Target Information

Target General Information

Top

Target ID

T31479 (Former ID: TTDS00065)

Target Name

Phospholipase A2 (PLA2G1B)

Synonyms

Secreted phospholipase A(2); Phosphatidylcholine 2-acylhydrolase 1B; PLA2G1B; Group IB phospholipase A2

Click to Show/Hide

Gene Name

PLA2G1B

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Leishmaniasis [ICD-11: 1F54]

Peroxisomal disease [ICD-11: 5C57]

Rosacea [ICD-11: ED90]

Synthesis disorder [ICD-11: 5C52-5C59]

Function

PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides, this releases glycerophospholipids and arachidonic acid that serve as the precursors of signal molecules.

Click to Show/Hide

BioChemical Class

Carboxylic ester hydrolase

UniProt ID

PA21B_HUMAN

EC Number

EC 3.1.1.4

Sequence

MKLLVLAVLLTVAAADSGISPRAVWQFRKMIKCVIPGSDPFLEYNNYGCYCGLGGSGTPV
DELDKCCQTHDNCYDQAKKLDSCKFLLDNPYTHTYSYSCSGSAITCSSKNKECEAFICNC
DRNAAICFSKAPYNKAHKNLDTKKYCQS

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

PDB

ADReCS ID

BADD_A06627

HIT2.0 ID

T30TYH

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 5 Approved Drugs

Cholic Acid

Drug Info

Approved

Synthesis disorder

[2]

Clobetasol

Drug Info

Approved

Rosacea

[3]

Clocortolone

Drug Info

Approved

Rosacea

[3]

Diflorasone

Drug Info

Approved

Rosacea

[3]

Miltefosine

Drug Info

Approved

Leishmaniasis

[4]

Clinical Trial Drug(s)

[+] 7 Clinical Trial Drugs

AllerB

Drug Info

Phase 2b

Allergy

[5]

MANOALIDE

Drug Info

Phase 2

Arthritis

[6]

MRX-4

Drug Info

Phase 2

Allergic rhinitis

[7]

MRX-6

Drug Info

Phase 2

Contact dermatitis

[8]

URSOLIC ACID

Drug Info

Phase 2

Metabolic syndrome x

[9]

Varespladib

Drug Info

Phase 2

Snakebite

[10]

Rilapladib

Drug Info

Phase 1

Cardiovascular disease

[11]

Discontinued Drug(s)

[+] 8 Discontinued Drugs

Darapladib

Drug Info

Discontinued in Phase 3

Arteriosclerosis

[12], [13]

BMY-30129

Drug Info

Discontinued in Phase 2

Pruritus

[14]

EPC-K1

Drug Info

Discontinued in Phase 2

Nerve injury

[15]

SC-106

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[16]

WAY-123641

Drug Info

Discontinued in Phase 2

Asthma

[17]

PF-05212372

Drug Info

Discontinued in Phase 1

Asthma

[18]

SB-435495

Drug Info

Discontinued in Phase 1

Arteriosclerosis

[19]

YM-26734

Drug Info

Terminated

Rheumatoid arthritis

[20]

Mode of Action

[+] 4 Modes of Action

Inhibitor

[+] 37 Inhibitor drugs

Cholic Acid

Drug Info

[21]

Clobetasol

Drug Info

[1]

Diflorasone

Drug Info

[23]

Miltefosine

Drug Info

[24]

AllerB

Drug Info

[25]

MRX-4

Drug Info

[28]

MRX-6

Drug Info

[29]

URSOLIC ACID

Drug Info

[30]

BMY-30129

Drug Info

[3], [35]

EPC-K1

Drug Info

[3], [36]

SC-106

Drug Info

[37]

WAY-123641

Drug Info

[38]

PF-05212372

Drug Info

[39]

SB-435495

Drug Info

[40]

2-Methyl-2,4-Pentanediol

Drug Info

[21]

3,9-dihydroxy-2,10-diprenylpterocap-6a-ene

Drug Info

[43]

4'-hydroxy-6,3',5'-triprenylisoflavonone

Drug Info

[43]

ABYSSINONE V

Drug Info

[43]

Acetate Ion

Drug Info

[21]

Alpha-D-Mannose

Drug Info

[21]

BM-162115

Drug Info

[45]

BOLINAQUINONE

Drug Info

[46]

CACOSPONGIONOLIDE

Drug Info

[47]

CACOSPONGIONOLIDE B

Drug Info

[47]

Cacospongionolide E

Drug Info

[47]

HELENAQUINONE

Drug Info

[49]

Heptanoic Acid

Drug Info

[50]

Hexane-1,6-Diol

Drug Info

[21]

Hyrtiosulawesine

Drug Info

[51]

Lpc-Ether

Drug Info

[21]

LY178002

Drug Info

[52]

Mepacrine

Drug Info

[53]

methylglyoxal

Drug Info

[21]

N-Tridecanoic Acid

Drug Info

[50]

P-Anisic Acid

Drug Info

[21]

Petrosaspongiolide M

Drug Info

[54]

Petrosaspongiolide P

Drug Info

[55]

Inducer

[+] 1 Inducer drugs

Clocortolone

Drug Info

[22]

Modulator

[+] 8 Modulator drugs

MANOALIDE

Drug Info

[26], [27]

Rilapladib

Drug Info

[32]

Darapladib

Drug Info

[33], [34]

YM-26734

Drug Info

[41], [42]

AGN-190383

Drug Info

[44]

folipastatin

Drug Info

[48]

SB-203347

Drug Info

[56]

WA-8242-A1

Drug Info

[57], [58]

Binder

[+] 1 Binder drugs

LY256548

Drug Info

[52]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Glycerophospholipid metabolism	hsa00564	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Ether lipid metabolism	hsa00565	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Arachidonic acid metabolism	hsa00590	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Linoleic acid metabolism	hsa00591	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
alpha-Linolenic acid metabolism	hsa00592	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Vascular smooth muscle contraction	hsa04270	Affiliated Target
Class: Organismal Systems => Circulatory system	Pathway Hierarchy
Pancreatic secretion	hsa04972	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Fat digestion and absorption	hsa04975	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.44E-01	Radiality	1.17E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	3.00E+00	Topological coefficient	1.00E+00	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

BioCyc

[+] 1 BioCyc Pathways

Phospholipases

KEGG Pathway

[+] 10 KEGG Pathways

Glycerophospholipid metabolism

Ether lipid metabolism

Arachidonic acid metabolism

Linoleic acid metabolism

alpha-Linolenic acid metabolism

Metabolic pathways

Ras signaling pathway

Vascular smooth muscle contraction

Pancreatic secretion

Fat digestion and absorption

PID Pathway

[+] 1 PID Pathways

Fc-epsilon receptor I signaling in mast cells

Reactome

[+] 3 Reactome Pathways

Acyl chain remodelling of PC

Acyl chain remodelling of PE

Acyl chain remodelling of PI

WikiPathways

[+] 1 WikiPathways

Glycerophospholipid biosynthesis

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action. Br J Dermatol. 1984 Jul;111 Suppl 27:195-203.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 609).

REF 3

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 4

2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.

REF 5

Clinical pipeline report, company report or official report of Anergis SA.

REF 6

In situ aquaculture methods for Dysidea avara (Demospongiae, Porifera) in the northwestern Mediterranean. Mar Drugs. 2010 May 26;8(6):1731-42.

REF 7

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026713)

REF 8

ClinicalTrials.gov (NCT02031445) Double-Blind, Trial to Evaluate the Safety and Efficacy of MRX-6 Cream 2%. U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT02337933) Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT05717062) Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Intravenous Varespladib Followed by Oral Varespladib in Addition to Standard of Care in Subjects Bitten by Venomous Snakes. U.S.National Institutes of Health.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018454)

REF 12

REF 13

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016591)

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005019)

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007770)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007225)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003918)

REF 18

ClinicalTrials.gov (NCT01415102) A First In Human Study In Healthy People To Evaluate Safety, Toleration And Time Course Of Plasma Concentration Of Single Inhaled Doses Of PF-05212372.. U.S. NationalInstitutes of Health.

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015443)

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005488)

REF 21

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 22

Clocortolone pivalate: a paired comparison clinical trial of a new topical steroid in eczema/atopic dermatitis. Cutis. 1980 Jan;25(1):96-8.

REF 23

Structures from powders: diflorasone diacetate. Steroids. 2009 Jan;74(1):102-11.

REF 24

Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.

REF 25

Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747-54.

REF 26

Manoalide, a phospholipase A2 inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat. Neurochem Res. 1998 Oct;23(10):1251-7.

REF 27

The effects of the phospholipase A2 inhibitor, manoalide, on cartilage degradation, stromelysin expression, and synovial fluid cell count induced b... Arthritis Rheum. 1996 Aug;39(8):1292-9.

REF 28

Phospholipase A2, group IVA (cytosolic, calcium-dependent) (PLA2G4A). SciBX 1(41); doi:10.1038/scibx.2008.999. Nov. 13 2008

REF 29

A novel treatment of contact dermatitis by topical application of phospholipase A2 inhibitor: a double-blind placebo-controlled pilot study. Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):191-5.

REF 30

Synthesis of benzoyl phenyl benzoates as effective inhibitors for phospholipase A2 and hyaluronidase enzymes. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4100-4.

REF 31

Varespladib in the Treatment of Snakebite Envenoming: Development History and Preclinical Evidence Supporting Advancement to Clinical Trials in Patients Bitten by Venomous Snakes. Toxins (Basel). 2022 Nov 11;14(11):783.

REF 32

Effect of treatment for 12 weeks with rilapladib, a lipoprotein-associated phospholipase A2 inhibitor, on arterial inflammation as assessed with 18F-fluorodeoxyglucose-positron emission tomography imaging.J Am Coll Cardiol.2014 Jan 7-14;63(1):86-8.

REF 33

Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease. IDrugs. 2009 Oct;12(10):648-55.

REF 34

Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema: a 3-month placebo-controlled study.Ophthalmology.2015 May;122(5):990-6.

REF 35

Inhibitor of phospholipase A2 blocks eicosanoid and platelet activating factor biosynthesis and has topical anti-inflammatory activity. J Pharmacol Exp Ther. 1994 Nov;271(2):852-9.

REF 36

Posttreatment with EPC-K1, an inhibitor of lipid peroxidation and of phospholipase A2 activity, reduces functional deficits after global ischemia in rats. Brain Res Bull. 1995;36(3):257-60.

REF 37

US patent application no. 6,673,908, Tumor necrosis factor receptor 2.

REF 38

Phosphodiesterase-IV inhibition, respiratory muscle relaxation and bronchodilation by WAY-PDA-641. J Pharmacol Exp Ther. 1994 Feb;268(2):888-96.

REF 39

Phagedena due to leishmaniasis. Immunologic and experimental studies. Ann Dermatol Syphiligr (Paris). 1976;103(1):23-30.

REF 40

The effect of lipoprotein-associated phospholipase A2 deficiency on pulmonary allergic responses in Aspergillus fumigatus sensitized mice. Respir Res. 2012 Nov 12;13:100.

REF 41

Simplified YM-26734 Inhibitors of Secreted Phospholipase A2 Group IIA

REF 42

Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular ... Br J Pharmacol. 1993 Sep;110(1):447-53.

REF 43

Phospholipase A2 Inhibitors from an Erythrina Species from Samoa J. Nat. Prod. 60(6):537-539 (1997).

REF 44

AGN 190383, a novel phospholipase inhibitor with topical anti-inflammatory activity. Agents Actions. 1991 Sep;34(1-2):70-2.

REF 45

Investigation on the effect of experimental phospholipase A2 inhibitors on the formyl-methionyl-leucyl-phenylalanine-stimulated chemotaxis of human leukocytes in vitro. Arzneimittelforschung. 1998 Jan;48(1):77-81.

REF 46

New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte... J Nat Prod. 2001 May;64(5):612-5.

REF 47

A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration... J Nat Prod. 1998 Jul;61(7):931-5.

REF 48

Folipastatin, a new depsidone compound from Aspergillus unguis as an inhibitor of phospholipase A2.Taxonomy, fermentation, isolation, structure determination and biological properties.J Antibiot (Tokyo).1992 Aug;45(8):1195-201.

REF 49

New bioactive halenaquinone derivatives from South Pacific marine sponges of the genus Xestospongia. Bioorg Med Chem. 2010 Aug 15;18(16):6006-11.

REF 50

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 51

Hyrtiazepine, an azepino-indole-type alkaloid from the Red Sea marine sponge Hyrtios erectus. J Nat Prod. 2006 Dec;69(12):1676-9.

REF 52

The anti-inflammatory effects of LY178002 and LY256548. Agents Actions. 1989 Jun;27(3-4):300-2.

REF 53

Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.

REF 54

Synthesis and pharmacological evaluation of a selected library of new potential anti-inflammatory agents bearing the gamma-hydroxybutenolide scaffo... J Med Chem. 2007 May 3;50(9):2176-84.

REF 55

Petrosaspongiolides M-R: new potent and selective phospholipase A2 inhibitors from the New Caledonian marine sponge Petrosaspongia nigra. J Nat Prod. 1998 May;61(5):571-5.

REF 56

SB 203347, an inhibitor of 14 kDa phospholipase A2, alters human neutrophil arachidonic acid release and metabolism and prolongs survival in murine... J Pharmacol Exp Ther. 1995 Sep;274(3):1254-62.

REF 57

WA8242A1, A2 and B, novel secretary phospholipase A2 inhibitors produced by Streptomyces violaceusniger. III. Structure elucidation and total synth... J Antibiot (Tokyo). 1998 Jul;51(7):655-64.

REF 58

WA8242A1, A2 and B, novel secretory phospholipase A2 inhibitors produced by Streptomyces violaceusniger. I. Taxonomy, production and purification. J Antibiot (Tokyo). 1998 Jan;51(1):1-7.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN