Digital inclusive finance, green technological innovation, and carbon emissions from a spatial perspective.

Based on the panel data of 276 prefecture-level cities in China from 2011 to 2020, this study explores the impact of digital inclusive finance (DIF) on carbon emissions and the intrinsic mechanism of green technological innovation from a spatial perspective by constructing a spatial econometric model, a mediating effect model, and a threshold model. The results show that DIF significantly inhibits carbon emissions, exhibiting a spatial spillover effect. The transmission mechanism from a spatial perspective shows that green technological innovation plays a partial mediating role between DIF and carbon emissions, with the mediating effect accounting for approximately 59.47%. The heterogeneity analysis suggests that the impact of DIF on the reduction of carbon emissions is more pronounced in large and medium-sized cities and eastern regions. Further discussion reveals that the carbon reduction effect of DIF is also influenced by green technological innovation and industrial structure upgrading, showing threshold effects with marginal decreases and gradual increases, respectively.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Four uncommon cycloamphilectane-type diterpenoids with antibacterial activity from the South China Sea soft coral Sinularia brassica.

The chemical investigation on the soft coral Sinularia brassica collected off Xuwen Country, Guangdong Province, China, has resulted in the isolation and characterization of three uncommon cycloamphilectane-type diterpenoids, namely sinucycloamtin A-C (1-3), along with two known analogues (5 and 6). In addition, compounds 2 and 3 were hydrolyzed and their hydrolytic derivative sinucycloamtin D (4) was obtained. The structures of these previously undescribed compounds were established on the basis of extensive spectroscopic analysis, X-ray diffraction analysis, chemical conversion, as well as the comparison with the literature reported data. Compounds 1-3 represented the first examples of benzene-containing cycloamphilectane-type diterpenoids isolated from soft coral of genus Sinularia. In the in vitro bioassays, all the isolated and derived diterpenoids exhibited significant antibacterial activities against the fish pathogenic bacteria Phoyobacterium damselae FP2244 and Streptococcus parauberis SPOF3K with MIC90 values ranging from 3.7 to 9.1 µM.

Lobosteroids A-F: Six New Highly Oxidized Steroids from the Chinese Soft Coral Lobophytum sp.

To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A-F (1-6), along with four known compounds 7-10, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,ß-α',ß'-unsaturated carbonyl, or an α,ß-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 6-10 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads.

Discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists with anti-psoriasis activity in a mouse model.

Aryl hydrocarbon receptor (AHR) is a ligand dependent transcription factor and participates in the regulation of the immune balance of Th17/22 and Treg cells. It has been found to be widely expressed in the skin, and involved in the pathology of psoriasis. Therefore, AHR is thought as a potential intervention target for psoriasis. Here, we report the discovery of 5-((1H-indazol-3-yl) methylene)-2-thioxoimidazolidin-4-one derivatives as a new class of AHR agonists. Structure-activity relationship analyses led to the identification of the most active compound, 5- ((1H-indazol-3-yl)methylene) -3- (prop-2-yn-1-yl) -2-thiooimidazolidin-4-one (24e), which exhibited an EC50 value of 0.015 µM against AHR. Mechanism of action studies showed that 24e regulated the expression of CYP1A1 by activating the AHR pathway. Topical administration of 24e substantially alleviated imiquimod (IMQ)-induced psoriasis-like skin lesion. Overall, compound 24e could be a good lead compound for drug discovery against psoriasis, and hence deserving further in-depth studies.

Gamabufotalin Induces Apoptosis and Cytoprotective Autophagy through the mTOR Signaling Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and a poor prognosis. Here, we investigated the effect and the potential antitumor mechanism of Gamabufotalin (CS-6) against HCC. Our results show that CS-6 strikingly reduced cell viability, inhibited colony formation, and promoted apoptosis in Hep3B and Huh7 cells. In vivo, CS-6 inhibited HCC xenograft tumor growth with no toxicity to normal tissues. Mechanistically, we found that CS-6 could induce cytoprotective autophagy through the mTOR-ULK1 signaling pathway through downregulation of p62 and upregulation of LC3 II/LC3 I. Meanwhile, CS-6 activated caspase-3 and PARP mediated apoptosis, and the caspase inhibitor Z-VAD-FMK blocked the CS-6-induced cell death in HCC cells. Moreover, autophagy and apoptosis were found to have antagonistic effects in Hep3B and Huh7 cells. Both the autophagy inhibitor chloroquine (CQ) and the mTOR activator MHY1485 blocked autophagy and further enhanced CS-6-induced apoptosis. Taken together, we demonstrated for the first time that CS-6 promotes apoptosis and cytoprotective autophagy through the mTOR signaling pathway in HCC, which proposes a novel strategy for HCC therapy.

A Synergetic Strategy for Brand Characterization of Colla Corii Asini (Ejiao) by LIBS and NIR Combined with Partial Least Squares Discriminant Analysis.

A synergetic strategy was proposed to address the critical issue in the brand characterization of Colla corii asini (Ejiao, CCA), a precious traditional Chinese medicine (TCM). In all brands of CCA, Dong'e Ejiao (DEEJ) is an intangible cultural heritage resource. Seventy-eight CCA samples (including forty DEEJ samples and thirty-eight samples from other different manufacturers) were detected by laser-induced breakdown spectroscopy (LIBS) and near-infrared spectroscopy (NIR). Partial least squares discriminant analysis (PLS-DA) models were built first considering individual techniques separately, and then fusing LIBS and NIR data at low-level. The statistical parameters including classification accuracy, sensitivity, and specificity were calculated to evaluate the PLS-DA model performance. The results demonstrated that two individual techniques show good classification performance, especially the NIR. The PLS-DA model with single NIR spectra pretreated by the multiplicative scatter correction (MSC) method was preferred as excellent discrimination. Though individual spectroscopic data obtained good classification performance. A data fusion strategy was also attempted to merge atomic and molecular information of CCA. Compared to a single data block, data fusion models with SNV and MSC pretreatment exhibited good predictive power with no misclassification. This study may provide a novel perspective to employ a comprehensive analytical approach to brand discrimination of CCA. The synergetic strategy based on LIBS together with NIR offers atomic and molecular information of CCA, which could be exemplary for future research on the rapid discrimination of TCM.

A noncoding regulatory RNA Gm31932 induces cell cycle arrest and differentiation in melanoma via the miR-344d-3-5p/Prc1 (and Nuf2) axis.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in inhibiting tumor cell proliferation and inducing differentiation. In this study, integrative analysis of whole transcriptome sequencing data demonstrated that lncRNA-Gm31932 is significantly decreased in all-trans retinoic acid (ATRA)-induced and sodium 4-phenylbutanoate (PB-4)-induced mouse melanoma B16 cells. Silencing lncRNA-Gm31932 could inhibit B16 cell proliferation, with cell cycle arrest at the G0/G1 phase and obvious differentiation characteristics, e.g., increased cell volume, melanin content and tyrosinase (Tyr) activity. Furthermore, a series of experiments (luciferase reporter assay, RNA pull-down assay, and western blotting) showed that lncRNA-Gm3932 down-regulated Prc1 and Nuf2 by competitively sponging miR-344d-3-5p, which subsequently reduced the expression of cell cycle-related proteins CDK2, CDC2, and Cyclin B1, and increased the expression of P21 and P27. Moreover, silencing lncRNA-Gm31932 could significantly inhibit tumor growth in B16 melanoma-bearing mice. Taken together, these results indicate that as a possible signaling pathway for ATRA and PB-4, lncRNA-Gm31932 can induce cell cycle arrest and differentiation via miR-344d-3-5p/Prc1 (and Nuf2) axis.

Identification of triazolopyridine derivatives as a new class of AhR agonists and evaluation of anti-psoriasis effect in a mouse model.

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, can regulate the immune balance of Th17/22 and Treg cells, which plays an important role in the development and maintenance of the skin barrier. We herein report the discovery of triazolopyridine derivatives as a new class of AhR agonists. Structure-activity relationship analyses led to the identification of the most active compound, 6-bromo-2-(4-bromophenyl)-[1,2,4]triazolo[1,5-a]pyridine (12a), with an EC50 (50% effective concentration) value of 0.03 nM. Compound 12a could induce rapid nuclear enrichment of AhR, trigger the transcription of downstream genes and promote skin barrier repair. Topical or oral administration of 12a could significantly alleviate imiquimod (IMQ)-induced psoriasis-like skin lesion. Considering the excellent in vivo anti-psoriasis activity as well as good pharmacokinetic properties, 12a could be a promising lead compound for drug discovery against psoriasis, and deserving further investigation.

Assessment of kidney function in chronic kidney disease by combining diffusion tensor imaging and total kidney volume.

OBJECTIVE: This study aimed to investigate the value and feasibility of combining fractional anisotropy (FA) values from diffusion tensor imaging (DTI) and total kidney volume (TKV) for the assessment of kidney function in chronic kidney disease (CKD). MATERIALS AND METHODS: Fifty-one patients were included in this study. All MRI examinations were performed with a 3.0 T scanner. DTI was used to measure FA values, and TKV was obtained from DTI and T2-weighted imaging (T2WI). Patients were divided into three groups (mild, moderate, severe) according to eGFR, which was calculated with serum creatinine. Differences in the FA values of the cortex and medulla were analysed among the three groups, and the relationships of FA values, TKV, and the product of the FA values and TKV with eGFR were analysed. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of the FA values, TKV, and the product of the FA values and TKV for kidney function in different CKD stages. RESULTS: Medullary FA values (m-FA), TKV, and the product of the m-FA values and TKV (m-FA-TKV) were significantly correlated with eGFR (r = 0.653, 0.685, and 0.797, respectively; all P < 0.001). ROC curve analysis showed that m-FA-TKV exhibited better diagnostic performance than m-FA values (P = 0.022). CONCLUSION: m-FA-TKV obtained by DTI significantly improves the accuracy of kidney function assessment in CKD patients.

Precise anatomical localization and classification of rib fractures on CT using a convolutional neural network.

OBJECTIVE: To develop a convolutional neural network (CNN) model for the detection, precise anatomical localization (right 1-12th and left 1-12th) and classification (fresh, healing and old fractures) of rib fractures automatically, and to compare the performance with the experienced radiologists. MATERIALS AND METHODS: A total of 640 rib fracture patients with 340,501 annotations were retrospectively collected from three hospitals. They consisted of a classification training dataset (n = 482), a localization training dataset (n = 30), an internal testing dataset (n = 90) and an external testing dataset (n = 38). RetinaNet with rib localization postprocessing and the result merging technique were employed to structure the CNN model. ROC curve, free-response ROC curve, AUC, precision, recall, and F1-score were calculated to choose the better option between model I (training classification and localization data together) and model II (adding an additional classification model to model I). RESULTS: The detection and classification performance of rib fractures was better in model II than in model I. The sensitivity of localization reached 97.11% and 94.87% on the right and left ribs, respectively. In the external dataset with different CT scanner and slice thickness, model II showed better diagnostic performance. Moreover, the CNN model was superior in diagnosing fresh and healing fractures to 5 radiologists and consumed shorter diagnosis time. CONCLUSIONS: Our CNN model was capable of detection, precise anatomical localization, and classification of rib fractures automatically.

Label-free fluorescence strategy for methyltransferase activity assay based on poly-thymine copper nanoclusters engineered by terminal deoxynucleotidyl transferase.

The assay of detecting DNA methyltransferase activity has been identified as one of the central challenges in cancer diagnostics as DNA methylation is closely related to the diagnosis and treatment of tumors. In this study, a label-free fluorescence probe based on poly-thymine copper nanoclusters engineered by terminal deoxynucleotidyl transferase is proposed for methyltransferase activity assay. Taking advantage of the efficient polymerization extension reaction catalyzed by terminal deoxynucleotidyl transferase and the copper nanoclusters with large Stokes shift instead of labeling fluorescent dyes, the strategy exhibits a broader linear scope from 1 to 300 U mL-1 with a detection limit of 0.176 U mL-1. The economical method is specificity for M.SssI and also provides a convenient and high-throughput platform for screening the DNA methylation inhibitors, which displays a great potential for the practical applications of the drug development and clinical cancer diagnosis in the future.

Automatic detection and classification of rib fractures based on patients' CT images and clinical information via convolutional neural network.

OBJECTIVE: To develop a convolutional neural network (CNN) model for the automatic detection and classification of rib fractures in actual clinical practice based on cross-modal data (clinical information and CT images). MATERIALS: In this retrospective study, CT images and clinical information (age, sex and medical history) from 1020 participants were collected and divided into a single-centre training set (n = 760; age: 55.8 ± 13.4 years; men: 500), a single-centre testing set (n = 134; age: 53.1 ± 14.3 years; men: 90), and two independent multicentre testing sets from two different hospitals (n = 62, age: 57.97 ± 11.88, men: 41; n = 64, age: 57.40 ± 13.36, men: 35). A Faster Region-based CNN (Faster R-CNN) model was applied to integrate CT images and clinical information. Then, a result merging technique was used to convert 2D inferences into 3D lesion results. The diagnostic performance was assessed on the basis of the receiver operating characteristic (ROC) curve, free-response ROC (fROC) curve, precision, recall (sensitivity), F1-score, and diagnosis time. The classification performance was evaluated in terms of the area under the ROC curve (AUC), sensitivity, and specificity. RESULTS: The CNN model showed improved performance on fresh, healing, and old fractures and yielded good classification performance for all three categories when both clinical information and CT images were used compared to the use of CT images alone. Compared with experienced radiologists, the CNN model achieved higher sensitivity (mean sensitivity: 0.95 > 0.77, 0.89 > 0.61 and 0.80 > 0.55), comparable precision (mean precision: 0.91 > 0.87, 0.84 > 0.77, and 0.95 > 0.70), and a shorter diagnosis time (average reduction of 126.15 s). CONCLUSIONS: A CNN model combining CT images and clinical information can automatically detect and classify rib fractures with good performance and feasibility in actual clinical practice. KEY POINTS: • The developed convolutional neural network (CNN) performed better in fresh, healing, and old fractures and yielded a good classification performance in three categories, if both (clinical information and CT images) were used compared to CT images alone. • The CNN model had a higher sensitivity and matched precision in three categories than experienced radiologists with a shorter diagnosis time in actual clinical practice.

Influence of Comorbidities on the Survival of COPD Patients According to Phenotypes.

Background: Chronic obstructive pulmonary disease (COPD) usually occurs alongside other conditions. Few studies on comorbidities have taken into account the phenotypes of COPD patients. The objective of this study is to evaluate the prevalence of comorbidities included in the Charlson index and their influence on the survival of patients with COPD, taking phenotypes into account. Methods: An observational study was conducted on a group of 273 patients who had COPD and underwent spirometry in the first half of 2011, with a median prospective follow-up period of 68.15 months. The survival of these patients was analyzed according to the presence of various comorbidities. Results: Of the 273 patients, 93 (34.1%) died within the follow-up period. An increased presence of chronic ischemic heart disease (CIHD), chronic heart failure (CHF), chronic kidney disease (CKD), and malignancy was found in deceased patients. All of these conditions shorten the survival of COPD patients globally; however, when considering phenotypes, only CHF influences the exacerbator with chronic bronchitis phenotype, CKD influences the non-exacerbator phenotype, and malignancy influences the positive bronchodilator test (BDT) and exacerbator with chronic bronchitis phenotypes. In the multivariate model, advanced age (hazard ratio, HR: 1.05; p=0.001), CHF (HR: 1.74; p=0.030), and the presence of malignancy (HR: 1.78; p=0.010) were observed as independent mortality risk factors. Conclusion: The survival is shorter in the presence of CIHD in overall COPD patients and also CHF, CKD, and malignancy for certain phenotypes. It is important to pay attention to these comorbidities in the comprehensive care of COPD patients.

Continuous butanol fermentation from inexpensive sugar-based feedstocks by Clostridium saccharobutylicum DSM 13864.

Corn stover hydrolysate (CSH) and cane molasses were studied for butanol fermentation by Clostridium saccharobutylicum DSM 13864 in continuous fermentation. Using cane molasses as substrate, solvent of 13.75 g/L (butanol 8.65 g/L) and productivity of 0.439 g/L/h were achieved in a four-stage continuous fermentation at a gradient dilution mode of 0.15-0.15-0.125-0.1 h(-1). In continuous fermentation using CSH as substrate, total solvent titer of 11.43 g/L (butanol 7.81 g/L) and productivity of 0.429 g/L/h were reached at a dilution rate of 0.15 h(-1), and the steady process was continuously operated for 220 h without compromise in solvent titer.