Hirschsprung's disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. We investigated changes in expression of microRNAs (miRNAs) and the genes they regulate in tissues of patients with HSCR. Quantitative real-time PCR and immunoblot analyses were used to measure levels of miRNA, mRNAs, and proteins in colon tissues from 69 patients with HSCR and 49 individuals without HSCR (controls). Direct interactions between miRNAs and specific mRNAs were indentified in vitro, while the function role of miR-218-1 was investigated by using miR-218 transgenic mice. An increased level of miR-218-1 correlated with increased levels of SLIT2 and decreased levels of RET and PLAG1 mRNA and protein. The reductions in RET and PLAG1 by miR-218-1 reduced proliferation and migration of SH-SY5Y cells. Overexpression of the secreted form of SLIT2 inhibited cell migration via binding to its receptor ROBO1. Bowel tissues from miR-218-1 transgenic mice had nerve fibre hyperplasia and reduced numbers of gangliocytes, compared with wild-type mice. Altered miR-218-1 regulation of SLIT2, RET and PLAG1 might be involved in the pathogenesis of HSCR.

Innate immunity is the first line of defense in human beings against pathogen infection; monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS) protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP) sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs); SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

Candida auris, C. haemulonii, C. duobushaemulonii, and C. pseudohaemulonii are closely related and highly multidrug resistant yeast pathogens. The high cost and low accuracy of current diagnostics may underestimate their prevalence, especially in medical resource-limited regions. In this study, we used 172 C. auris stains and its relatives and 192 other fungal strains to establish and validate a novel multiplex end-point PCR. A prospective and a retrospective clinical screenings using this assay were further performed in China and Iran respectively. We identified the first isolate of C. pseudohaemulonii in China and the first isolate of C. haemulonii in Iran from 821 clinical isolates in total, without any false positive. Animal models of C. auris and C. haemulonii were established for validation. The overall positive rates of the assay for mice blood and tissue were 28.6 and 92.9%, respectively. Compared with previously developed assays, our assay is more available and affordable to the developing countries, and may contribute to a better understanding of the epidemiology of C. auris and its relatives in these regions.

This study aims to develop an impedance-based drug screening platform that will help identify drugs that can enhance the vascular barrier function by stabilizing vascular endothelial cell junctions.

Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.

With the development of a large number of tall dams and large cascade reservoir projects in the Lantsang River Basin, a large water level fluctuating zone (WLFZ) containing cascading reservoirs has formed. This newborn ecosystem is related to the sustainable development of hydropower projects, and has become a new problem to be studied urgently. Taking WLFZs in the Huangdeng, Xiaowan and Nuozhadu Reservoirs in the Lantsang River Basin as study areas, this study used multi-spectral remote-sensing field data obtained with unmanned aerial vehicles (UAVs) to ascertain the species types, coverage, distribution characteristics, dominant species and pioneer species of naturally restored vegetation. The considered data were subjected to UAV data processing, vegetation classification using multi-spectral images and a geographic information system (GIS) terrain-distribution analysis. Results show that: Polygonum Plebeium, Cynodon dactylon, Xanthium sibiricum, Ageratum conyzoides, Eleusine indica, Digitaria sanguinalis and Verbena officinalis are the dominant species of vegetation that could be naturally restored in the WLFZ; the vegetation coverage and the number of species are significantly positively correlated with the age and restoration periods of the WLFZ; the vegetation coverage of each study area increases at first, and then decreases, as a function of elevation; gentle slopes about 0-25°are more suitable for vegetation restoration. This study provides first-hand data on the natural restoration of vegetation in WLFZs, and gives a useful reference for its ecological restoration as a consequence of hydropower cascade development in the Lantsang River Basin. Finally, the study demonstrates that light UAV remote sensing is an attractive choice for investigating vegetation in reservoir WLFZs.

Candida auris is an emerging multidrug-resistant fungus that may cause infections with a high mortality rate. The first case of C. auris infection was reported in 2009 and infections have been reported in 44 countries. The fungus now represents a major global public health threat. We analyzed cases from the emergence of C. auris infections up until the end of 2020. It is hoped that the results of this analysis will raise awareness in scientists to promote protection and control research pertaining to this pathogen.

Background: The farnesoid X receptor (FXR) is a key factor regulating hepatic bile acid synthesis and enterohepatic circulation. Repression of bile acid synthesis by the FXR is a potential strategy for treating cholestatic liver disease. However, the role of intestinal FXR on the intestinal barrier and intestinal microbiota needs further investigation. Materials: Intestinal tissues were collected from patients with biliary atresia or without hepatobiliary disease. Then, intestinal mRNA levels of FXR-related molecules were determined. To investigate the effect of FXR activation, bile-duct-ligation rats were treated with obeticholic acid [OCA (5 mg/kg/day)] or vehicle (0.5% methyl cellulose) per oral gavage for 14 days. The mRNA levels of intestinal FXR, SHP, TNF-α, FGF15 and bile acid transporter levels were determined. In addition, the intestinal permeability, morphologic changes, and composition of the intestinal microbiota were evaluated. Gut Microbiome was determined by 16S rDNA MiSeq sequencing, and functional profiling of microbial communities was predicted with BugBase and PICRUSt2. Finally, the role of OCA in injured intestinal epithelial cell apoptosis and proliferation was examined by pretreatment with lipopolysaccharide (LPS) in Caco-2 cells. Results: The downstream of the FXR in ileum tissues was inhibited in biliary obstruction. Activation of the FXR signaling pathway by OCA significantly reduced liver fibrosis and intestinal inflammation, improved intestinal microbiota, and protected intestinal mucosa in BDL rats. OCA also altered the functional capacities of ileum microbiota in BDL rats. Significant differences existed between the controls and BDL rats, which were attenuated by OCA in the alpha diversity analysis. Principal coordinates analysis showed that microbial communities in BDL rats clustered separately from controls, and OCA treatment attenuated the distinction. Bugbase and PICRUSt2 analysis showed that OCA changed the composition and structure of the intestinal microbiota and improved the metabolic function of the intestinal microbiota by increasing the relative abundance of beneficial bacteria and reducing the relative abundance of harmful bacteria. Moreover, OCA reduced the apoptosis induced by LPS in Caco-2 cells. Conclusion: The FXR agonist, OCA, activates the intestinal FXR signaling pathway and improves the composition and structure of the intestinal microbiota and intestinal barrier in BDL rats.

The World Health Organization (WHO) recommends a six-step hand hygiene technique. Although multiple studies have reported that this technique yields inadequate skin coverage outcomes, they have relied on manual labeling that provided low-resolution estimations of skin coverage outcomes. We have developed a computational system to precisely quantify hand hygiene outcomes and provide high-resolution skin coverage visualizations, thereby improving hygiene techniques. We identified frequently untreated areas located at the dorsal side of the hands around the abductor digiti minimi and the first dorsal interosseous. We also estimated that excluding Steps 3, 6R, and 6L from the six-step hand hygiene technique leads to cumulative coverage loss of less than 1%, indicating the potential redundancy of these steps. Our study demonstrates that the six-step hand hygiene technique could be improved to reduce the untreated areas and remove potentially redundant steps. Furthermore, our system can be used to computationally validate new proposed techniques, and help optimise hand hygiene procedures.

Bone undergoes constant remodeling of formation by osteoblasts and resorption by osteoclasts. In particular, macrophages have been reported to play an essential role in the regulation of bone homeostasis and regeneration. Naringenin, the predominant flavanone in citrus fruits, is reported to exert anti-inflammatory, anti-osteoclastic, and osteogenic effects. However, whether naringenin could modulate the crosstalk between macrophages and osteoblasts/osteoclasts remains to be investigated. In this study, we confirmed that naringenin enhanced osteogenesis and inhibited osteoclastogenesis directly. Naringenin promoted M2 transition and the secretion of osteogenic cytokines including IL-4, IL-10, BMP2, and TGF-β, while suppressing LPS-induced M1 polarization and the production of proinflammatory factors such as TNF-α and IL-1β. In addition, the coculture of primary bone mesenchymal stem cells (BMSCs)/bone marrow monocytes (BMMs) with macrophages showed that the naringenin-treated medium significantly enhanced osteogenic differentiation and impeded osteoclastic differentiation in both inflammatory and non-inflammatory environment. Moreover, in vivo experiments demonstrated that naringenin remarkably reversed LPS-induced bone loss and assisted the healing of calvarial defect. Taken together, naringenin serves as a potential anabolic treatment for pathological bone loss.

Lysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown.

Researches over the past decade suggest that lipopolysaccharide is a dominant driver of gastrointestinal motility and could damage the enteric neuron of rat or porcine. However, it remains poorly defined whether LPS participates in Hirschsprung's disease (HSCR). Here, we discovered that LPS increased in HSCR tissues. Furthermore, LPS treatment suppressed the proliferation and differentiation of neural precursor cells (NPCs) or proliferation and migration of human 293T cells. ADAR2 (adenosine deaminase acting on RNA2)-mediated post-transcriptional adenosine-to-inosine RNA editing promotes cancer progression. We show that increased LPS activates ADAR2 and subsequently regulates the A-to-I RNA editing which suppresses the miR-142 expression. RNA sequencing combined with qRT-PCR suggested that ADAR2 restrain cell migration and proliferation via pri-miR-142 editing and STAU1 up-regulation. In conclusion, the findings illustrate that LPS participates in HSCR through the LPS-ADAR2-miR-142-STAU1 axis.

The gut microbiota is associated with nonalcoholic fatty liver disease (NAFLD). We isolated the Escherichia coli strain NF73-1 from the intestines of a NASH patient and then investigated its effect and underlying mechanism.

Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. Both transfemoral (TF-TAVR) and transapical (TA-TAVR) approach were widely adopted while their performances are limited to a few studies with controversial results. This meta-analysis aimed to compare the mortality and morbidity of complications between TF- versus TA-TAVR based on the latest data.

To explore whether the effect of β-catenin on MI and MI-induced cardiomyocyte apoptosis is YAP-dependent.

Insulin growth factor‑1 (IGF‑1) is an endocrine regulator that plays an important role in normal growth and development. IGF‑1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether IGF‑1 has a protective effect on fatty acid‑induced macrophages damage. In the present study, THP‑1 cells were differentiated into macrophages and stimulated with palmitic acid (PA) in the absence or presence of IGF‑1. Macrophages apoptosis was measured by Cell Counting Kit‑8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using JC‑1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF‑1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. In addition, IGF‑1 protected the mitochondrial damage induced by PA. Furthermore, PA induced mitophagy via phosphatase and tensin homolog‑induced putative kinase protein 1/Parkin, which was reversed by IGF‑1. Taken together, the present study demonstrated the protective effect of IGF‑1 on PA‑induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.

Previous studies have shown that lutein can inhibit the proliferation of breast cancer cells. However, the mechanism of lutein inhibiting the proliferation of breast cancer cells remains unclear. The present study aimed to determine whether the long non-coding RNA (lncRNA) Cancer Susceptibility 9 (CASC9)/microRNA (miR)-590-3p axis participates in the antiproliferative effects of lutein via lncRNA microarray hybridization, reverse transcription-quantitative PCR, dual-luciferase reporter and MTT assays. The results demonstrated that CASC9 was the most significantly downregulated lncRNA in MCF7 cells treated with lutein. miR-590-3p was identified as the target of CASC9. In addition, lutein downregulated CASC9 expression and upregulated miR-590-3p expression in dose- and time-dependent manners, respectively. CASC9 knockdown or overexpression of miR-590-3p inhibited the proliferation of breast cancer cells. Notably, simultaneous transfection with miR-590-3p mimics and CASC9 small interfering RNA increased the potency of lutein in inhibiting the proliferation of breast cancer cells. Taken together, these results suggest that the CASC9/miR-590-3p axis participates in the antiproliferative effects of lutein on breast cancer.

As a representative of shared mobility, bike sharing has become a green and convenient way to travel in cities in recent years. Bike usage prediction becomes more important for supporting efficient operation and management in bike share systems as the basis of inventory management and bike rebalancing. The essential of usage prediction in bike sharing systems is to model the spatial interactions of nearby stations, the temporal dependence of demands, and the impacts of environmental and societal factors. Deep learning has shown a great advantage of making a precise prediction for bike sharing usage. Recurrent neural networks capture the temporal dependence with the memory cell and gate mechanisms. Convolutional neural networks and graph neural networks learn spatial interactions of nearby stations with local convolutional operations defined for the grid-format and graph-format inputs respectively. In this survey, the latest studies about bike sharing usage prediction with deep learning are reviewed, with a classification for the prediction problems and models. Different applications based on bike usage prediction are discussed, both within and beyond bike share systems. Some research directions are pointed out to encourage future research. To the best of our knowledge, this paper is the first comprehensive survey that focuses on bike sharing usage prediction with deep learning techniques.

Intracerebral hemorrhage (ICH) is a fatal disease with high mortality and poor prognosis that triggers multiple severe brain injuries associated with an inflammatory cascade response that cannot be treated with any effective medication. Atorvastatin (ATO) suppresses inflammation, alleviates brain trauma, and eliminates subdural hematoma. Dexamethasone (DXM) also has the capacity to inhibit inflammation. Thus, we combined ATO with low-dose DXM to treat ICH mice in vivo to examine whether the combined treatment can inhibit secondary inflammation around the cerebral hemorrhage and decrease overall mortality. Compared to the monotherapy by either ATO or DXM, the combined treatment significantly improves the survivorship of the ICH mice, accelerates their recovery of impaired neurological function, and modulates the circulating cytokines, oxidative products, and apoptosis. Moreover, the benefit of ATO-DXM combination therapy was most pronounced on day 3 after dosing compared to ATO or DXM alone. Thus, early administration of ATO combined with low-dose-DXM promotes better survival of ICH and improves neurological function by reducing neuroinflammation and brain edema in their early phase.

Ceria-based nanomaterials have aroused major attentions among the biomedical application research field in recent years. Most of the researches have mainly focused on promoting the functional healing therapies of normal cells/organs with cerium oxide compounds, while the applications of ceria-based materials employed on cancer curing processes have been merely mentioned. To explore the possible capabilities of cerium oxide nanomaterials exterminating tumor cells, innovatively, we synthesized the eco-friendly pure cerium oxide nanodots (CNDs), proving the prominent ability of CNDs used in tumor chemotherapy (CDT) via Fenton reaction with the highly presence of H2O2 (acidic pH) in tumor tissues. CNDs reacted with the self-produced H2O2 of tumor cells, which generated piled up toxic hydroxyl radical (·OH). The accumulated virulent ·OH restrained the growth of cancer cells intensively. This peroxidase-like activity, provided a distinguished paradigm for effective cancer curing treatment. We also verified the biosafety of CNDs applied on normal cells. Notably, not only did CNDs be harmless to normal cells, but also it protected them from the damages of reactive oxygen species (ROS). In normal cells/tissues, under the microenvironment of neutral pH and low level of H2O2, the CNDs could effectively function as an annihilator inhibiting ROS. They reduced the damages caused by ROS, exhibiting catalase-like activity. The research we studied, which estimated CNDs thoroughly, has provided a new perspective to the future researches of the cerium oxide biomaterial applications.