Genomic hallmarks and therapeutic targets of ribosome biogenesis in cancer.

Hyperactive ribosome biogenesis (RiboSis) fuels unrestricted cell proliferation, whereas genomic hallmarks and therapeutic targets of RiboSis in cancers remain elusive, and efficient approaches to quantify RiboSis activity are still limited. Here, we have established an in silico approach to conveniently score RiboSis activity based on individual transcriptome data. By employing this novel approach and RNA-seq data of 14 645 samples from TCGA/GTEx dataset and 917 294 single-cell expression profiles across 13 cancer types, we observed the elevated activity of RiboSis in malignant cells of various human cancers, and high risk of severe outcomes in patients with high RiboSis activity. Our mining of pan-cancer multi-omics data characterized numerous molecular alterations of RiboSis, and unveiled the predominant somatic alteration in RiboSis genes was copy number variation. A total of 128 RiboSis genes, including EXOSC4, BOP1, RPLP0P6 and UTP23, were identified as potential therapeutic targets. Interestingly, we observed that the activity of RiboSis was associated with TP53 mutations, and hyperactive RiboSis was associated with poor outcomes in lung cancer patients without TP53 mutations, highlighting the importance of considering TP53 mutations during therapy by impairing RiboSis. Moreover, we predicted 23 compounds, including methotrexate and CX-5461, associated with the expression signature of RiboSis genes. The current study generates a comprehensive blueprint of molecular alterations in RiboSis genes across cancers, which provides a valuable resource for RiboSis-based anti-tumor therapy.

Modulation of Buried Interface by 1-(3-aminopropyl)-Imidazole for Efficient Inverted Formamidinium-Cesium Perovskite Solar Cells.

Considering the direct influence of substrate surface nature on perovskite (PVK) film growth, buried interfacial engineering is crucial to obtain ideal perovskite solar cells (PSCs). Herein, 1-(3-aminopropyl)-imidazole (API) is introduced at polytriarylamine (PTAA)/PVK interface to modulate the bottom property of PVK. First, the introduction of API improves the growth of PVK grains and reduces the Pb2+ defects and residual PbI2 present at the bottom of the film, contributing to the acquisition of high-quality PVK film. Besides, the presence of API can optimize the energy structure between PVK and PTAA, which facilitates the interfacial charge transfer. Density functional theory (DFT) reveals that the electron donor unit (R-C ═ N) of the API prefers to bind with Pb2+ traps at the PVK interface, while the formation of hydrogen bonds between the R-NH2 of API and I- strengthens the above binding ability. Consequently, the optimum API-treated inverted formamidinium-cesium (FA/Cs) PSCs yields a champion power conversion efficiency (PCE) of 22.02% and exhibited favorable stability.

Multifunctional Imidazolidinyl Urea Additive Initiated Complex with PbI2 Toward Efficient and Stable Perovskite Solar Cells.

High-quality perovskite absorption layer is the fundamental basis for efficient and stable perovskite solar cells (PSCs). Due to the ionic nature of perovskite components, plentiful charged defects and suspension bonds remain on the surface of perovskite grains after continuous high-temperature annealing. Here, the complex initiated by the introduction of a multifunctional imidazolidinyl urea (IU) additive into the PbI2 precursor solution could serve as nucleation sites and crystallization templates for perovskite crystals to optimize the growth of high-quality perovskite films. By anchoring at the grain boundaries of perovskite films, IU molecules could passivate various types of defects, improve the hydrophobic properties, and inhibit lead leakage. Attributed to reduced defect density, improved charge transport, and inhibited α-FAPbI3 transition, the PSCs prepared based on IU additives achieved a champion power conversion efficiency of 23.18% (21.51% for the control PSCs) with negligible hysteresis and satisfactory stability.

Detection of respiration changes inside biofilms with microelectrodes during exposure to antibiotics.

In order to evaluate the influence of antibiotics on the respiration of subpopulations in biofilms, dissolved oxygen microelectrodes were used to determine the oxygen concentration inside E. Coli biofilms. Based on the results, the oxygen consumption rate varying with depth in the biofilms was calculated before and after the treatment with antibiotics. For both ceftriaxone sodium and chloramphenicol, significant attenuation of oxygen consumption was identified when the system reached steady state. However, by monitoring the oxygen concentration change induced by ceftriaxone sodium, an increased oxygen consumption rate and a shortened oxygen penetration depth were identified in the first few hours, which indicated the accelerated respiration of the subpopulation. Followed by cellular death, the induced respiration acceleration seems to be part of the action mechanism of ceftriaxone sodium. Compared to the planktonic cells, the biofilms showed much higher tolerance to ceftriaxone sodium, which may be attributed to the extended hypoxic zone induced by the accelerated respiration.

The Influence of Oxygen Atoms on Conformation and π-π Stacking of Ladder-Type Donor-Based Polymers and Their Photovoltaic Properties.

A novel ladder-type donor pyran-bridged indacenodithiophene (IDTP) is developed by introducing two oxygen atoms into indacenodithiophene unit. IDTP possesses a twisted backbone and leads to facially asymmetric arrangement of side chains, resulting in enhanced local π-π stacking of according polymer poly[(5,5,11,11-tetrakis(4-octylphenyl)-5,11-dihydrothieno[2',3':5,6]pyrano[3,4-g]thieno[3,2-c]isochromene)-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT, which shows extended absorption range. Moreover, oxygen atoms render deeper highest occupied molecular orbital (HOMO) levels of poly[indacenodithiophene-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT compared with PIDT-FBT, therefore bringing a higher open-circuit voltage (Voc ).

[Assessment of congenital vascular rings with MDCT on children].

OBJECTIVE: To evaluate the value of MDCT on diagnosis of congenital vascular rings on children. METHODS: Retrospective analysis on 43 cases of congenital vascular rings, which underwent MDCT during Oct 2008 to Dec 2014 in Beijing Anzhen hospital affiliated to capital medical university. 21 males, 22 females; age from 29 days to 8 years, mean age 1.46 years, 33 cases are not beyond 1 year. All the results were compared with that of the echocardiogram or record of the surgery. The CT data were read and reconstructed with multiplanar reconstruction (MPR), maximum intensity projection (MPR), minimum intensity projection (MinIP), volume rendering (VR). The image quality was evaluated and the diagnostic value and the standard diagnostic program were discussed. RESULTS: Of 43 cases of vascular rings:there were 6 cases of pulmonary artery sling (13.95%), 9 cases of right aortic arch /aberrant left subclavian artery(20.93%), 18 cases of left aortic arch/aberrant right subclavian artery (41.86%), 10 cases of double aortic arch (23.26%). Forty cases (93.02%) were combined with other cardiovascular or pulmonary malformations. Every malformation was revealed clearly and proved by echocardiogram. Of 3 cases (6.98%) without any other malformation, 2 cases were combined tracheal stenosis. A pulmonary artery sling was proved by surgery; the other 2 cases were double aortic arch. All the images of 43 cases could be reconstructed well. MPR and VR showed the origin, shape, and whole course of vascular rings directly; MinIP and VR could display the shape, width and development of trachea, revealed the relationship between vascular rings, trachea and esophagus. It was important to show and measure the component vascular of the ring. Attention should be paid to the whole course of trachea and esophagus, especially those segments which were close to the ring vascular. The tracheal stenosis as well as intra-cardio anatomy malformations should be measured on MPR images if existed. According to the segmental analysis method, comes the overall final diagnosis. A standard diagnostic program on vascular ring was proposed. CONCLUSION: MDCT axis images with various 3D post processing methods could reveal the compose of vascular rings and the relationship between vascular rings, trachea and esophagus.

Mass Spectrometry-Imaging Analysis of Active Ingredients in the Leaves of Taxus cuspidata.

BACKGROUND: Taxus cuspidata is an endangered evergreen conifer mainly found in Northeast Asia. In addition to the well-known taxanes, several active ingredients were detected in the leaves of T. cuspidata. However, the precise spatial distribution of active ingredients in the leaves of T. cuspidata is largely unknown. RESULTS: in the present study, timsTOF flex MALDI-2 analysis was used to uncover the accumulation pattern of active ingredients in T. cuspidata leaves. In total, 3084 ion features were obtained, of which 944 were annotated according to the mass spectrometry database. The principal component analysis separated all of the detected metabolites into four typical leaf tissues: mesophyll cells, upper epidermis, lower epidermis, and vascular bundle cells. Imaging analysis identified several leaf tissues that specifically accumulated active ingredients, providing theoretical support for studying the regulation mechanism of compound biosynthesis. Furthermore, the relative accumulation levels of each identified compound were analyzed. Two flavonoid compounds, ligustroflavone and Morin, were identified with high content through quantitative analysis of the ion intensity. CONCLUSIONS: our data provides fundamental information for the protective utilization of T. cuspidata.

Unravelling Alkali-Metal-Assisted Domain Distribution of Quasi-2D Perovskites for Cascade Energy Transfer toward Efficient Blue Light-Emitting Diodes.

Solution processable quasi-2D (Q-2D) perovskite materials are emerging as a promising candidate for blue light source in full-color display applications due to their good color saturation property, high brightness, and spectral tunability. Herein, an efficient energy cascade channel is developed by introducing sodium bromide (NaBr) in phenyl-butylammonium (PBA)-containing mixed-halide Q-2D perovskites for a blue perovskite light-emitting diode (PeLED). The incorporation of alkali metal contributes to the nucleation and growth of Q-2D perovskites into graded distribution of domains with different layer number . The study of excitation dynamics by transient absorption (TA) spectroscopy confirms that NaBr induces more Q-2D perovskite phases with small n number, providing a graded energy cascade pathway to facilitate more efficient energy transfer processes. In addition, the nonradiative recombination within the Q-2D perovskites is significantly suppressed upon Na+ incorporation, as validated by the trap density estimation. Consequently, the optimized blue PeLEDs manifest a peak external quantum efficiency (EQE) of 7.0% emitting at 486 nm with a maximum luminance of 1699 cd m-2 . It is anticipated that these findings will improve the understanding of alkali-metal-assisted optimization of Q-2D perovskites and pave the way toward high-performance blue PeLEDs.

Transcriptomic signatures associated with autoimmune thyroiditis in papillary thyroid carcinoma and cancer immunotherapy-induced thyroid dysfunction.

Up to 20% of patients treated with anti-PD-1/PD-L1 inhibitors suffered from thyroid dysfunctions, yet the mediators associated with their occurrence remain unclear. The increasing coincidence of papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) and the high vulnerability of thyroid to immunotherapy motivated us to discover the similarities and their underlying transcriptomic basis. Clinical characteristics analysis of 468 PTC patients from two independent cohorts and meta-analysis of 22,155 PTC patients unveiled a strong negative association between HT and recurrence in PTC patients. Transcriptome analysis of both cohorts showed PTC patients with HT were enriched in macrophages, CD8+ and CD4+ cytotoxic T cells, which was further validated by single-cell transcriptome analysis of 17,438 cells from PTC patients, and CD8+ T cells were correlated with disease-free survival of PTC patients. In both cohorts and single-cell dataset, elevated expression of PD-1-related genes was observed in the HT group, and CD3D appeared to be a target for enhancing the activation of CD8+ T cells. Correlation analysis of 3,318 thyroid adverse events from 39,123 patients across 24 tumor types and molecular signatures demonstrated similar signatures associated with autoimmune thyroiditis in PTC and thyroid immune-related adverse events (irAEs), and several multi-omics signatures, including signatures of CD8A and CD8+ T cells, showed positive associations with the odds ratio of thyroid irAEs. Our results unveil shared molecular signatures underlying thyroid dysfunction between patients receiving immunotherapies and PTC patients suffering from HT, which may shed light on managing the adverse events during cancer immunotherapy.

Stratification of Health Professional Education and Its Funding Disparities: Evidence From China During the Period of 1998-2017.

Background: The finance of health professional education (HPE) is of immense importance for effective and sustainable health systems, yet relevant empirical research was scarce due to the lack of financial data. The study aimed to bridge the gap by presenting the scenario of finance for health professional institutions (HPIs) of different tiers in China and exploring how the stratification of institutions affected their funding disparities. Methods: The study employed data collected from the Ministry of Education in China, and selected the HPIs mainly based on the World Directory of Medical Schools. The funding levels and disparities of China's HPIs during the period (1998-2017) were analyzed with descriptive statistics, and the indicators of funding per institution and funding per student were both considered. The average funding in HPIs was presented by tiers, and the Gini coefficient and Theil index were employed to describe the differences in financing among HPIs over the span. Results: The study found that the number of HPIs has kept growing over the past two decades, with both the funding per institution and the funding per student increasing steadily. Specifically, the average funding per institution of the three tiers increased by 31.5 times, 13.4 times, and 10.5 times separately, with the first-tier universities having an absolute advantage compared to lower tiers. As for the financing disparities among HPIs, the Gini coefficient of the funding per institution maintained to be over 0.5, with the third-tier institutions scoring the highest, while the Gini coefficient of the funding per student all ranged approximately from 0.2 to 0.3. Through the decomposition of the inequalities measured by the Theil index, the share of the between-tier difference in per-institution funding grew from 29.7 in 1998 to 77.9% in 2017. Conclusions: The funding disparities between tiers of HPIs in China gradually became more accentuated, with the top-tier institutions taking up the largest share. Although the stratified development in HPE has posed a challenge to the unified quality assurance of medical personnel training, it may also be regarded as an effective pathway for developing countries like China to achieve stable development in health professional education.

GanMeijian ameliorates lipid accumulation and oxidative damage in alcoholic fatty liver disease in Wistar rats.

Alcoholic fatty liver disease (AFLD), a major public health problem, has drawn clinical and scientific attention. The study aims to investigate the effect of Ganmeijian [crude extract of malt root, phosphoesterase complex (Pho)] on AFLD, and explore the possible mechanisms. An AFLD rat model was made. 30 and 60 mg/kg Pho were administrated through intestinal fistula for 5 weeks. Compared with those in model group, AST, LDL-C and TC in 30 mg/kg Pho group and TC in 60 mg/kg Pho group decreased. The mRNA level of Fas, Gpat1 and Srebp-1c in Pho groups was significantly reduced. The level of GSH-Px was increased, mitochondrial activity was improved, and the level of MDA and ROS was reduced in Pho groups. Pho shows a beneficial effect on AFLD. The mechanisms are possibly related to Pho inhibiting the expression of fat synthesis genes, protecting the function and increasing the activity of mitochondria in hepatocytes, then reducing the accumulation of ROS and the level of oxidative stress in the liver.

Recombinant Lactobacillus acidophilus expressing S1 and S2 domains of porcine epidemic diarrhea virus could improve the humoral and mucosal immune levels in mice and sows inoculated orally.

Porcine epidemic diarrhea (PED) is a highly contagious intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV), which is characterized by a high mortality rate in piglets. Since 2012, a remarkable growth in PED outbreaks occurred in many pig farms in China, landing a heavy blow on the pig industry. In order to develop a new effective vaccine for the current PEDV, oral vaccines were generated by transferring eukaryotic expression recombinant plasmids carrying the S1 and S2 (antigenic sites of the S protein) epitopes of PEDV into a swine-origin Lactobacillus acidophilus (L. acidophilus). After oral immunization of the BALB/c mice, higher levels of anti-PEDV specific IgG and SIgA antibodies and cellular immune responses were detected in mice orally administered with the recombinant L. acidophilus-S1 compared to the L. acidophilus-S2. Furthermore, L. acidophilus-S1 was used to inoculate the pregnant sows orally and the results showed that the recombinant L. acidophilus-S1 could elicit a specific systemic and mucosal immune response. In summary, our study demonstrated that oral immunization with L. acidophilus-S1 could improve the humoral and mucosal immune levels in sows and would be a promising candidate vaccine against PEDV infection in piglets.

Microscopic imaging quality improvement through L0 gradient constraint model based on multi-fields of view analysis.

The degradation of optical microscopic imaging is space-variant, and how to fast restore optical degraded image remains a special problem. Based on point spread function (PSF) estimation under each field of view (FOV), a L0 gradient-constrained image restoration method is proposed to solve optical degradation in microscopic imaging. Firstly, the whole scene is segmented into several different regions according to different FOV. The PSFs for each region are estimated from modulation transfer function (MTF) measured in advance. Secondly, a penalty function is designed using L0 gradient constraint to deblur the degraded images of each sub-FOV. Finally, a weighted stitching approach is used to stitch the restored images of multiple FOV (m-FOV). Experimental results indicate that the m-FOV analysis could well solve the problem of space-variant degradation. Compared with the other methods, both subjective and objective evaluation results prove that the L0 norm idea could rapidly and effectively restore the degraded image. The approach could be well applied to a real product.

MicroRNA-214 promotes the calcification of human aortic valve interstitial cells through the acceleration of inflammatory reactions with activated MyD88/NF-κB signaling.

Calcific aortic valve disease (CAVD) is a complex active process involving in endothelial injury, lipid infiltration, chronic inflammation, matrix remodeling, cell differentiation, progressive bone formation, and new angiogenesis. The excess inflammatory responses induced by aortic valve interstitial cells (AVICs) are one of the common pathogeneses of this disease. Although many microRNAs (miRs) have been identified to play crucial roles in the calcification process of the aortic valve, numerous miRs are still waiting to be explored. In this study, we explored the functional role of miR-214 in the inflammatory reaction and calcification of human AVICs and its underlying molecular mechanism. Alizarin red staining was used to determine the number of calcified nodules. The protein levels of ICAM-1, IL-6, IL-8, and MCP-1 detected by enzyme-linked immunosorbent assay (ELISA) were used to assess the inflammatory reaction of AVICs; expression levels of RUNX2, Msx2, and BMP2 were used to evaluate AVICs osteoblast differentiation. Results showed that the expression levels of TLR4, MyD88, NF-κB, and miR-214 were up-regulated in the blood and aortic valve tissue samples of patients with CAVD when compared with normal individuals. Knockdown of miR-214 in AVICs inhibited the secretion of IL-6, IL-8, ICAM-1, and MCP-1, while this effect was repressed when lipopolysaccharide (LPS) was added to AVICs. LPS also enhanced the effects of miR-214 in promoting the secretion of pro-inflammatory factors. Besides, up-regulation of miR-214 promoted the protein expression of MyD88 and NF-κB but had no influence on TLR4, and miR-214 could directly combine with MyD88 protein. Up-regulation of MyD88 facilitated the secretion of pro-inflammatory factors and increased calcified nodules number and accelerated the expression of RUNX2, Msx2, and BMP2. Moreover, promotion of the expressions of pro-inflammatory factors and "osteoblast-like" cell markers induced by miR-214 overexpression was abolished when MyD88 was down-regulated in AVICs. In conclusion, this study revealed that miR-214 promoted calcification by facilitating inflammatory reaction through MyD88/NF-κB signaling pathway in AVICs.

Apple Polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats.

The saying "An apple a day keeps the doctor away" has been known for over 150 years, and numerous studies have shown that apple consumption is closely associated with reduced risks of chronic diseases. It has been well accepted that dysbiosis is the reflection of various chronic diseases. Therefore, this study investigates the effects of apple polysaccharides (AP) on gut dysbiosis. High-fat diet (HFD) fed rats were treated for 14 weeks with AP. The microbiota composition, microbiota-generated short chain fatty acids (SCFAs), gut permeability and chronic inflammation were analyzed. AP treatment showed higher abundance of Bacteroidetes and Lactobacillus while lower Firmicutes and Fusobacteium. AP significantly increased total SCFAs level that contributed by acetic acid and isobutyric acid. Moreover, AP dramatically alleviated dysbiosis-associated gut permeability and chronic inflammation with decreased plasma LBP, up-regulation of Occludin, down-regulation of tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), chemokine ligand 1 (CXCL-1) and interleukin 1 beta (IL-1ß). The potential mechanism is due to the fact that AP reduces gut permeability, which involves the induction of autophagy in goblet cells. Therefore, AP exerts health benefits through inhibiting gut dysbiosis and chronic inflammation and modulating gut permeability in HFD-induced dysbiosis rats.

[Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with anterior myocardial infarction].

OBJECTIVES: To investigate the efficacy of intracoronary transfer of autologous bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction (MI) on left ventricular function and myocardial perfusion. METHODS: Thirty-five patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled study (20 patients in cell transplantation group; 15 patients in control group). All patients were treated by standard drug therapy and percutaneous coronary intervention (PCI). Baseline and 3 months follow-up evaluations included complete clinical and laboratory examinations, six minutes walk test, echocardiography, Dual-isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) and cardiac magnetic resonance imaging (MRI). RESULTS: Baseline parameters were similar between the two groups. NYHA classification and six minutes walk test at 3 months follow-up were also similar between the two groups. However, left ventricular ejection fraction (LVEF) determined by echocardiography and DISA-SPECT was significantly higher; regional wall motion measured by echocardiography and cardiac MRI, myocardial viability and myocardial perfusion in the infarct zone assessed by DISA-SPECT were all significantly improved than before transplantation and than that in control group at 3 months follow-up. CONCLUSIONS: Our results indicate that intracoronary transplantation of ABMMNCs could improve the left ventricular systolic function and beneficially affect myocardial perfusion up to 3 months post transplantation in patients with myocardial infarction.

Modulate Organic-Metal Oxide Heterojunction via [1,6] Azafulleroid for Highly Efficient Organic Solar Cells.

By creating an effective π-orbital hybridization between the fullerene cage and the aromatic anchor (addend), the azafulleroid interfacial modifiers exhibit enhanced electronic coupling to the underneath metal oxides. High power conversion efficiency of 10.3% can be achieved in organic solar cells using open-cage phenyl C61 butyric acid methyl ester (PCBM)-modified zinc oxide layer.

CSN6, a subunit of the COP9 signalosome, is involved in early response to iron deficiency in Oryza sativa.

The COP9 signalosome (CSN) plays an important role in proteasome-mediated degradation by regulating CUL1 rubylation of the SCF ligase and is involved in many crucial biological processes. Here, we demonstrate a link between IDEF1 accumulation and the decline in COP9 derubylation activity in response to iron deficiency (-Fe) in rice (Oryza sativa). CSN6 expression is rapidly down-regulated during Fe depletion, contributing to reduced CSN activity, as judged by CSN5 and CUL1 expression, indicating CSN6 is involved in the early stage response of -Fe. In contrast to CSN6, the IDEF1 protein and expression of several iron uptake/utilisation-related genes are increased in response to -Fe. Thus, we constructed CSN6 transgenic sense and antisense lines and found that experimental depletion of CSN6 results in accumulation of the IDEF1 protein and up-regulation of several iron uptake/utilisation-related genes. Furthermore, IDEF1 can be decorated with K48-linked polyubiquitin and degraded via the 26S proteasome. Accumulated IDEF1 in antisense lines led to increased chlorophyll and Fe content in seedlings during -Fe. Collectively, the cellular CSN6 level is decreased during early stages of -Fe to ensure the rapid accumulation of IDEF1, which in turn up-regulates several iron uptake/utilisation-related genes to help overcome -Fe stress in rice.

Microcavity-enhanced light-trapping for highly efficient organic parallel tandem solar cells.

A high-performance parallel tandem solar cell employing ultra-thin Ag as the intermediate anode is demonstrated, which comprises a semitransparent front sub-cell and a microcavity assisted back sub-cell. In addition to the extended optical field as a result of the tandem architecture, the prominent microcavity resonance formed in the back sub-cell enables such a parallel tandem configuration to possess high light utilization efficiency (the peak EQE value is over 80%) and a high photovoltaic performance of 9.2%. This study establishes an effective architecture that can be generally applicable to all organic materials for improving their performance.