Respiratory Distress Resulting from Gastroesophageal Reflux Is not Asthma,but Laryngotracheal Irritation,Spasm,even Suffocation

ESPITE the strong association between gastroesophageal reflux disease （GERD） and asthma has been undisputedly established and widely recognized by experts in advanced countries. Yet few topics in medicine are as controversial as the causal relationship between GERD and asthma： some argue that GERD causes asthma, while others think the other way around is true, still quite a few believe that bronchodilator medications are to blame. This controversy continues to be a conundrum or more piece of the puzzle.1 We would like to share two thoughts which might be a belated revelation with scholars and experts and invite them for further cooperative studies： the GERD-derived respiratory distress is not asthma, but GERD pure and simple; and the pathogenesis of respiratory distress is not asthma, but laryngotracheal irritation/spasm/suffocation.

Growth inhibition of high-intensity focused ultrasound on hepatic cancer in vivo

AIM： To investigate the damaging effect of high-intensity focused ultrasound （HIFU） on cancer cells and the inhibitory effect on tumor growth. METHODS： Hurine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length oftime in vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically.RESULTS： The death rate of cancer cells treated with HIFU at 1 000 W/cm^2 for 0.5, 1, 2, 4, 8, and 12 s was 3.11±1.21%, 13.37±2.56%, 38.84±3.68%, 47.22±5.76%,87.55±7.32%, and 94.33±8.11%, respectively. A positive relationship between the death rates of cancer cells and the length of HIFU treatment time was found （r = 0.96,P〈0.01）. The death rate of cancer cells treated with HIFU at the intensity of 100, 200, 400, 600, 800, and 1 000 W/cm^2 for 8 s was 26.31±3.26%, 31.00±3.87%, 41.97±5.86%,72.23±8.12%, 94.90±8.67%, and 99.30±9.18%, respectively. A positive relationship between the death rates of cancer cells and the intensities of HIFU treatment was confirmed （r= 0.98, P〈0.01）. The cancer cells treated with HIFU at 1 000 W/cm^2 for 8 s were inoculated intomice ed into. The tumor inhibitory rate was 90.35% compared to the control （P〈0.01）. In the experimental group inoculated with the cancer cells treated with HIFU at 1 000 W/cm^2 for 0.5 s, the tumor inhibitory rate was 22.9% （P〈0.01）. By pathological examination, tumor growth was confirmed in 8 out of 14 mice （57.14%, 8/14） inoculated with the cancer cells treated with HIFU at 1 000 W/cm^2 for 8 s, which was significantly lower than that in the control （100%, 15/15, P〈O.05）.CONCLUSION： HIFU is effective on killing or damage of H22 hepatic cancer cells in vitro and on inhibiting tumor growth in mice ex vivo.

The S100 protein family and its application in cardiac diseases

The S100 protein family is the largest group of EF-hand signaling proteins in humans. The members of the S100 protein family are expressed in many tissues and play different functions. Many diseases are related to S100 proteins, which function as new biochemical markers especially in cardiac diseases. The most studied members, protein S100Β and protein S100A1, exhibit activities in cardiac diseases, and these immunohistochemical expressions or serum levels have been used in predicting neurologic outcome after resuscitation of cardiac arrest or recovery of cardioprotective function.

Comparative Analysis of JmjC Domain-containing Proteins Reveals the Potential Histone Demethylases in Arabidopsis and Rice

Histone methylation homeostasis is achieved by controlling the balance between methylation and demethylation to maintain chromatin function and developmental regulation. In animals, a conserved Jumonji C （JmjC） domain was found in a large group of histone demethylases. However, it is still unclear whether plants also contain the JmjC domain- containing active histone demethylases. Here we performed genome-wide screen and phylogenetic analysis of JmjC domain-containing proteins in the dicot plant, Arabidopsis, and monocot plant rice, and found 21 and 20 JmjC domain-containing, respectively. We also examined the expression of JmjC domain-containing proteins and compared them to human JmjC counterparts for potential enzymatic activity. The spatial expression patterns of the Arabidopsis JmjC domain-containing genes revealed that they are all actively transcribed genes. These active plant JmjC domain-containing genes could possibly function in epigenetic regulation to antagonize the activity of the large number of putative SET domain-containing histone methyltransferase activity to dynamically regulate histone methylation homeostasis.

N^6 -methyl-adenosine (m^6 A) in RNA: An Old Modification with A Novel Epigenetic Function

N6-methyl-adenosine （m6A） is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation ofm6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 （METTL3）. m6A modification on messenger RNAs （mRNAs） mainly occurs in the exonic regions and 3＇-untranslated region （3＇-UTR） as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity- associated （FTO） gene and ALKBH5, which catalyze m6A demethylation in an cx-ketoglutarate （a-KG）- and FeZ ＋ -dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from devel- opment and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role ofm6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.

Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

Coronaviruses,members of the family Coronaviridae and sub-family Coronavirinae,are enveloped positive-strand RNA viruses which have spikes of glycoproteins projecting from their viral envelopes,thus exhibit a corona or halo-like appearance(Masters and Perlman,2013;Cui et al..2019).Coronaviruses are the causal path-ogens for a wide spectrum of respiratory and gastrointestinal diseases in both wild and domestic animals,including birds,pigs,rodents,etc(Dhama et al,2014).Previous studies have found that six strains of coronaviruses are capable to infect humans,including four strains circulating yearly to cause common cold,and other two strains which are the source for severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS-CoV),respectively(Dhama et al,2014;Cui et al..2019).

A long noncoding RNA involved in rice reproductive development by negatively regulating osa-miR160

Long noncoding RNAs （IncRNAs） participate in the regulation of multiple biological processes via diverse manners, one of which is functioning as endogenous target mimics （eTMs） to modulate microRNAs （miRNAs） by competing for their targets. Previously, we have predicted one IncRNA （osa-eTM160） as an endogenous repressor of osa-miR160 and validated the target mimicry ability of osa-eTM160 for ath-miR160 in Arabidopsis thaliana, yet the functions of osa-eTM160 in rice remain obscure. Here, we demonstrated that osa-eTM160 attenuated the repression of osa-miR160 on osa-ARF18 mRNAs during early anther developmental stages through the target mimicry manner, therefore to regulate rice seed setting and seed size. These findings revealed the roles of osa-eTM160 in rice, and indicated that lncRNAs with eTM functions may serve as temporal regulators to modulate the effects of miRNAs at specific developmental stages.

Pseudogenes:Pseudo or Real Functional Elements?

Pseudogenes are genomic remnants of ancient protein-coding genes which have lost their coding potentials through evolution.Although broadly existed,pseudogenes used to be considered as junk or relics of genomes which have not drawn enough attentions of biologists until recent years.With the broad applications of high-throughput experimental techniques,growing lines of evidence have strongly suggested that some pseudogenes possess special functions,including regulating parental gene expression and participating in the regulation of many biological processes.In this review,we summarize some basic features of pseudogenes and their functions in regulating development and diseases.All of these observations indicate that pseudogenes are not purely dead fossils of genomes,but warrant further exploration in their distribution,expression regulation and functions.A new nomenclature is desirable for the currently called ＇pseudogenes＇ to better describe their functions.

A multi-axis robot-based bioprinting system supporting natural cell function preservation and cardiac tissue fabrication

Despite the recent advances in artificial tissue and organ engineering,how to generate large size viable and functional complex organs still remains as a grand challenge for regenerative medicine.Three-dimensional bioprinting has demonstrated its advantages as one of the major methods in fabricating simple tissues,yet it still faces difficulties to generate vasculatures and preserve cell functions in complex organ production.Here,we overcome the limitations of conventional bioprinting systems by converting a six degree-of-freedom robotic arm into a bioprinter,therefore enables cell printing on 3D complex-shaped vascular scaffolds from all directions.We also developed an oil bath-based cell printing method to better preserve cell natural functions after printing.Together with a self-designed bioreactor and a repeated print-and-culture strategy,our bioprinting system is capable to generate vascularized,contractible,and long-term survived cardiac tissues.Such bioprinting strategy mimics the in vivo organ development process and presents a promising solution for in vitro fabrication of complex organs.

Dynamic and Coordinated Expression Changes of Rice Small RNAs in Response to Xanthomonas oryzae pv.oryzae

Endogenous small RNAs are newly identified players in plant immune responses, yet their roles in rice （Oryza sativa） responding to pathogens are still less understood, especially for pathogens that can cause severe yield losses. We examined the small RNA expression profiles of rice leaves at 2, 6, 12, and 24 hours post infection ofXanthomonas oryzae pv. oryzae （Xoo） virulent strain PXO99, the causal agent of rice bacterial blight disease. Dynamic expression changes of some miRNAs and trans-acting siRNAs were identified, together with a few novel miRNA targets, including an RLK gene targeted by osa-miR159a. 1. Coordinated expression changes were observed among some small RNAs in response to Xoo infection, with small RNAs exhibiting the same expression pattern tended to regulate genes in the same or related signaling pathways, including auxin and GA signaling pathways, nutrition and defense-related pathways. These findings reveal the dynamic and complex roles of small RNAs in rice-Xoo interactions, and identify new targets for regulating plant responses to Xoo.

Bioinformatic analysis of microRNA biogenesis and function related proteins in eleven animal genomes

MicroRNAs are -22 nt long small non-coding RNAs that play important regulatory roles in eukaryotes. The biogenesis and functional processes of microRNAs require the participation of many proteins, of which, the well studied ones are Dicer, Drosha, Argonaute and Exportin 5. To systematically study these four protein families, we screened 11 animal genomes to search for genes encoding above mentioned proteins, and identified some new members for each family. Domain analysis results revealed that most proteins within the same family share identical or similar domains. Alternative spliced transcript variants were found for some proteins. We also examined the expression patterns of these proteins in different human tissues and identified other proteins that could potentially interact with these proteins. These findings provided systematic information on the four key proteins involved in microRNA biogenesis and functional pathways in animals, and will shed light on further functional studies of these proteins.

Single-cell transcriptome analysis reveals widespread monoallelic gene expression in individual rice mesophyll cells

Monoallelic gene expression refers to the phenomenon that all transcripts of a gene in a cell are expressed from only one of the two alleles in a diploid organism. Although monoallelic gene expression has been occasionally reported with bulk transcriptome analysis in plants, how prevalent it is in individual plant cells remains unknown. Here, we developed a single-cell RNA-seq protocol in rice and investigated allelic expression patterns in mesophyll cells of indica （93-11 ） and japonica （Nipponbare） inbred lines, as well as their F1 reciprocal hybrids. We observed pervasive monoallelic gene expression in individual mesophyll cells, which could be largely explained by stochastic and independent transcription of two alleles. By con- trast, two mechanisms that were proposed previously based on bulk transcriptome analyses, parent-of- origin effects and allelic repression, were not well supported by our data. Furthermore, monoallelically expressed genes exhibited a number of characteristics, such as lower expression levels, narrower H3K4me3/H3K9acJH3K27me3 peaks, and larger expression divergences between 93-11 and Nipponbare. Taken together, the development of a single-cell RNA-seq protocol in this study offers us an excellent opportunity to investigate the origins and prevalence of monoallelic gene expression in plant cells.

Potential coexistence of both bacterial and eukaryotic small RNA biogenesis and functional related protein homologs in Archaea

RNA silencing plays crucial roles in both bacteria and eukaryotes, yet its machinery appears to differ in these two kingdoms. A couple of Argonaute protein homologs have been reported in some archaeal species in recent years. As Argonaute protein is the key component of eukaryotic RNA silencing pathways, such findings suggested the possibility of existence of eukaryotic RNA silencing like pathways in Archaea, which present the life forms between prokaryotes and eukaryotes. To further explore such hypothesis, we systematically screened 71 fully sequenced archaeal genomes, and identified some proteins containing homologous regions to the functional domains of eukaryotic RNA silencing pathway key proteins. The phylogenetic relationships of these proteins were analyzed. The conserved functional amino acids between archaeal and eukaryotic Piwi domains suggested their fimctional similarity. Our results provide new clues to the evolution of RNA silencing pathways.

Endogenous Small RNA Clusters in Plants

In plants, small RNAs（sRNAs） usually refer to non-coding RNAs（ncRNAs） with lengths of 20–24 nucleotides. sRNAs are involved in the regulation of many essential processes related to plant development and environmental responses. sRNAs in plants are mainly grouped into microRNAs（miRNAs） and small interfering RNAs（siRNAs）, and the latter can be further classified into trans-acting siRNAs（ta-siRNAs）, repeat-associated siRNAs（ra-siRNAs）, natural anti-sense siRNAs（nat-siRNAs）, etc. Many sRNAs exhibit a clustered distribution pattern in the genome. Here, we summarize the features and functions of cluster-distributed sRNAs, aimed to not only provide a thorough picture of sRNA clusters（SRCs） in plants, but also shed light on the identification of new classes of functional sRNAs.

Early transcriptomic profiling variation caused by cluster allergen immunotherapy

Allergen immunotherapy is executed by the repeated administration of specific allergens to patients with allergic disorders to protect against allergic reactions.It is the only disease-modifying therapy for allergic rhinitis and asthma,and many clinical trials and meta-analyses have demonstrated its beneficial effects.[1]Immunologic changes associated with immunotherapy are complicated,and the underlying mechanism needs further elucidation.Cluster immunotherapy is an improved immunotherapy with an accelerated build-up schedule that achieves symprom improvement earlier than the conventional way.

Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro

Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.

Rising from Ashes:Non-Coding RNAs Come of Age

It was recognized that a majority of the whole human genome is transcribed but only about 2% of genome actually encode all the proteins that were supposed, according to the central dogma, executing most of the biological functions of an organism. At an age proteins dominate, over 90% nonprotein coding regions were long regarded as trash, but nevertheless it was puzzling why god would allocate such a big portion of a genome to things without obvious meanings, and such curiosity has heightened when it was shown among various genome sequencing projects that the percentage of non-coding sequences is in almost strict correlation with the complexity of the organisms.

Bioinformaticians wrestling with the big biomedical data

Database plays a critical role throughout the history of the development of bioinformatics and omics.In 1980s,a number of databases such as GenBank（NCBI Resource Coordinators,2017）,European Nucleotide Archive（ENA）（Toribio et al,2017）,and DNA Data Bank of Japan（DDBJ）（Mashima et al.,2017）were established and have still acted as major data resources for maintaining nucleotide sequences and other types of biological data until today.

Abnormal expression of miR-331 leads to impaired heart function

MicroRNAs (miRNAs) play important roles in maintaining normal heart function. Abnormal expression of miR-331 has been observed in the hearts of patients with atrial fibrillation and Marfan syndrome. However, whether miR-331 regulates cardiac function under physiological and pathological conditions still remains unknown. In the present study, we investigated the function and underlying mechanisms of miR-331 in a pressure overload-induced heart failure model and miR-331 transgenic rat model. First, we found that the expression of miR-331-3p exhibited a 1.7-fold increase in hypertrophy compared with that in the sham group (P<0.01), yet the expression of miR-331-5p remained unchanged. Furthermore, overexpression of miR-331 in cardiomyocytes and defective excitation-contraction (E-C) coupling efficiency were observed. Luciferase assays showed that miR-331-3p suppressed JPH2 expression by binding to the coding region of JPH2 mRNA. Finally, in the miR-331 transgenic rat model, JPH2 expression was suppressed at both the mRNA and protein levels in vivo, which resulted in impairment of both the E-C coupling efficiency of cardiomyocytes and systolic function of the heart. This finding mechanistically linked miR-331 to JPH2 downregulation and suggested an important role for the abnormal expression of miR-331 leading to the dysfunction of E-C coupling in heart failure.