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Cisplatin resistance is a major cause of therapeutic failure in patients with high-grade serous ovarian cancer (HGSOC). Long noncoding RNAs (lncRNAs) have emerged as key regulators of human cancers; however, their modes of action in HGSOC remain largely unknown. Here, we provide evidence to demonstrate that lncRNA Platinum sensitivity-related LncRNA from Ascites-Derived Exosomes (PLADE) transmitted by ascites exosomes enhance platinum sensitivity in HGSOC. PLADE exhibited significantly decreased expression in ascites exosomes and tumor tissues, as well as in the corresponding metastatic tumors from patients with HGSOC cisplatin-resistance. Moreover, HGSOC patients with higher PLADE expression levels exhibited longer progression-free survival. Gain- and loss-of-function studies have revealed that PLADE promotes cisplatin sensitivity by suppressing cell proliferation, migration and invasion, and enhancing apoptosis in vitro and in vivo. Furthermore, the functions of PLADE in increasing cisplatin sensitivity were proven to be transferred by exosomes to the cultured recipient cells and to the adjacent tumor tissues in mouse models. Mechanistically, PLADE binds to and downregulates heterogeneous nuclear ribonucleoprotein D (HNRNPD) by VHL-mediated ubiquitination, thus inducing an increased amount of RNA: DNA hybrids (R-loop) and DNA damage, consequently promoting cisplatin sensitivity in HGSOC. Collectively, these results shed light on the understanding of the vital roles of long noncoding RNAs in cancers., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Autophagy is a lysosome-dependent bulk degradation process essential for cell viability but excessive autophagy leads to a unique form of cell death termed autosis. Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with notable defect in its autophagy process. In previous studies, we developed stapled peptides that specifically targeted the essential autophagy protein Beclin 1 to induce autophagy and promote endolysosomal trafficking. Here we show that one lead peptide Tat-SP4 induced mild increase of autophagy in TNBC cells but showed potent anti-proliferative effect that could not be rescued by inhibitors of programmed cell death pathways. The cell death induced by Tat-SP4 showed typical features of autosis including sustained adherence to the substrate surface, rupture of plasma membrane and effective rescue by digoxin, a cardioglycoside that blocks the Na + /K + ATPase. Tat-SP4 also induced prominent mitochondria dysfunction including loss of mitochondria membrane potential, elevated mitochondria reactive oxygen species and reduced oxidative phosphorylation. The anti-proliferative effect of Tat-SP4 was confirmed in a TNBC xenograft model. Our study uncovers three notable aspects of autosis. Firstly, autosis can be triggered by moderate increase in autophagy if such increase exceeds the endogenous capacity of the host cells. Secondly, mitochondria may play an essential role in autosis with dysregulated autophagy leading to mitochondria dysfunction to trigger autosis. Lastly, intrinsic autophagy deficiency and quiescent mitochondria bioenergetic profile likely render TNBC cells particularly susceptible to autosis. Our designed peptides like Tat-SP4 may serve as potential therapeutic candidates against TNBC by targeting this vulnerability., (© 2023. Cell Death Differentiation Association (ADMC).)

Septic shock, largely caused by intestinal perforation, is a common critical disease in intensive care unit (ICU). For hospitals and health systems, a performance improvement program for sepsis was strong recommended in guidelines. Numerous studies have shown that improved quality control improves outcomes in patients with septic shock. Nevertheless, association between quality control and outcomes of septic shock caused by intestinal perforation are not fully revealed. Thus we designed this study to investigate effects of quality control on septic shock caused by intestinal perforation in China. This was a multicenter observational study. A total of 463 hospitals were enrolled in this survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018 to December 31, 2018. In this study, the indicators of quality control included the proportion of ICU patient bed occupancy to total inpatient bed occupancy, the proportion of ICU patients with APACHE II score ≥ 15, and the microbiology detection rate before antibiotic use. The outcome indicators included hospital stays, hospitalization costs, complications, and mortality. Generalized linear mixed models were used to analyse the association between quality control and septic shock caused by intestinal perforation. The proportion of ICU patient bed occupancy to total inpatient bed occupancy is positively correlated with hospital stays, incidence of complications (ARDS, AKI) and costs in septic shock caused by intestinal perforation (p < 0.05). The proportion of ICU patients with APACHE II score ≥ 15 was not associated with hospital stays and incidence of ARDS and AKI (p < 0.05). Increasing of the proportion of ICU patients with APACHE II score ≥ 15 decreased the costs of patients with septic shock caused by intestinal perforation (p < 0.05). The microbiology detection rate before antibiotic use was not associated with hospital stays, incidence of AKI and costs of patients with septic shock caused by intestinal perforation (p < 0.05). Surprisingly, the increase of microbiology detection rate before antibiotic use increased the incidence of ARDS in patients with septic shock caused by intestinal perforation (p < 0.05). The above three indicators of quality control were not associated with mortality of the patients with septic shock caused by intestinal perforation. On the one hand, the number of ICU patients admitted should be controlled to reduce the proportion of ICU patients out of total inpatient bed occupancy. On the other hand, intensive care unit admission of severe patients (patients with APACHE II score ≥ 15) should be encouraged to improve the proportion of patients with APACHE II score ≥ 15 in the ICU, so that ICU can focus more on the treatment of severe patients and promote the professionalization of severe patient management. It is not advisable to collect sputum specimens too frequently for patients without pneumonia., (© 2023. The Author(s).)

Androgenesis is an important chromosome set manipulation technique used in sex control in aquaculture. Haploid embryos exhibit haploid syndrome with body abnormalities and even die during early embryonic development. In this study, we used whole genome bisulfite sequencing (WGBS) to investigate the genome-wide DNA methylation profiles in haploid females (1n-X) and males (1n-Y), and diploid females (2n-XX) and males (2n-XY) of tiger pufferfish (Takifugu rubripes), an economically important fish in China. A total of 96.32 Gb clean data was produced. Differentially methylated regions (DMRs) were found between haploids and diploids, which may be related to abnormal development and early embryonic death in haploids. There were 3,641 hyper-methylated differentially methylated genes (DMGs) and 2,179 hypo-methylated DMGs in haploid vs. diploid comparisons in both females and males. These DMGs were mainly related to genomic stability maintenance and cell cycle regulation. slf1, actr8, gas2, and pbrm1 genes were selected to validate the methylation sequencing. After combining the methylation data with the corresponding transcriptome data, we identified several genes, including guca2a, myoc, fezf2, rprml, telo2, s100a1, and marveld1, which exhibited differential expression levels modulated by DNA methylation. In conclusion, our study revealed different methylation and expression profiles between haploid and diploid T. rubripes for the first time. Several DMGs were identified between different ploidy levels, which may be related to haploid syndrome formation. The results expand the understanding of the effects of ploidy on the early development of teleosts and provide knowledge about target genes and networks to improve the survival rate of haploids., (© 2022. The Author(s).)

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2 + hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis., (© 2021. The Author(s).)

The development of flexible capacitive pressure sensors has wide application prospects in the fields of electronic skin and intelligent wearable electronic devices, but it is still a great challenge to fabricate capacitive sensors with high sensitivity. Few reports have considered the use of interdigital electrode structures to improve the sensitivity of capacitive pressure sensors. In this work, a new strategy for the fabrication of a high-performance capacitive flexible pressure sensor based on MXene/polyvinylpyrrolidone (PVP) by an interdigital electrode is reported. By increasing the number of interdigital electrodes and selecting the appropriate dielectric layer, the sensitivity of the capacitive sensor can be improved. The capacitive sensor based on MXene/PVP here has a high sensitivity (~1.25 kPa -1 ), low detection limit (~0.6 Pa), wide sensing range (up to 294 kPa), fast response and recovery times (~30/15 ms) and mechanical stability of 10000 cycles. The presented sensor here can be used for various pressure detection applications, such as finger pressing, wrist pulse measuring, breathing, swallowing and speech recognition. This work provides a new method of using interdigital electrodes to fabricate a highly sensitive capacitive sensor with very promising application prospects in flexible sensors and wearable electronics., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

High quality silage containing abundant lactic acid is a critical component of ruminant diets in many parts of the world. Silage deterioration, a result of aerobic metabolism (including utilization of lactic acid) during storage and feed-out, reduces the nutritional quality of the silage, and its acceptance by animals. In this study, we introduce a novel non-disruptive dual-sensor method that provides near real-time information on silage aerobic stability, and demonstrates for the first time that in situ silage temperature (T si ) and pH are both associated with preservation of lactic acid. Aerobic deterioration was evaluated using two sources of maize silage, one treated with a biological additive, at incubation temperatures of 23 and 33 °C. Results showed a time delay between the rise of T si and that of pH following aerobic exposure at both incubation temperatures. A 11 to 25% loss of lactic acid occurred when T si reached 2 °C above ambient. In contrast, by the time the silage pH had exceeded its initial value by 0.5 units, over 60% of the lactic acid had been metabolized. Although pH is often used as a primary indicator of aerobic deterioration of maize silage, it is clear that T si was a more sensitive early indicator. However, the extent of the pH increase was an effective indicator of advanced spoilage and loss of lactic acid due to aerobic metabolism for maize silage.

Amyloid-[Formula: see text] (A[Formula: see text]) is the target in many clinical trials for Alzheimer's disease (AD). Preclinical AD patients are heterogeneous with regards to different backgrounds and diagnosis. Accurately predicting A[Formula: see text] status of participants by using machine learning (ML) models based on easily accessible data, could improve the effectiveness of AD clinical trials. We will develop optimal ML models for each subpopulation stratified by sex and disease stages using sub scores from screening neurological tests. Data from the AD Neuroimaging Initiative (ADNI) were used to build the ML models, for three groups: individuals with significant memory concern, early mild cognitive impairment (MCI), and late MCI. Data were further separated into 6 groups by disease stage (3 levels) and sex (2 categories). The outcome was defined as the A[Formula: see text] status confirmed by the PET imaging, and the features include demographic data, newly identified risk factors, screening tests, and the domain scores from screening tests. Monte Carlo simulation studies were used together with k-fold cross-validation technique to compute model performance metric. We also develop a new feature selection method based on the stochastic ordering to avoiding searching all possible combinations of features. Accuracy of the identified optimal model for SMC male was over 90% by using domain scores, and accuracy for LMCI female was above 86%. Domain scores can improve the ML model prediction as compared to the total scores. Accurate ML prediction models can identify the proper population for AD clinical trials.

Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-β pathway. Inhibition of the TGF-β pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-β pathway. This study may allow the development of novel approaches for PC.

Few studies have investigated the prevalence of myopia in Northwest China. This cross-sectional study aimed to investigate the prevalence and associated factors of myopia and high myopia in adults aged 40-80 years in the Han and Yugur populations living in Gansu Province, Northwest China. A total of 3,845 participants were included. The overall age- and sex-adjusted prevalence of myopia (spherical equivalent (SE) < -0.5 D), high myopia (SE < -6.0 D) and hyperopia (SE > + 0.5 D) were 16.4%, 0.7% and 26.2% in Yugur participants, respectively, and 34.3%, 5.0% and 19.2% in Han participants, respectively. The prevalence of myopia and high myopia in Han participants was significantly higher than that in Yugur participants (both P < 0.001). Yugur population, birth in rural areas, smoking history and outdoor work were found to be negatively associated with myopia. Higher education level and a family history of myopia were found to be positively associated with myopia in the study population. High myopia was negatively associated with Yugur population, aging, birth in rural areas and was positively associated with a family history of myopia. This study provided valuable information regarding the environmental risk factors of myopia and revealed an ethnic disparity in the prevalence of myopia in Gansu Province, Northwest China.

Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable transcripts locate preferentially to chromatin, where some regulate chromatin structure, transcription and RNA processing 1-13 . Although several RNA sequences responsible for nuclear localization have been identified-such as repeats in the lncRNA Xist and Alu-like elements in long RNAs 14-16 -how lncRNAs as a class are enriched at chromatin remains unknown. Here we describe a random, mutagenesis-coupled, high-throughput method that we name 'RNA elements for subcellular localization by sequencing' (mutREL-seq). Using this method, we discovered an RNA motif that recognizes the U1 small nuclear ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to chromatin. Across the genome, chromatin-bound lncRNAs are enriched with 5' splice sites and depleted of 3' splice sites, and exhibit high levels of U1 snRNA binding compared with cytoplasm-localized messenger RNAs. Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts, without altering the overall transcription rate in cells. In addition, rapid degradation of SNRNP70 reduces the localization of both nascent and polyadenylated lncRNA transcripts to chromatin, and disrupts the nuclear and genome-wide localization of the lncRNA Malat1. Moreover, U1 snRNP interacts with transcriptionally engaged RNA polymerase II. These results show that U1 snRNP acts widely to tether and mobilize lncRNAs to chromatin in a transcription-dependent manner. Our findings have uncovered a previously unknown role of U1 snRNP beyond the processing of precursor mRNA, and provide molecular insight into how lncRNAs are recruited to regulatory sites to carry out chromatin-associated functions.

As a kind of excellent photoluminescent material, carbon quantum dots have been extensively studied in many fields, including biomedical applications and optoelectronic devices. They have been dispersed in polymer matrices to form luminescent films which can be used in LEDs, displays, sensors, etc. Owing to the total internal reflection at the flat polymer/air interfaces, a significant portion of the emitted light are trapped and dissipated. In this paper, we fabricate free standing flexible PVA films with photoluminescent carbon quantum dots embedded in them. We disperse silica microspheres at the film surfaces to couple out the total internal reflection. The effects of sphere densities and diameters on the enhancement of photoluminescence are experimentally investigated with a homemade microscope. The enhancement of fluorescence intensity is as high as 1.83 when the film is fully covered by spheres of 0.86 [Formula: see text]m diameter. It is worth noting that the light extraction originates from rather the scattering of individual spheres than the diffraction of ordered arrays. The mechanism of scattering is confirmed by numerical simulations. The simulated results show that the evanescent wave at the flat PVA/air interface can be effectively scattered out of the film.

The molecular basis underlying the aggressive nature and excessive proliferation of cervical squamous cancer cell remains unclear. ΔNp63α is the predominant isotype of p63 expressed in the epithelia and regulates epithelial cell differentiation. The pro-/anti-tumor role of ΔNp63α in different kinds of solid tumors remains controversial and the precise molecular mechanisms are still elusive. In this study, we uncovered the molecular functions of ΔNp63α in cervical squamous cell carcinoma to clarify its roles as a tumor suppressor. We demonstrated that ΔNp63α suppressed cell migration, invasiveness, and tumor growth in SiHa and ME-180 cells with both in vivo and in vitro assays. Mechanistic investigation via RNA-sequencing and chromatin immunoprecipitation-sequencing revealed that ΔNp63α exerted its antitumor capacity via regulating the expression of a cohort of cell junction genes. Further, we showed that ZNF385B and CLDN1 were two direct ΔNp63α targets with significant relevance to cervical squamous cell carcinoma examined in cell cultures, tumor xenografts, and clinic tumors. We also demonstrated that ΔNp63α downregulated NFATC1 to reduce cisplatin resistance. These findings shed new lights on functions of ΔNp63α in tumors and providing novel insights in targeted therapy of cervical cancers.

Objectives: To assess the prevalence of and risk factors for refractive error (RE) in Han and Mongolian adults aged 40-80 years in Inner Mongolia in China and to identify ethnic differences in RE between these populations., Methods: Our cross-sectional study is part of the China National Health Survey (CNHS). The age-adjusted prevalence of RE in Han and Mongolian adults aged 40-80 in Inner Mongolia were compared. A multivariable logistic regression model was used to identify risk factors., Results: Among 2090 people, the age-adjusted prevalence of myopia (SE < -0.5D), hyperopia (SE > 0.5D), high myopia (SE < -6.0D) and astigmatism (cylinder ≥ 0.5D) were 29.4% (95% confidence interval (CI), 27.4-31.3%), 28.4% (95% CI, 26.4-30.5%), 3.6% (95% CI, 2.8-4.4%) and 65.9% (95% CI, 63.9-67.9%), respectively. The age-adjusted prevalence of myopia in the Han population was higher than that in the Mongolian population (31.8% vs. 23.0%, p < 0.001), but the prevalence of hyperopia was lower (25.8% vs. 35.3%, p = 0.002). In the multivariable logistic regression, ethnicity was associated with myopia (p = 0.001) and hyperopia (p = 0.001). Myopia was also associated with age, time spent in rural areas (p < 0.001) and middle/high school and undergraduate/graduate education levels (p = 0.027 and p < 0.001, respectively, compared with lower education levels). Additionally, age, height (p = 0.015) and pterygium (p = 0.014) were associated with hyperopia., Conclusions: Ethnicity is closely related to RE in Inner Mongolia in mainland China. Our study investigates differences in prevalence of and risk factors for RE between the Han and Mongolian populations, which could not be explained by differences in the risk factors investigated in this study.

Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Highly fluorescent carbon dots (CDs) exhibiting molecular fluorescence were synthesized and successfully used for sensing ferricyanide based on fluorescence quenching. We conducted dialysis to purify the CDs and found that the dialysate is also fluorescent. From the mass spectra and quantum yield analyses of the dialysate, it is demonstrated that molecular fluorophores were also synthesized during the synthesis of CDs. By the comparison of fluorescence spectra between CDs and dialysate, it is established that the fluorescence emission of CDs partly originates from fluorophores that are attached to CDs' surface. The fluorescence quenching caused by ferricyanide is proved to be the overlap of absorption spectra between ferricyanide and CDs. The changes of the absorbance and fluorescence spectra are combined to enhance the detection sensitivity, and the limit of detection is calculated to be 1.7 μM. A good linear response of fluorescence-absorbance combined sensing toward ferricyanide is achieved in the range of 5-100 µM. This method is highly selective to ferricyanide among other common cations and anions, and it is also successfully applied in detecting ferricyanide in real water samples.

Silage is a critical global feedstock, but is prone to aerobic deterioration. The dominant mechanism of O 2 transport into silage remains unresolved. Here, multiple sensors tracked O 2 and CO 2 , gas pressure (ΔP) between internal silage and ambient air, pH and silage temperature (T si ) during the ensilage of maize and ryegrass. We report the first observation that CO 2 produced from microbial respiration was partially dissolved in silage water, with evidence of negative or positive ΔP depending on the changing balance between CO 2 production and dissolution. The ΔP < 0 reflected an apparent respiratory quotient (RQ) < 1. Net CO 2 production was much greater in anaerobic fermentation stage than in initial aerobic phase or later aerobic feed-out phase. O 2 transport into silage is intimately linked to the dynamics of net CO 2 , ΔP, microbial activity, pH and T si . These results suggested that both gas diffusion (based on Fick's law) and advective transfer (Darcy's law) play equally important roles in governing the complex temporal progression of inward and outward gas fluxes to and from the silage interior. Even though low pH suppressed microbial activity and supported aerobic stability, the negative ΔP increased the risk of O 2 entry and aerobic deterioration during feed-out phase.

Gaussian network model (GNM), regarded as the simplest and most representative coarse-grained model, has been widely adopted to analyze and reveal protein dynamics and functions. Designing a variation of the classical GNM, by defining a new Kirchhoff matrix, is the way to improve the residue flexibility modeling. We combined information arising from local relative solvent accessibility (RSA) between two residues into the Kirchhoff matrix of the parameter-free GNM. The undetermined parameters in the new Kirchhoff matrix were estimated by using particle swarm optimization. The usage of RSA was motivated by the fact that our previous work using RSA based linear regression model resulted out higher prediction quality of the residue flexibility when compared with the classical GNM and the parameter free GNM. Computational experiments, conducted based on one training dataset, two independent datasets and one additional small set derived by molecular dynamics simulations, demonstrated that the average correlation coefficients of the proposed RSA based parameter-free GNM, called RpfGNM, were significantly increased when compared with the parameter-free GNM. Our empirical results indicated that a variation of the classical GNMs by combining other protein structural properties is an attractive way to improve the quality of flexibility modeling.

MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation. When erythropoiesis proceeds, the concomitant decrease of QKI5 releases Microprocessor from pri-124-1 and reduces mature miR-124 levels to facilitate erythrocyte maturation. Mechanistically, miR-124 targets TAL1 and c-MYB, two transcription factors involved in normal erythropoiesis. Importantly, this QKI5-mediated regulation also gives rise to a unique miRNA signature, which is required for erythroid differentiation. Taken together, these results demonstrate the pivotal role of QKI5 in primary miRNA processing during erythropoiesis and provide new insights into how a distal element on primary transcripts affects miRNA biogenesis.

MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively. Q-PCR data indicated that ATP4, which was expressed inversely in relation to Cre-miR906-3p under stress conditions. Overexpressing of Cre-miR906-3p enhanced resistance to multiple stresses; conversely, overexpressing of ATP4 produced the opposite effect. These data of Q-PCR, degradome sequencing and adaptation of overexpressing lines indicated that Cre-miR906-3p and its target ATP4 were a part of the same pathway for stress adaptation. We found that Cre-miR910 and its target NCR2 were also a part of this pathway. Overexpressing of Cre-miR910 decreased, whereas that of NCR2 increased the adaption to multiple stresses. Our findings suggest that the two classes of miRNAs synergistically mediate stress adaptation in algae.

Solution-processable light-emitting electrochemical cells (LECs) with simple device architecture have become an attractive candidate for application in next generation lighting and flat-panel displays. Herein, single layer LECs employing two cationic Ir(III) complexes showing highly efficient blue-green and yellow electroluminescence with peak current efficiency of 31.6 cd A(-1) and 40.6 cd A(-1), respectively, have been reported. By using both complexes in the device, color-tunable LECs with a single spectral peak in the wavelength range from 499 to 570 nm were obtained by varying their rations. In addition, the fabrication of efficient LECs was demonstrated based on low cost doctor-blade coating technique, which was compatible with the roll to roll fabrication process for the large size production. In this work, for the first time, 4 inch LEC devices by doctor-blade coating were fabricated, which exhibit the efficiencies of 23.4 cd A(-1) and 25.4 cd A(-1) for the blue-green and yellow emission, respectively. The exciting results indicated that highly efficient LECs with controllable color could be realized and find practical application in large size lighting and displays.

MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5' untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed "miRancers", can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5' UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization.

Human BST-2 inhibits HIV-1 replication by tethering nascent virions to the cell surface. HIV-1 codes Vpu that counteracts BST-2 by down-regulating this restriction factor from the cell surface. This important function makes Vpu a potential therapeutic target. Yet, no agents have been reported to block Vpu from antagonizing BST-2. In this study, we report a small molecule compound IMB-LA that abrogates the function of Vpu and thereby strongly suppresses HIV-1 replication by sensitizing the virus to BST-2 restriction. Further studies revealed that IMB-LA specifically inhibits Vpu-mediated degradation of BST-2 and restores the expression of BST-2 at the cell surface. Although IMB-LA does not prevent Vpu from interacting with BST-2 or β-TrCP2-containing ubiquitin E3 ligase, sorting of BST-2 into lysosomes in Vpu-expressing cells is blocked by IMB-LA. Most importantly, HIV-1 release and infection is inhibited by IMB-LA only in BST-2-expressing cells. In summary, results herein demonstrated that IMB-LA could specifically inhibit the degradation of BST-2 induced by Vpu, and impair HIV-1 replication in a BST-2 dependent manner, suggesting the feasibility of utilizing small molecule compounds to disable the antagonist function of Vpu and thereby expose HIV-1 to the restriction by BST-2.

The RNAi machinery is a mighty regulator in a myriad of life events. Despite lines of evidence that small RNAs and components of the RNAi pathway may be associated with structure and behavior of mitotic chromosomes in diverse organisms, a direct role of the RNAi pathway in mammalian mitotic chromosome segregation remains elusive. Here we report that Dicer and AGO2, two central components of the mammalian RNAi pathway, participate in the chromosome segregation. Knockdown of Dicer or AGO2 results in a higher incidence of chromosome lagging, and this effect is independent from microRNAs as examined with DGCR8 knockout cells. Further investigation has revealed that α-satellite RNA, a noncoding RNA derived from centromeric repeat region, is managed by AGO2 under the guidance of endogenous small interference RNAs (ASAT siRNAs) generated by Dicer. Furthermore, the slicer activity of AGO2 is essential for the chromosome segregation. Level and distribution of chromosome-associated α-satellite RNA have crucial regulatory effect on the localization of centromeric proteins such as centromere protein C1 (CENPC1). With these results, we also provide a paradigm in which the RNAi pathway participates in vital cellular events through the maintenance of level and distribution of noncoding RNAs in cells.

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.

Our aim was to clarify whether substitution of cytosine for adenine at position 1166 (A1166C) polymorphism of the angiotensin II type 1 receptor (AT1R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymelase chain reaction of genomic DNA and restriction fragment length polymorphism (PCR-RFLP) in genomic DNA. The data were analyzed by analysis of covariance (ANCOVA), X2 test, and multiple logistic regression. In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (X2=4.166, p=0.125). The frequency of the A1166 allele was significantly higher in Tibetan male hypertensives than that in normotensives (X2=11.46, p=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (p=0.465) or Yi (p=0.357) populations. Body mass index in the Han and Yi populations (p=0.0001), age in the Tibetan and Yi populations (p=0.0001), and AA genotype in the Tibetan male population (p=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (p=0.0040). We concluded that the A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT1R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT1R gene is probably not involved in the pathogenesis of essential hypertension in Han or Yi populations.

To investigate the relationship between the A-6G variant in the promoter of the angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi populations. All patients with essential hypertension were selected by WHO criteria. And the polymorphism of the A-6G variant was determined by PCR/RFLP. The data were analyzed by t test and chi2 test. There was no significant difference in the genotype or allele frequencies between normotensives and hypertensives in the Han, Tibetan, and Yi populations, respectively. However, when the subjects were divided into male and female subgroups, the genotype distributions among hypertensives and normotensives of the Tibetan female group were as follows: AA, 37% vs. 48%; AG, 52% vs. 48%; GG, 11% vs. 4%, respectively and the frequency of the G allele was significantly higher in hypertensives than in normotensives in the Tibetan female group (0.37 vs. 0.28, chi2=4.25, p<0.05). In addition, we observed that there was a significant difference between the Han and Tibetan normotensive groups in the distributions of the allele and genotype frequencies of the A-6G variant. The frequency of the G allele was 0.29 and 0.17 in the Tibetan normotensive and Han groups, respectively (p<0.001). The G allele of the A-6G variant was associated with hypertension in the Tibetan females, but not in the Yi or Han females. And we confirmed that there was a significant difference in the prevalence of the allele frequencies of the A-6G variant between the Han and Tibetan normotensive groups.