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"Luo"
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The unceasing storm : memories of the Chinese Cultural Revolution
The author writes about her experiences and the personal struggles she faced in China during China's Cultural Revolution after moving there in 1955 to study drama and opera.
Book
S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Vaccines for SARS-CoV-2 are needed to fight the pandemic. Here the authors show immunogenicity of an adjuvanted subunit vaccine, SARS-CoV-2 spike protein trimerized with trimer-tag technology, in small animal models and protection from SARS-CoV-2 challenge in non-human primates.
Journal Article
Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor
Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.
Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.
Journal Article
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei
Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.
Journal Article
Strangers in the Land : Exclusion, Belonging, and the Epic Story of the Chinese in America
\"From New Yorker editor and writer Michael Luo, a vivid, urgent history of two centuries of Chinese exclusion and the birth of anti-Asian feeling in America. In 1889, when the Supreme Court upheld the Chinese Exclusion Act-a measure barring Chinese laborers from entering the United States that remained in effect for more than fifty years-Justice Stephen Johnson Field characterized the Chinese as a people \"residing apart by themselves.\" They were, Field concluded, \"strangers in the land.\" Today, there are more than twenty-two million people of Asian descent in the United States, yet this label still hovers over Asian Americans. In Strangers in the Land, Luo traces anti-Asian feeling in America to the first wave of immigrants from China in the mid-nineteenth-century: laborers who traveled to California in search of gold and railroad work. Their communities almost immediately faced mobs of white vigilantes who drove them from their workplaces and homes. In his rich, character-driven history, Luo tells stories like that of Denis Kearney, the sandlot demagogue who became the face of the anti-Chinese movement, and of activists who fought back, like Massachusetts Senator George Frisbie Hoar and newspaperman Wong Chin Foo. After the halt on immigration in 1889, the Chinese-American community who remained struggled to survive and thrive on the margins of American life. In 1965, when LBJ's Immigration and Nationality Act forbade discrimination by national origin, America opened its doors wide to families like those of Luo's parents, but he finds that the centuries of exclusion of Chinese-Americans left a legacy: many Asians are still treated, and feel, like outsiders today. Strangers in the Land is a sweeping narrative of a forgotten chapter in American history, and a reminder that America's present reflects its exclusionary past\"-- Provided by publisher.
BOOK
Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem
Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer that is generally regarded as a genetic disease with diverse intertumor and intratumor heterogeneity. This perspective review mainly outlines the up-to-date knowledge of cancer ecology and NPC progression, and presents a number of conceptual stepping-stones. At the beginning, I explicitly advocate that the nature of NPC (cancer) is not a genetic disease but an ecological disease: a multidimensional spatiotemporal \"unity of ecology and evolution\" pathological ecosystem. The hallmarks of cancer is proposed to act as ecological factors of population fitness. Subsequently, NPC cells are described as invasive species and its metastasis as a multidirectional ecological dispersal. The foundational ecological principles include intraspecific relationship (e.g. communication) and interspecific relationship (e.g. competition, predation, parasitism and mutualism) are interpreted to understand NPC progression. \"Mulberry-fish-ponds\" model can well illustrate the dynamic reciprocity of cancer ecosystem. Tumor-host interface is the ecological transition zone of cancer, and tumor buddings should be recognized as ecological islands separated from the mainland. It should be noted that tumor-host interface has a significantly molecular and functional edge effect because of its curvature and irregularity. Selection driving factors and ecological therapy including hyperthermia for NPC patients, and future perspectives in such field as \"ecological pathology\", \"multidimensional tumoriecology\" are also discussed. I advance that \"nothing in cancer evolution or ecology makes sense except in the light of the other\". The cancer ecology tree is constructed to comprehensively point out the future research direction. Taken together, the establishment of NPC ecology theory and cancer ecology tree might provide a novel conceptual framework and paradigm for our understanding of cancer complex causal process and potential preventive and therapeutic applications for patients.
Journal Article
Asset price response to new information : the effects of conservatism bias and representativeness heuristic
Asset Price Response to New Information examines the effect of two types of psychological biases (namely, conservatism bias and representativeness heuristic) on the asset price reaction to new information. The author constructs various models of a competitive securities market or a security market allowing for strategic interaction among traders to prove rigorously that either conservatism or representativeness is capable of generating both asset price overreaction and underreaction to new information. The results shed some new insights on the phenomena of the asset price overreaction and underreaction to new information. In the literature, very little has been published in this area of behavioral finance. This volume will appeal to graduate-level students and researchers in finance, behavioral finance, and financial engineering.
Book
Coherence-controlled chaotic soliton bunch
Controlling the coherence of chaotic soliton bunch holds the promise to explore novel light-matter interactions and manipulate dynamic events such as rogue waves. However, the coherence control of chaotic soliton bunch remains challenging, as there is a lack of dynamic equilibrium mechanism for stochastic soliton interactions. Here, we develop a strategy to effectively control the coherence of chaotic soliton bunch in a laser. We show that by introducing a lumped fourth-order-dispersion (FOD), the soliton oscillating tails can be formed and generate the potential barriers among the chaotic solitons. The repulsive force between neighboring solitons enabled by the potential barriers gives rise to an alleviation of the soliton fusion/annihilation from stochastic interactions, endowing the capability to control the coherence in chaotic soliton bunch. We envision that this result provides a promising test-bed for a variety of dynamical complexity science and brings new insights into the nonlinear behavior of chaotic laser sources.
Controlling the coherence of chaotic waveforms holds the promise to explore novel light‐matter interactions. Here, the authors demonstrate a fourth‐order‐dispersion driven laser that delivers the coherence‐controlled chaotic soliton bunch.
Journal Article