Advances in Small-Molecule Dual Inhibitors Targeting EGFR and HER2 Receptors as Anti-Cancer Agents.

As members of the protein tyrosine kinase family, the Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) play essential roles in cellular signal transduction pathways. Overexpression or abnormal activation of EGFR and HER2 can lead to the development of various solid tumors. Therefore, they have been confirmed as biological targets for the development of anticancer drugs. Due to the fact that many cancers are highly susceptible to developing resistance to single-target EGFR inhibitors in clinical practice, dual inhibitors that target both EGFR and HER2 have been developed to increase efficacy, reduce drug resistance and interactions, and improve patient compliance. Currently, a variety of EGFR/HER2 dual inhibitors have been developed, with several drugs already approved for marketing or in clinical trials. In this review, we summarize recent advancements in small-molecule EGFR/HER2 dual inhibitors by focusing on structure-activity relationships and share novel insights into developing anticancer agents.

New record of Joffre's pipistrelle, Mirostrellusjoffrei (Chiroptera, Vespertilionidae), in China.

Background: Mirostrellusjoffrei Thomas, 1915 is the sole species within the genus Mirostrellus and its occurrence is notably rare in China. Despite the recent discovery of four previously unreported specimens from western Yunnan, China (Zaoteng River, 25.31°N, 98.80°E, altitude 1451 m) at the National Museum of Prague in the Czech Republic, comprehensive descriptions or detailed accounts of this species within China have yet to be published. New information: During a field expedition within the Guanyinshan Provincial Nature Reserve, Yuanyang, Yunnan, China, a bat was captured using a mist net. The specimen was of moderate size, with its ventral surface presenting a golden-brown hue and its dorsal surface ranging from dark brown to obsidian. The forearm measured 37.31 mm, while the fifth digit was conspicuously diminished in comparison to the others. The snout was robust, featuring prominent buccal glands. It was characterised by a well-developed upper frame and a barely visible low sagittal crest. The upper canines possessed well-developed posterior cusps. The dentition comprised two upper and two lower premolars, with the first upper premolar being notably small and the lower molars being distinctly myotodont. These attributes correspond with the known traits of Mirostrellusjoffrei. Phylogenetically, the sequence of this specimen clustered with that of M.joffrei, forming an independent clade. Through an examination of its morphological characteristics and a phylogenetic analysis of the mitochondrial cytochrome b (Cyt b), cytochrome oxidase subunit I (COI) and recombination activating gene 2 (RAG2) sequences, we identified the specimen as M.joffrei, thus confirming the presence of Joffre's pipistrelle in China.

New records of Harpiolaisodon (Chiroptera, Vespertilionidae) from the Chinese mainland.

Background: The new species, Harpiolaisodon Kuo et al., 2006, was described from Taiwan, China. So far, no distribution of this species outside Taiwan has been reported. New information: During two field investigations of small mammals in Guanyin Mountains Provincial Nature Reserve, Yuanyang, Yunnan, China, in April 2022 and May 2023, five individuals of Harpiola were collected in the mid-montane evergreen broad-leaved forest. Our morphological and molecular results reveal that these individuals from the Chinese mainland belong to Harpiolaisodon, extending the occurrence of this species well beyond its known distributions in Taiwan, China and Vietnam.

Effect of intravenous thrombolysis combined with endovascular treatment on vascular recanalization rate and peak systolic velocity in patients with acute cerebral infarction.

Objectives: To investigate the efficacy of intravenous thrombolysis (IVT) combined with endovascular treatment (EVT) on vascular recanalization rate and peak systolic velocity (PSV) in patients with acute cerebral infarction (ACI). Methods: A retrospective observational study was conducted from January 2019 to December 2021 in Chengdu First People's Hospital. The clinical data of 96 patients with ACI were reviewed and the patients were assigned to either the control group (IVT alone, n=54) or the observation group (IVT+EVT, n=42). The vascular recanalization rate, PSV, neurological function, modified Rankin Scale (mRS) score and major adverse cardiovascular events (MACE) were compared between groups. Results: The vascular recanalization rate and PSV in the observation group were higher than the control group (P<0.05). The NIHSS scores of the observation group at 24 hour, one week and one month after treatment were significantly lower than those of the control group (P<0.05). The mRS scores of the observation group were significantly lower than the control group after treatment (P<0.05), while there was no difference in the incidence of MACE between groups (P>0.05). Conclusions: IVT combined with EVT can improve the vascular recanalization rate and PSV in patients with ACI, which is worthy of promotion in clinical practice.

Trends in innovative pediatric drug development in China based on clinical trial registration data.

In China, the focus of drug research and development has gradually shifted from generic to innovative drugs. Using the Chinese Clinical Trials Registry and Information Transparency Platform, we retrospectively analyzed clinical trials of innovative pediatric drugs conducted in mainland China over the last decade. The goal of this work was to better understand the characteristics of and historical changes in innovative pediatric drug research and development (R&D) in China and to provide effective data support for policy makers and other stakeholders. This study included 198 innovative pediatric drug clinical trials. The data showed that, although some progress has been made in the R&D of innovative pediatric drugs in China, many factors limiting this progress still exist, such as concentrated R&D areas, inadequate pediatric participants, and unbalanced source distributions. The level of innovative pediatric drug R&D in China currently lags behind the global level and has not kept pace with anti-neoplastic drug R&D in China. To promote the innovative development of pediatric drugs in China, the Chinese government must develop an R&D supervision framework, improve the motivation and innovation capabilities of pharmaceutical companies, and optimize the source distribution between regions.

Recent advances on dual inhibitors targeting HIV reverse transcriptase associated polymerase and ribonuclease H.

Reverse transcriptase (RT) plays an indispensable role in the replication of human immunodeficiency virus (HIV) through its associated polymerase and ribonuclease H (RNase H) activities during the viral RNA genome transformation into proviral DNA. Due to the fact that HIV is a highly mutagenic virus and easily resistant to single-target RT inhibitors, dual inhibitors targeting HIV RT associated polymerase and RNase H have been developed. These dual inhibitors have the advantages of increasing efficacy, reducing drug resistance, drug-drug interactions, and cytotoxicity, as well as improving patient compliance. In this review, we summarize recent advances in polymerase/RNase H dual inhibitors focusing on drug design strategies, and structure-activity relationships and share new insights into developing anti-HIV drugs.

Metallic-semiconducting transition and spin polarized-unpolarized transition in a single molecule with a negative Poisson's ratio.

Different from conventional materials, structures with a negative Poisson's ratio (NPR) contract/expand laterally under a longitudinal compressive/tensile strain, usually exhibiting peculiar features. Through first-principles calculations, we investigate the electronic and transport properties of Pd9B16 molecules. Its Poisson's ratio is found to be negative under uniaxial strain along a specific direction. By contacting with Au nanowires, atomic Au chains and atomic C chain electrodes, two kinds of transitions for transmission states could be realized by the modulation of the strain and the contacting site, i.e., metallic-semiconducting transition and spin polarized-unpolarized transition. Further analysis shows that it is the suppression and shifting of density of states, caused by the strain or contacting electrodes, that trigger the transitions. Those findings combine NPR and spintronics at the single-molecule level, which may throw light on the development of nanoelectronic devices.

Altered White Matter Integrity in Patients with Retinal Vein Occlusion: A Diffusion Tensor Imaging and Tract-Based Spatial Statistics Study.

BACKGROUND: To investigate microstructural alterations of white matter in retinal vein occlusion (RVO) patients by tract-based spatial statistics (TBSS) and diffusion tensor imaging (DTI). Material/Methods. DTI was performed on 14 RVO patients and 14 normal controls (HCs). We measured and recorded fractional anisotropy (FA) and radial diffusivity (RD) of white matter fibers and classified them through the receiver operating characteristic (ROC) curve and correlation analysis, respectively. RESULTS: The mean FA value of white matter in RVO patients is lower than the HCs, and the mean RD value in RVO patients increased, especially in the bilateral posterior thalamic, bilateral sagittal stratum, body of corpus callosum, cingulum, and fornix. The ROC curve of different brain regions showed high accuracy. Moreover, the mean FA and RD values were significantly correlated with visual and psychological disorders. CONCLUSION: TBSS could be regarded as an important method to reveal the alterations of white matter in RVO patients, indicating the underlying neurological mechanism of the RVO.

Altered spontaneous brain activity patterns in patients with diabetic retinopathy using amplitude of low-frequency fluctuation.

BACKGROUND: Diabetes mellitus is a metabolic disorder characterized by prolonged elevation of blood glucose due to various causes. Currently, the relationship between diabetic retinopathy (DR) and altered connectivity of brain function is unclear. AIM: To investigate the relationship between this brain activity and clinical manifestations and behaviors of DR patients by using the amplitude of low-frequency fluctuation (ALFF) technique. METHODS: Twenty-four DR patients and 24 healthy controls (HCs) matched for age and gender were enrolled. We measured and recorded average ALFF values of DR patients and HCs and then classified them using receiver operating characteristic (ROC) curves. RESULTS: ALFF values of both left and right posterior cerebellar lobe and right anterior cingulate gyrus were remarkably higher in the DR patients than in the HCs; however, DR patients had lower values in the bilateral calcarine area. ROC curve analysis of different brain regions demonstrated high accuracy in the area under the curve analysis. There was no significant relationship between mean ALFF values for different regions and clinical presentations in DR patients. Neuronal synchronization abnormalities in some brain regions of DR patients were associated with cognitive and visual disorders. CONCLUSION: Abnormal spontaneous brain activity was observed in many areas of DR patients' brains, which may suggest a possible link between clinical manifestations and behaviors in DR patients.

Sleep Quality Improvement Enhances Neuropsychological Recovery and Reduces Blood Aß42/40 Ratio in Patients with Mild-Moderate Cognitive Impairment.

Background and objectives: Alzheimer's disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid ß peptide-42/40 (Aß42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these biomarkers due to sleep disturbance, especially sleep-disordered breathing (SDB). However, it is not clear if sleep quality improvement reduces the blood levels of Ab42/40 ratio and Tau-pT181 in Alzheimer's disease patients. Materials and Methods: In this prospective study, a longitudinal analysis was conducted on 64 patients with mild-moderate cognition impairment (MCI) due to Alzheimer's disease accompanied by SDB. Another 33 MCI cases without sleep-disordered breathing were included as the control group. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) score system. Neuropsychological assessments were conducted using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), 24-h Hamilton Rating Scale for Depression (HRSD-24), and Hamilton Anxiety Rating Scale (HAMA) scoring systems. Aß42, Aß40, and Tau-pT181 protein levels in blood specimens were measured using ELISA assays. All patients received donepezil treatment for Alzheimer's disease. SDB was managed with continuous pressure ventilation. Results: A significant correlation was found among PSQI, HRSD-24, HAMA, Aß42/40 ratio, and Tau-pT181 level in all cases. In addition, a very strong and negative correlation was discovered between education level and dementia onset age. Compared to patients without SDB (33 non-SD cases), patients with SDB (64 SD cases) showed a significantly lower HRSD-24 score and a higher Aß42/40 ratio Tau-pT181 level. Sleep treatment for patients with SDB significantly improved all neuropsychological scores, Aß42/40 ratio, and Tau-pT181 levels. However, 11 patients did not completely recover from a sleep disorder (PSQI > 5 post-treatment). In this subgroup of patients, although HAMA score and Tau-pT181 levels were significantly reduced, MoCA and HRSD-24 scores, as well as Aß42/40 ratio, were not significantly improved. ROC analysis found that the blood Aß42/40 ratio held the highest significance in predicting sleep disorder occurrence. Conclusions: This is the first clinical study on sleep quality improvement in Alzheimer's disease patients. Sleep quality score was associated with patient depression and anxiety scores, as well as Aß42/40 ratio and Tau-pT181 levels. A complete recovery is critical for fully improving all neuropsychological assessments, Aß42/40 ratio, and Tau-pT181 levels. Blood Aß42/40 ratio is a feasible prognostic factor for predicting sleep quality.

Molecular and functional characterization of HtrA protein in Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae (A.pleuropneumoniae) causes serious economic loss for the swine industry. A high-temperature requirements A (HtrA)-like protease and its homologs have been reported to be involved in protein quality control and expression of important immunoprotective antigens in many pathogens. In this study, we showed that HtrA of A.pleuropneumoniae exhibited both chaperone and proteolytic activities. Moreover, Outer membrane protein P5 (OmpP5) in A.pleuropneumoniae and Heat shock protein 90 (Hsp90) in porcine lung tissues were first discovered and identified as specific proteolytic substrates for rHtrA. The maximum cleavage activity occurs at 50 ℃ in a time-dependent manner. In addition, rHtrA mainly induced IgG 2a subtype of IgG and Th1 (IFN-γ, IL-2) response in a mice model, and promoted a significant proliferation of spleen lymphocytes compare with negative control (P < 0.05). The survival rates of 37.5 % were observed against A.pleuropneumoniae strain. Together, these data demonstrate that rHtrA plays a multi-functional role in A.pleuropneumoniae.

Chronic treatment with anti-GIPR mAb alone and combined with DPP-4 inhibitor correct obesity, dyslipidemia and nephropathy in rodent animals.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide receptor (GIPR) has been identified as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). Therefore, we developed the anti-GIPR antagonistic monoclonal antibody (mAb) alone and in combination with DPP-4 inhibitor as potential therapeutic strategy for treating obesity and dyslipidemia based on this genetic evidence. METHODS: Fully neutralized GIPR activity of GIPR-monoclonal antibody (mAb) was assessed by regulating the in vitro production of cAMP in the mouse GIPR stably expressing cells. Chronic efficacies of GIPR-mAb alone and in combination with DPP-4 inhibitor Sitagliptin in diabetic or DIO mice were both investigated. Multiple metabolic parameters including body weight, glucose level, fat mass, lipid metabolism-related indicators as well as H&E staining and immunohistochemical analysis were performed. Role of GIPR in pancreatic cells on regulating fat metabolism was explored in GIPR ß-cell knockout mouse model. RESULTS: Chronic treatment of GIPR-mAb improved body weight control, glucose metabolism, and was associated with reduced fat mass, enhanced pancreatic function and exchange ratio of the resting respiratory in diabetic mice. In addition, further study of anti-GIPR mAb combined with Sitagliptin in DIO mice demonstrated significantly improved weight loss compare to the both monomer treatment. Furthermore, we demonstrated important role of GIPR in ß-cell in regulating the fat mass and response to antagonistic GIPR-mAb in a conditional GIPR-knockout mouse. CONCLUSION: Chronic treatment with anti-GIPR mAb alone and combined with DPP-4 inhibitor provide preclinical therapeutic approaches to treat obesity.

Amygdalin alleviates renal injury by suppressing inflammation, oxidative stress and fibrosis in streptozotocin-induced diabetic rats.

AIMS: To explore the protective efficacies and potent mechanism of amygdalin on high glucose-cultured renal cell HBZY-1 in vitro and streptozotocin (STZ)-induced diabetic nephropathy (DN) rat in vivo. MAIN METHODS: The cellar proliferation and generation of ROS in high-glucose cultured HBZY-1 cell were assessed by MTT and DCFH-DA assay, respectively. The fasting blood glucose levels, renal function and inflammation indexes as well as oxidative stress markers in STZ-induced diabetic rats were all measured. The histologic renal section was stained with Mason and periodic acid-Schiff (PAS) method. Immunohistochemistry and western blotting methods were applied to assess expression levels of extracellular matrix (ECM), epithelial-mesenchymal transition (EMT)-related as well as TGF-ß1/Smad signaling pathway-related proteins. KEY FINDINGS: Firstly, amygdalin significantly suppressed the excessive cell proliferation and ROS generation in HBZY-1 cells cultured with high glucose. The hyperglycemia, 24 h-UP excretion, BUN and Scr of DN rats were significantly attenuated after the chronic treatment of amygdalin. Moreover, MDA, SOD, IFN-γ and IL-12 levels in kidney tissues were all effectively reduced. Besides, amygdalin can suppress the ECM accumulation and EMT transformation by inhibiting Smad/TGF-ß pathway to alleviate the renal fibrosis in renal tissues of DN model rats. SIGNIFICANCE: Amygdalin ameliorates excessive oxidative stress, inflammation and renal tissue fibrosis of DN mainly by suppressing TGF-ß1/Smad signaling pathway and regulating the key enzymes of ECM degradation.

Acarbose ameliorates spontaneous type­2 diabetes in db/db mice by inhibiting PDX­1 methylation.

Pancreatic and duodenal homeobox (PDX)­1 is a gene that plays an important role in pancreatic development and function. Type­2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and impaired islet ß­cell function. There is evidence that methylation of PDX­1 plays a role in the development of T2DM. Acarbose is an α­glucosidase inhibitor that can effectively delay the absorption of glucose by the body. The aim of the present study was to examine the effect of acarbose on PDX­1 methylation in islet ß­cells in spontaneous type­2 diabetic db/db mice. The effect of acarbose on glucose and lipid metabolism in these mice was assessed by measuring food intake, body weight, glycated hemoglobin (HbA1c), glucagon, serum total cholesterol and triglyceride levels, and fasting blood glucose (FBG). Blood glucose levels were also analyzed using intraperitoneal glucose tolerance and insulin tolerance tests. Immunohistochemistry was used to evaluate the effect of acarbose on pathological changes in the pancreas. Moreover, a BrdU assay was used to analyze cell proliferation. Lastly, the effect of acarbose on PDX­1 methylation was evaluated in mice using methylation­specific PCR and western blot analysis. In the present study, body weight significantly increased in the acarbose group, compared to the normal group. The levels of HbA1c and glucagon in the T2DM group significantly increased, compared with the normal group, but significantly decreased in acarbose­treated mice. Moreover, FBG levels significantly decreased in the acarbose groups compared with T2DM mice. Acarbose also promoted cell proliferation, compared with untreated T2DM mice. In addition, PDX­1 methylation and cytoplasmic expression levels were both downregulated in the acarbose group, compared with the T2DM group. In conclusion, these results suggested that acarbose could promote the proliferation of islet ß­cells and inhibit PDX­1 methylation in islet ß cells from diabetic mice. Thus, acarbose may provide a new strategy to treat T2DM.

In silico prediction and validation of potential therapeutic genes in pancreatic ß-cells associated with type 2 diabetes.

Diabetes mellitus is becoming a major health burden worldwide. Pancreatic ß-cell death is a characteristic of type 2 diabetes (T2D), but the underlying mechanisms of pancreatic ß-cell death remain unknown. Therefore, the aim of the present study was to identify potential targets in the pancreatic islet of T2D. The GSE20966 dataset was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using the GEO2R tool. The Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis of DEGs were further assessed using the Database for Annotation, Visualization and Integrated Discovery. Furthermore, protein-protein interaction (PPI) networks were constructed for the up- and downregulated genes using STRING databases and were then visualized with Cytoscape. The body weight, fasting blood glucose (FBG), pancreatic index and biochemistry parameters were measured in db/db mice. Moreover, the morphology of the pancreas was detected by hematoxylin and eosin staining, and hub genes were assessed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. In total, 570 DEGs were screened, including 376 upregulated and 194 downregulated genes, which were associated with 'complement activation, classical pathway', 'proteolysis', 'complement activation' and 'pancreatic secretion pathway'. It was found that the body weight, FBG, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, blood urea nitrogen, creatinine, fasting serum insulin, glucagon and low-density lipoprotein cholesterol levels were significantly higher in db/db mice, while high-density lipoprotein cholesterol levels and the pancreatic index were significantly decreased. Furthermore, albumin, interleukin-8, CD44, C-C motif chemokine ligand 2, hepatocyte growth factor, cystic fibrosis transmembrane conductance regulator, histone cluster 1 H2B family member n, mitogen-activated protein kinase 11 and neurotrophic receptor tyrosine kinase 2 were identified as hub genes in PPI network. RT-qPCR and western blotting results demonstrated the same expression trend in hub genes as found by the bioinformatics analysis. Therefore, the present study identified a series of hub genes involved in the progression of pancreatic ß-cell, which may help to develop effective therapeutic strategy for T2D.

A novel identified circular RNA, circ_0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR­101b by targeting TGFßRI.

Circular RNAs (circRNAs) have crucial roles in various diseases; however, the mechanisms of action underlying circRNAs in the occurrence and development of diabetic nephropathy (DN) remains largely unknown. The present study investigated the differentially expressed circRNAs in the DN mice kidney cortex using circRNA sequencing and elucidated the role of circRNAs in mesangial cells. It was revealed that 40 circRNAs were unconventionally expressed, including 18 upregulated circRNAs and 22 downregulated circRNAs. Furthermore, circ_0000491 levels were significantly augmented in both DN mice and high glucose (HG, 30 mM)­induced mouse mesangial cells (MES13 cells). Knockdown of circ_0000491 significantly suppressed the increase of vimentin, fibronectin and α­smooth muscle actin, as well as collagen type I, III and IV, whilst reversing the decrease of E­cadherin in HG­induced MES13 cells. It was further revealed that circRNA_0000491 sponged miR­101b and that miR­101b directly targets TGFßRI. In addition, the expression levels of miR­101b were negatively associated with the transcriptional level of circRNA_0000491 and miR­101b inhibitors reversed the suppression of extracellular matrix (ECM)­associated protein synthesis mediated by knocking­down circRNA_0000491. In conclusion, the present study investigated the circRNA_0000491/miR­101b/TGFßRI axis in ECM accumulation and fibrosis­associated protein expression levels of mesangial cells, which suggested that circRNA_0000491 may be beneficial for the development of an effective therapeutic target for DN.

Hepatic Proteomic Changes and Sirt1/AMPK Signaling Activation by Oxymatrine Treatment in Rats With Non-alcoholic Steatosis.

BACKGROUND: Currently, active ingredients of herbal extracts that can suppress lipid accumulation in the liver have been considered a potential treatment option for non-alcoholic fatty liver disease. METHODS: Steatosis rat model was created by high fat and high sucrose diet feeding and treated with oxymatrine (OMT). Serum biochemical parameters, liver histology and lipid profiles were examined. Hepatic differentially expressed proteins (DEPs) which were significantly changed by OMT treatment were identified by iTRAQ analysis. The expressions of representative DEPs, Sirt1 and AMPKα were evaluated by western blotting. RESULTS: OMT significantly reduced the body weight and liver weight of steatosis animals, decreased the serum levels of triglyceride and total cholesterol as well as the hepatic triglyceride and free fatty acid levels, and effectively alleviated fatty degeneration in the liver. A list of OMT-related DEPs have been screened and evaluated by bioinformatics analysis. OMT significantly decreased the expressions of L-FABP, Plin2, FASN and SCD1 and increased Sirt1 expression and AMPKα phosphorylation in the liver of rats with steatosis. CONCLUSION: The present study has confirmed the significant efficacy of OMT for improving steatosis and revealed hepatic proteomic changes and Sirt1/AMPK signaling activation by OMT treatment in rats with steatosis.

[Clinical features and chest CT findings of coronavirus disease 2019 in infants and young children].

OBJECTIVE: To study the clinical features and chest CT findings of coronavirus disease 2019 (COVID-19) in infants and young children. METHODS: A retrospective analysis was performed for the clinical data and chest CT images of 9 children, aged 0 to 3 years, who were diagnosed with COVID-19 by nucleic acid detection between January 20 and February 10, 2020. RESULTS: All 9 children had an epidemiological history, and family clustering was observed for all infected children. Among the 9 children with COVID-19, 5 had no symptoms, 4 had fever, 2 had cough, and 1 had rhinorrhea. There were only symptoms of the respiratory system. Laboratory examination showed no reductions in leukocyte or lymphocyte count. Among the 9 children, 6 had an increase in lymphocyte count and 2 had an increase in leukocyte count. CT examination showed that among the 9 children, 8 had pulmonary inflammation located below the pleura or near the interlobar fissure and 3 had lesions distributed along the bronchovascular bundles. As for the morphology of the lesions, 6 had nodular lesions and 7 had patchy lesions; ground glass opacity with consolidation was observed in 6 children, among whom 3 had halo sign, and there was no typical paving stone sign. CONCLUSIONS: Infants and young children with COVID-19 tend to have mild clinical symptoms and imaging findings not as typical as those of adults, and therefore, the diagnosis of COVID-19 should be made based on imaging findings along with epidemiological history and nucleic acid detection. Chest CT has guiding significance for the early diagnosis of asymptomatic children.

A bioinformatics and network pharmacology approach to the mechanisms of action of Shenxiao decoction for the treatment of diabetic nephropathy.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells is the main pathological alteration in diabetic nephropathy (DN). Traditional Chinese medicine (TCM) has been used for the treatment of DN in clinical practice and has been proven to be effective. PURPOSE: This aim of this study was to shed light on the efficacy of Shenxiao decoction (SXD) on the EMT of renal tubular epithelial cells and the molecular mechanisms of SXD in mice with DN, as well as on the high glucose (HG)- and TGF-ß1-induced EMT of NRK-52E and HK-2 cells. STUDY DESIGN AND METHODS: A bioinformatics and network pharmacology method were utilized to construct the active ingredient-target networks of SXD that were responsible for the beneficial effects against DN. The effects of RUNX3 were validated in HG- and TGF-ß1-induced EMT processes in NRK-52E and HK-2 cells. RESULTS: Bioinformatics analysis revealed that 122 matching targets were closely associated with the regulation of cell migration and the AGE-RAGE signaling pathway in diabetic complications. The results also revealed that, relative to the mice with DN, the mice in the treatment group had an improved general state and reduced blood glucose levels. The degradation of renal function was ameliorated by SXD. Moreover, the protective effects of SXD were also observed on renal structural changes. Furthermore, SXD suppressed the activation of the transforming growth factor (TGF)-ß1/Smad pathway and upregulated the RUNX3 and E-cadherin levels and downregulated the extracellular matrix (ECM) protein levels in mice with DN. SXD was further found to prevent the HG- and TGF-ß1-induced EMT processes in NRK-52E and HK-2 cells. Additionally, the overexpression of RUNX3 markedly inhibited the EMT and TGF-ß1/Smad pathway induced by HG and TGF-ß1 in NRK-52E and HK-2 cells. CONCLUSION: Taken together, these results suggest that SXD maybe alleviate EMT in DN via the inhibition of the TGF-ß1/Smad/RUNX3 signaling pathway under hyperglycemic conditions.

Visual Life Sciences Workflow Design Using Distributed and Heterogeneous Resources.

Programming or querying usually presupposes some degree of technical familiarity with the syntax of a language and the peculiarity of the objects it manipulates to produce useful information. The degree of abstractions supported in a language helps lessen the depth of such familiarity needed, and aids in improving access to and usability of these resources. To help biologists concentrate more on their science questions and not on how to compute it, several successful workflow orchestration languages and systems have been proposed. Despite their popularity, significant limitations reduce their usability and limit applicability in novel applications. In this paper, we present a visual language, called VisFlow, for workflow orchestration using heterogeneous and distributed resources. We advance the idea that once resources are minimally described and abstracted, arbitrary workflows can be designed solely using query primitives supported in VisFlow. Its capabilities can be augmented by including computational artifacts in the form of library functions written in R, Python, and Java, or even in SQL and XQuery, making it a truly extensible system. We discuss its salient features and illustrate its capabilities using a substantial set of examples.