A metastasis map of human cancer cell lines.

Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical owing to the complexity of in vivo models. Here we introduce an in vivo barcoding strategy that is capable of determining the metastatic potential of human cancer cell lines in mouse xenografts at scale. We validated the robustness, scalability and reproducibility of the method and applied it to 500 cell lines1,2 spanning 21 types of solid tumour. We created a first-generation metastasis map (MetMap) that reveals organ-specific patterns of metastasis, enabling these patterns to be associated with clinical and genomic features. We demonstrate the utility of MetMap by investigating the molecular basis of breast cancers capable of metastasizing to the brain-a principal cause of death in patients with this type of cancer. Breast cancers capable of metastasizing to the brain showed evidence of altered lipid metabolism. Perturbation of lipid metabolism in these cells curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a resource to support metastasis research.

Programmable Proteolysis-Activated Transcription for Highly Sensitive Ratiometric Electrochemical Detection of Viral Protease.

Viral proteases play a crucial role in viral infection and are regarded as promising targets for antiviral drug development. Consequently, biosensing methods that target viral proteases have contributed to the study of virus-related diseases. This work presents a ratiometric electrochemical sensor that enables highly sensitive detection of viral proteases through the integration of target proteolysis-activated in vitro transcription and the DNA-functionalized electrochemical interface. In particular, each viral protease-mediated proteolysis triggers the transcription of multiple RNA outputs, leading to amplified ratiometric signals on the electrochemical interface. Using the NS3/4A protease of the hepatitis C virus as a model, this method achieves robust and specific NS3/4A protease sensing with sub-femtomolar sensitivity. The feasibility of this sensor was demonstrated by monitoring NS3/4A protease activities in virus-infected cell samples with varying viral loads and post-infection times. This study provides a new approach to analyzing viral proteases and holds the potential for developing direct-acting antivirals and novel therapies for viral infections.

Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study.

INTRODUCTION/AIMS: NURTURE (NCT02386553) is an open-label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 y of follow-up (data cut: February 15, 2021) are reported. METHODS: The primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety. RESULTS: Median age of children was 4.9 (3.8-5.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three SMN2 copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two SMN2 copies achieved sitting without support, 14/15 walking with assistance, and 13/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two SMN2 copies, minimum baseline compound muscle action potential amplitude ≥2 mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two SMN2 copies. DISCUSSION: These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5 y of nusinersen treatment. Inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.

[Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway].

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

Spatial and temporal patterns of prostate cancer burden and their association with Socio-Demographic Index in Asia, 1990-2019.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer for males worldwide, but the spatial and temporal trends of prostate cancer burden remain unknown in Asia. This study aimed to investigate the changing spatial and temporal trends of incidence, prevalence, mortality, disability-adjusted life year (DALY), and mortality-to-incidence ratio (MIR) of prostate cancer, and their association with the Socio-Demographic Index (SDI) in 48 Asian countries from 1990 to 2019. METHODS: Data were extracted from the Global Health Data Exchange query tool, covering 48 Asian countries from 1990 to 2019. The average annual percent change was calculated to evaluate temporal trends. Spatial autocorrelation analysis was used to obtain spatial patterns, and the association between SDI and prostate cancer burden was estimated using a spatial panel model. RESULTS: In Asia, the age-standardized incidence and prevalence of prostate cancer increased in almost all countries, and its mortality and DALY also increased in over half of the countries. Significantly regional disparities were found in Asia, and the hot spots for incidence, prevalence, mortality, and DALY were all located in Western Asia, the hot spots of percent change also occurred in Western Asia for incidence and DALY. Furthermore, SDI had a positive association with mortality (coef = 2.51, 95% confidence interval [CI]: 2.13-2.90) and negative association with DALY (coef = -14.99, 95% CI: -20.37 to -9.60) and MIR (coef = -0.95, 95%CI: -0.99 to -0.92). CONCLUSIONS: Prostate cancer burden increased rapidly throughout Asia and substantial disparities had persisted between countries. Geographically targeted interventions are needed to reduce the prostate cancer burden throughout Asia and in specific countries.

Secular trends of morbidity and mortality of prostate, bladder, and kidney cancers in China, 1990 to 2019 and their predictions to 2030.

BACKGROUND: Prostate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies. METHODS: Numbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI). RESULTS: Predictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the < 60 and the ≥ 60 age groups. CONCLUSION: Morbidity and mortality of the three genitourinary cancers are predicted to increase further over the next decade. It highlights the need for timely development and implementation of optimal health policies to curb the epidemic trends.

Access to Sulfur-Containing Bisheterocycles through Base-Promoted Consecutive Tandem Cyclization/Sulfenylation with Elemental Sulfur.

A convenient and efficient tandem cyclization/sulfenylation of o-alkynyl-phenols/-anilines/enaminones for the synthesis of diverse sulfur-containing bisheterocycles has been developed using stable, odorless, and easy-to-handle elemental S8 as a building block under green chemistry conditions. Notably, a one-step simple base-mediated organic transformation affords a benzofuran (indole or chromone) ring and two C-S bonds. Attractive features of this methodology include the absence of a metal catalyst, mild conditions, good functional group tolerance, and valuable product structures.

Synergistic effects of Rapamycin and Fluorouracil to treat a gastric tumor in a PTEN conditional deletion mouse model.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) in PI3K/Akt/mTOR pathway is essential in inhibiting tumor growth and metastasis. However, whether the mutation of PTEN gene could induce tumorigenesis and impact the treatment of gastric cancer is still unclear. The purpose of the study was to investigate the combined treatment of gastric tumorigenesis using Rapamycin and Fluorouracil (5-Fu) through interfering with the Akt/mTOR pathway in a mouse model with PTEN conditional deletion. Three groups of mice were exposed for 5 days to Rapamycin and 5-Fu separately and together. The gene expression of the Akt/mTOR pathway, the protein expression of caspase-3 and p-Akt, p-S6K and p-4EBP1, and the pathological changes in stomachs were analyzed. Our study demonstrates that the conditional PTEN deletion in the cells of glandular stomach induces hyperplastic gastric tumors in mice. The combined Rapamycin administration with 5-Fu resulted in better outcomes than their separate administration for the treatment of gastric cancer by inhibiting the mTOR signal pathway. Our study indicates that Rapamycin has a synergistic interaction with chemotherapeutic 5-Fu, and demonstrates a potential therapeutic combination treatment on glandular stomach tumor with PTEN functional absence or aberrantly activated Akt/mTOR pathway. It provides important insights into the inhibition of the Akt/mTOR pathway in gastric cancer clinical therapy.

Interactive effects of aquatic nitrogen and plant biomass on nitrous oxide emission from constructed wetlands.

Understanding of mechanisms in nitrous oxide (N2O) emission from constructed wetland (CW) is particularly important for the establishment of related strategies to reduce greenhouse gas (GHG) production during its wastewater treatment. However, plant biomass accumulation, microbial communities and nitrogen transformation genes distribution and their effects on N2O emission from CW as affected by different nitrogen forms in aquatic environment have not been reported. This study investigated the interactive effects of aquatic nitrogen and plant biomass on N2O emission from subsurface CW with NH4+-N (CW-A) or NO3--N (CW-B) wastewater. The experimental results show that NH4+-N and NO3--N removal efficiencies from CW mesocosms were 49.4% and 87.6%, which indirectly lead to N2O emission fluxes of CW-A and CW-B maintained at 213 ± 67 and 462 ± 71 µg-N/(m2·h), respectively. Correlation analysis of nitrogen conversion dynamic indicated that NO2--N accumulation closely related to N2O emission from CW. Aquatic NH4+-N could up-regulate plant biomass accumulation by intensifying citric acid cycle, glycine-serine-threonine metabolism etc., resulting in more nitrogen uptake and lower N2O emission/total nitrogen (TN) removal ratio of CW-A compared to CW-B. Although the abundance of denitrifying bacteria and N2O reductase nosZ in CW-B were significantly higher than that of CW-A, after fed with mixed NH4+-N and NO3--N influent, N2O fluxes and N2O emission/TN removal ratio in CW-A were extremely close to that of CW-B, suggesting that nitrogen form rather than nitrogen transformation microbial communities and N2O reductase nosZ determines N2O emission from CW. Hence, the selection of nitrate-loving plants will play an important role in inhibiting N2O emission from CW.

A potential therapeutic strategy for prostatic disease by targeting the oral microbiome.

Nowadays, human microbiome research is rapidly growing and emerging evidence has witnessed the critical role that oral microbiome plays in the process of human health and disease. Oral microbial dysbiosis has been confirmed as a contributory cause for diseases in multiple body systems, ranging from the oral cavity to the gastrointestinal, endocrine, immune, cardiovascular, and even nervous system. As research progressing, oral microbiome-based diagnosis and therapy are proposed and applied, which may represent potential drug targets in systemic diseases. Recent studies have uncovered the possible association between periodontal disease and prostatic disease, suggesting new prevention and therapeutic treatment for the disease by targeting periodontal pathogens. Thus, we performed this review to first explore the association between the oral microbiome and prostatic disease, according to current knowledge based on published articles, and then mainly focus on the underlying molecular and cellular mechanisms and the potential prevention and treatment derived from these mechanistic studies.

Whole-genome classification of rotavirus C and genetic diversity of porcine strains in the USA.

Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19-G31, P[22]-P[26], R5, A9-A12, N9-N10, T7-T9 and E6-E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.

Combination of optimized tissue engineering bone implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits.

In this study, effects of combining optimized tissue engineering bone (TEB) implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits were investigated. Physiological characteristics of bone marrow mesenchymal stem cells (BMMSCs), compact bone cells (CBCs), and bone marrow and compact bone coculture cells (BMMSC-CBCs) were compared to select the optimal seed cells for optimized TEB construction. Rabbits with segmental bone defects were treated in different ways (cancellous bone scaffold for group A, cancellous bone scaffold and mechanical loading for group B, optimized TEB for group C, optimized TEB and mechanical loading for group D, n = 4), and the bone repair were compared. BMMSC-CBCs showed better proliferation capacity than CBCs (p < 0.01) and stronger osteogenic differentiation ability than BMMSCs (p < 0.05). Heel-strike like mechanical loading improved proliferation and osteogenic differentiation ability and expression levels of TGFß1 as well as BMP2 of seed cells in vitro (p < 0.05). At week 12 post-operation, group D showed the best bone repair, followed by groups B and C, while group A finished last (p < 0.05). During week 4 to 12 post-operation, group D peaked in terms of expression levels of TGFß1, BMP2, and OCN, followed by groups B and C, while group A finished last (p < 0.05). Thus, BMMSC-CBCs showed good proliferation and osteogenic differentiation ability, and they were thought to be better as seed cells than BMMSCs and CBCs. The optimized TEB implantation combined with heel-strike like mechanical loading had a synergistic effect on bone defect healing, and enhanced expression of TGFß1 and BMP2 played an important role in this process.

Diastasis recti abdominis in adult women based on abdominal computed tomography imaging: Prevalence, risk factors and its impact on life.

AIMS AND OBJECTIVES: This study aimed to obtain the incidence of diastasis recti abdominis (DRA) and analyse possible risk factors in adult females. Moreover, the relationships between DRA and lower back pain, pelvic floor function and quality of life were also analysed. BACKGROUND: Diastasis recti abdominis is a separation of the abdominal muscles at the linea alba. Currently, studies on the prevalence rates, risk factors and consequences of DRA are varied. In particular, reports on DRA among adult women are lacking. DESIGN: A one-sample questionnaire study design is used following the STROBE checklist. METHODS: The inter-rectus distance was measured by computed tomography in 644 women. Custom questionnaires, the Oswestry Disability Index, The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were used to investigate personal information, the subjects' back pain, pelvic floor function and quality of life, respectively. RESULTS: The incidence of DRA was 28.4%. Age, the number of pregnancies, BMI and diabetes were influencing factors for DRA. After age stratification, pregnancy and diabetes were found to be risk factors for DRA in young women, and obesity and diabetes were risk factors for DRA in older women. This study showed that the association between DRA and low back pain was highly significant. CONCLUSIONS: Diastasis recti abdominis is common in adult women. Avoiding multiple pregnancies, preventing diabetes and controlling weight may prevent DRA, which may be beneficial for decreasing low back pain in women. RELEVANCE TO CLINICAL PRACTICE: The findings have important implications for the health of adult women which can provide the basis for appropriate nursing implementation for DRA patients. The application of specific prevention and intervention measures for the risk factors may reduce the severity of low back pain.

Metabolomic Pattern Predicts Incident Coronary Heart Disease.

Objective- Alterations in the serum metabolome may be detectable in at-risk individuals before the onset of coronary heart disease (CHD). Identifying metabolomic signatures associated with CHD may provide insight into disease pathophysiology and prevention. Approach and Results- Metabolomic profiling (chromatography-mass spectrometry) was performed in 2232 African Americans and 1366 European Americans from the ARIC study (Atherosclerosis Risk in Communities). We applied Cox regression with least absolute shrinkage and selection operator to select metabolites associated with incident CHD. A metabolite risk score was constructed to evaluate whether the metabolite risk score predicted CHD risk beyond traditional risk factors. After 30 years of follow-up, we observed 633 incident CHD cases. Thirty-two metabolites were selected by least absolute shrinkage and selection operator to be associated with CHD, and 19 of the 32 showed significant individual associations with CHD, including a sugar substitute, erythritol. Theophylline (hazard ratio [95% CI] =1.16 [1.09-1.25]) and gamma-linolenic acid (hazard ratio [95% CI] =0.89 [0.81-0.97]) showed the greatest positive and negative associations with CHD, respectively. A 1 SD greater standardized metabolite risk score was associated with a 1.37-fold higher risk of CHD (hazard ratio [95% CI] =1.37 [1.27-1.47]). Adding the metabolite risk score to the traditional risk factors significantly improved model predictive performance (30-year risk prediction: Δ C statistics [95% CI] =0.016 [0.008-0.024], continuous net reclassification index [95% CI] =0.522 [0.480-0.556], integrated discrimination index [95% CI] =0.038 [0.019-0.065]). Conclusions- We identified 19 metabolites from known and novel metabolic pathways that collectively improved CHD risk prediction. Visual Overview- An online visual overview is available for this article.

Preparation of pyramidal SnO/CeO2 nano-heterojunctions with enhanced photocatalytic activity for degradation of tetracycline.

Pyramidal SnO/CeO2 nano-heterojunction photocatalysts were successfully synthesized via a facile hydrothermal method. The structural characterization was investigated by using common characterization tools. The content of SnO affected the morphology and photocatalytic performance of the SnO/CeO2 nano-heterojunctions. With the increase of the SnO content, the morphology of the samples changed from a spherical structure to a pyramidal structure. The photocurrent of the SnO/CeO2 (1:6) sample was about 36 times that of pure CeO2. With SnO/CeO2 (1:6) as the photocatalyst, the degradation rate of tetracycline (TC) was 99% within 140 min under visible light and after five cyclic tests the photocatalytic efficiency of TC remained at 98%, which suggests that the SnO/CeO2 (1:6) nano-heterojunction had a high photocatalytic efficiency and stable photocatalytic performance. These results indicate that SnO/CeO2 (1:6) nano-heterojunction possesses broad prospects for industrial application.

A lightweight convolutional neural network for assessing an EEG risk marker for sudden unexpected death in epilepsy.

BACKGROUND: Convolutional neural network (CNN) has achieved state-of-art performance in many electroencephalogram (EEG) related studies. However, the application of CNN in prediction of risk factors for sudden unexpected death in epilepsy (SUDEP) remains as an underexplored area. It is unclear how the trade-off between computation cost and prediction power varies with changes in the complexity and depth of neural nets. METHODS: The purpose of this study was to explore the feasibility of using a lightweight CNN to predict SUDEP. A total of 170 patients were included in the analyses. The CNN model was trained using clips with 10-s signals sampled from the original EEG. We implemented Hann function to smooth the raw EEG signal and evaluated its effect by choosing different strength of denoising filter. In addition, we experimented two variations of the proposed model: (1) converting EEG input into an "RGB" format to address EEG channels underlying spatial correlation and (2) incorporating residual network (ResNet) into the bottle neck position of the proposed structure of baseline CNN. RESULTS: The proposed baseline CNN model with lightweight architecture achieved the best AUC of 0.72. A moderate noise removal step facilitated the training of CNN model by ensuring stability of performance. We did not observe further improvement in model's accuracy by increasing the strength of denoising filter. CONCLUSION: Post-seizure slow activity in EEG is a potential marker for SUDEP, our proposed lightweight architecture of CNN achieved satisfying trade-off between efficiently identifying such biomarker and computational cost. It also has a flexible interface to be integrated with different variations in structure leaving room for further improvement of the model's performance in automating EEG signal annotation.

Triplex-Functionalized DNA Tetrahedral Nanoprobe for Imaging of Intracellular pH and Tumor-Related Messenger RNA.

A new triplex-functionalized DNA tetrahedral nanoprobe is proposed herein for monitoring pH and messenger RNA (mRNA) in living cells. Different from traditional DNA tetrahedron-based nanoprobes, DNA triplex was employed to serve as important conformational conversion elements. Inspired by the low extracellular pH in tumor cells, the mRNA-targeted H1 and H2 were stably assembled on the extended short hairpin probes of DNA tetrahedron via Hoogsteen bonding to form DNA triplex. Due to the high intracellular pH and presence of target mRNA, hybridization chain reaction (HCR) was triggered between H1 and H2 which were released from the dissociation of DNA triplex, and the generated long double-stranded DNA activated a Föster resonance energy transfer (FRET) signal indicating target mRNA expression even at very low contents. By combining the distinguishing feature of DNA triplex structure (pH-responsive) and HCR (signal amplification), sensitive imaging of intracellular pH and tumor-related mRNA can be realized. As a further application, dynamic imaging of intracellular pH and mRNA during "mitochondria-dependent" pathway apoptosis was successfully achieved in human breast cancer cells, which indicated huge potential of our proposed nanoprobe in early diagnosis and treatment of diseases.

Dexamethasone-induced cytotoxicity in human osteoblasts is associated with circular RNA HIPK3 downregulation.

Dexamethasone (DEX) exerts potent cytotoxicity against cultured human osteoblasts. The current study examined the role of the circular RNA HIPK3 (circHIPK3) in the mechanism of cell death. We found that circHIPK3 expression was downregulated in DEX-treated human osteoblasts and circHIPK3 levels decreased in human necrotic femoral head tissues. In OB-6 osteoblastic cells and primary human osteoblasts ectopic overexpression of circHIPK3 potently suppressed DEX-induced apoptosis and programmed necrosis. Conversely, knockdown of circHIPK3by targeted siRNAs enhanced DEX-induced cytotoxicity in human osteoblasts. We further observed that microRNA-124 (miR-124), a key miRNA sponged by circHIPK3, accumulated following DEX treatment in OB-6 cells and primary osteoblasts. Confirming the role of miR-124 in DEX-induced cytotoxicity, miR-124 inhibitor attenuated cell death in human osteoblasts. Conversely, forced overexpression of miR-124 mimicked DEX-induced actions and induced cytotoxicity in human osteoblasts. We conclude that DEX-induced cytotoxicity in human osteoblasts is associated with circHIPK3 downregulation.

Reaction Kinetics at PDMS-E Emulsion Droplet-Gelatin Interface.

In this work, interfacial reaction kinetics between α-[3-(2,3-epoxypropoxy)propyl]-ω-butyl-polydimethylsiloxane emulsion droplets with different sizes and gelatin was studied. The results of amino conversion rate determination show that the reaction proceeded in two steps. Fluorescence spectra analysis indicates that step 1 (0-2 h) should be the adsorption of gelatin on droplet surface. In step 2 (2-13 h), amino conversion rate increased rapidly. The reaction rate in step 2 ( k2) was obtained by using the 2nd-order approach to model the grafting reaction kinetics. The quantitative relationships among amino conversion rate, droplet size, the concentration of surfactant, reaction temperature, and time were described by linear regression models in given ranges of conditions in step 2. Thermodynamic analysis indicates that the interfacial reaction is an endothermic reaction. After 13 h, the reaction was almost stopped.