July 2009 Volume 15 Number 7, pp 707 - 819
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CYTOKINE BIOCHIP ARRAYS
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Nature Reviews Microbiology
Poster on inhibition of the replicative cycle of hepatitis C virus
It is estimated that 170 million people are infected with the hepatitis C virus (HCV). Because current drugs against HCV have poor safety profiles and limited effectiveness, there is considerable interest in identifying specific inhibitors of HCV replication.
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NATURE MEDICINE PODCAST
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Chasing cancer
We review the latest biomedical news and jump into the world of scientists who are trying to understand how cancer outsmarts a potent pharmaceutical.
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EDITORIAL
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The insider's guide to plagiarism p707
Scientific plagiarism-a problem as serious as fraud-has not received all the attention it deserves.
doi:10.1038/nm0709-707
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NEWS
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Conflict of interest rules seen by some as too stringent p709
Cassandra Willyard
doi:10.1038/nm0709-709
http://links.ealert.nature.com/ctt?kn=72&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
A close look at acid reflux drugs points to possible risks p710
Alisa Opar
doi:10.1038/nm0709-710
http://links.ealert.nature.com/ctt?kn=25&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Report details changes and challenges for women in biomedicine p711
Melinda Wenner
doi:10.1038/nm0709-711a
http://links.ealert.nature.com/ctt?kn=66&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
NIH pushes for rare disease drugs p711
Stu Hutson
doi:10.1038/nm0709-711b
http://links.ealert.nature.com/ctt?kn=43&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
New initiative launched to support research in Africa p712
Charlotte Schubert
doi:10.1038/nm0709-712a
http://links.ealert.nature.com/ctt?kn=85&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Medical research charities brace for economic impact p712
Stu Hutson
doi:10.1038/nm0709-712b
http://links.ealert.nature.com/ctt?kn=116&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
High-tech bandages lighten the load of light therapy p713
Jon Evans
doi:10.1038/nm0709-713a
http://links.ealert.nature.com/ctt?kn=54&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Nuclear watchdog and WHO move forward against cancer p713
Karen Dente
doi:10.1038/nm0709-713b
http://links.ealert.nature.com/ctt?kn=136&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
News in brief pp714 - 715
doi:10.1038/nm0709-714
http://links.ealert.nature.com/ctt?kn=39&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Straight talk with... Mauro Ferrari pp716 - 717
Mauro Ferrari has Texas-size aspirations for using nanotechnology to treat illness. This past June, Ferrari became professor and chairman of the newly established Department of Nanomedicine and Biomedical Engineering (nBME) at the University of Texas Health Science Center at Houston. Ferrari met with Jon Evans to discuss nanomedicine, the importance of matching technology to therapeutic need and becoming a medical student in his mid-40s.
Jon Evans
doi:10.1038/nm0709-716
Abstract: http://links.ealert.nature.com/ctt?kn=92&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=168&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Outpacing Cancer pp718 - 722
In the late 1990s the drug gefitinib became a new tool in treating the most common type of lung cancer, called non-small cell lung cancer. But doctors found that even with continued gefitinib treatment, some patients experienced a cancer relapse within a year. For the past several years, researchers have been working to uncover why these patients lost sensitivity to gefitinib and seeking how to overcome resistance to the drug. Kirsten Dorans reports on the strategies scientists are developing to outpace continually evolving cancer.
Kirsten Dorans
doi:10.1038/nm0709-718
http://links.ealert.nature.com/ctt?kn=176&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Australian funding overhaul set into motion p723
Simon Grose
doi:10.1038/nm0709-723a
http://links.ealert.nature.com/ctt?kn=1&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Lawsuit sparks calls for libel law reform p723
Cassandra Willyard
doi:10.1038/nm0709-723b
http://links.ealert.nature.com/ctt?kn=80&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Indian universities face misconduct allegations p723
Killugudi Jayaraman
doi:10.1038/nm0709-723c
http://links.ealert.nature.com/ctt?kn=155&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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BOOK REVIEW
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Drug development's dark side p724
Joseph T. Coyle reviews Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial by Alison Bass
doi:10.1038/nm0709-724
http://links.ealert.nature.com/ctt?kn=174&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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CORRESPONDENCE
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Antibody affinity maturation and respiratory syncytial virus disease p725
Christine A Shaw et al.
doi:10.1038/nm0709-725a
http://links.ealert.nature.com/ctt?kn=183&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Reply to: "Antibody affinity maturation and respiratory syncytial virus disease" pp725 - 726
Maria Florencia Delgado, Pablo M Irusta and Fernando P Polack
doi:10.1038/nm0709-725b
http://links.ealert.nature.com/ctt?kn=153&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Will integrin inhibitors have proangiogenic effects in the clinic? p726
Michael Weller, David Reardon, Burt Nabors and Roger Stupp
doi:10.1038/nm0709-726
http://links.ealert.nature.com/ctt?kn=6&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Reply to: "Will integrin inhibitors have proangiogenic effects in the clinic?" p727
Andrew R Reynolds and Kairbaan M Hodivala-Dilke
doi:10.1038/nm0709-727
http://links.ealert.nature.com/ctt?kn=145&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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NEWS AND VIEWS
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Receptors identified for hand, foot and mouth virus pp728 - 729
Two receptors have now been identified for the virus behind severe hand, foot and mouth disease (pages 794-797 and 798-801).
Kunal P. Patel and Jeffrey M. Bergelson
doi:10.1038/nm0709-728
http://links.ealert.nature.com/ctt?kn=74&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Coupling bone degradation to formation pp729 - 731
To maintain skeletal integrity and prevent fractures, degradation and rebuilding of bone must occur in synchrony. Transforming growth factor-B1 is now found to coordinate this restructuring process: the molecule is released during bone degradation and stimulates bone rebuilding (pages 757-765).
Jameel Iqbal, Li Sun and Mone Zaidi
doi:10.1038/nm0709-729
http://links.ealert.nature.com/ctt?kn=184&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Tumor immunotherapy: making an immortal army pp731 - 732
Manipulation of cell renewal pathways creates T memory stem cells that can generate a sustained and targeted immune response. These findings have broad implications for vaccine development and immunotherapy (pages 808-813).
Brent H. Koehn and Stephen P. Schoenberger
doi:10.1038/nm0709-731
http://links.ealert.nature.com/ctt?kn=32&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Targeting lymphotoxin depletes pathogenic T cells pp732 - 733
A monoclonal antibody directed against lymphotoxin-A (LT-A) expressed by pathogenic T cells can prompt the clearance of these cells from the body (pages 766-773). The findings bring us one step closer to targeting only the cell populations that cause harm in autoimmune diseases while leaving beneficial arms of the immune system largely intact.
Anna M. Hansen and Rachel R. Caspi
doi:10.1038/nm0709-732
http://links.ealert.nature.com/ctt?kn=17&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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COMMUNITY CORNER
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Hedgehog inhibitor pokes tumor p734
doi:10.1038/nm0709-734
http://links.ealert.nature.com/ctt?kn=87&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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BETWEEN BEDSIDE AND BENCH
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Damage control in the nervous system
People with damage to the central nervous system often undergo rehabilitation therapy. James Fawcett and Armin Curt examine how such therapy might work in conjunction with experimental approaches that increase the ability of neurons to form new connections. They discuss how animal studies raise questions about how to test such approaches in people in a field where firm data are already hard to come by. Phillip Popovich and Dana McTigue take a look at a specific type of nervous system damage-spinal cord injury-and argue that the role of the immune system is underappreciated. They also suggest that one common therapy, application of glucocorticoids, might actually exacerbate the condition.
Damage control in the nervous system: rehabilitation in a plastic environment pp735 - 736
James W Fawcett and Armin Curt
doi:10.1038/nm0709-735
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Damage control in the nervous system: beware the immune system in spinal cord injury pp736 - 737
Phillip Popovich and Dana McTigue
doi:10.1038/nm0709-736
http://links.ealert.nature.com/ctt?kn=150&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research Highlights pp738 - 739
doi:10.1038/nm0709-738
http://links.ealert.nature.com/ctt?kn=162&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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BRIEF COMMUNICATIONS
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GOAT links dietary lipids with the endocrine control of energy balance pp741 - 745
It has been a long-held belief that the hormone ghrelin is activated when an animal is hungry, inducing the brain to increase food intake. Now, Matthias Tschop and his colleagues show in vivo that it is not the deficiency of calories per se that activates ghrelin, but rather the presence of energy-rich medium-chain dietary fats.
Henriette Kirchner et al.
doi:10.1038/nm.1997
Abstract: http://links.ealert.nature.com/ctt?kn=44&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=133&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates pp746 - 749
Immunosuppressive regimens used to prevent rejection of transplanted organs are associated with many adverse side effects. Weaver et al. report that by combining the use of a CD2-targeting reagent (alefacept) with a co-stimulation blockade-based protocol, they can prolong survival of kidney allografts in macaques while avoiding the use of standard immunosuppressive agents.
Tim A Weaver et al.
doi:10.1038/nm.1993
Abstract: http://links.ealert.nature.com/ctt?kn=131&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=189&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
=========================== ADVERTISEMENT ===========================
UCSD Clinical and Translational Research Institute and Nature Medicine present:
Frontiers of Clinical Investigation Symposium
Metabolism 2009: From Bench to Bedside
October 8-10, 2009
La Jolla, California, USA
The theme for this year's symposium explores innovative approaches to bridge laboratory investigation to clinical research in metabolism.
Early Bird Deadline: September 8, 2009
Abstract Submission: Deadline: August 21, 2009
For more information visit: http://links.ealert.nature.com/ctt?kn=149&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
anatureconference
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ARTICLES
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A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma pp750 - 756
Ewing's sarcoma family tumors are dependent on an oncogenic fusion protein, most commonly EWS-FLI1, which interacts with RNA helicase A (RHA) in transcriptional complexes. Erkizan et al. have identified a small molecule that inhibits the interaction of RHA with EWS-FLI1 and impairs the growth of Ewing's sarcoma xenografts in mice. The findings provide evidence that targeting tumor-specific transcription factors may be a feasible approach to treating cancer.
Hayriye V Erkizan et al.
doi:10.1038/nm.1983
Abstract: http://links.ealert.nature.com/ctt?kn=124&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=139&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
TGF-B1-induced migration of bone mesenchymal stem cells couples bone resorption with formation pp757 - 765
Bone is a dynamic tissue and requires the precise coordination of formation with loss. Here, Xu Cao and his colleagues show that the bone-chewing activity of osteoclasts results in the local release of active TGF-B1 from the surface of the bone, inducing the migration of nearby bone-forming osteoblastic progenitor cells to this resorbed region. In this manner, proper matching of the localized rates of bone loss and bone creation is ensured (pages 729-731).
Yi Tang et al.
doi:10.1038/nm.1979
Abstract: http://links.ealert.nature.com/ctt?kn=77&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=110&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Targeted depletion of lymphotoxin-A-expressing TH1 and TH17 cells inhibits autoimmune disease pp766 - 773
B cell-depleting antibodies have therapeutic efficacy against arthritis. Here Jane Grogan and her colleagues report a new approach to depleting pathogenic T cells. They show that lymphotoxin-A is upregulated on the surface of activated TH1 and TH17 CD4+ cells, which have a pathogenic role in several autoimmune diseases, and a monoclonal antibody targeted to lymphotoxin-a can inhibit collagen-induced arthritis and EAE in mice (pages 732-733).
Eugene Y Chiang et al.
doi:10.1038/nm.1984
Abstract: http://links.ealert.nature.com/ctt?kn=93&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=21&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease pp774 - 780
TLR4 has a key role in driving inflammation in mouse models of arthritis and may also have a role in the human disease. The extracellular matrix protein tenascin-C is upregulated in the joints of individuals with rheumatoid arthritis. Here Kim Midwood and her colleagues show that tenascin-C is an endogenous activator of TLR4 and that it contributes to the maintenance of arthritis in mice.
Kim Midwood et al.
doi:10.1038/nm.1987
Abstract: http://links.ealert.nature.com/ctt?kn=57&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=114&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis pp781 - 787
Christopher Kirk and his colleagues have developed the first specific inhibitor of the immunoproteasome. They find that the immunoproteasome has a major role in regulating cytokine production, as well as antigen presentation, and their inhibitor has good efficacy in animal models of arthritis.
Tony Muchamuel et al.
doi:10.1038/nm.1978
Abstract: http://links.ealert.nature.com/ctt?kn=51&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=99&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
=========================== ADVERTISEMENT ===========================
Roche and Nature Medicine present:
Translational Neuroscience Symposium 2009
Autism and Other Developmental Brain Disorders
This year's symposium successfully brought together leaders in the field to discuss recent advances on the pathophysiology of neurodevelopmental disorders and the search for their cure.
For more information visit: http://links.ealert.nature.com/ctt?kn=179&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
anatureconference
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LETTERS
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Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system pp788 - 793
Modulating the entry of inflammatory T cells into the brain could be one way to treat the autoimmune disease multiple sclerosis. Now, Frauke Zipp and colleagues demonstrate that activation of kinin receptor B1 can block autoimmune T cell migration into the brain and can therefore inhibit experimental autoimmune encephalomyelitis in mice.
Ulf Schulze-Topphoff et al.
doi:10.1038/nm.1980
Abstract: http://links.ealert.nature.com/ctt?kn=41&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=126&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71 pp794 - 797
Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild infectious disease that can, however, occasionally lead to severe neurological impairments. These two studies, by Nishimura et al. and Yamayoshi et al., independently identify two different receptors for EV71-P-selectin glycoprotein ligand-1 ((PSGL-1) and scavenger receptor class B, member 2 (SCARB2) (pages 728-729) and (pages 798-801).
Yorihiro Nishimura et al.
doi:10.1038/nm.1961
Abstract: http://links.ealert.nature.com/ctt?kn=98&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=130&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Scavenger receptor B2 is a cellular receptor for enterovirus 71 pp798 - 801
Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild infectious disease that can, however, occasionally lead to severe neurological impairments. These two studies, by Nishimura et al. and Yamayoshi et al., independently identify two different receptors for EV71-P-selectin glycoprotein ligand-1 ((PSGL-1) and scavenger receptor class B, member 2 (SCARB2) (pages 728-729) and (pages 794-797).
Seiya Yamayoshi et al.
doi:10.1038/nm.1992
Abstract: http://links.ealert.nature.com/ctt?kn=83&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=177&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain pp802 - 807
Pain is one of the many debilitating side effects of cancer. Now, Rohini Kuner and her colleagues show that blocking hematopoietic colony-stimulating factor signaling on neurons can inhibit pain caused by bone cancer.
Matthias Schweizerhof et al.
doi:10.1038/nm.1976
Abstract: http://links.ealert.nature.com/ctt?kn=34&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=84&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells pp808 - 813
The Wnt pathway has a central role in stem cell regulation. Gattinoni et al. now show that activation of the Wnt signaling cascade in naive CD8+ T cells blocks their differentiation into effector T cells and triggers instead a memory stem cell-like phenotype. These T memory stem cells show enhanced antitumor efficacy in mice compared with other T cell subsets, arguing for their further evaluation in adoptive immunotherapies (pages 731-732).
Luca Gattinoni et al.
doi:10.1038/nm.1982
Abstract: http://links.ealert.nature.com/ctt?kn=42&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=100&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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TECHNICAL REPORT
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Validated germline-competent embryonic stem cell lines from nonobese diabetic mice pp814 - 818
Jennifer Nichols et al.
doi:10.1038/nm.1996
Abstract: http://links.ealert.nature.com/ctt?kn=164&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=142&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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ERRATUM
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Erratum: Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer p819
Wennuan Liu et al.
doi:10.1038/nm0709-819a
http://links.ealert.nature.com/ctt?kn=171&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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CORRIGENDUM
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Corrigendum: Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies p819
Marc Pellegrini et al.
doi:10.1038/nm0709-819b
http://links.ealert.nature.com/ctt?kn=88&m=33536527&r=MTc2NTQyNDEzOQS2&b=2&j=NTI3NjAyODgS1&mt=1&rt=0
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