Fragments of gD Protein as Inhibitors of BTLA/HVEM Complex Formation-Design, Synthesis, and Cellular Studies

One of many main present tendencies in most cancers immunotherapy is the blockade of immune checkpoint proteins that negatively regulate the immune response. This has been achieved by antibodies blocking PD-1/PD-L1 and CTLA-4/CD80/CD86 interactions. Such antibodies have revolutionized oncological remedy and proven a brand new method to battle most cancers. Further (unfavourable) immune checkpoints are additionally promising targets in most cancers remedy and there’s a demand for inhibitors for these molecules. Our research are targeted on BTLA/HVEM advanced, which inhibits T-cell proliferation and cytokine manufacturing and subsequently has nice potential as a brand new goal for most cancers remedy. The purpose of the offered research was the design and synthesis of compounds in a position to block BTLA/HVEM interactions.

For that objective, the N-terminal fragment of glycoprotein D (gD), which interacts with HVEM, was used. Based mostly on the crystal construction of the gD/HVEM advanced and MM/GBSA evaluation carried out on it, a number of peptides had been designed and synthesized as potential inhibitors of the BTLA/HVEM interplay. Affinity checks, ELISA checks, and cellular-based reporter assays had been carried out on these compounds to verify their capacity to bind to HVEM and to inhibit BTLA/HVEM advanced formation. For main peptides candidates, all-atom and subsequent docking simulations with a coarse-grained pressure area had been carried out to find out their binding modes.

To additional consider their potential as drug candidates, their stability in plasma and their cytotoxicity results on PBMCs had been assessed. Our information point out that the peptide gD(1-36)(Okay10C-T29C) is the greatest candidate as a future drug. It interacts with HVEM protein, blocks the BTLA/HVEM interplay, and is unhazardous to cells. The current examine gives a brand new perspective on the event of BTLA/HVEM inhibitors that disrupt protein interactions.

Outcomes of an early security evaluation of a examine of the mixture of pembrolizumab and pelvic chemoradiation in regionally superior cervical most cancers

Background: Immune checkpoint inhibitors are being thought-about for regionally superior cervical most cancers (LACC) along with standard-of-care pelvic chemoradiation (CRT). Nevertheless, the protection of the mixture and its optimum schedule are unknown. Defining the protection of the mixture is a major goal of a examine inspecting concurrent and sequential schedules. This text presents a security evaluation that was totally accrued and met reporting necessities.

Strategies: Pembrolizumab was given after CRT (arm 1) or throughout CRT (arm 2) in keeping with a randomized part 2 design. Sufferers who had been 18 years previous or older and had LACC (levels IB-IVA in keeping with the 2009 Worldwide Federation of Gynecology and Obstetrics system) had been randomized 1:1 to the remedy regimens. The CRT was equivalent within the 2 arms. Pembrolizumab was administered each three weeks for three doses; no upkeep was allowed. All sufferers receiving any remedy had been evaluated for security. Security assessments included the incidence and severity of adversarial occasions (AEs) and the prevalence of protocol-defined dose-limiting toxicity (DLT) by 30 days after the final pembrolizumab infusion.

Outcomes: As of August 2019, 52 of the 88 deliberate sufferers had accomplished remedy and had been evaluable for toxicity. Remedy-related grade 2 or increased toxicity was skilled by 88%; 11 had at the least 1 grade Four AE, and one other 23 had at the least 1 grade three AE. Grade 1 or increased diarrhea was reported in 34 sufferers, and there was no distinction between arms. Two sufferers skilled three DLTs. Most sufferers accomplished cisplatin (100% in arm 1 vs 82% in arm 2); 83% in each arms accomplished all pembrolizumab.

Conclusions: Preliminary outcomes help the protection and feasibility of including pembrolizumab to pelvic CRT concurrently or sequentially.

Lay abstract: Pembrolizumab is a humanized antibody towards programmed cell demise protein 1 that’s utilized in most cancers immunotherapy. Preliminary information counsel that pembrolizumab may be safely mixed with chemotherapy and pelvic radiation within the remedy of regionally superior cervical most cancers. Future research of the addition of immunotherapy to conventional chemoradiation are deliberate to find out the greatest method to ship the remedy and whether or not any enchancment is seen with the addition of immunotherapy to conventional remedy.

Balancing the Affinity and Pharmacokinetics of Antibodies by Modulating the Dimension of Cost Patches on Complementarity-Figuring out Areas

A localized optimistic cost on IgG (known as a “cost patch”) exhibits an adversarial impact on pharmacokinetics (PK), so it will appear to be greatest follow to keep away from cost patches through the discovery stage and intently monitor cost interactions through the growth course of. In sure circumstances, nevertheless, cost patches are required for goal binding, through which case fully eradicating cost patches just isn’t possible.

Due to this fact, quantitative measurement of a cost patch and its impression on PK is important to the success of therapeutic antibody growth. On this article, we generated mutations of a recombinant human antibody (known as mAb1) with disrupted cost patches to research how cost patches on IgG antibodies impression each target-binding affinity and PK-related elements. We conclude that you will need to modulate the dimensions of the cost patch to be able to steadiness target-binding affinity and PK.

HO-1 ELISA Kit

SKT-111-96 1 plate of 96 wells
EUR 702
Description: Sandwich ELISA kit used for quantitate HO-1 concentration in Cell Lysates, Tissue, Serum, Cyst fluid samples from Human, Rat

HO-1 ELISA Kit| Rat Heme Oxygenase 1 ELISA Kit

EF017799 96 Tests
EUR 826.8

HO-1 ELISA Kit| Mouse Heme Oxygenase 1 ELISA Kit

EF013687 96 Tests
EUR 826.8

Plant heme oxygenase 1, HO-1 ELISA ELISA Kit

SL0102PI - Ask for price

ELISA kit for Human HO-1/HMOX1

EK5397 96 tests
EUR 663.6
Description: Enzyme-linked immunosorbent assay kit for quantification of Human HO-1/HMOX1 in samples from serum, plasma, tissue homogenates and other biological fluids.

Rat heme oxygenase 1,HO-1 ELISA Kit

CN-01878R1 96T
EUR 548.4

Rat heme oxygenase 1,HO-1 ELISA Kit

CN-01878R2 48T
EUR 367.2

Rat heme oxygenase 1, HO-1 ELISA Kit

CSB-E08267r-24T 1 plate of 24 wells
EUR 198
Description: Quantitativesandwich ELISA kit for measuring Rat heme oxygenase 1, HO-1 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.

Rat heme oxygenase 1, HO-1 ELISA Kit

1-CSB-E08267r
  • EUR 1160.40
  • EUR 7110.00
  • EUR 3760.80
  • 1 plate of 96 wells
  • 10 plates of 96 wells each
  • 5 plates of 96 wells each
Description: Quantitativesandwich ELISA kit for measuring Rat heme oxygenase 1, HO-1 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.

Rat HO-1(Heme Oxygenase 1) ELISA Kit

ER1041 96T
EUR 628.92
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Rattus;Sensitivity: 0.188 ng/ml

Rat heme oxygenase 1(HO-1)ELISA Kit

GA-E0684RT-48T 48T
EUR 380.4

Rat heme oxygenase 1(HO-1)ELISA Kit

GA-E0684RT-96T 96T
EUR 595.2

Rat heme oxygenase 1(HO-1)ELISA Kit

QY-E10968 96T
EUR 433.2

Rat heme oxygenase 1,HO-1 ELISA Kit

EKC40418-48T 48T
EUR 647.15

Rat heme oxygenase 1,HO-1 ELISA Kit

EKC40418-5x96T 5x96T
EUR 4391.38

Rat heme oxygenase 1,HO-1 ELISA Kit

EKC40418-96T 96T
EUR 924.5

Rat HO-1(Heme Oxygenase 1) ELISA Kit

EKF58725-48T 48T
EUR 396.9

Rat HO-1(Heme Oxygenase 1) ELISA Kit

EKF58725-5x96T 5x96T
EUR 2693.25

Rat HO-1(Heme Oxygenase 1) ELISA Kit

EKF58725-96T 96T
EUR 567

Rat heme oxygenase 1(HO-1)ELISA Kit

NSL1430r 96 Tests
EUR 498

Rat heme oxygenase 1,HO-1 ELISA Kit

SL0341Ra -
EUR 498

Rat heme oxygenase 1,HO-1 ELISA Kit

YLA0269RA-48T 48T
EUR 465

Rat heme oxygenase 1,HO-1 ELISA Kit

YLA0269RA-96T 96T
EUR 600

Rat heme oxygenase 1(HO-1) Elisa Kit

EK720658 96 Wells
EUR 0.59

Goat Heme oxygenase 1(HO-1) ELISA Kit

NSL0619Gt 96T
EUR 528

Human HO-1/HMOX1 PicoKine ELISA Kit

EK0888 96 wells
EUR 510
Description: For quantitative detection of human HO-1 in cell culture supernates, cell lysates, serum and plasma (heparin, EDTA).

Human heme oxygenase 1,HO-1 ELISA Kit

201-12-0933 96 tests
EUR 528
Description: A quantitative ELISA kit for measuring Human in samples from biological fluids.

Mouse heme oxygenase 1,HO-1 ELISA Kit

CN-02756M1 96T
EUR 548.4

Mouse heme oxygenase 1,HO-1 ELISA Kit

CN-02756M2 48T
EUR 367.2

Human heme oxygenase 1,HO-1 ELISA Kit

CN-04663H1 96T
EUR 556.8

Human heme oxygenase 1,HO-1 ELISA Kit

CN-04663H2 48T
EUR 375.6

Human heme oxygenase 1, HO-1 ELISA Kit

CSB-E08266h-24T 1 plate of 24 wells
EUR 198
Description: Quantitativesandwich ELISA kit for measuring Human heme oxygenase 1, HO-1 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.

Human heme oxygenase 1, HO-1 ELISA Kit

1-CSB-E08266h
  • EUR 1080.00
  • EUR 6571.20
  • EUR 3480.00
  • 1 plate of 96 wells
  • 10 plates of 96 wells each
  • 5 plates of 96 wells each
Description: Quantitativesandwich ELISA kit for measuring Human heme oxygenase 1, HO-1 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.

Mouse heme oxygenase 1, HO-1 ELISA Kit

CSB-E08268m-24T 1 plate of 24 wells
EUR 198
Description: Quantitativesandwich ELISA kit for measuring Mouse heme oxygenase 1, HO-1 in samples from serum, plasma, cell culture supernates, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.

Mouse heme oxygenase 1, HO-1 ELISA Kit

1-CSB-E08268m
  • EUR 1135.20
  • EUR 6938.40
  • EUR 3672.00
  • 1 plate of 96 wells
  • 10 plates of 96 wells each
  • 5 plates of 96 wells each
Description: Quantitativesandwich ELISA kit for measuring Mouse heme oxygenase 1, HO-1 in samples from serum, plasma, cell culture supernates, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.

Human heme oxygenase 1(HO-1)ELISA Kit

GA-E0949HM-48T 48T
EUR 346.8

Human heme oxygenase 1(HO-1)ELISA Kit

GA-E0949HM-96T 96T
EUR 559.2

Mouse heme oxygenase 1(HO-1)ELISA Kit    

GA-E0279MS-48T 48T
EUR 403.2

Mouse heme oxygenase 1(HO-1)ELISA Kit    

GA-E0279MS-96T 96T
EUR 640.8

Mouse HO-1(Heme Oxygenase 1) ELISA Kit

EM1128 96T
EUR 628.92
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Mus ;Sensitivity: 9.375pg/ml

Mouse heme oxygenase 1(HO-1)ELISA Kit

QY-E20729 96T
EUR 433.2

Mouse HO-1(Heme Oxygenase 1) ELISA Kit

EKF60777-48T 48T
EUR 400.4

Mouse HO-1(Heme Oxygenase 1) ELISA Kit

EKF60777-5x96T 5x96T
EUR 2717

Mouse HO-1(Heme Oxygenase 1) ELISA Kit

EKF60777-96T 96T
EUR 572

Human heme oxygenase 1,HO-1 ELISA Kit

EKC33968-48T 48T
EUR 597.24

Human heme oxygenase 1,HO-1 ELISA Kit

EKC33968-5x96T 5x96T
EUR 4052.7

Human heme oxygenase 1,HO-1 ELISA Kit

EKC33968-96T 96T
EUR 853.2

Mouse heme oxygenase 1,HO-1 ELISA Kit

EKC37032-48T 48T
EUR 631.26

Mouse heme oxygenase 1,HO-1 ELISA Kit

EKC37032-5x96T 5x96T
EUR 4283.55

Mouse heme oxygenase 1,HO-1 ELISA Kit

EKC37032-96T 96T
EUR 901.8

Human heme oxygenase 1(HO-1)ELISA Kit

NSL1998Hu 96 wells
EUR 468

Mouse heme oxygenase 1(HO-1) ELISA Kit

NSL1498m 96 Test
EUR 528

Human heme oxygenase 1(HO-1)ELISA Kit

QY-E00664 96T
EUR 433.2

Human Heme oxygenase 1 (HO-1) ELISA Kit

RK09069 96T
EUR 280

Human heme oxygenase 1,HO-1 ELISA Kit

SL0839Hu 96 Tests
EUR 468

Mouse heme oxygenase 1, HO-1 ELISA Kit

SL0260Mo -
EUR 528

Mouse heme oxygenase 1,HO-1 ELISA Kit    

YLA0195MO-48T 48T
EUR 465

Mouse heme oxygenase 1,HO-1 ELISA Kit    

YLA0195MO-96T 96T
EUR 600

Human heme oxygenase 1,HO-1 ELISA Kit

YLA0935HU-48T 48T
EUR 435

Human heme oxygenase 1,HO-1 ELISA Kit

YLA0935HU-96T 96T
EUR 562.5

Mouse heme oxygenase 1,HO-1 Elisa Kit

EK730175 96 Wells
EUR 0.66

Human heme oxygenase 1(HO-1) Elisa Kit

EK700064 96 Wells
EUR 0.62

Bovine Heme oxygenase 1(HO-1) ELISA Kit

NSL0384Bo 96 T
EUR 528

Canine Heme oxygenase 1(HO-1) ELISA Kit

NSL0461Ca 556 wells
EUR 528

Chicken Heme oxygenase 1(HO-1) ELISA Kit

NSL0672Ch 767 T
EUR 528

Porcine Heme oxygenase 1(HO-1) ELISA Kit

NSL0517Po 96T
EUR 528

Guinea pig Heme oxygenase 1(HO-1) ELISA Kit

NSL0693Gp 96T
EUR 528

Human heme oxygenase 1,HO-1 ELISA Kit (Enzyme activity)

SL0839Hu_1 96 Tests Ask for price

Sheep Heparin-binding growth factor 1(HO-1)ELISA Kit

YLA0056SH-48T 48T
EUR 540

Sheep Heparin-binding growth factor 1(HO-1)ELISA Kit

YLA0056SH-96T 96T
EUR 645

HO-2 ELISA Kit| Rat heme oxygenase 2 ELISA Kit

EF017800 96 Tests
EUR 826.8

Brms1 ELISA Kit| Mouse Breast cancer metastasis-suppressor 1 ho

EF014335 96 Tests
EUR 826.8

Rat heme oxygenase 2,HO-2 ELISA Kit

CN-01837R1 96T
EUR 556.8

Rat heme oxygenase 2,HO-3 ELISA Kit

CN-01837R2 48T
EUR 375.6

Rat HO-2(heme oxygenase 2) ELISA Kit

ER1042 96T
EUR 628.92
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Rattus;Sensitivity: 0.938mU/ml

Rat heme oxygenase 2(HO-2)ELISA Kit

GA-E0685RT-48T 48T
EUR 380.4

Rat heme oxygenase 2(HO-2)ELISA Kit

GA-E0685RT-96T 96T
EUR 595.2

Rat heme oxygenase 2(HO-2)ELISA Kit

QY-E10967 96T
EUR 433.2

Rat Heme oxygenase 2(HO-2) ELISA Kit

NSL0477r 96 Tests
EUR 498

Rat heme oxygenase 2,HO-2 ELISA Kit

SL0342Ra -
EUR 498

Rat heme oxygenase 2,HO-2 ELISA Kit

YLA0449RA-48T 48T
EUR 465

Rat heme oxygenase 2,HO-2 ELISA Kit

YLA0449RA-96T 96T
EUR 600

Goat Heme oxygenase 2(HO-2) ELISA Kit

NSL0618Gt 96T
EUR 528

Human heme oxygenase 2,HO-2 ELISA Kit

201-12-0894 96 tests
EUR 528
Description: A quantitative ELISA kit for measuring Human in samples from biological fluids.

Mouse heme oxygenase 2,HO-2 ELISA Kit

CN-02714M1 96T
EUR 549.6

Mouse heme oxygenase 2,HO-2 ELISA Kit

CN-02714M2 48T
EUR 368.4

Human heme oxygenase 2,HO-2 ELISA Kit

CN-04658H1 96T
EUR 529.2

Human heme oxygenase 2,HO-2 ELISA Kit

CN-04658H2 48T
EUR 349.2

Human heme oxygenase 2, HO-2 ELISA Kit

CSB-E08408h-24T 1 plate of 24 wells
EUR 198
Description: Quantitativesandwich ELISA kit for measuring Human heme oxygenase 2, HO-2 in samples from serum, plasma, cell culture supernates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.

Human heme oxygenase 2, HO-2 ELISA Kit

1-CSB-E08408h
  • EUR 1080.00
  • EUR 6571.20
  • EUR 3480.00
  • 1 plate of 96 wells
  • 10 plates of 96 wells each
  • 5 plates of 96 wells each
Description: Quantitativesandwich ELISA kit for measuring Human heme oxygenase 2, HO-2 in samples from serum, plasma, cell culture supernates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.

Human heme oxygenase 2(HO-2)ELISA Kit

GA-E0910HM-48T 48T
EUR 346.8

Human heme oxygenase 2(HO-2)ELISA Kit

GA-E0910HM-96T 96T
EUR 559.2

Mouse heme oxygenase 2(HO-2)ELISA Kit

GA-E0394MS-48T 48T
EUR 403.2

Mouse heme oxygenase 2(HO-2)ELISA Kit

GA-E0394MS-96T 96T
EUR 640.8

Mouse heme oxygenase 2(HO-2)ELISA Kit

QY-E20730 96T
EUR 433.2

Human heme oxygenase 2,HO-2 ELISA Kit

EKC42261-48T 48T
EUR 604.03

Human heme oxygenase 2,HO-2 ELISA Kit

EKC42261-5x96T 5x96T
EUR 4098.78

Human heme oxygenase 2,HO-2 ELISA Kit

EKC42261-96T 96T
EUR 862.9

Human heme oxygenase 2(HO-2) ELISA Kit

NSL1997Hu 96 wells
EUR 468

Human heme oxygenase 2(HO-2)ELISA Kit

QY-E00663 96T
EUR 433.2

Human Heme oxygenase 2 (HO-2) ELISA Kit

RK07040 96T
EUR 280

Mouse Heme oxygenase 2 (HO-2) ELISA Kit

RK07041 96T
EUR 280

Human heme oxygenase 2,HO-2 ELISA Kit

SL0840Hu 96 Tests
EUR 468

Mouse heme oxygenase 2,HO-2 ELISA Kit

SL0261Mo -
EUR 528

Mouse heme oxygenase 2,HO-2 ELISA Kit

YLA0805MO-48T 48T
EUR 465

Mouse heme oxygenase 2,HO-2 ELISA Kit

YLA0805MO-96T 96T
EUR 600

Human heme oxygenase 2,HO-2 ELISA Kit

YLA0842HU-48T 48T
EUR 435

Human heme oxygenase 2,HO-2 ELISA Kit

YLA0842HU-96T 96T
EUR 562.5

Mouse heme oxygenase 2,HO-2 Elisa Kit

EK730176 96 Wells
EUR 0.66

Human heme oxygenase 2(HO-2) Elisa Kit

EK700065 96 Wells
EUR 0.63

HO-2 ELISA Kit| Mouse Heme Oxygenase 2, Decycling ELISA Kit

EF013688 96 Tests
EUR 826.8

Bovine Heme oxygenase 2(HO-2) ELISA Kit

NSL0385Bo 96 T
EUR 528

Canine Heme oxygenase 2(HO-2) ELISA Kit

NSL0462Ca 557 wells
EUR 528

Chicken Heme oxygenase 2(HO-2) ELISA Kit

NSL0671Ch 766 T
EUR 528

Porcine Heme oxygenase 2(HO-2) ELISA Kit

NSL0516Po 96T
EUR 528

Rat heme oxygenase 1, HO-1 GENLISA ELISA

KLR0676 1 x 96 wells
EUR 341

Human heme Oxygenase 1, HO-1 GENLISA ELISA

KBH0932 1 x 96 wells
EUR 286

Mouse heme oxygenase 1, HO-1 GENLISA ELISA   

KLM0266 1 x 96 wells
EUR 341

Rat Heme oxygenase 2 (HO-2/Hmox2) ELISA Kit

RK07042 96T
EUR 280

Guinea pig Heme oxygenase 2(HO-2) ELISA Kit

NSL0692Gp 96T
EUR 528

Mouse HO-2(Heme Oxygenase 2, Decycling) ELISA Kit

EM1129 96T
EUR 628.92
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Mus ;Sensitivity: 0.375 ng/ml

Smad1/MADH1 ELISA Kit| Rabbit Mothers Against Decapentaplegic Ho

EF016874 96 Tests
EUR 826.8

Human heme oxygenase 2,HO-2 ELISA Kit (Enzyme activity)

SL0840Hu_1 96 Tests Ask for price

Anti-HO-1 Monoclonal Antibody (HO-1-2)

M00253-1 1mg
EUR 476.4
Description: Mouse Monoclonal HO-1 Antibody (HO-1-2). Validated in Flow Cytometry, IHC, WB and tested in Human, Mouse, Rat.

Sheep Heparin-Binding Growth Factor 1, HO-1 GENLISA ELISA

KLS0067 1 x 96 wells
EUR 341

Rtf1 ELISA Kit| Mouse RNA polymerase-associated protein RTF1 ho

EF016125 96 Tests
EUR 826.8

OAED00115-50UG - Anti-HO-1 (HO-1-1) Antibody

OAED00115-50UG 50ug
EUR 269

HO- 1 Antibody

ABF5393 100 ug
EUR 525.6

HO-1 protein

E20-80037 20ug
EUR 489.6

HO-1 Antibody

AF5393 100ul
EUR 280
Description: Human,Mouse,Rat

HO-1 Antibody

DF6391 100ul
EUR 280
Description: Human,Mouse,Rat

HO-1 Antibody

R31625 100 ug
EUR 356.15
Description: Heme oxygenase (decycling) 1, also known as HO-1, is an essential enzyme in heme catabolism. HO-1 belongs to the heme oxygenase family. The HMOX1 gene is located on the long (q) arm of chromosome 22 at position 12.3, from base pair 34,101,636 to base pair 34,114,748. HO-1, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. HO-1 activity is induced by its substrate heme and by various nonheme substances.

HO-1 Antibody

AF5393-100ul 100ul
EUR 280

Avelumab, an antiprogrammed demise ligand-1 antibody, is authorized as a monotherapy for remedy of metastatic Merkel cell carcinoma and superior urothelial carcinoma, and together with axitinib for superior renal cell carcinoma. We report the efficacy and security of first-line avelumab in superior non-small cell lung most cancers (NSCLC).

Dalton

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