 67). Cardiovascular risk factors, diffusion-weighted imaging patterns of cryptogenic stroke, blood routine, coagulation routine, and biochemical routine were compared between the two groups. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine associations between the two groups.ResultsCompared with the non-cancer group, the cancer group exhibited higher D-dimer levels (P < 0.001), fibrin degradation product (FDP, P < 0.001), international normalized ratio (INR, P = 0.014), neutrophil to lymphocyte ratio (NLR, P < 0.001), platelets to lymphocyte ratio (PLR, P = 0.001), activated partial thromboplastin time (APTT, P = 0.039), more frequent multiple lesions in three circulations (P < 0.001) and lower lymphocytes (P < 0.001), red blood cells (P < 0.001), and thrombin time (TT, P = 0.034). Furthermore, D-dimer [area under the curve (AUC) = 0.915, P < 0.001)], FDP (AUC = 0.923, P < 0.001), INR (AUC = 0.617, P = 0.014), NLR (AUC = 0.700, P < 0.001), PLR (AUC = 0.658, P = 0.001), and multiple lesions in three circulations (AUC = 0.786, P < 0.001) had potential diagnostic value in cryptogenic stroke. When combining these 6 parameters, the predictive power was improved (AUC = 0.949, P < 0.001).ConclusionCryptogenic stroke involving three circulations with cancer has unique clinical features, and these potential diagnostic indicators could help patients identify CCS earlier.

The atmospheric oxidation of dimethyl sulfide affects the Earth’s climate, but the intricate pathways of this complex reaction are still not fully described. Here, the authors use an optimized flash pyrolysis method for gas-phase generation of the methylthio radical to study its O2-oxidation via matrix-isolation spectroscopy, and unambiguously identify two peroxyl radical intermediates.

With the large-scaling and intensification of crude oil reserves, storage tanks are also developed in the direction of large capacity. Hence, it is easy to trigger a chain fire effect in the tank farm once a fire occurs, causing huge economic losses and even casualties. In order to reasonably design the safety distance of large crude oil storage tanks and reduce the heat radiation effect of the firing tank on the adjacent tanks, the fire of the storage tank was numerically simulated with the CFD technology. Meanwhile, the influence of the three factors, including the wind speed, spray intensity and oil burning rate, on the safety distance of large crude oil storage tanks were analyzed by controlling a single variable and designing the orthogonal working conditions. The results show that the three factors ranking in a decreasing order of influence are the spray intensity, wind speed and oil burning rate successively. To reduce the safety distance between the storage tanks, it is recommended to increase the spray intensity of cooling water. Thereby, the research results could provide guidance for the layout design of crude oil reserves.

Background: Tumor-infiltrating lymphocytes (TILs), investigated using routine hematoxylin and eosin (H&E)-stained section slides (H&E-sTILs), provide a robust prognostic biomarker in various types of solid cancer. The purpose of the present study was to investigate the prognostic significance of H&E-sTILs in patients with small cell lung cancer (SCLC). Methods: The clinical data of patients with SCLC who had been treated in our cancer center between January 2013 and October 2019 were collected and retrospectively reviewed. The H&E-sTILs were re-assessed by two experienced pathologists independently. H&E-sTILs that affected the overall survival (OS), progression free survival (PFS) and brain-metastasis free survival (BMFS) rates were explored using the Kaplan–Meier method, and the log-rank test was used to assess the differences. Multivariate analysis was subsequently performed using the Cox proportion hazards model. Results: A total of 159 patients with SCLC who fulfilled the inclusion criteria were enrolled in the current study. The OS rates at 1, 2 and 3 years were 59.8, 28.6 and 19.8%, respectively, for the whole group. The 3-year OS, PFS and BMFS rates for the H&E-sTILs(+) and H&E-sTILs(−) groups were 25.1% cf. 5.1% (P = 0.030), 14.0% cf. 4.0% (P = 0.013), and 66.0% cf. 11.4% (P = 0.023), respectively. Multivariate analyses subsequently revealed that H&E-sTILs, clinical M stage, the cycles of chemotherapy and short-term response to thoracic radiotherapy were independent factors affecting OS, whereas H&E-sTILs, clinical N stage, clinical M stage and short-term response to chemotherapy were factors affecting PFS. The H&E-sTILs affected OS, PFS and BMFS simultaneously. Conclusions: The results of this retrospective study have shown that H&E-sTILs may be considered as a prognostic biomarker affecting the short-term response to treatment, and they are the one and only risk factor for BMFS. However, due to the limitations of the nature of the retrospective design and shortcomings in visually assessing the TILs based on the H&E-stained slides, further prospective studies are required to confirm these conclusions. [ABSTRACT FROM AUTHOR]

Objective: Non‐small cell lung cancer (NSCLC) is a prevailing LC characterized by poor outcomes. AlkB homolog 5 (ALKBH5) functions as a tumor suppressor in several cancers. This study delved into the role of ALKBH5 in NSCLC development. Methods: TCGA database predicted ALKBH5 expression in NSCLC patients. ALKBH5 levels in NSCLC and human bronchial epithelial cells were determined. pcDNA3.1‐ALKBH5/NC, pcDNA3.1‐SLC7A11/NC, and ferrostatin‐1 were used to explore the interactions among ALKBH5, SLC7A11, and ferroptosis. SLC7A11 mRNA and its protein levels were measured by RT‐qPCR and Western blot. Cell viability, apoptosis, migration, and invasion were assessed by CCK‐8, flow cytometry, and Transwell. Total N6‐methyladenosine (m6A) quantification and its enrichment on SLC7A11 mRNA were determined, followed by the observation of Ki67, ALKBH5 and SLC7A11‐positive cell numbers. Glutathione (GSH), lipid reactive oxygen species (lipid‐ROS), malondialdehyde (MDA), and iron ion contents were determined. Animal experiments further analyzed the role of ALKBH5 in tumor development and glutathione peroxidase 4 (GPX4) expression. Results: Bioinformatics analysis revealed the lowly‐expressed ALKBH5 in LC patients. ALKBH5 was downregulated in NSCLC cells and its upregulation repressed proliferation activity, invasion, and migration, and facilitated apoptosis. ALKBH5 upregulation decreased GSH, increased lipid‐ROS, MDA, and iron ion contents, and downregulated SLC7A11 by reducing m6A modification. SLC7A11 upregulation partly annulled the effect of ALKBH5 overexpression on cell ferroptosis and malignant behaviors. In vivo assays elucidated the suppression of ALKBH5 upregulation on tumor development and GPX4 levels. Conclusion: ALKBH5 upregulation downregulates SLC7A11 transcription by decreasing m6A modification, thus promoting NSCLC cell ferroptosis and ultimately repressing NSCLC progression. [ABSTRACT FROM AUTHOR]

It is known that, long-distance concrete pipeline transportation often causes pipe blocking accidents. For the problem of pipeline blockage, we have invented a swirl speed-increasing device. In this study, the discrete element method was used to calibrate the parameters of the contact model through the slump bucket experiment, and a discrete element model of horizontal pumping concrete was established. Based on the particle unit, the flow-promoting mechanism of the swirl speed-increasing device was studied, and the effects of the pumping speed, the volume fraction of coarse aggregate and the wind speed output of the device on the movement state of the particles and the flow-promoting distance were analyzed. The results show that the maximum velocity and flow-promoting distance of the particle unit increase with the increase of pumping speed and wind speed, and decrease with the increase of the coarse aggregate volume fraction. When the pumping speed and wind speed are large, the installation distance of the flow promoting device should be increased. When the volume fraction of concrete aggregate is large, the installation distance of the flow promoting device should be shortened. Our swirl speed-increasing device can solve the problem of pumping concrete pipeline blockage. The discrete element model of pumping concrete established in this study can well reflect the motion state of the concrete unit in the pipeline, which verifies the applicability of the discrete element model. The numerical simulation conclusion in this paper can avoid system energy waste and pipeline blockage caused by improper selection of device installation spacing.

BackgroundAxial disturbances are the most disabling symptoms of Parkinson’s disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity.PurposeThe present research aimed to quantify the therapy–response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera.Materials and methodsWe enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman’s correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data.ResultsAll the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P < 0.001), the height of foot lift (P < 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (rs = 0.345, P = 0.022; rs = 0.382, P = 0.010; rs = 0.314, P = 0.038; rs = 0.518, P < 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (β = 0.593, 95% CI = 0.023–1.164, P = 0.042).ConclusionAxial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.

Lean burn combustor can save fuel and reduce pollutant emissions. The exit of the lean burn combustor generates strong swirling flow, which has a significant influence on the heat transfer performance of the downstream turbine. Turbine cooling systems have been designed under uniform inflow in the past, lean burn combustor pose new challenges to the design of cooling systems for downstream turbines. In this paper, the effect of swirling inflow on the film cooling effectiveness on the pressure and suction sides of the turbine was experimentally investigated, and the performance of the cylindrical film hole and water-drop shaped hole and fan shaped hole were compared. The results show that the swirling inflow makes the distribution of film uneven and reduces the average value. The swirling inflow reduces the area averaged cooling effectiveness by 5.5% under design working condition. The expanded film hole can improve the cooling effectiveness under swirling inflow. On the suction side, the fan shaped hole performs better than the water-drop shaped hole. On the pressure side, the water-drop shaped hole performs better than the fan-shaped hole. As for area averaged value, the water-drop shaped hole and fan shaped hole perform 46.6% and 51.5% improvement, respectively, compared with cylindrical hole under design working condition.