Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy.

BACKGROUND: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. METHODS: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. RESULTS: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2- M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. CONCLUSIONS: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.

The effect of hypothyroidism on the risk of diabetes and its microvascular complications: a Mendelian randomization study.

Context: Several observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified. Objective: The aim of the study was to examine the causality of such associations by a Mendelian randomization study. Methods: Two-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR-Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy. Results: Inverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (ß= 9.059926, se= 1.762903, P = 2.76E-07 and ß= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (ß= 8.427943, se= 2.142493, P = 8.36E-05 and ß= 3.100939, se= 0.74956, P=3.52E-05, respectively). Conclusions: The study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.

Identification of the immunogenic membrane proteins, catalase, PgbA, and PgbB, as potential antigens against Helicobacter pylori.

AIMS: This study aims to investigate the specific membrane antigens that are targeted by antibodies raised against Helicobacter pylori. METHODS AND RESULTS: Bovine milk antibodies were prepared using whole H. pylori, purified membrane proteins, or both. Enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments revealed that these immunogens triggered anti-H. pylori antibody production in milk. The highest antibody titer was induced by the mixture of whole bacteria and purified membrane proteins. The antibodies induced by mixed immunogens significantly inhibited H. pylori growth in vitro and were used to identify catalase, plasminogen-binding protein A (PgbA), and PgbB via western blotting, immunoprecipitation, and two-dimensional western blotting followed by liquid chromatography with tandem mass spectrophotometry. The immunogenicity of PgbA and PgbB was verified in mice vaccinated with their B-cell epitope vaccines. Following prophylactic vaccination of C57BL/6 mice, each of the three antigens alone and their combination reduced the weight loss in mice, increased antibody titers, and relieved the inflammatory status of the gastric mucosa following H. pylori infection. CONCLUSIONS: Catalase, PgbA, and PgbB could serve as valuable membrane antigens for the development of anti-H. pylori immunotherapies.

Rebuilding high-quality near-surface ozone data based on the combination of WRF-Chem model with a machine learning method to better estimate its impact on crop yields in the Beijing-Tianjin-Hebei region from 2014 to 2019.

In recent years, the problem of surface ozone pollution in China has been of great concern. According to observation data from monitoring stations, the concentration of near-surface ozone (O3) in China has gradually increased in recent years, and ozone concentration often exceeds the contaminant limit standard, especially in the Beijing-Tianjin-Hebei (BTH) region. High O3 concentration pollution will adversely affect crop growth, which can cause crop yield losses. Therefore, it is urgent to recognize the situation of ozone pollution in the BTH region and quantitatively evaluate the crop yield losses caused by ozone pollution to develop more effective pollution prevention and control policies. However, the monitoring of ozone concentration in China started relatively late compared with some developed countries, and currently, long-time series data covering the BTH region cannot be obtained, which makes it difficult to evaluate the impact of ozone on crop yield. Therefore, a new method (WRFC-XGB) was proposed in this study to establish a high-precision near-surface O3 concentration dataset covering the whole BTH region from 2014 to 2019 by integrating the Weather Research and Forecasting with Chemistry (WRF-Chem) model with the extreme gradient boosting (XGBoost) machine learning algorithm. Through verification with ground observation station data, the results of WRFC-XGB are satisfactory, and R2 can reach 0.78-0.91. Compared with other algorithms, the accuracy of the near-surface ozone concentration dataset is greatly improved, which can be used to estimate the impact of surface ozone on crop yield. Based on this dataset, the yield loss of winter wheat, rice, and maize caused by O3 pollution was estimated by using the response equation of the relative yield and ozone dose index. The results showed that the total yield losses of winter wheat, rice and maize from 2014 to 2019 were 2659.21 million tons, 49.23 million tons and 1721.56 million tons due to ozone pollution in the BTH region, respectively, and the highest relative yield loss of crops caused by O3 pollution could be 29.37% during 2014-2019, which indicated that the impact of ozone pollution on crop yield cannot be ignored, and effective measures need to be developed to control ozone pollution, prevent crop production loss, and ensure people's food security.

Fenofibrate Attenuates Renal Tubular Cell Apoptosis by Up-Regulating MCAD in Diabetic Kidney Disease.

Background: Diabetic kidney disease (DKD) is a major diabetic microvascular complication. Fatty acid-induced lipotoxicity and apoptosis were associated with the exacerbation of DKD. However, the association of lipotoxicity with renal tubular apoptosis and the effects of fenofibrate on DKD are not fully understood. Methods: Eight-week-old db/db mice were given fenofibrate or saline by gavage for 8 weeks. Human kidney proximal tubular epithelial (HK2) cells stimulated with palmitic acid (PA) and high glucose (HG) were used as a model of lipid metabolism disorders. Apoptosis was assessed with or without fenofibrate. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and AMPK inhibitor Compound C were used to determine the involvement of AMPK and Medium-chain acyl-CoA dehydrogenase (MCAD) in the regulation of lipid accumulation by fenofibrate. MCAD silencing was achieved by small interfering RNA (siRNA) transfection. Results: Fenofibrate reduced triglyceride (TG) content and lipid accumulation in DKD. Importantly, renal function and tubular cell apoptosis were significantly improved by fenofibrate. Fenofibrate reduced apoptosis, accompanied by increased activation of the AMPK/FOXA2/MCAD pathway. MCAD silencing resulted in apoptosis and lipid accumulation despite fenofibrate treatment. Conclusion: Fenofibrate improves lipid accumulation and apoptosis through the AMPK/FOXA2/MCAD pathway. MCAD may be a potential therapeutic target of DKD, and the use of fenofibrate as a treatment for DKD warrants further study.

Closed or Unclosed Mesentery? A Meta-analysis of Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass.

During the laparoscopic Roux-en-Y gastric bypass procedure, closing mesentery or not was still controversial according to preexisted studies. So, the current meta-analysis aimed to compare the outcome of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass. Fifteen studies were included, enrolling 53,488 patients. Based on the outcome of analysis, regarding internal hernia, Petersen space's IH, jejunal mesenteric's IH, hospital days, and reoperation, closure of the mesentery was better than non-closure. Besides, small bowel obstruction, anastomosis ulcer, stenosis, leakage, bleeding, gastrointestinal perforation, and postoperative BMI of patients show no difference between non-closure and closure.

The Status of Blood Lipids Among Children and Adolescents - China, 2016-2017.

What is already known about this topic?: Dyslipidemia is attributed to cardiovascular disease (CVD). A recent report suggests dyslipidemia prevalence has increased among children and adolescents. What is added by this report?: Dyslipidemia prevalence was 19.43% among Chinese children and adolescents aged 6-17 years in 2016-2017. The abnormal blood lipid prevalence and the average blood lipid levels showed a diversified distribution across demographics. What are the implications for public health practice?: Continued monitoring of abnormal blood lipids among Chinese children and adolescents, especially triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), may inform public health interventions to promote long-term cardiovascular health and prevent CVD in adulthood.

Single-cell transcriptomics-based multidisease analysis revealing the molecular dynamics of retinal neurovascular units under inflammatory and hypoxic conditions.

The retinal neurovascular unit (NVU) is paramount to maintaining the homeostasis of the retina and determines the progression of various diseases, including diabetic retinopathy (DR), glaucoma, and retinopathy of prematurity (ROP). Although some studies have investigated these diseases, a combined analysis of disease-wide etiology in the NUV at the single-cell level is lacking. Herein, we constructed an atlas of the NVU under inflammatory and hypoxic conditions by integrating single-cell transcriptome data from retinas from wild-type, AireKO, and NdpKO mice. Based on the heterogeneity of the NVU structure and transcriptome diversity under normal and pathological conditions, we discovered two subpopulations of Müller cells: Aqp4hi and Aqp4lo cells. Specifically, Aqp4lo cells expresses phototransduction genes and represent a special type of Müller cell distinct from Aqp4hi cells, classical Müller cells. AireKO mice exhibit experimental autoimmune uveitis (EAU) with severe damage to the NVU structure, mainly degeneration of Aqp4hi cells. NdpKO mice exhibited familial exudative vitreoretinopathy (FEVR), with damage to the endothelial barrier, endothelial cell tight junction destruction and basement membrane thickening, accompanied by the reactive secretion of proangiogenic factors by Aqp4hi cells. In both EAU and FEVR, Aqp4hi cells are a key factor leading to NVU damage, and the mechanism by which they are generated is regulated by different transcription factors. By studying the pattern of immune cell infiltration in AireKO mice, we constructed a regulatory loop of "inflammatory cells/NVU - monocytes - APCs - Ifng+ T cells", providing a new target for blocking the inflammatory cascade. Our elucidation of the cell-specific molecular changes, cell-cell interactions and transcriptional mechanisms of the retinal NVU provides new insights to support the development of multipurpose drugs to block or even reverse NVU damage.

ChREBP-ß/TXNIP aggravates frucose-induced renal injury through triggering ferroptosis of renal tubular epithelial cells.

High fructose intake is an essential risk factor for kidney injury. However, the specific mechanism underlying high fructose-induced kidney injury remains unclarified. Carbohydrate response element-binding protein (ChREBP) is a key transcriptional activator that regulates fructose metabolism. ChREBP-ß exhibits sustained activity due to the lack of a low glucose inhibitory domain, and is thus described as the active form of ChREBP. In this study, a mouse model with specific overexpression of ChREBP-ß in the renal tubule was established by using the Cre/LoxP method. Quantitative proteomic analysis and experimental verification results suggest that ChREP-ß overexpression leads to ferroptosis of renal tubular epithelial cells and kidney injury. ChREPB-ß promotes the gene transcription of thioredoxin-interacting protein (TXNIP) and thereby increases its expression level. TXNIP is associated with activation of ferroptosis. TXNIP can initiate ferroptosis and eventually contribute to high fructose-induced renal tubular epithelial cell damage. Through down-regulating ChREBP-ß, metformin can inhibit gene transcription of TXNIP, attenuate high fructose-induced ferroptosis in renal tubular epithelial cells, and alleviate kidney injury. In conclusion, ChREBP-ß mediates fructose-induced ferroptosis of renal tubular epithelial cells, and metformin with a ChREBP-ß inhibitory effect may be a potential treatment for ferroptosis of renal tubular epithelial cells.

Single-cell RNA sequencing reveals the Müller subtypes and inner blood-retinal barrier regulatory network in early diabetic retinopathy.

As the basic pathological changes of diabetic retinopathy (DR), the destruction of the blood-retina barrier (BRB) and vascular leakage have attracted extensive attention. Without timely intervention, BRB damage will eventually lead to serious visual impairment. However, due to the delicate structure and complex function of the BRB, the mechanism underlying damage to the BRB in DR has not been fully clarified. Here, we used single-cell RNA sequencing (RNA-seq) technology to analyze 35,910 cells from the retina of healthy and streptozotocin (STZ)-induced diabetic rats, focusing on the degeneration of the main cells constituting the rat BRB in DR and the new definition of two subpopulations of Müller cells at the cell level, Ctxn3 +Müller and Ctxn3 -Müller cells. We analyzed the characteristics and significant differences between the two groups of Müller cells and emphasized the importance of the Ctxn3 +Müller subgroup in diseases. In endothelial cells, we found possible mechanisms of self-protection and adhesion and recruitment to pericytes. In addition, we constructed a communication network between endothelial cells, pericytes, and Müller subsets and clarified the complex regulatory relationship between cells. In summary, we constructed an atlas of the iBRB in the early stage of DR and elucidate the degeneration of its constituent cells and Müller cells and the regulatory relationship between them, providing a series of potential targets for the early treatment of DR.

PRR15 Is a Novel Diagnostic and Prognostic Biomarker in Papillary Thyroid Cancer and Modulates the Tumor Microenvironment.

Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with PTC who are already in an advanced state have a dismal outlook. This study aimed to establish the diagnostic relevance of PRR15 expression in PTC patients as well as its levels in PTC samples and its connection with immune infiltrates. The TCGA and GEO datasets were combed through to obtain information on PTC patients. The "Limma" program was used to screen for differentially expressed mRNAs (DEMs), and the results were displayed using volcano plots and heat maps. The Wilcoxon test was used to examine the level of PRR15 expression in PTC patients in comparison with that of normal tissues. To study the connection between the immune infiltration level and PRR15 expression in PTC, the single-sample sequence set enrichment analysis (ssGSEA) from the R package was utilized. The expression of PRR15 was analyzed with RT-PCR in PTC cells and normal cells. In order to evaluate the diagnostic significance of PRR15 expression, ROC assays were carried out. Experiments using CCK-8 were carried out to investigate the impact that PRR15 knockdown could have on the proliferation of PTC cells. In this study, 17 overlapped DEMs between PTC specimens and normal specimens were identified, including MPPED2, IPCEF1, SLC4A4, PKHD1L1, DIO1, CRABP1, TPO, TFF3, SPX, TCEAL2, ZCCHC12, SYTL5, PRR15, CHI3L1, SERPINA1, GABRB2, and CITED1. Our attention focused on PRR15 which was highly expressed in PTC specimens as compared with nontumor specimens. PRR15 had an AUC value of 0.926 (95% CI 0.902-0.950) for PTC based on TCGA datasets. Pan-cancer assays suggested PRR15 as an oncogenic gene in many types of tumors. Moreover, we found that PRR15 expression was positively correlated with eosinophils, NK cells, NK CD56bright cells, IDC, macrophages, DC, mast cells, and Th1 cells. Further investigations with CCK-8 demonstrated that inhibiting PRR15 resulted in a decrease in the proliferation of PTC cells. Overall, PRR15 was confirmed to be a biomarker for PTC patients and a predictor of response to immunotherapy.

Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Non-Hypertensive Adults - China, 2018-2019.

What is already known about this topic?: High sodium and low potassium in 24 h urinary excretion were associated with elevated blood pressure. What is added by this report?: With increasing body mass index levels, decreasing unit urinary sodium excretion was more effective in reducing systolic and diastolic blood pressure, and increasing unit urinary potassium excretion was more effective in reducing diastolic blood pressure. What are the implications for public health practice?: Reducing sodium and increasing potassium intake was more effective in reducing blood pressure in overweight and obese non-hypertensive adults compared to underweight and normal weight adults.

Outer Membrane Vesicles Secreted by Helicobacter pylori Transmitting Gastric Pathogenic Virulence Factors.

Helicobacter pylori (H. pylori) is known to be a major pathogen causing gastric diseases through its direct localization in gastric epithelium cells. H. pylori releases outer membrane vesicles (OMVs) throughout the growth process. The content, function, and mechanism of H. pylori OMVs in gastric epithelial cells remain unclear. In this study, we extracted and characterized H. pylori OMVs of two strains (standard strain NCTC11637 and clinical strain Hp-400) and analyzed the specific content by proteomic technology. We identified more than 400 proteins in H. pylori OMVs. In addition, we investigated the impact of H. pylori OMVs on cellular functions by detecting proteomic changes in GES1 cells. GES1 cells cocultured with increasing concentrations of H. pylori OMVs were subjected to quantitative proteomic analyses using label-free methods for relative quantitation. The results showed that a total of 4261 proteins were verified, 153 of which were significantly altered in abundance when cocultured with NCTC11637 OMVs, and a total of 4234 proteins in Hp-400 OMVs, 390 of which were significantly altered. Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway mapping identified significantly altered inflammatory and cancer signaling pathways, including metabolic pathways and the PI3K-Akt signaling pathway. Furthermore, we explored the proteomic changes in GES1 cells induced by H. pylori. Bioinformatics analysis showed that changes in multiple pathways coincided with OMV-mediated proteomic changes. Based on these results, H. pylori induced pathogenicity in epithelial cells at least partially by secreting OMVs that mediated dramatic and specific proteomic changes in host cells. Data are available via ProteomeXchange with identifiers PXD025216, PXD025259, and PXD025281.

Prostaglandin F2α protects against pericyte apoptosis by inhibiting the PI3K/Akt/GSK3ß/ß-catenin signaling pathway.

BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the main cause of non-traumatic blindness in adults. Pericyte loss is known to be an early pathological change of DR. Our group's previous research indicated that prostaglandin F2α (PGF2α) acts as an eicosanoidal protector against non-proliferative DR that can regulate the mobility of pericytes in a RhoA-mediated manner. However, the effect of PGF2α on pericyte apoptosis has yet to be described. METHODS: Two animal models were constructed: a high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mouse model and a spontaneous type 2 diabetes db/db mouse model. We analyzed pathological changes, and performed TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining and western blot to detect apoptosis in the retinas of diabetic mice. For our in vitro experiments, we selected human retinal pericytes and subjected them to high-glucose (HG), PGF2α, and AL8810 (an antagonist of the PGF2α receptor) treatment. Subsequently, apoptosis and the levels of PI3K/Akt/GSK3ß/ß-catenin pathway-related proteins were detected by TUNEL staining and western blot, respectively. RESULTS: The levels of apoptosis were increased in the retinas of diabetic mice in both T2DM models. In vitro, HG treatment increased apoptosis and inhibited PI3K/Akt/GSK3ß/ß-catenin signaling in pericytes. In contrast, PGF2α treatment inhibited pericyte apoptosis while increasing the levels of the PI3K, p-Akt/t-Akt, p-GSK3ß/t-GSK3ß, and ß-catenin proteins; however, these PGF2α-induced effects were eliminated by ALL80. CONCLUSIONS: PGF2α may make a key contribution to reducing pericyte apoptosis and protecting against DR via its inhibition of the PI3K/Akt/GSK3ß/ß-catenin signaling pathway.

Aerosol-induced direct radiative forcing effects on terrestrial ecosystem carbon fluxes over China.

Atmospheric aerosols can change vegetation photosynthesis through the effects of aerosols on radiation, which will affect the peak carbon dioxide emissions and carbon neutrality at global scales. In this study, we quantify the aerosol-induced direct radiation forcing (ADRF) in China from 2001 to 2014 based on the radiation flux simulation used by the Fu-Liou radiation transfer model under with-aerosols and no-aerosols scenarios. Using the radiation simulation results, we modify the atmospheric forcing datasets to drive Community Land Model 4.5 (CLM4.5) to gain the changes in carbon fluxes in China caused by ADRF. The results show that these two models are accurate in estimating radiation (R2 = 0.78-0.88) and carbon fluxes (R2 = 0.73-0.75) in China. High levels of ADRFs were captured in China, especially with increasing diffuse fraction, resulting in the diffusing fertilization effect occurring in most areas of China. The ADRF can increase cumulative gross primary productivity (GPP) and total ecosystem respiration (ER) by 3.20 gC m-2 and 5.13 gC m-2 per year, respectively. From 2001 to 2014, the diffusing fertilization effects experienced trends of increasing first and then decreasing. However, ADRFs in some regions of China show negative effects on carbon fluxes due to vulnerable vegetation functional types and high aerosol loading. The ADRF will also enable soil temperature decreases and volumetric soil water increases, which is closely related to changes in carbon fluxes. Meanwhile, due to changes in soil water and heat conditions, N2O and CH4 production will also be disturbed, and ADRF increases the global warming potential (GWP) for both greenhouse gases. This phenomenon indicated that atmospheric aerosol pollution control is far-reaching significance for peaking carbon dioxide emissions before 2030.

Effects of Two Starch Synthase IIa Isoforms on Grain Components and Other Grain Traits in Barley.

Starch biosynthesis in cereal crops is a complex pathway regulated by multiple starch synthetic enzymes. Starch synthase IIa (SSIIa) is well-known to be one of the major starch synthases and is very important in amylopectin biosynthesis. It has significant effects on grain composition and kernel traits. However, there are few reports on the association of natural variation of SSIIa in barley and grain composition and characteristics. In this work, two SSIIa isoforms were first identified as SSIIaH and SSIIaL by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mass spectrometry, and Western blotting. Sequence analysis of the SSIIa gene demonstrated that a 33 bp insertion coding a peptide of APPSSVVPAKK caused different SSIIa, e.g., SSIIaH and SSIIaL. Based on this molecular difference, a polymerase chain reaction marker was developed, which could be used to screen different SSIIa genotypes easily. Kernel hardness of SSIIaL genotypes was significantly higher than that of SSIIaH Chinese barley cultivars. The proportion of SSIIaL genotypes was extremely low in Australian barley cultivars (5/24) and much higher in Tibetan hull-less barley cultivars (46/74), consistent with the end-use requirements of barley grain. This study provided new information in barley endosperm starch synthesis and indicated that it is valuable for choosing the preferred SSIIa genotype according to the end-use requirements.

Insight into the Properties of Plasmonic Au/TiO2 Activated by O2/Ar Plasma.

The performance of CO oxidation over plasmonic Au/TiO2 photocatalysts is largely determined by the electric discharge characteristics and physicochemical properties of discharge gas. To explore the activation mechanism of Au/TiO2, an O2 and Ar mixture gas as a discharge gas was employed to activate Au/TiO2. The photocatalytic activity in CO oxidation over activated Au/TiO2 was obtained, and the electric discharge characteristics, Au nanoparticle size, surface chemical state, optical property and CO chemisorption were thoroughly characterized. As the O2 content increases from 10% to 50%, the amplitude of the current pulses increases, but the number of pulses and the discharge power decrease. The photocatalytic activity of Au/TiO2 rises rapidly at first and then remains constant at 75% when the O2 content is above 50%. Compared with the discharge gas of 10% and 30% O2/Ar, the sample activated by 50% O2/Ar plasma possesses less metallic Au and more surface oxygen species and carbonate species by X-ray photoelectron spectroscopy, which is consistent with UV-vis diffuse reflectance spectra and CO chemisorption. The CO chemisorption capacities of the activated samples are the same at a long exposure time due to the approximate Au nanoparticle size observed by transmission electron microscopy. An increase in carbonate species generated from the oxygen species on the surface of TiO2 is discovered.

p-Hydroxylcinnamaldehyde from cochinchinamomordica seed reverses resistance to TRAIL in human oesophageal squamous cell carcinoma via the activation of the p38 mitogen-activated protein kinase signalling pathway.

BACKGROUND: Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. METHODS: MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. RESULTS: We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. CONCLUSION: Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.

Colon-specific microspheres loaded with puerarin reduce tumorigenesis and metastasis in colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) is a common malignancy that develops in chronically inflamed mucosa and is usually accompanied by metastases at other sites. Puerarin, a natural isoflavone isolated from the root of the Pueraria lobata (Willd.) Ohwi, has potential anti-colon cancer activity. However, the poor solubility and low bioavailability of puerarin has restricted its application in the pharmaceutical industry. In the present study, pH-responsive alginate microspheres loaded with puerarin were prepared by emulsification/internal gelation for targeted treatment of colitis-associated colorectal cancer. Herein, puerarin, as an active drug, could participate in the construction of alginate microspheres with hydrogen bonding. The microspheres exhibited pH-responsive release behavior with little release of puerarin in simulated gastric fluid and high amounts (approximately 55%) of release in simulated colonic fluid. A fluorescence tracer indicated microspheres had high retention time of more than 20 h in the colon. Meanwhile, puerarin-loaded alginate microspheres not only significantly decreased the inflammatory response by downregulating the levels of pro-tumorigenic cytokines, but they reduced tumorigenesis and metastasis by inhibiting epithelial-mesenchymal transitions in AOM/DSS-induced colitis-associated colorectal cancer in mice. The overall results suggested that puerarin-loaded alginate microspheres could effectively inhibit development of colonic tumors, which could be developed as a promising therapeutic strategy for colitis-associated colorectal cancer.

Seaweed-Liked WS2/rGO Enabling Ultralong Cycling Life and Enhanced Rate Capability for Lithium-Ion Batteries.

WS2 is considered as a potential anode material for lithium ion batteries (LIBs) with superior theoretical capacity and stable structure with two-dimensional which facilitates to the transportation and storage of lithium ion. Nevertheless, the commercial recognition of WS2 has been impeded by the intrinsic properties of WS2, including poor electrical conductivity and large volume expansion. Herein, a seaweed-liked WS2/reduced graphene oxide (rGO) composites has been fabricated through a procedure involving the self-assembling of WO42-, hexadecyl trimethyl ammonium ion with graphene oxide (GO) and the subsequent thermal treatment. The WS2/rGO nanocomposite exhibited the outstanding electrochemical property with a stable and remarkable capacity (507.7 mAh·g-1) at 1.0 A·g-1 even after 1000 cycles. This advanced electrochemical property is due to its seaweed-liked feature which can bring in plentiful active sites, ameliorate the stresses arisen from volume variations and increase charge transfer rate.