Jian Li

GlobalFoundries Inc. · AME

Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depr...

Wide-spread use of daptomycin unavoidably resulted in the emergence of daptomycin-resistant pathogens. In the hunt for more active daptomycin derivatives through medicinal chemistry studies, we established a concise semisynthetic approach to modify the L-Kyn13 on daptomycin specifically and effectively. Here, 19 novel derivatives with certain diver...

Strategies that can selectively eliminate senescent cells (SnCs), namely senolytics, have been shown to promote healthy lifespan. However, it is challenging to achieve precise, broad-spectrum and tractable senolysis. Here, we integrate multiple technologies that combine the enzyme substrate of senescence-associated β-galactosidase (SA-β-gal) with f...

Liquid biofuels (LBFs) that are renewable and sulfur-free, are one important part of future energy supplements. The advantage of ready availability of LBFs with high efficiencies and clean emissions is highly favored by solid oxide fuel cells (SOFCs), and wide applications in power generation, transportation, and aviation are expected. Direct and i...

Conjunctival melanoma (CM), a rare and fatal malignant ocular tumor, lacks proper diagnostic biomarkers and therapy. Herein, we revealed the novel application of propafenone, an FDA-approved antiarrhythmic medication, which was identified effective in inhibiting CM cells viability and homologous recombination pathway. Detailed structure-activity re...

Протонно-керамические топливные элементы способны генерировать электроэнергию путем непосредственного преобразования химической энергии топлива в ходе электрохимических реакций и имеют значительный потенциал практического использования благодаря своей высокой эффективности, малым выбросам и гибкости в отношении топлив. Более низкие и средние рабочи...

Dry reforming of methane (DRM) can convert the greenhouse gases to more valuable and easy separated syngas, which is of industrial and environmental importance. However, the reaction suffers from catalyst deactivation arising from the carbon deposition. Herein, we developed a perovskite PrCrO3-δ-supported nickel catalyst with high conversion rates...

Considering the earth powered by intermittent renewable energy in the coming future, solid oxide electrolysis cell (SOEC) will play an indispensable role in efficient energy conversion and storage on demand. The thermolytic and kinetic merits grant SOEC a bright potential to be directly integrated with electrical grid and downstream chemical synthe...

Slow oxygen reduction reaction (ORR) involving proton transport remains the limiting factor for electrochemical performance of proton-conducting cathodes. To further reduce the operating temperature of protonic ceramic fuel cells (PCFCs), developing triple-conducting cathodes with excellent electrochemical performance is required. In this study, K-...

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese he...

Selective elimination of senescent cells (senolysis) has become a promising therapeutic strategy for the management of chronic renal failure (CRF), but the senolytic molecular pathways towards CRF therapy are limited. Here, we present for the first time a senescence-associated β-galactosidase (SA-β-gal) activatable theragnostic prodrug strategy to...

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-low...

Double perovskite material PrBa0.9K0.1Fe1.9Zn0.1O5+δ (PBKFZ) has been designed using the first-principle calculations and synthesized as a new cathode for proton-conducting solid oxide fuel cells. The influence of K-doping on the crystal structure, structure stability, thermal expansion behavior, electronic conductivity, proton uptake, and electroc...

An efficient online energy-distribution management system (EMS) that ensures cells operate under optimized conditions, is critical for the high performance and long-term service of large energy storage or generation systems. In this work, a novel two-level structure EMS based on model predictive control (MPC) is proposed to achieve fast energy bala...

Reduced Ce0.9Ni0.1O2-δ consists of Ni nanoparticles and Ni-doped CeO2 (CNO), named ([email protected]) with Ni nanoparticles uniformly distributed on CNO substrate with high oxygen vacancy concentration and good water absorption capability. Thus [email protected] demonstrates moderate catalytic activity and high carbon deposition resistance during...

The development of solid oxide electrochemical cells (SOCs) coincides with the policy of emission peak and carbon neutrality, and possesses significant commercial prospects in the future energy market. Developing perovskite oxides with mixed oxygen ionic and electronic conductivity is an effective approach to alleviate the issues caused by lowering...

As the traditional conservative remedy for endometrial carcinoma (EC), progesterone has great limitations due to its poor performance, and a new strategy is urgently needed. Our previous work revealed that the antipsychotic drug chlorpromazine (CPZ) has stronger antitumor activity on EC than progesterone does, which may provide a promising conserva...

Overexpression, point mutations, or translocations of protein lysine methyltransferase NSD2 occur in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of multiple domains including a SET catalytic domain and two PWWP domains binding to methylated histone prot...

Aconitum episcopale Leveille is an important medicinal plant from the genus Aconitum L. of Ranunculaceae family and has been used as conventional medicine in Bai, Yi, and other ethnic groups of China. According to the available data and Ethno folk applications, A. episcopale is the only Aconitum species that has detoxifying and antialcoholic proper...

In our previous work, the clinical phase II HDAC inhibitor quisinostat was identified as a promising antimalarial agent through a drug repurposing strategy, but its safety was a matter of concern. Herein, further medicinal chemistry methods were used to identify new chemical entities with greater effectiveness and safety than quisinostat. In total,...

While screening our in-house 1072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans ( C. elegans ) as an animal model, crotamiton ( N -ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotami...

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also...

Aconitum is an important medicinal group of the Ranunculaceae family and has been used as conventional medicine in Bai, Yi, and other ethnic groups of China. There are about 350 Aconitum species globally and about 170 species in China. It is challenging to identify the species in morphology, and the lack of molecular biology information hinders the...

Depression is identified as one of the most common psychiatric symptoms in Alzheimer's disease (AD). The comorbidity of AD and depression increases the burden of clinical treatment and care in elderly patients. In order to find new treatment options, we first proposed the dual RAGE/SERT inhibitors by fusing the key pharmacophore of vilazodone and a...

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging...

Pseudomonas aeruginosa (P. aeruginosa) DK2 is a multidrug-resistant (MDR) gram-negative bacterial pathogen, being observed serious resistance to the ‘last-resort’ antibiotic, polymyxin B (PB). Combination therapies with adjuvants have emerged as effective strategies to reactivate the antibiotics resisted by MDR bacteria. Herein, we screened a libra...

NiMn2O4 (NMO) coated Gd-doped CeO2 (GDC) and NiO powders are prepared by a hydrothermal method for the anode of a metal (Ni-10 at.% Fe)-supported solid oxide fuel cell fueled by wet CH4 (3 vol.% H2O). NMO remains on NiO but dissolves into GDC at 1400 °C. Upon reduction in H2 at 700 °C for 2 h, Ni nanoparticles exsolve on the doped-CeO2 (DCO) substr...

Aging is a time-dependent decline in physiological function that affects most organisms and is the major risk factor for many non-communicable diseases. The early diagnosis of aging is critical for the treatment of aging and aging-related diseases. In recent years, extensive efforts have attempted to accurately diagnose aging. To date, multiple typ...

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we report...

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we report...

Depression is one of the most frequent comorbid psychiatric symptoms of Alzheimer's disease (AD), and no efficacious drugs have been approved specifically for this purpose thus far. Herein, we proposed a novel therapeutic strategy that merged the key pharmacophores of the antidepressant vilazodone (5-HT1A receptor partial agonist and serotonin tran...

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we report...

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we report...

High cost and short life-span hinder the large-scale commercial application of solid oxide fuel cell technology. System performance inevitably degrades and gradually evolves into faults in the long run, leading to the change of system input-output characteristics. The control system designed based on initial conditions faces with problems such as p...

While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans ( C. elegans ) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamit...

Diagnosing aging for preventative intervention generally relies on the tracking of aging biomarkers in the resting state. However, the static marker levels are insufficient to fully evaluate aging, particularly given that the stress response capacity (SRC) decay is currently viewed as a critical feature of aging. Therefore, we have developed a dual...

Catalysts for dry reforming of methane (DRM) based on Ni are used widely. However, due to carbon deposition or active metal sintering, deactivation is inevitably attached to these catalysts. Ni catalysts supported on mesoporous MgO–ZrO2 have been synthesized by surfactant-assisted route and impregnation method, and their catalytic performance for D...

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced prem...

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients’ lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chl...

Monoamine oxidase A (MAO-A) is a prominent myocardial source of reactive oxygen species (ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAO-A activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart fa...

In the current study, the microstructural consistency in a laser powder bed fusion (L-PBF) AlSi10Mg material is investigated. A rectangular sample with a height of 40 mm is fabricated through the L-PBF technique. The main aim of the study is to analyze the effect of the repeated thermal cycles on the hierarchical characteristics of the microstructu...

The commercialization of solid oxide fuel cells (SOFCs) can be significantly promoted with the direct utilization of methane, which is the primary component in natural gas and the second most abundant anthropogenic greenhouse gas. However, carbon deposition on most commonly used Ni-based anode is the bottle-necking issue inhibiting long-term stabil...

The evolution of solid oxide fuel cell anode microstructure during operation has important affects on cell performances and degradation. The degradation expectation requires a quantitative evaluation of the microstructure. In this work, anode support unit cells from 4 stacks are sampled and their anode functional layers and supports’ microstructure...

Coking is a major issue with the traditional Ni-based anodes when directly oxidizing CH4 in solid oxide fuel cells (SOFCs). Dry reforming to convert CH4–CO2 into CO–H2 syngas before entering Ni-based anode may potentially be an effective and economical method to address the coking problem. Consequently, an on-cell reforming layer outside the Ni-bas...

Herein, we report the total and semisyntheses of a series of polymyxin analogues with 2-Thr and 10-Thr modifications to reveal the structure-activity relationship (SAR), which has not been fully elucidated previously. We employed two total-synthetic strategies to facilitate the diversified replacements on 2-Thr or 10-Thr, respectively. Moreover, se...

Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to significantly inhibit the growth of...

Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote...

Medroxyprogesterone acetate (MPA) is the main conservative treatment for endometrial cancer (EC) patients desirable to preserve fertility and those who cannot suffer from surgery. Considering the high incidence of progestin resistance and recurrence of MPA treatment, we reproposed antipsychotics chlorpromazine (CPZ) as a new strategy for both proge...

To quickly and accurately obtain the multi-dimensional state in a sealing reactor is critical for the safety and high performance of industrial system. In this work, a generic machine learning based multi-dimensional soft sensor and a long-term calibration scheme is proposed by using the case of steam reforming solid oxide fuel cell (SR-SOFC) syste...

Effective strategies are needed to deal with invasive fungal infections caused by drug-resistant fungi. Previously, we designed a series of antifungal benzocyclane derivatives based on the drug repurposing of haloperidol. Herein, further structural optimization and antifungal mechanism studies were performed, leading to the discovery of new piperid...

Previously, we identified the clinical anticancer drug candidate quisinostat as a novel and potent antimalarial lead compound. To further enhance the antimalarial effect and improve safety, 31 novel spirocyclic hydroxamic acid derivatives were synthesized based on the structure of quisinostat, and their antimalarial activities and cytotoxicity were...

We report a two-dimensional design strategy to construct smart fluorescent probes for the precise tracking of senescence. Our approach relies on the detection of senescence-associated β-galactosidase activity in combination with the monitoring of lysosomal microenvironmental pH since de-acidification is a unique feature of the lysosomes in senescen...

The tracking of cellular senescence usually depends on the detection of senescence‐associated β‐galactosidase (SA‐β‐gal). Previous probes for SA‐β‐gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous β‐gal enriched i...

It is crucial to design effective cathode catalysts for high performance of Li–O2 batteries (LOBs). Herein, porous LaCo0.6Ni0.4O3 nanofibers decorated with ultrafine Co3O4 nanoparticles (Co3O4@LCN NFs) are designed and employed as cathode catalyst for LOBs. The X-ray photoelectron spectroscopy measurement results suggested that uniform dispreading...

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum , is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compou...

Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in clinical. Our previous research revealed that clinical phase Ⅱ antitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum (P. falciparum) histone deacetylase (PfH...

Symmetrical solid oxide cells (SSOCs) have been extensively recognized due to their simple cell configuration, low cost and reliability. High performance electrode is the key determinant of SSOCs. Herein, a multifunctional perovskite oxide La0.6Ca0.4Fe0.8Ni0.2O3-δ (LCaFN) is investigated as electrode for SSOCs. The results confirm that LCaFN shows...

Glass-based materials are usually considered as excellent seals for jointing adjacent components in planar solid oxide fuel cells, but the uncontrollable crystallization in the glass may cause delamination and micro-cracks in such seals. To solve this problem, Al2O3 ceramic particles were added to a BaO–CaO–Al2O3–B2O3–SiO2 glass system to reduce ne...

Reduced La0.6Sr0.2Cr0.85Ni0.15O3 (LSCrN) contains exsolved Ni nanoparticles ([email protected]) and abundant oxygen vacancies. Thus, it is an excellent catalyst for CO2 dry reforming of CH4. To use CH4 directly in solid oxide fuel cells, Ni–Ce0.9Gd0.1O1.95 (GDC) anode-supported cells are fabricated with and without a layer of [email protected] wt%...

Solid oxide fuel cell (SOFC) has attracted more and more attention for its advantages of high efficiency, low emission, and strong fuel adaptability. However, the fuel adaptability also brings issues for thermoelectric cooperative optimization of SOFC system because different fuel compositions can result in different thermal stresses and system per...

Ubiquitin-like protein neddylation is overactivated in various human cancers and correlates with disease progression, and targeting this pathway represents a valuable therapeutic strategy. Our previous work disclosed an antihypertensive agent, candesartan cilexetic (CDC), serves as a novel neddylation inhibitor for suppressing tumor growth by targe...

Zn-doped PrBa0.9Ca0.1Co2-xZnxO5+δ (PBCCZx) with x equaling 0, 0.05, 0.10, 0.15, and 0.2, designated as PBCCZ00, PBCCZ05, PBCCZ10, PBCCZ15, and PBCCZ20, respectively, are prepared and investigated in the aspects of crystal structure, thermal expansion behavior, defect chemistry, and electrochemical performance as the cathode of proton-conducting sol...

The exploitation of efficient electrocatalysts with specific morphology toward oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is crucial for Li–O2 batteries (LOBs). Perovskites are among the most promising electrocatalyst candidates mainly due to their tunable structure and facile preparation. In this study, porous double-doped...

Electrocatalysis CO2 to valuable chemical production is one important strategy to combat global warming. Symmetrical solid oxide electrolysis cells have been extensively recognized for their electrolysis of CO2 due to their high efficiency, low cost and reliability. Here, we propose a novel electrode with calcium oxide-looping and in situ exsolved...

To achieve high performance and carbon-deposition resistance, solid oxide fuel cells (SOFCs) with a nickel-10 wt.% iron alloy support, a 10 wt.% gadolinium doped cerium oxide electrolyte (GDC), a La0.6Sr0.4Co0.2Fe0.8O3-GDC (LSCF-GDC) cathode, and a Ni-GDC anode with (modified anode cell, MAC) or without (conventional anode cell, CAC) NiMn2O4 modifi...

Detection of senescence-associated β-galactosidase (SA-β-gal) activity at an increased lysosomal pH is one of the most reliable approaches for probing senescent cells. Herein, we developed a novel near-infrared fluorescent probe (KSL0401) for sensing SA-β-gal activity and applying in visualization of aging. This probe was designed by connecting a c...

A solid oxide cell (SOC) integrating solid oxide fuel cell (SOFC) and solid oxide electrolysis cell (SOEC) usually utilizes two different materials as the anode and cathode prepared by the costly multi-elements co-doping process. In this work, LaCo0.6Ni0.4O3−δ (LCN) is employed as the contact material and the electrode for the symmetrical SOC and e...

Human senescence-associated β-galactosidase (SA-β-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell ‘healthy aging’ and potentially predicting the health life span of an individual. Human SA-β-gal is an endogenous lysosomal enzyme expressed from GLB1, the catalytic domain of which is very different f...

La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) is a common cathode material for intermediate temperature solid oxide fuel cells due to its excellent oxygen reduction reaction catalytic activity. However, the Cr-poisoning effect is a severe issue causing its electrochemical performance degrada-tion. To develop a LSCF-based cathode with excellent Cr-tolerance, LaCr...

The novel h-BN/glass compressive seals were investigated for use in solid oxide fuel cell. The glass was mixed with h-BN powders to obtain composite materials using tape casting technique. Leakage rates were measured below 0.012 sccm/cm under input gas pressure of 6.8 kPa. Seals containing 40% by weight glass showed excellent thermal cycle and long...

Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of allosteric...

Computational fluid dynamics (CFD) technique and experimental measurement are combined to investigate the effects of several geometric parameters on flow uniformity and pressure distribution in an external manifold solid oxide fuel cell (SOFC) stack. The model of numerical simulation is composed of channels, tubes and manifolds based on a realistic...

Additive manufacturing of a low carbon Fe–Cr–Ni–Al maraging stainless steel (with the brand name CX) through the laser-powder bed fusion (LPBF) process is studied. Since the strength of this material is enhanced through precipitation hardening, the effect of different heat treatment cycles on the hardness and microstructure is assessed. The LPBF-CX...

La0.8Ce0.2Mn0.6Ni0.4O3 with ([email protected]) and without (LCMN) CuO addition are prepared by solution methods, followed by reduction in 5% H2–N2 stream at 650 °C to form Ni exsolved and CuO reduced catalysts, [email protected] and [email protected]/Cu, for ethanol (EtOH) steam reforming (ESR). The catalysts are characterized by X-ray diffraction...

A 5-cell stack with external manifold is thermal cycled between room temperature and 750 °C fifteen times. The electric performances after each cycle are measured and compared. The stack has an initial peak output of 328.44 W and shows excellent stability in thermal cycling. The average operating voltage degradation rate is only 0.8% corresponding...

To directly use CO2-CH4 mixture gas for power and CO co-production by proton-conducting solid oxide fuel cells (H-SOFC), a layer of in situ reduced La0.6Sr0.2Cr0.85Ni0.15O3-δ (LSCrN@Ni) is fabricated on a Ni-BaZr0.1Ce0.7Y0.1Yb0.1O3-δ (BZCYYb) anode-supported H-SOFC (H-DASC) for on-cell CO2 dry reforming of CH4 (DRC). For demonstrating the effective...