Clinical Evaluation of Cystic Renal Masses With Bosniak Classification by Contrast-Enhanced Ultrasound and Contrast-Enhanced Computer Tomography.

OBJECTIVES: The study aims to compare retrospectively three clinically applied methods for the diagnostic performance of cystic renal masses (CRMs) by contrast-enhanced ultrasound (CEUS) and contrast-enhanced computer tomography (CECT) with Bosniak classification system. METHODS: A total of 52 cases of Bosniak II-IV CRMs in 49 consecutive patients were diagnosed from January 2013 to July 2022 and their data were analyzed. All patients had been subjected to CEUS and CECT simultaneously. Pathological diagnoses and masses stability were used as standard references to determine whether lesions were malignant or benign. Then 49 CRMs only with pathologic results were classified into group 1 and 2. RESULTS: A total of 52 CRMs in 49 enrolled patients were classified into 8 category II, 16 category IIF, 15 category III, and 13 category IV by CEUS (EFSUMB 2020), 10 category II, 13 category IIF, 16 category III, and 13 category IV by CEUS (V2019), while 15 category II, 9 category IIF, 13 category III, and 15 category IV by CECT (V2019). Pathological results and masses stability longer than 5 years follow-up performed substantially for CEUS (EFSUMB 2020), CEUS (V2019), and CECT (V2019) (kappa values were 0.696, 0.735, and 0.696, respectively). Among 49 pathologic approving CRMs, wall/septation thickness ≥4 mm, wall/septation thickness, presence of enhancing nodule and the diameter were found to be statistically significant for malignancy. Twenty-two malignant masses were correctly diagnosed by CEUS (V2019), while 21 malignant masses were both correctly diagnosed by CEUS (EFSUMB 2020) and CECT (V2019), and 1 mass was misdiagnosed. CONCLUSIONS: Bosniak classification of EFSUMB 2020 version might be as accurate as version 2019 CEUS and version 2019 CECT in diagnosing CRMs, and CEUS is found to have an excellent safety profile in dealing with clinical works.

Characteristics and risk assessment of sewage sludge from urban wastewater treatment plants in Shaanxi Province, China.

In this study, an investigation of important properties, including moisture content, pH, plant nutrients, organic matter, mineral oil, and the contents of heavy metals (HMs) in sewage sludge (SS) collected from 32 urban treatment plants in Shaanxi Province, China, was carried out. The test results showed that the pH and the moisture, organic matter, total nitrogen (TN), total phosphorus (TP), and mineral oil contents of the SS varied over different rainfall periods, and most of the indicators met the standard criteria for SS agricultural reuse in China. Principal component analysis (PCA) and correlation analysis indicated that the pollutant characteristics of the SS depended on time span and geographical distribution. The mean contents of Pb, Cd, Cu, Zn, Ni, Cr, Hg, and As in SS were 3.95, 16.38, 5.43, 7.70, 1.31, 1.53, 32.77, and 1.40 times higher than the soil background values, respectively. Speciation analysis showed that the forms of HMs in the SS were significantly different. Assessments based on the geoaccumulation index (Igeo), Nemerow integrated pollution index (NIPI), and potential ecological risk index (RI) suggested that HM pollution risk levels were either uncontaminated or moderately contaminated in some regions and that SS recycled for agricultural applications carried a low risk. In conclusion, certain potential ecological risks exist for SS agricultural utilization in Shaanxi Province, and it is necessary to reduce the HM content before SS resource utilization for land application.

Cd-Based Metal-Organic Framework for Selective Turn-On Fluorescent DMSO Residual Sensing.

Dimethyl sulfoxide (DMSO) is a universally used solvent in various synthetic reactions, and trace amounts of DMSO residual are often seen on the surface of chemical product. It is difficult to quickly determine whether the residual DMSO is washed completely. This work reports a CdII metal-organic framework (MOF) SXU-4 which can detect trace amounts of DMSO in various solvents. Fluorescence experiments reveal its turn-on fluorescence effect toward DMSO with high selectivity and sensitivity, indicating that it can be used as an effective luminescent probe for rapid chemical product purity detection by testing the washing solution. Crystallographically characterized DMSO loaded SXU-4 (DMSO@SXU-4), in combination with computational results uncover that the enhanced DMSO-MOF conjugation through multiple DMSO-MOF supramolecule interactions and charge rearrangement are the main causes of fluorescence intensification.

The effect of two endodontic sealers and interval before post-preparation and cementation on the bond strength of fiber posts.

OBJECTIVES: To evaluate the effect of different endodontic sealers (epoxy resin-based and bioceramic-based) and the time of post-cementation on the bond strength of a fiber post cemented with resin cement. METHODS: Forty human premolars were instrumented and divided into 4 groups. According to the type of sealer and the time of post-cementation: AH-IM (AH Plus, post-cemented immediately after root canal treatment), SP-IM (iRoot SP, post-cemented immediately after root canal treatment), AH-OW (AH Plus, post-cementation after one week), and SP-OW (iRoot SP, post-cementation after one week). In each group, the samples were submitted to push-out test, and failure mode was assessed. Levene's test, one-way ANOVA, and Kruskal-Wallis analysis were applied for statistical analysis (α = 5%). RESULTS: The highest mean push-out bond strength was obtained from the SP-IM group in the apical part (10.45 ± 5.15MPa), while the lowest was observed in samples from the AH-OW group in the middle part (2.63 ± 1.54 MPa). One-way ANOVA showed that within the same root region, the time of post-cementation had a negative influence on the bonding strength in the SP groups in the middle and apical portion (P<0.05), however, when comparing the effect of type of sealers on bonding strength between the OW groups or IM groups within the same root region, no significant difference was observed regardless of the post cementation time (P>0.05). CONCLUSIONS: The bond strength of the fiber post was higher when the post was cemented immediately after root canal treatment when the bioceramic sealer was applied. CLINICAL RELEVANCE: The correct choice of an endodontic sealer and the proper time of post-cementation may help to obtain the best quality of post-and-core restoration.

TAI-SARNET: Deep Transferred Atrous-Inception CNN for Small Samples SAR ATR.

Since Synthetic Aperture Radar (SAR) targets are full of coherent speckle noise, the traditional deep learning models are difficult to effectively extract key features of the targets and share high computational complexity. To solve the problem, an effective lightweight Convolutional Neural Network (CNN) model incorporating transfer learning is proposed for better handling SAR targets recognition tasks. In this work, firstly we propose the Atrous-Inception module, which combines both atrous convolution and inception module to obtain rich global receptive fields, while strictly controlling the parameter amount and realizing lightweight network architecture. Secondly, the transfer learning strategy is used to effectively transfer the prior knowledge of the optical, non-optical, hybrid optical and non-optical domains to the SAR target recognition tasks, thereby improving the model's recognition performance on small sample SAR target datasets. Finally, the model constructed in this paper is verified to be 97.97% on ten types of MSTAR datasets under standard operating conditions, reaching a mainstream target recognition rate. Meanwhile, the method presented in this paper shows strong robustness and generalization performance on a small number of randomly sampled SAR target datasets.

AidB, a Novel Thermostable N-Acylhomoserine Lactonase from the Bacterium Bosea sp.

Many Gram-negative bacteria employ N-acylhomoserine lactones (AHLs) as quorum-sensing (QS) signal molecules to regulate virulence expression in a density-dependent manner. Quorum quenching (QQ) via enzymatic inactivation of AHLs is a promising strategy to reduce bacterial infections and drug resistance. Herein, a thermostable AHL lactonase (AidB), which could degrade different AHLs, with or without a substitution of carbonyl or hydroxyl at the C-3 position, was identified from the soil bacterium Bosea sp. strain F3-2. Ultrahigh-performance liquid chromatography analysis demonstrated that AidB is an AHL lactonase that hydrolyzes the ester bond of the homoserine lactone (HSL) ring. AidB was thermostable in the range 30 to 80°C and showed maximum activity after preincubation at 60°C for 30 min. The optimum temperature of AidB was 60°C, and the enzyme could be stably stored in double-distilled water (ddH2O) at 4°C or room temperature. AidB homologs were found only in Rhizobiales and Rhodospirillales of the Alphaproteobacteria AidB from Agrobacterium tumefaciens and AidB from Rhizobium multihospitium (with amino acid identities of 50.6% and 52.8% to AidB, respectively) also showed thermostable AHL degradation activity. When introduced into bacteria, plasmid-expressed AidB attenuated pyocyanin production by Pseudomonas aeruginosa PAO1 and the pathogenicity of Pectobacterium carotovorum subsp. carotovorum Z3-3, suggesting that AidB is a potential therapeutic agent by degrading AHLs.IMPORTANCE A quorum-sensing system using AHLs as the signal in many bacterial pathogens is a critical virulence regulator and an attractive target for anti-infective drugs. In this work, we identified a novel AHL lactonase, AidB, from a soil bacterial strain, Bosea sp. F3-2. The expression of aidB reduced the production of AHL signals and QS-dependent virulence factors in Pseudomonas aeruginosa and Pectobacterium carotovorum The homologs of AidB with AHL-degrading activities were found only in several genera belonging to the Alphaproteobacteria Remarkably, AidB is a thermostable enzyme that retained its catalytic activity after treatment at 80°C for 30 min and exhibits reliable storage stability at both 4°C and room temperature. These properties might make it more suitable for practical application.

A Millimeter-Scale Snail Robot Based on a Light-Powered Liquid Crystal Elastomer Continuous Actuator.

Crawling by means of the traveling deformation of a soft body is a widespread mode of locomotion in nature-animals across scales, from microscopic nematodes to earthworms to gastropods, use it to move around challenging terrestrial environments. Snails, in particular, use mucus-a slippery, aqueous secretion-to enhance the interaction between their ventral foot and the contact surface. In this study, a millimeter-scale soft crawling robot is demonstrated that uses a similar mechanism to move efficiently in a variety of configurations: on horizontal, vertical, as well as upside-down surfaces; on smooth and rough surfaces; and through obstacles comparable in size to its dimensions. The traveling deformation of the robot soft body is generated via a local light-induced phase transition in a liquid crystal elastomer and resembles the pedal waves of terrestrial gastropods. This work offers a new approach to micro-engineering with smart materials as well as a tool to better understand this mode of locomotion in nature.

[The present situation and countermeasures of Uighur medicine compound].

Uighur medicine compound, which created and used by Uighur nationality, is under the guidance of the Uighur medical theory system of herbal formula and dialectical use of minority nationality conventional medicines. In recent years, Uighur medicine attracted more and more attention of people which have used and were using it. Combining the history of Uighur medicine, this article summarizes the Uighur resources, medicinal materials, drugs preparation, ancient documents, and the establishment of the clinical evaluation system and so on, and then analyzes the status quo and the existing problems in Uighur medicine compound research and industry. On this basis, we put forward countermeasures and suggestions for the development of Uighur medicine.

Frequency steps and compositions determine properties of nee- dling sensation during electroacupuncture.

OBJECTIVE: To investigate the relationship of electro-parameters and the electroacupuncture sensation (EAS), which is thought to be an important factor for optimal treatment. METHODS: The frequency steps and compositions of three frequently used electrical stimulations were set when the switch of the electroacupuncture apparatus was turned to the second or third grade of the dense-disperse frequency wave (DD2 and DD3, respectively) or the second grade of the continuous wave (C2). Three groups of patients according to the three electroacupuncture stimulations were divided again into three sub-groups according to the stimulated acupoints: the face acupoint Quanliao (SI 18), the upper-limb acupoint Quchi (LI 11) and the back acupoint Dachangshu (BL 25). The EAS values were measured every 5 min during 30 min electroacupuncture treatments using a visual analogue scale. RESULTS: The frequency compositions of the three electroacupuncture stimulations were 3.3 and 33 Hz, 12.5 and 66.7 Hz, and 3.3 and 3.3 Hz; each frequency step was 30, 54 and 0 Hz, respectively. In each sub-group of the C2 group, the EAS values from 10 to 30 min were significantly weaker than at 0 min. The sensation fluctuations in the DD2 and DD3 groups were different during the 30 min. CONCLUSION: The greater the frequency step of the electroacupuncture stimulation, the longer the needling sensation lasted. The electroacupuncture stimulations of the DD3 group were unsuitable for the facial acupoint because of its painful and uncomfortable EAS, but more suitable for the back acupoint.

Aggregation-Induced Emission Luminogens: A New Possibility for Efficient Visualization of RNA in Plants.

RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants' spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid-liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.

Caffeic-Acid-Functionalized MWCNTs and PEDOT:PSS Formed Composite Flexible Films with "Reinforced Concrete" Structure for Electrical Heating and EMI Shielding.

Nowadays, flexible multifunctional composites are attracting much attention and are practically being used in various emerging electronic devices. However, most composites suffer from the disadvantages of high loadings of conductive fillers, complicated preparation processes, and low energy conversion efficiency. In this article, Caffeic acid-modified multiwalled carbon nanotubes (C-MWCNTs)/poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS)/polyimide (PI) composite films (CPFs) were prepared using a simple layer-by-layer deposition method. The "reinforced concrete" structure of the C-MWCNTs/PEDOT:PSS layer ensures high electrical conductivity of the film, while the PI layer provides excellent mechanical properties (72.69 MPa). The composite film exhibits excellent electrothermal response and thermal stability up to approximately 125 °C at 5 V. In addition, the good conductivity of the film provides its electromagnetic shielding effectiveness (32.69 dB). With these advantages, we expect that flexible CPFs will be widely utilized in wearable devices, electromagnetic interference (EMI) shielding applications, and thermal management of personal or electronic devices.

MXene and AgNW based flexible transparent conductive films with sandwich structure for high-performance EMI shielding and electrical heaters.

With the popularization of 5G technology and the development of science and technology, flexible and transparent conductive films (TCF) are increasingly used in the preparation of optoelectronic devices such as electromagnetic shielding devices, transparent flexible heaters, and solar cells. Silver nanowires (AgNW) are considered the best material for replacing indium tin oxide to prepare TCFs due to their excellent comprehensive properties. However, the loose overlap between AgNWs is a significant reason for the high resistance. This article investigates a sandwich structured conductive network composed of AgNW and Ti3C2Tx MXene for high-performance EMI shielding and transparent electrical heaters. Polyethylene pyrrolidone (PVP) solution was used to hydrophilic modify PET substrate, and then MXene, AgNW, and MXene were assembled layer by layer using spin coating method to form a TCF with a sandwich structure. One-dimensional AgNW is used to provide electron transfer channels and improve light penetration, while two-dimensional MXene nanosheets are used for welding AgNWs and adding additional conductive channels. The flexible TCF has excellent transmittance (85.1 % at 550 nm) and EMI shielding efficiency (27.1 dB). At the voltage of 5 V, the TCF used as a heater can reach 85.6 °C. This work offers an innovative approach to creating TCFs for the future generation.

Liver metabolomic characteristics in three different rat models of deficiency based on ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

OBJECTIVE: To investigate the mechanism of deficiency syndrome (YDS) by analyzing the liver metabolomic characteristics of three different deficiency rat models METHODS: Following the TCM etiology, for clinical features and pathological manifestations of modern medicine, three kinds of animal models of deficiency were induced and replicated. Totally 48 Sprague-Dawley (SD) male rats were randomly divided into blank group, irritation induced model group, Fuzi-Ganjiang induced model group, and thyroxine-reserpine induced model group. After successful development of model, the ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was carried out to detect metabolites in each group. The metabolites of rat liver were analyzed for the characteristics of their biomarkers. The pathway enrichment analysis and metabolic network construction were performed through various online databases including Metabolite Biology Role, Human Metabolome Database, MetaboAnalyst, and Kyoto Encyclopedia of Genes and Genomes. RESULTS: The SD rats in the experimental group showed symptoms like less weight gain, reduced diet and water intake, high body temperature, increased liver and kidney indexes, and abnormal liver and kidney tissue morphology. Moreover, the rats showed high increased levels of serum cyclic adenosine monophosphate, estradiol, alanine transaminase, and aspartate aminotransferase and decreased levels of cyclic guanosinc monophosphate and testosterone. We found four key interrelated metabolic pathways in the liver tissue metabolomics, including the biosynthesis of pantothenic acid and coenzyme A, and metabolism of alpha-linolenic acid metabolism, glycerophospholipid metabolism, and sphingolipid. CONCLUSION: The liver and kidney YDS is closely related to the biosynthesis of pantothenic acid and CoA and abnormal metabolism of α-linolenic acid, glycerophospholipid, and sphingolipid in SD rats.

High-Throughput, Quantitative Screening of Quorum-Sensing Inhibitors Based on a Bacterial Biosensor.

Quorum sensing (QS) is a cell-cell communication mechanism by which bacteria synchronize social behaviors such as biofilm formation and virulence factor secretion by producing and sensing small molecular signals. Quorum quenching (QQ) by degrading signals or blocking signal transmissions has become a promising strategy for disrupting QS and preventing bacterial infection and biofilm formation. However, studies of high-throughput screening and identification approaches for quorum-sensing inhibitors (QSIs) are still inadequate. In this work, we developed a sensitive, high-throughput approach for screening QSIs based on the bacterial biosensor strain Agrobacterium tumefaciens N5 (pBA7P), which contains a traG gene promoter induced by QS signals fused with a promoterless ß-lactamase gene reporter. Using this approach, we identified 31 QQ bacteria from ∼2000 soil bacterial isolates, some belonging to the genera Bosea, Cupriavidus, and Flavobacterium that have not been reported previously as QQ bacteria. We also identified four QS inhibitory compounds and one QS signal analogue from ∼5000 small-molecule compounds, which profoundly affected the expression of QS-regulated genes and phenotypes of the pathogenic bacteria. This high-throughput screening system is effective and sensitive for screening of both QQ microbes and small molecules, enabling the discovery of a wide variety of biocompatible compounds.

Effectiveness of Traditional Chinese Medicine on coronavirus disease 2019 in 92 patients: a retrospective study.

OBJECTIVE: To investigate the antipyretic effect of early treatment with Traditional Chinese Medicine (TCM) on coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed 369 patients from January 26th, 2020 to April 15th, 2020, who had been diagnosed with COVID-19. Among 92 eligible cases, 45 cases were identified as treatment group Ⅰ ( 45) and 47 cases were identified as treatment group Ⅱ. Patients in the treatment group Ⅰ were treated with TCM herbal decoction within 5 d after admission. Patients in the treatment group Ⅱ were treated with TCM herbal decoction after the 6th admission day. The onset time of antipyretic effect, the antipyretic time, the time of negative oropharyngeal swab nucleic acid conversion, and the changes of cell count in blood routine test were compared. RESULTS: The treatment group I showed shorter average antipyretic duration (4 7 d; <0.05), and shorter average time for polymerase chain reaction (PCR) nucleic acid test results to turn negative (7 11 d; <0.05) than the treatment group II. For patients ( 54) with body temperature>38 ℃, patients in the treatment group I had shorter median onset time of antipyretic effect than those in the treatment group II (3 4 d; <0.05). The absolute lymphocyte (LYMPH) count and absolute eosinophil (EOS) count on the 3rd day after admission and the neutrophil/lymphocyte ratio on the 6th day after admission of patients in the treatment group I were notably different from those in the treatment group II at the same time point (0.05). Based on Spearman's rank correlation analysis, the change of body temperature on the 3rd day after admission was positively correlated with the increase of EOS count and the increase of EOS count and LYMPH counts on the 6th day after admission (0.01). CONCLUSIONS: Early TCM intervention within 5 d after hospital admission shortened the onset time of antipyretic effect and fever duration of COVID-19 patients, reduced the time required for PCR test results to turn negative. Moreover, early TCM intervention also improved the results of inflammatory markers for COVID-19 patients. LYMPH and EOS counts can be used as indicators of TCM antipyretic effect.

Layer-Structured Multitransition-Metal Oxide Cathode Materials for Potassium-Ion Batteries with Long Cycling Lifespan and Superior Rate Capability.

Manganese (Mn)-based layer-structured transition metal oxides are considered as excellent cathode materials for potassium ion batteries (KIBs) owing to their low theoretical cost and high voltage plateau. The energy density and cycling lifetime, however, cannot simultaneously satisfy the basic requirements of the market for energy storage systems. One of the primary causes results from the complex structural transformation and transition metal migration during the ion intercalation and deintercalation process. The orbital and electronic structure of the octahedral center metal element plays an important role for maintaining the octahedral structural integrity and improving the K+ diffusivity by the introduced heterogeneous [Me-O] chemical bonding. A multitransition metal oxide, P3-type K0.5Mn0.85Co0.05Fe0.05Al0.05O2 (KMCFAO), was synthesized and employed as a cathode material for KIBs. Beneficial from the larger layer spacing for K+ to better accommodate and effectively preventing the irreversible structural transformation in the insertion/extraction process, it can reach a superior capacity retention up to 96.8% after 300 cycles at a current density of 500 mA g-1. The full cell of KMCFAO//hard carbon exhibits an encouraging promising energy density of 113.8 W h kg-1 at 100 mA g-1 and a capacity retention of 72.6% for 500 cycles.

Network Pharmacology and In Vivo Analysis of Dahuang-Huangqi Decoction Effectiveness in Alleviating Renal Interstitial Fibrosis.

Dahuang and Huangqi are the most frequently prescribed treatment methods for chronic kidney disease in China. Our study aimed to clarify the pharmacological mechanism of action of Dahuang-Huangqi decoction (DHHQD) in renal interstitial fibrosis (RIF). The intersection of genes targeted by DHHQD active ingredients and RIF target genes was searched using network pharmacology to build a chemical ingredient and disease target network. For in vivo analysis, Sprague-Dawley rats with unilateral urethral obstruction (UUO) were administered DHHQD, and their kidney function-related indicators and pathological indices were determined. The expression of core targets was quantified using real-time polymerase chain reaction and western blotting. A total of 139 common targets for DHHQD and RIF in chronic kidney disease were detected. Compared with the untreated UUO rats, the DHHQD-treated rats showed reductions in the following: blood urea nitrogen and serum creatinine levels, kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia and abnormal deposition of extracellular matrix, and microstructural changes in the mesangial matrix and glomerular basement membrane. DHHQD treatment significantly regulated the levels of renal core proteins, such as eNOS, IL-6, EGFR, and VEGF and reduced the mRNA and protein expression of the core targets involved in inflammation pathways, such as PI3K/AKT and TLR4/NF-κB. DHHQD treatment ameliorated the severity of RIF by potentially regulating the AKT/PI3K and TLR4/NF-κB signaling pathways. Our study findings provide insights into the mechanisms associated with DHHQD action and essential data for future research.

Inhibitory Effects of Rhein on Renal Interstitial Fibrosis via the SHH-Gli1 Signal Pathway.

Background: Rhein is the main extract of Rheum palmatum L., which has been proved to improve the renal function of chronic kidney disease, but its mechanism is not clear. Therefore, this experiment explored the potential pharmacological effect of rhein on renal interstitial fibrosis rats. Methods: This study explores the potential pharmacological action of rhein. In this work, we investigate the potential pharmacological action of rhein in unilateral urethral obstruction (UUO) rats. Thirty Sprague Dawley rats were randomly divided into three groups: sham, UUO, and rhein (rhein-treated UUO rats) groups. The left ureters of the UUO group rats were exposed and bluntly dissected. The rhein group rats were administered an intragastric gavage of rhein (2 mg·kg-1·d-1) for 14 d. Kidney function-related indicators were monitored in these rats, while indexes of pathologic aspects were determined histologically. The expression of α-SMA, TGF-ß1, SHH, Gli1, and Snail was quantified using real-time polymerase chain reaction and western blotting. The NRK-49F cells were incubated with and without SHH (100 ng·ml-1) for 48 hours. The SHH-activated NRK-49F cells were incubated with cyclopamine (CNP, 20 umol L-1) or rhein (1 ng·ml-1). The Gli1 and Snail mRNA and protein level were detected. Results: In the in vivo experiment, the results exhibited that UUO caused renal pathological damages. However, these changes could be significantly reversed by the administration of rhein. Compared with the untreated UUO group, the rhein group showed reduced kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia, and abnormal deposition of extracellular matrix. Rhein reduced the RNA and protein expression of SHH, Gli1, and Snail of the UUO rats. In the in vitro experiment, CNP or rhein treatment decreased the expression of Gli1 and Snail on mRNA and protein levels in SHH-induced NRK-49F cells, suggesting that CNP or rhein suppresses SHH-induced NRK-49F activation. Taken together, these results demonstrated that rhein suppresses SHH-Gli1-Snail signal pathway activation, with potential implications for the treatment of renal fibrosis. Conclusions: Treatment with rhein remarkably ameliorated renal interstitial fibrosis in UUO rats by regulating the SHH-Gli1-Snail signal pathway.

Yiqi Huayu decoction alleviates bleomycin-induced pulmonary fibrosis in rats by inhibiting senescence.

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

Network analysis for the identification of hub genes and related molecules as potential biomarkers associated with the differentiation of bone marrow-derived stem cells into hepatocytes.

The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING and Cytoscape v 3.8.2, revealing that twenty-four hub genes, play a pivotal role in the differentiation of BMSCs into hepatocytes. The expression of the hub genes in the BMSCs and hepatocytes was verified by reverse transcription-quantitative PCR (RT-qPCR). Next, the target miRNAs of hub genes were predicted, and then the lncRNAs regulating miRNAs was discovered, thus forming the lncRNA-miRNA-mRNA interaction chain. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.