A novel lncRNA PLK4 up‐regulated by talazoparib represses hepatocellular carcinoma progression by promoting YAP‐mediated cell senescence

A growing number of studies recognize that long non‐coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA‐regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo‐like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11‐50D9.3), whose expression was dramatically down‐regulated in hepatocellular carcinoma (HCC) tissues and cells. Interestingly, talazoparib, a novel and highly potent poly‐ADP‐ribose polymerase 1/2 (PARP1/2) inhibitor, could increase lncRNA PLK4 expression in HepG2 cells. Importantly, we showed that talazoparib‐induced lncRNA PLK4 could function as a tumour suppressor gene by Yes‐associated protein (YAP) inactivation and induction of cellular senescence to inhibit liver cancer cell viability and growth. In summary, our findings reveal the molecular mechanism of talazoparib‐induced anti‐tumor effect, and suggest a potential clinical use of talazoparib‐targeted lncRNA PLK4/YAP‐dependent cellular senescence for the treatment of HCC.     

Reduction of SOST gene promotes bone formation through the Wnt/β-catenin signalling pathway and compensates particle-induced osteolysis

The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO-Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase- (ALP) and osterix-positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3-E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β-catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β-catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β-catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.     

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe^−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe^−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe^−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.     

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)‐3‐hydroxy‐12‐O‐demethyl‐11‐deoxy‐19(4→3)‐abeo‐cryptojaponol, 12,19‐dihydroxyabieta‐8,11,13‐trien‐7‐one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D‐ and 2D‐NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non‐small‐cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA‐MB‐231 and MCF‐7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC₅₀ values ranging from 16.28 to 40.67 μM.     

A Review on Additives for Halide Perovskite Solar Cells

Additives are widely adopted for efficient, stable, and hysteresis‐free perovskite solar cells and play an important role in various breakthroughs of perovskite solar cells (PSCs). Herein the various additives adopted for PSCs are reviewed and their functioning mechanism and influence on device performance is described. The main roles of additives, modulating morphology of perovskite films, stabilizing phase of formamidinium (FA) and cesium (Cs)‐based perovskites, adjusting energy level alignment in PSCs, suppressing nonradiative recombination in perovskites, eliminating hysteresis, enhancing operational stability of PSCs, are summarized.     

Serologic Response to SARS-CoV-2 in COVID-19 Patients with Different Severity

Virologica Sinica - The immense patient number caused by coronavirus disease 2019 (COVID-19) global pandemic brings the urge for more knowledge about its immunological features, including the...     

Evidence of compliance with and effectiveness of guidelines for noninvasive prenatal testing in China: a retrospective study of 189,809 cases

In China,the medical guidelines recommend performing noninvasive prenatal testing (NIPT) with caution for pregnant women aged 35 years or older.However,the Mother and Child Health Care Law suggests that all primiparous women whose age is older than 35 years undergo prenatal diagnosis.These two inconsistent suggestions/recommendations have made obstetricians confused about whether to offer NIPT to these older pregnant women.To face this issue and find out the solution we performed a retrospective study of 189,809 NIPT samples collected from 28 provincial-leveled administrative units in China.Of 1,564women with high-risk pregnancies who underwent NIPT,459 (29.3%) did not participate in follow-up.The compound sensitivity and specificity of NIPT for trisomies 21,18 and 13 detection was 99.1%(95%CI,98.0%-99.6%) and 99.9%(95%CI,98.8%-99.9%),respectively.In secundiparous women,NIPT showed high sensitivity and specificity similar to that in primiparous women.The observed risk for trisomies 21 and 18 significantly increased when the maternal age was 39 and older.After the publication of the current NIPT policy,the follow-up rate at our center was 97.9%;however,a large number of women are not in maternal and infant care networks nationwide,and that makes the follow-up rate outside our center relatively low.Our study shows that to balance the prevention of major aneuploidies and the limited resources for prenatal diagnosis,the cut-off age of 35for invasive prenatal diagnosis might be unnecessary.Although the NIPT guidelines are well written,how to practice it effectively,especially in less industrialized areas,is worth discussing.     

Nanopore sequencing of African swine fever virus

正Dear Editor,African swine fever (ASF) is one of the most pathogenic viral diseases in pigs caused by African swine fever virus(ASFV). The fatality rate is almost 100%, which brings huge economic losses to the hog industry in countries with epi-     

Molecular diversity of the 5S nuclear ribosomal DNA in Campeiostachys with StHY haplome constitution

To detect the genomic constitutions and investigate the evolutionary relationships between Campeiostachys Drobov and Elymus L. species, we have cloned and analyzed 271 5S nuclear ribosomal DNA sequences from 27 accessions of these species, mostly of Chinese origin. We identified Long H1, Short S1, and Long Y1 unit classes in nine Campeiostachys or Elymus species. The identification of the three orthologous unit classes was confirmed by the neighbor‐joining tree of each unit class from PAUP and the phylogeny tree of three unit classes from MrBayes. The results suggested that these Elymus species comprise StYH haplomes and should be included in Campeiostachys. The phylogeny tree showed a clear separation between the S1 unit class and Y1 unit class. However, Y1 unit class sequences formed a sister clade to the S1 unit class, implying that although the St and Y haplomes might have some affinity, they are distinct from one another. The phylogeny tree also indicated that the five species in sect. Turczaninovia (C. dahurica var. cylindrica, C. dahurica var. dahurica, C. dahurica var. tangutorum, E. purpuraristatus, and E. dahuricus Turcz. ex Griseb. var. violeus C. P. Wang & H. L. Yang) might share a more recent common ancestor, whereas the four species in sect. Elymus (C. nutans, E. breviaristatus (Keng) Keng ex Keng f., E. sinosubmuticus (Keng) Keng f., and E. atratus (Nevski) Hand.‐Mazz.) share a close relationship. By identifying only one type of unit class for each haplome, we propose that the 5S nuclear ribosomal DNA sequences of species within Campeiostachys might have undergone haplome‐specific concerted evolution.     

The functional roles of species in metacommunities,as revealed by metanetwork analyses of bird–plant frugivory networks

Understanding how biodiversity and interaction networks change across environmental gradients is a major challenge in ecology. We integrated metacommunity and metanetwork perspectives to test species’ functional roles in bird–plant frugivory interactions in a fragmented forest landscape in Southwest China, with consequences for seed dispersal. Availability of fruit resources both on and under trees created vertical feeding stratification for frugivorous birds. Bird–plant interactions involving birds feeding only on‐the‐tree or both on and under‐the‐tree (shared) had a higher centrality and contributed more to metanetwork organisation than interactions involving birds feeding only under‐the‐tree. Moreover, bird–plant interactions associated with large‐seeded plants disproportionately contributed to metanetwork organisation and centrality. Consequently, on‐the‐tree and shared birds contributed more to metanetwork organisation whereas under‐the‐tree birds were more involved in local processes. We would expect that species’ roles in the metanetwork will translate into different conservation values for maintaining functioning of seed‐dispersal networks.