University of Illinois

University of California

Tsinghua University

Chinese Academy of Sciences

Rutgers, The State University of New Jersey

Yonghui Zhang

Eric Oldfield

John M Sanders

Yongcheng Song

Julian M W Chan

Xiaolong Du

Zengxia Mei

Xin Li

Yicheng Lu

Meng Zhao

Ke Wang

Wei Zhu

Liping Li

Fenglin Yin

Wen-Chiang Hong

Yun Xia

William Sinko

Yonghua Xie

Zhengsen Yu

Weixue Wang

Xiaoying Zhou

James Andrew McCammon

Kai Li

Wanli Liu

Steffen Lindert

Huili Liang

Yunyun Yang

Kanzhao Gao

Disclosed are inhibitors of mevalonate pathway as an efficient vaccine adjuvant and use thereof. In particular, the inhibitor is an acetoacetyl-CoA transferase inhibitor, a HMG-CoA synthase inhibitor, a HMG-CoA reductase inhibitor, a mevalonate kinase inhibitor, a phosphomevalonate kinase inhibitor, a mevalonate-5-pyrophosphate decarboxylase inhibitor, an isopentenyl pyrophosphate isomerase inhibitor, a farnesyl pyrophosphate synthase inhibitor, a geranylgeranyl pyrophosphate synthase inhibitor or a geranylgeranyl transferase (I, II) inhibitor. Also disclosed is an immunogenic composition comprising inhibitors of mevalonate pathway as an adjuvant.

Mevalonate pathway inhibitor as highly-efficient vaccine adjuvant

Embodiments are directed to a flexible high voltage thin film transistor (f-HVTFT) with a center-symmetric circular configuration. The f-HVTFT includes a ring-shaped oxide semiconductor channel, a ring-shaped gate, a ring-shaped source, and a circular drain. The source and gate each have multiple connections to respective electrode pads, enabling stable and identical electrical characteristics and blocking voltage while the f-HVTFT is subject to bending from random directions. The f-HVTFT enables a high blocking voltage over 100 V, on-current over 100 &#x3bc;A, and low off-current of 0.1 pA, which makes it suitable for power management of self-powered wearable electronic systems.

Oxide-based flexible high voltage thin film transistor

The present invention provides a preparation method for a fully-transparent thin film transistor, wherein a transparent conductive gate electrode layer of the fully-transparent thin film transistor is used as a photolithographic mask, a photoresist is exposed through a rear surface of a transparent substrate, the transparent substrate has a transmittance higher than 60% to an exposure light beam, and the transparent conductive gate electrode layer has a transmittance lower than 5% to the exposure light beam. In the preparation method for a fully-transparent thin film transistor provided by the present invention, by using a self-aligned technology, the process complexity and the feature size of the device can both be reduced.

Preparation method for fully transparent thin film transistor

With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. The invention provides small molecules that inhibit cellular drug targets such as UPPS and FPPS by interacting with binding pockets, thereby preventing enzyme function. Compounds described herein are also active against(MIC90&#x2dc;0.25 &#x3bc;g/mL), can potently synergize with methicillin (fractional inhibitory concentration index=0.25), and are protective in a mouse infection model. The invention therefore provides numerous compounds for anti-bacterial treatments and for restoring sensitivity to drugs such as methicillin, using combination therapies.

Antibacterial compounds targeting isoprenoid biosynthesis

The invention provides compounds, compositions, and methods for studying the Rohmer pathway and for treating bacterial infections or parasitic infections. The parasitic infection can be a protozoan infection, such as malaria. The compounds and compositions can also be used as antibiotics, for example, to kill bacteria or parasites, or to inhibit bacterial or parasite growth. The invention further provides inhibitors of isoprenoid biosynthesis enzymes, and methods of inhibiting the activity of isoprenoid biosynthesis enzymes. The compounds can be, for example, alkynes or allenes that bind to a unique Fe of an Fe4S4 cluster of an isoprenoid biosynthesis enzyme.

Enzyme inhibiting compounds and methods

Bisphosphonate compounds and related methods of making and using are disclosed, including pyridinium-1-yl, quinolinium-1-yl, and related compounds. The activity of compounds is disclosed in the context of functional assays such asfarnesyl diphosphate synthase (FPPS) inhibition,growth inhibition, human gamma delta T cell activation, and bone resorption. The applicability of bisphosphonate compounds in the context of parasitic infections, for example against trypanosomes, is disclosed. Further potential applications of the invention are disclosed regarding the treatment of one or more conditions such as bone resorption disorders, cancer, bone pain, infectious diseases, and in immunotherapy.

Bisphosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases

The disclosure provides, inter alia, novel bisphosphonate compounds and methods of making and using such compounds. In certain embodiments, compounds of the invention include bisphosphonates that are capable of selectively inhibiting one or more of farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS), and decaprenyl pyrophosphate synthase (DPPS). In preferred embodiments, compounds of the invention are capable of selectively inhibiting two or more of FPPS, GGPPS, and DPPS. In embodiments, compounds and methods of the invention demonstrate superior activity levels, such as in the anti-cancer context, immunostimulation context, and other contexts, which in several cases exceed the activity levels of previous generation bisphosphonate drugs by orders of magnitude. In embodiments, the invention provides compounds and methods in connection with research and therapeutic applications, e.g., for tumor or cancer cell growth inhibition, activation of gammadelta T cells, inhibition of certain enzymes related to the mevalonate metabolic pathway, bone resorption diseases, cancer, immune disorders, immunotherapy, and infectious diseases.

Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS

The invention provides, inter alia, novel bisphosphonate compounds and methods of making and using. In embodiments, the invention provides compounds and methods in connection with research and therapeutic applications, e.g., for tumor cell growth inhibition, activation of gammadelta T cells, inhibition of farnesyldiphosphate (FPPS) and/or undecaprenyldiphosphate synthase enzymes, bone resorption diseases, cancer, immune disorders, immunotherapy, and infectious diseases. In regards to certain embodiments, a surprising advance has been the recognition that certain structural features can significantly enhance the activity of the compounds. For example, the presence of particular cationic species e.g., phosphonium, sulfonium, and arsonium moieties can contribute to desirable functional activity when positioned near a bisphosphonate moiety. In other embodiments of non-nitrogen containing bisphosphonates, terphenyl and benzyl bisphosphonate compounds and methods are provided. Further variations are also provided.

Bisphosphonate compounds and methods

Biophosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases

Growing community of inventors

Urbana, IL, United States of America

Yonghui Zhang