[Progress on historical evolution, clinical application, and pharmacological effects of Dachaihu Decoction and predictive analysis of its quality markers].

Dachaihu Decoction is a classic prescription with the function of harmonizing Shaoyang and purging away internal stasis of heat, which was specially developed by Master ZHANG Zhongjing for the concurrent disease of Shaoyang and Yangming. A large number of international studies have shown that Dachaihu Decoction has liver protection, gallbladder benefit, anti-inflammatory, and other pharmacological effects and is mostly used in modern clinical treatment of acute pancreatitis, acute cholecystitis, cholelithiasis, and other digestive diseases. This paper combined bibliography and statistics and selected the ancient book database and CNKI database to search the relevant literature on Dachaihu decoction, verify the composition and dosage, processing method, main diseases, and modern clinical application, and predict its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggest that saikosaponin a, baicalin, and 6-gingerol can be selected as potential Q-markers for Dachaihu Decoction, so as to provide a basis for the clinical research of traditional Chinese medicine and the development and application of compound preparations.

[Effect of Polyethylene Microplastics on the Microbial Community of Saline Soils].

Mulching to conserve moisture has become an important agronomic practice in saline soil cultivation, and the effects of the dual stress of salinity and microplastics on soil microbes are receiving increasing attention. In order to investigate the effect of polyethylene microplastics on the microbial community of salinized soils, this study investigated the effects of different types (chloride and sulphate) and concentrations (weak, medium, and strong) of polyethylene (PE) microplastics (1% and 4% of the dry weight mass of the soil sample) on the soil microbial community by simulating microplastic contamination in salinized soil environments indoors. The results showed that:PE microplastics reduced the diversity and abundance of microbial communities in salinized soils and were more strongly affected by sulphate saline soil treatments. The relative abundance of each group of bacteria was more strongly changed in the sulphate saline soil treatment than in the chloride saline soil treatment. At the phylum level, the relative abundance of Proteobacteria was positively correlated with the abundance of fugitive PE microplastics, whereas the relative abundances of Bacteroidota, Actinobacteriota, and Acidobacteria were negatively correlated with the abundance of fugitive PE microplastics. At the family level, the relative abundances of Flavobacteriaceae, Alcanivoracaceae, Halomonadaceae, and Sphingomonasceae increased with increasing abundance of PE microplastics. The KEGG metabolic pathway prediction showed that the relative abundance of microbial metabolism and genetic information functions were reduced by the presence of PE microplastics, and the inhibition of metabolic functions was stronger in sulphate saline soils than in chloride saline soils, whereas the inhibition of genetic information functions was weaker than that in chloride saline soils. The secondary metabolic pathways of amino acid metabolism, carbohydrate metabolism, and energy metabolism were inhibited. It was hypothesized that the reduction in metabolic functions may have been caused by the reduced relative abundance of the above-mentioned secondary metabolic pathways. This study may provide a theoretical basis for the study of the effects of microplastics and salinization on the soil environment under the dual pollution conditions.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

[Effects of Straw Biochar on Carbon Footprint of Maize Farmland Ecosystem Under Mulched Drip Irrigation in Hetao Irrigation District].

To explore the effect of biochar on greenhouse gas emissions and the carbon footprint of a corn farmland ecosystem under drip irrigation with film in an arid region, biochar treatments with different application rates[0 (CK), 15 (C15), 30 (C30), and 45 t·hm-2 (C45)] were established. The seasonal changes in soil greenhouse gases (CO2, N2O, and CH4) and their comprehensive warming potential in the maize farmland ecosystem were monitored for two consecutive years after a one-time application of biochar. The carbon emissions caused by agricultural production activities and their carbon footprint were estimated using the life cycle assessment method. Compared with that in CK, the cumulative CO2 emissions in the crop growing season decreased by 17.6%-24.7%, the cumulative N2O emissions decreased by 71.1%-110.4%, and the global warming potential decreased by 19.5%-25.9%. In the second year of the crop growing season after biochar application, the cumulative CO2 emissions were reduced by 19.2%-40.6%, the cumulative N2O emissions were reduced by 38.7-46.7%, and the comprehensive warming potential was reduced by 19.7%-40.5%. For two consecutive years, the treatment of C15 and C30 increased the cumulative absorption of CH4 to different degrees, whereas the treatment of C45 significantly decreased the cumulative absorption of CH4. C15 and C45 were the treatments with the least carbon footprint per unit yield in the current and the succeeding year of biochar application, and their carbon footprint per unit yield was 10.1% and 26.2% lower than that of CK, respectively. Soil greenhouse gas emissions showed the most contribution to the carbon footprint of the maize farmland ecosystem (38.1%-59.2%), followed by nitrogen fertilizer production (19.8%-33.4%), electric energy production (6.7%-8.8%), and plastic film mulching (4.4%-7.4%). Biochar contributed 5.7%-13.8% to the ecosystem's carbon footprint. The application of 30 t·hm-2 biochar had a better effect on carbon reduction, carbon fixation, and yield increase in the farmland ecosystem. Improving the biochar production process and transportation route, increasing nitrogen use efficiency, and developing water-saving and energy-saving irrigation technology are important ways to reduce the carbon footprint of farmland ecosystems in arid regions.

Cannabinoid receptor 2 alleviates sepsis-associated acute lung injury by modulating maturation of dendritic cells.

BACKGROUND: Dendritic cells (DCs) play a key role in a variety of inflammatory lung diseases, but their role in sepsis-associated acute lung injury (SA-ALI) is currently not been illuminated. Cannabinoid receptor 2 (CNR2) has been reported to regulate the DCs maturation. However, whether the CNR2 in DCs contributes to therapeutic therapy for SA-ALI remain unclear. In current study, the role of CNR2 on DCs maturation and inflammatory during SA-ALI is to explored. METHODS: First, the CNR2 level was analyzed in isolated Peripheral Blood Mononuclear Cells (PBMCs) and Bronchoalveolar Lavage Fluid (BALF) from patient with SA-ALI by qRT-PCR and flow cytometry. Subsequently, HU308, a specific agonist of CNR2, and SR144528, a specific antagonist of CNR2, were introduced to explore the function of CNR2 on DCs maturation and inflammatory during SA-ALI. Finally, CNR2 conditional knockout mice were generated to further confirm the function of DCs maturation and Inflammation during SA-ALI. RESULTS: First, we found that the expression of CNR2 on DCs was decreased in patient with SA-ALI. Besides, the result showed HU308 could decrease the maturation of DCs and the level of inflammatory cytokines, simultaneously reduce pulmonary pathological injury after LPS-induced sepsis in mice. In contrast of HU308, SR144528 exhibits opposite function of DCs maturate, inflammatory cytokines and lung pathological injury. Furthermore, comparing with SR144528 treatment, similar results were obtained in DCs specific CNR2 knockout mice after LPS treatment. CONCLUSION: CNR2 could alleviate SA-ALI by modulating maturation of DCs and inflammatory factors levels. Targeting CNR2 signaling specifically in DCs has therapeutic potential for the treatment of SA-ALI.

Spatiotemporal dynamics of confirmed case distribution during the COVID-19 pandemic in China: data comparison between 2020/04-2020/08 and 2021/04-2021/08.

The COVID-19 pandemic across Chinese mainland was gradually stabilized at a low level with sporadic outbreaks, before the emergence of Omicron variant. Apart from non-pharmacological interventions (NPIs), COVID-19 vaccine has also been implemented to prevent and control the pandemic since early 2021. Although many aspects have been focused, the change of the spatiotemporal distribution of COVID-19 epidemic across Chinese mainland responding to the change of prevention and control measures were less concerned. Here, we collected the confirmed case data (including domestic cases and overseas imported cases) across Chinese mainland during both 2020/04-2020/08 and 2021/04-2021/08, and then conducted a preliminary data comparison on the spatiotemporal distribution of confirmed cases during the identical period between the two years. Distribution patterns were evaluated both qualitatively by classification method and quantitatively through employing coefficient of variation. Results revealed significant differences in the homogeneity of spatiotemporal distributions of imported or domestic cases between the two years, indicating that the important effect of the adjustment of prevention and control measures on the epidemic evolution. The findings here enriched our practical experience of COVID-19 prevention and control. And, the collected data here might be helpful for improving or verifying spatiotemporally dynamic models of infectious diseases.

Green-Solvent-Processed High-Performance Broadband Organic Photodetectors.

Solution-processed organic photodetectors with broadband activity have been demonstrated with an environmentally benign solvent, ortho-xylene (o-xylene), as the processing solvent. The organic photodetectors employ a wide band gap polymer donor PBDB-T and a narrow band gap small-molecule non-fullerene acceptor CO1-4F, both dissolvable in o-xylene at a controlled temperature. The o-xylene-processed devices have shown external quantum efficiency of up to 70%, surpassing the counterpart processed with chlorobenzene. With a well-suppressed dark current, the device can also present a high specific detectivity of over 1012 Jones at -2 V within practical operation frequencies and is applicable for photoplethysmography with its fast response. These results further highlight the potential of green-solvent-processed organic photodetectors as a high-performing alternative to their counterparts processed in toxic chlorinated solvents without compromising the excellent photosensing performance.

Bupleurum scorzonerifolium: Systematic research through pharmacodynamics and serum pharmacochemistry on screening antidepressant Q-markers for quality control.

Bupleurum scorzonerifolium (BS) is one of the sources of Bupleuri Radix, which was first recorded in Shennong's classic of materia medica. It has a medicinal history of 2000 years and is now widely used for the treatment of depression clinically. However, the material basis of antidepressant effects is unclear, and the quality evaluation method is lacking. The paper aims to investigate the antidepressant quality markers (Q-markers) of BS by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Firstly, the rat depression model was established by using chronic unpredictable mild stress (CUMS) combined with the solitary confinement method to evaluate the pharmacodynamics of BS. After verification of the antidepressant effect of BS, UPLC-ESI-Q-TOF-MS was used to analyze BS and the blood components of BS. A total of 34 components were identified in BS, in which 8 components, including saikosaponin a (SSa), saikosaponin c (SSc), saikosaponin d (SSd), saikosaponin b1 (SSb1), saikosaponin b2 (SSb2), glycyrrhetinic acid, nootkatone and valerenic acid, were detected in serum. SSa, SSc, SSd, SSb1 and SSb2 were found as metabolites, and glycyrrhetinic acid, nootkatone and valerenic Acid were identified as the prototypes in the blood. The depression model of zebrafish was established with reserpine to verify the antidepressant effect of the potential eight active components. The results showed that all these components could markedly improve the depressive behavior of zebrafish, increase the content of 5-HT and reduce the cortisol content. Finally, according to the principles of effectiveness, accessibility and measurability for Q-markers, SSa, SSc, and SSd were confirmed as Q-markers of BS, and the contents of 3 Q-markers in 10 batches of BS from different origins were determined to be 0.0728-1.465%. In addition, the total contents of 3 Q-markers in BS produced in Lindian, Heilongjiang Province, were higher than those in other origins. This paper provided a reliable method for the quality evaluation of BS for depression treatment.

Intensive follow-up vs conventional follow-up for patients with non-metastatic colorectal cancer treated with curative intent: A meta-analysis.

BACKGROUND: The frequency and content of follow-up strategies remain controversial for colorectal cancer (CRC), and scheduled follow-ups have limited value. AIM: To compare intensive and conventional follow-up strategies for the prognosis of non-metastatic CRC treated with curative intent using a meta-analysis. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched for potentially eligible randomized controlled trials (RCTs) from inception until April 2023. The Cochrane risk of bias was used to assess the methodological quality of the included studies. The hazard ratio, relative risk, and 95% confidence interval were used to calculate survival and categorical data, and pooled analyses were performed using the random-effects model. Additional exploratory analyses were performed for sensitivity, subgroups, and publication bias. RESULTS: Eighteen RCTs involving 8533 patients with CRC were selected for the final analysis. Intensive follow-up may be superior to conventional follow-up in improving overall survival, but this difference was not statistically significant. Moreover, intensive follow-up was associated with an increased incidence of salvage surgery compared to conventional follow-up. In addition, there was no significant difference in the risk of recurrence between intensive and conventional follow-up strategies, whereas intensive follow-up was associated with a reduced risk of interval recurrence compared to conventional follow-up. Finally, the effects of intensive and conventional follow-up strategies differed when stratified by tumor location and follow-up duration. CONCLUSION: Intensive follow-up may have a beneficial effect on the overall survival of patients with non-metastatic CRC treated with curative intent.

Gasdermin D is involved in switching from apoptosis to pyroptosis in TLR4-mediated renal tubular epithelial cells injury in diabetic kidney disease.

BACKGROUND: Toll-like receptor 4 (TLR4) mediated pathway plays a pivotal role in promoting tubulointerstitial inflammation and contributes to the progression in type 2 diabetic kidney disease (T2DKD). As the first identified key pyroptosis executor, gasdermin D (GSDMD) is activated by caspases and might be the key protein to switch apoptosis to pyroptosis. It remains unclear that role of TLR4 on canonical pyroptosis pathway, and whether GSDMD is involved in switching from apoptosis to pyroptosis in the TLR4-related tubular injury in T2DKD. METHODS: Immunohistochemistry staining was used to detect the expression of pyroptosis-related proteins in renal tissues of T2DKD patients. T2DKD models was induced in TLR4 knockout (TLR4-/-) mice through a high-fat diet combined with streptozotocin. Pyroptosis (caspase-1, GSDMD, interleukin 18(IL-18), interleukin 1ß(IL-1ß)) and apoptosis levels (caspase-3, Bax and Bcl-2) were detected by Western blot. HK-2 cells were cultured under high-glucose (HG) conditions as an in vitro model and then challenged with a TLR4-specific antagonist (TAK-242). GSDMD small interfering RNA (siRNA) and overexpression plasmid were transfected into HK-2 cells to down- or up-regulate GSDMD. The pyroptosis and apoptosis rates were determined by flow cytometry. RESULTS: The expression levels of caspase-1, GSDMD, IL-18 and IL-1ß were increased in renal biopsy tissues of T2DKD patients and GSDMD expression was positively correlated with tubular injury. Silencing GSDMD attenuated HG-induced IL-18, IL-1ß, FN and α-SMA, and reduced pyroptotic cells rate in HK-2 cells. Up-regulation of GSDMD inhibited HG-induced expression of Bax and cleaved caspase-3 and reduced apoptosis rate. TLR4 knockout alleviated tubular injury and interstitial macrophages infiltration, improved impaired renal dysfunction, and decreased the expressions of active N-terminal of GSDMD(GSDMD-N), cleaved caspase-1(cl-caspase-1) and cleaved caspase-3(cl-caspase-3) in T2DKD mice. TLR4 inhibition reduced HG-induced pyroptosis and apoptosis level in HK-2 cells, while GSDMD up-regulation increased pyroptosis rate and decreased apoptosis rate. CONCLUSIONS: TLR4 could exacerbate tubular injury and fibrosis via GSDMD-mediated canonical pyroptosis pathway in T2DKD. Activation of GSDMD could inhibit apoptosis and activate pyroptosis, which may involve the potential switch mechanism between TLR4-mediated pyroptosis and apoptosis in T2DKD.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Exploring the Scientific Rationality of the Phenomenon of "Different Dosage Forms of the Same Prescription" of Chinese Proprietary Medicine Based on Biopharmaceutical Properties of Powder and Pill of Chuanxiong Chatiao Prescription.

Background: The 2020 edition of the Pharmacopoeia of the People's Republic of China (Chinese Pharmacopoeia 2020 edition) has 255 Chinese prescriptions with different dosage forms, accounting for 21.09% of the total prescriptions (1,209) in Chinese Pharmacopoeia 2020 edition. However, the scientific rationality of the phenomenon of "Different Dosage Forms of the Same Prescription" of Chinese proprietary medicine has been less explored. Based on the dosage form theory of "components in pills release slowly and take effect in slow-acting manner, while in powders release quickly and take effect in fast-acting way," we provided the in vitro dissolution experiment and in vivo pharmacokinetics of Chuanxiong Chatiao powders and pills in order to rationalize the phenomenon of "Different Dosage Forms of the Same Prescription" of Chuanxiong Chatiao prescription. Materials and Methods: Chuanxiong Chatiao powders and pills were prepared in the laboratory referring to the preparation methods in the Chinese Pharmacopoeia 2020 edition, and the contents of tetramethylpyrazine, ferulic acid, nodakenin, and isoimperatorin were determined by the external standard method. We measured the in vitro dissolution of four analytes of Chuanxiong Chatiao powders and pills according to the second method for dissolution determination (paddle method) in the Chinese Pharmacopoeia 2020 edition, and their corresponding contents in each sampling point were determined by LC-MS/MS. We also provided a pharmacokinetic study of Chuanxiong Chatiao powders and pills. Six female domestic rabbits were divided into two groups (powder and pill groups) and given Chuanxiong Chatiao powders and pills (9.85 g/kg) by surgical administration separately. Blood samples were collected at 5, 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720, and 1,440 min after drug administration to measure the plasma concentration of the four analytes by LC-MS/MS. Results: The results of in vitro dissolution experiment showed that the dissolution rate of four analytes in the powder group was greater than that of the pill group. However, the solubilities of tetramethylpyrazine and isoimperatorin were very low in the powder and pill, which may be related to their low solubility properties. The results of the in vivo pharmacokinetic study of Chuanxiong Chatiao powders and pills showed that T max (h) of ferulic acid and nodakenin in the powder group was 0.420 and 0.053 times that of the pill group and t 1/2 (h) of ferulic acid, nodakenin, and isoimperatorin of the powder group was 0.910, 0.262, and 0.661 times that of the pill group, respectively. Conclusion: The in vitro dissolution rate and in vivo pharmacokinetic parameters of four analytes in CXCTF could partly explain the scientific rationality of the classic theory of ", " as in Chinese, which is helpful for providing a basis for the comparison of subsequent dosage forms. The results of our studies also suggest the complexity of the design of dosage forms of Chinese proprietary medicines and imply that we should pay more attention to the scientific rationality of the phenomenon of "Different Dosage Forms of the Same Prescription."

Targeting the PDGF/PDGFR signaling pathway for cancer therapy: A review.

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are expressed in a variety of tumors. Activation of the PDGF/PDGFR signaling pathway is associated with cancer proliferation, metastasis, invasion, and angiogenesis through modulating multiple downstream pathways, including phosphatidylinositol 3 kinase/protein kinase B pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Therefore, targeting PDGF/PDGFR signaling pathway has been demonstrated to be an effective strategy for cancer therapy, and accordingly, some great progress has been made in this field in the past few decades. This review will focus on the PDGF isoforms and their binding with the related PDGFRs, the PDGF/PDGFR signaling and regulation, and especially present strategies and inhibitors developed for cancer therapy, and the related clinical benefits and side effects.

A Deeply Supervised Convolutional Neural Network for Pavement Crack Detection With Multiscale Feature Fusion.

Automatic crack detection is vital for efficient and economical road maintenance. With the explosive development of convolutional neural networks (CNNs), recent crack detection methods are mostly based on CNNs. In this article, we propose a deeply supervised convolutional neural network for crack detection via a novel multiscale convolutional feature fusion module. Within this multiscale feature fusion module, the high-level features are introduced directly into the low-level features at different convolutional stages. Besides, deep supervision provides integrated direct supervision for convolutional feature fusion, which is helpful to improve model convergency and final performance of crack detection. Multiscale convolutional features learned at different convolution stages are fused together to robustly represent cracks, whose geometric structures are complicated and hardly captured by single-scale features. To demonstrate its superiority and generalizability, we evaluate the proposed network on three public crack data sets, respectively. Sufficient experimental results demonstrate that our method outperforms other state-of-the-art crack detection, edge detection, and image segmentation methods in terms of F1-score and mean IU.

Predictive value of sub classification of focal segmental glomerular sclerosis in Oxford classification of IgA nephropathy.

BACKGROUND: The Oxford classification of IgA nephropathy (IgAN) was revised in 2016 which lacked sufficient evidence for prognostic value of subclassification of focal segmental glomerular sclerosis (S lesion), and the proper proportion of S lesion for subclassification remains undetermined. AIM: This study aimed to explore the predictive value of the new subclassification of S score on renal outcomes of IgAN patients. METHODS: 348 patients with IgAN-associated S lesion were enrolled. According to the optimal cut-off of 25% established by receiver operating characteristic (ROC) curves, we divided S1 patients into two groups: S1a group (S lesion < 25%) and S1b group (S lesion ≥ 25%). IgAN patients with mild lesion (M0E0S0T0C0) were set as the control group. The clinical features at renal biopsy, pathological findings, and follow-up parameters (follow-up time ranged from 1 to 5 years) were collected. We used univariate and multivariate analyses to assess whether the subclassification of S score could refine risk prediction and clinical utility. RESULTS: We demonstrated that S lesion ≥ 25% was associated with a more rapid GFR loss and a lower rate of complete remission of proteinuria even adjusted for multiple clinic pathological variables, compared to S1a group (All p values <.05). And the ratio of glomeruli with T lesion and crescents were higher in patients with S lesion ≥ 25%. Data showed that IgAN patients with S lesion ≥ 25% were at an increased risk of poor renal outcomes even with immunosuppression. CONCLUSION: This study might recommend new subclassification of S scores (S0 (no S lesion), S1 (S lesion <25% of glomeruli), and S2 (S lesion ≥ 25% of glomeruli)) for the Oxford classification. This model may also help to evaluate pros and cons of immunosuppressive therapy in IgAN patients with different level of S lesion.KEY MESSAGESS lesion ≥ 25% is an independent risk factor for poor renal outcome in IgAN patients.This new subclassification of S scores may help to evaluate pros and cons of immunotherapy in IgAN patients with different level of S lesion.

An Unordered Image Stitching Method Based on Binary Tree and Estimated Overlapping Area.

Aiming at the complex computation and time-consuming problem during unordered image stitching, we present a method based on the binary tree and the estimated overlapping areas to stitch images without order in this paper. For image registration, the overlapping areas between input images are estimated, so that the extraction and matching of feature points are only performed in these areas. For image stitching, we build a model of the binary tree to stitch each two matched images without sorting. Compared to traditional methods, our method significantly reduces the computational time of matching irrelevant image pairs and improves the efficiency of image registration and stitching. Moreover, the stitching model of the binary tree proposed in this paper further reduces the distortion of the panorama. Experimental results show that the number of extracted feature points in the estimated overlapping area is approximately 0.3∼0.6 times of that in the entire image by using the same method, which greatly reduces the computational time of feature extraction and matching. Compared to the exhaustive image matching method, our approach only takes about 1/3 of the time to find all matching images.

Potential suppressive functions of microRNA-504 in cervical cancer cells malignant process were achieved by targeting PAICS and regulating EMT.

PURPOSE: The present study aimed to investigate the effects of miR-504 in cervical cancer. METHODS: Normal and cervical cancer tissue specimens derived from TCGA and GTEx databases were employed to analyze the miR-504 and PAICS (one of potential target gene of miR-504) expression. Kaplan-Meier strategy was applied to analyze the prognostic powers of miR-504 and PAICS. The proliferation, clonogenic ability, invasion, and migration of cervical cancer cells (C-33A and HeLa) were detected using Cell Counting Kit 8, colony formation, and transwell assays. Pearson correlation analysis was used to assess the correlation between miR-504 and PAICS, which was confirmed using luciferase reporter assay. The mRNA and protein levels were detected by qRT-PCR and western blot, respectively. RESULTS: TCGA data revealed that miR-504 expression might be decreased in cervical cancer, which was correlated with unfavorable prognosis. Further experiments exhibited that abnormal miR-504 expression negatively affected malignant cellular behaviors in cervical cancer, including proliferation, colony formation, invasion, and migration. PAICS was identified as a putative target of miR-504, and negatively related with miR-504 expression. PAICS expression was increased in cervical cancer and its high-regulation-induced worse outcomes of patients with cervical cancer. Rescue experiments indicated that PAICS restricted the impacts of miR-504 in cervical cancer cells. Analysis of western blot suggested that overexpression of PAICS overturned the miR-504-induced EMT inactivation. CONCLUSION: Our observations elucidated that miR-504, acting as a suppressor for the progression of cervical cancer, inhibits cell proliferation, invasion and migration, and mediates EMT via negatively regulating PAICS.

TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease.

Gasdermin D (GSDMD) has been proven to be a key protein in the activation of pyroptosis. Pyroptosis of renal tubular epithelial cells contributes to the progression of tubular injury in kidney diseases. However, it remains elusive whether and how GSDMD is involved in the regulation of diabetic kidney disease (DKD). In this study, we found that tubular injury is accompanied by the up-regulation of Toll-like receptor 4 (TLR4) and GSDMD in patients with diabetic kidney disease. In addition, we discovered that the expressions of cleaved Caspase-1, active N-terminal fragments of GSDMD (GSDMD-NT), IL-18, and the secretion of IL-1ß also increased in the kidneys of db/db mice. These changes were partially ameliorated following intraperitoneal injection of TAK-242, an inhibitor of TLR4. Similar results were observed in human tubular cells (HK-2) subjected to high-glucose (HG) conditions and treated with TAK-242 or parthenolide (inhibitor of NF-κB) by Western blot, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry. These results indicated that TLR4/NF-κB signaling could induce GSDMD-mediated pyroptosis in tubular cells in DKD.

An algorithm of image mosaic based on binary tree and eliminating distortion error.

The traditional image mosaic result based on SIFT feature points extraction, to some extent, has distortion errors: the larger the input image set, the greater the spliced panoramic distortion. To achieve the goal of creating a high-quality panorama, a new and improved algorithm based on the A-KAZE feature is proposed in this paper. This includes changing the way reference image are selected and putting forward a method for selecting a reference image based on the binary tree model, which takes the input image set as the leaf node set of a binary tree and uses the bottom-up approach to construct a complete binary tree. The root node image of the binary tree is the ultimate panorama obtained by stitching. Compared with the traditional way, the novel method improves the accuracy of feature points detection and enhances the stitching quality of the panorama. Additionally, the improved method proposes an automatic image straightening model to rectify the panorama, which further improves the panoramic distortion. The experimental results show that the proposed method cannot only enhance the efficiency of image stitching processing, but also reduce the panoramic distortion errors and obtain a better quality panoramic result.

Cyclometalated Ir(iii) complexes [Ir(tpy)(bbibH2)Cl][PF6] and [Ir(tpy)(bmbib)Cl][PF6]: intramolecular ππ interactions leading to facile synthesis and enhanced luminescence.

Cyclometalated Ir(iii) complexes [Ir(tpy)(bbibH2)Cl][PF6] (1·PF6) and [Ir(tpy)(bmbib)Cl][PF6] (2·PF6), and the control complex [Ir(tpy)(mbib)Cl][PF6] (3·PF6) were synthesized at 135 °C for 10 hours for the former two complexes, while at 190 °C for 24 hours for the latter complex, in which the cyclometalated ligands bbibH2-, bmbib- and mbib- incorporate one or two N-methylbenzoimidazole/benzimidazole units in order to explore the influence of the molecular structures of these complexes on their synthesis conditions and luminescence behaviors. The 1H NMR and crystal structure measurements indicate that both 1·PF6 and 2·PF6 contain intramolecular ππ stacking interactions between the non-coordinated N-methylbenzoimidazole/benzimidazole unit and the tpy ligand, but there are no such ππ interactions in 3·PF6. At room temperature, these complexes in CH3CN reveal an emission with a combination of 3MLCT and 3LC characteristics, occurring at 534 nm with a quantum yield Φ = 39.5% and a lifetime τ = 2.39 µs for 1·PF6, 536 nm with Φ = 66.4% and τ = 2.94 µs for 2·PF6, and 558 nm with Φ = 27.0% and τ = 1.75 µs for 3·PF6. Moreover, both 1·PF6 and 2·PF6 exhibit a TFA-induced luminescence decrease. Based on the comparison among 1·PF6, 2·PF6 and 3·PF6, we discuss the influence of intramolecular ππ interactions and Nimidazole-H/Nimidazole-CH3 units in 1·PF6 and 2·PF6 on their syntheses and luminescence.