Xiangtong Zhang’s study on dendritic function:Gold is shining everywhere

It was in 1900,16 years after Gregor Johann Mendel's death,that Mendel's laws were widely accepted and the significance was well acknowledged by the scientific world.Similarly,it was in 1983,30 years after Barbara McClintock’s innovative discoveries,that she won an unshared Nobel Prize in Physiology or Medicine for the theory of jumping genes.Those touching stories have been talked a lot in scientific field,and those outstanding biologists have been memorized for their advanced theories,their persistence and their legacies.History always repeats itself.The neurophysiologist Xiangtong Zhang(Hsiang-tung Chang)also had a same experience,while he was rarely recognized by people.

Class Ⅰ histone deacetylase inhibition is synthetic lethal with BRCA1 deficiency in breast cancer cells

Breast cancer susceptibility gene 1(BRCA1)is a tumor suppressor gene,which is frequently mutated in breast and ovarian cancers.BRCA1 plays a key role in the homologous recombination directed DNA repair,allowing its deficiency to act as a therapeutic target of DNA damaging agents.In this study,we found that inhibition of the classⅠhistone deacetylases(HDAC)exhibited synthetic lethality with BRCA1 deficiency in breast cancer cells.Transcriptome profiling and validation study showed that HDAC inhibition enhanced the expression of thioredoxin interaction protein(TXNIP),causing reactive oxygen species(ROS)-mediated DNA damage.This effect induced preferential apoptosis in BRCA1-/-breast cancer cells where DNA repair system is compromised.Two animal experiments and gene expression-associated patients’survival analysis further confirmed in vivo synthetic lethality between BRCA1 and HDAC.Finally,the combination of inhibitors of HDAC and bromodomain and extra-terminal motif(BET),another BRCA1 synthetic lethality target that also works through oxidative stress-mediated DNA damage,showed a strong anticancer effect in BRCA1-/-breast cancer cells.Together,this study provides a new therapeutic strategy for BRCA1-deficient breast cancer by targeting two epigenetic machineries,HDAC and BET.

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma

More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.

Richang Cao:pioneer advocate of dialectical materialism applied to psychological research

“Don’t tell me what for or for what,just tell me what I should do!”It is an urgent demand that we always heard in our labs.However,the results end up being far from satisfaction when postgraduate do experiments strictly by their adviser’s guidance.There are many students who are completely indifferent to the theoretical hypothesis and concluding analysis of their research;even if they have read a lot of literature and repeated a lot of experiments in their daily routine.

Dr.Chen-lu Tsou:a tireless advocate for advancement in the standards of scientific research in China

The history of modern science in China is relatively short compared to that in western countries.For example,it was not until the 1920s that genetics and evolutionary theory were introduced to China.Most of the earliest Chinese biologists were trained overseas and returned to their beloved homeland to become pioneers of biomedical disciplines like zoology,plant biology,physiology,and neuroscience in China.

Yinglai Wang:an admirable biochemist for his foresightedness and selflessness

On July 5,2001,Nature published an article:“Wang Ying-lai(1907–2001)”in honor of Dr.Yinglai Wang and his contributions to the advancement of total chemical synthesis of biological molecules.It is rather rare for Nature to describe a biochemist in this manner.However,Yinglai Wang is an admired and revered scientist,and as such,deserves such an honor!

Surpassing the advanced comes from continuous accumulation

As a famous Chinese saying goes, ＂A journey of a thousand miles begins with a single step＂. It teaches us that perse- verance and steadfastness are absolutely essential for success and progress. This philosophy has been illustrated by an exemplary Chinese microbiologist, Taosheng Chen.