Shuyuan Zhang

Northwest University

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Yitai Qian

Chinese Academy of Medical Sciences & Peking Union Medical College

Hao Zhu

Nanjing Sport Institute

Sara L. Kendrick

The University of Texas Southwestern Medical Center

Robert D. Gerard

Edwards Lifesciences (United States)

Shun Tan

Southwest Jiaotong University

Hao Zhu

Beihang University

Liem H. Nguyen

The University of Texas Southwestern Medical Center

Jan M. Skotheim

Stanford University

Yi Xie

Collaborative Innovation Center of Chemistry for Energy Materials

Lin Li

Chinese Academy of Sciences

Cooperative Institutions

Google (United States)

413

Chinese Academy of Sciences

254

University of Science and Technology of China

179

DeepMind (United Kingdom)

160

University of Chinese Academy of Sciences

125

Stanford University

109

Chinese Academy of Medical Sciences & Peking Union Medical College

Shanghai Jiao Tong University

Zhejiang University

Sichuan University

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OpenAI o1 System Card

arXiv (Cornell University) (2024)

OpenAI NULL AUTHOR_ID Aaron Jaech Adam Tauman Kalai Adam Lerer

The o1 model series is trained with large-scale reinforcement learning to reason using chain of thought. These advanced reasoning capabilities provide new avenues for improving the safety and robustness of our models. In particular, our models can reason about our safety policies in context when responding to potentially unsafe prompts, through deliberative alignment. This leads to state-of-the-art performance on certain benchmarks for risks such as generating illicit advice, choosing stereotyped responses, and succumbing to known jailbreaks. Training models to incorporate a chain of thought before answering has the potential to unlock substantial benefits, while also increasing potential risks that stem from heightened intelligence. Our results underscore the need for building robust alignment methods, extensively stress-testing their efficacy, and maintaining meticulous risk management protocols. This report outlines the safety work carried out for the OpenAI o1 and OpenAI o1-mini models, including safety evaluations, external red teaming, and Preparedness Framework evaluations.

10.48550/arxiv.2412.16720

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Dendrimer‐Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I

Advanced Materials (2018)

Qiang Cheng Tuo Wei Yuemeng Jia Lukas Farbiak Ke‐Jin Zhou

mRNA-mediated protein replacement represents a promising concept for the treatment of liver disorders. Children born with fumarylacetoacetate hydrolase (FAH) mutations suffer from Hepatorenal Tyrosinemia Type 1 (HT-1) resulting in renal dysfunction, liver failure, neurological impairments, and cancer. Protein replacement therapy using FAH mRNA offers tremendous potential to cure HT-1, but is currently hindered by the development of effective mRNA carriers that can function in diseased livers. Structure-guided, rational optimization of 5A2-SC8 mRNA-loaded dendrimer lipid nanoparticles (mDLNPs) increases delivery potency of FAH mRNA, resulting in functional FAH protein and sustained normalization of body weight and liver function in FAH-/- knockout mice. Optimization using luciferase mRNA produces DLNP carriers that are efficacious at mRNA doses as low as 0.05 mg kg-1 in vivo. mDLNPs transfect > 44% of all hepatocytes in the liver, yield high FAH protein levels (0.5 mg kg-1 mRNA), and are well tolerated in a knockout mouse model with compromised liver function. Genetically engineered FAH-/- mice treated with FAH mRNA mDLNPs have statistically equivalent levels of TBIL, ALT, and AST compared to wild type C57BL/6 mice and maintain normal weight throughout the month-long course of treatment. This study provides a framework for the rational optimization of LNPs to improve delivery of mRNA broadly and introduces a specific and viable DLNP carrier with translational potential to treat genetic diseases of the liver.

Tyrosinemia

10.1002/adma.201805308

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Citations (175)

A high-resolution electron microscopy study of microstructure of ZnS powder phosphors with different dopants

Philosophical Magazine A (1990)

Shuyuan Zhang Changxin Guo Li Bilin Shun Tan

Abstract The microstructures of ZnS phosphors with different dopants and different luminescence mechanisms have been investigated by transmission electron microscopy (TEM). Our observations show that there are evident differences in the microstructures of ZnS: Fe, ZnS: Cu and ZnS: Mn. It is reasonable to infer from the TEM experiments that the photoluminescence probably relates mainly to the various stacking faults and dislocations, whereas the a.c. electroluminescence may have a relationship with the microtwin structure, and the coherent growth state of α- and β-phases may be the reason for the d.c. electroluminescence.

10.1080/01418619008244786

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Citations (7)

Multitargeted Platinum(IV) Anticancer Complexes Bearing Pyridinyl Ligands as Axial Leaving Groups

Angewandte Chemie International Edition (2023)

Qiyuan Zhou Shu Chen Zoufeng Xu Gongyuan Liu Shuyuan Zhang

Abstract Although multitargeted Pt IV anticancer prodrugs have shown significant activities in reducing drug resistance, the types of bioactive ligands and drugs that can be conjugated to the Pt center remain limited to O‐donors. Herein, we report the synthesis of Pt IV complexes bearing axial pyridines via ligand exchange reactions. Unexpectedly, the axial pyridines are quickly released after reduction, indicating their potential to be utilized as axial leaving groups. We further expand our synthetic approach to obtaining two multitargeted Pt IV prodrugs containing bioactive pyridinyl ligands: a PARP inhibitor and an EGFR tyrosine kinase inhibitor; these conjugates exhibit great potential for overcoming drug resistance, and the latter conjugate inhibits the growth of Pt‐resistant tumor in vivo. This research adds to the array of synthetic methods for accessing Pt IV prodrugs and significantly increases the types of bioactive axial ligands that can be conjugated to a Pt IV center.

Conjugate

10.1002/anie.202302156

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Citations (16)

Reflections on major epidemics in history reported by online English news media and literature: interaction between epidemics and social conditions

Frontiers in Public Health (2023)

Xiaorui Chen Xinyu Wei Yuanfeng Zhang Ying Sun Zihan Xu

OPINION article Front. Public Health, 11 April 2023Sec. Public Health Education and Promotion Volume 11 - 2023 | https://doi.org/10.3389/fpubh.2023.1160756

10.3389/fpubh.2023.1160756

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Data Supplement from TALEN-Mediated Somatic Mutagenesis in Murine Models of Cancer

Shuyuan Zhang Lin Li Sara L. Kendrick Robert D. Gerard Hao Zhu

<p>Supplementary Figure 3. liver picture, genotyping and sequencing data for β-catenin TALENs plus DEN induced liver tumor in C3H mice</p>

Liver Cancer

10.1158/0008-5472.22404515

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MIR390 Is Involved in Regulating Anthracnose Resistance in Apple

Plants (2022)

Jiajun Shi Qiu Jiang Shuyuan Zhang Xinyu Dai Feng Wang

As an important cash crop in China, apple has a good flavor and is rich in nutrients. Fungal attacks have become a major obstacle in apple cultivation. Colletotrichum gloeosporioides is one of the most devastating fungal pathogens in apple. Thus, discovering resistance genes in response to C. gloeosporioides may aid in designing safer control strategies and facilitate the development of apple resistance breeding. A previous study reported that 'Hanfu' autotetraploid apple displayed higher C. gloeosporioides resistance than 'Hanfu' apple, and the expression level of mdm-MIR390b was significantly upregulated in autotetraploid plants compared to that in 'Hanfu' plants, as demonstrated by digital gene expression (DGE) analysis. It is still unclear, however, whether mdm-MIR390b regulates apple anthracnose resistance. Apple MIR390b was transformed into apple 'GL-3' plants to identify the functions of mdm-MIR390b in anthracnose resistance. C. gloeosporioides treatment analysis indicated that the overexpression of mdm-MIR390b reduced fungal damage to apple leaves and fruit. Physiology analysis showed that mdm-MIR390b increased C. gloeosporioides resistance by improving superoxide dismutase (SOD) and peroxidase (POD) activity to alleviate the damage caused by O2- and H2O2. Our results demonstrate that mdm-MIR390b can improve apple plants' anthracnose resistance.

10.3390/plants11233299

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Citations (5)

Non‐Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co‐Delivery of Cas9 mRNA and sgRNA

Angewandte Chemie International Edition (2016)

Jason B. Miller Shuyuan Zhang Petra Kós Hu Xiong Ke‐Jin Zhou

Abstract CRISPR/Cas is a revolutionary gene editing technology with wide‐ranging utility. The safe, non‐viral delivery of CRISPR/Cas components would greatly improve future therapeutic utility. We report the synthesis and development of zwitterionic amino lipids (ZALs) that are uniquely able to (co)deliver long RNAs including Cas9 mRNA and sgRNAs. ZAL nanoparticle (ZNP) delivery of low sgRNA doses (15 n m ) reduces protein expression by >90 % in cells. In contrast to transient therapies (such as RNAi), we show that ZNP delivery of sgRNA enables permanent DNA editing with an indefinitely sustained 95 % decrease in protein expression. ZNP delivery of mRNA results in high protein expression at low doses in vitro (<600 pM) and in vivo (1 mg kg −1 ). Intravenous co‐delivery of Cas9 mRNA and sgLoxP induced expression of floxed tdTomato in the liver, kidneys, and lungs of engineered mice. ZNPs provide a chemical guide for rational design of long RNA carriers, and represent a promising step towards improving the safety and utility of gene editing.

Subgenomic mRNA

Guide RNA

10.1002/anie.201610209

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Citations (466)

Rough surface of copper-bearing titanium alloy with multifunctions of osteogenic ability and antibacterial activity

Journal of Material Science and Technology (2020)

Hui Liu Rui Liu Ihsan Ullah Shuyuan Zhang Ziqing Sun

Osteopontin

Titanium alloy

10.1016/j.jmst.2019.12.019

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