科研思路来自科研实践、来自文献信息、来自同行交流。

科研思路和科研选题也可以来自知识发现，在我的博客“知识发现栏目”http://blog.sciencenet.cn/home.php?mod=space&uid=280034&do=blog&classid=115378&view=me&from=space有大量的科学研究知识发现的实例和分析，知识发现只提供非相关文献中的隐含知识概念，对于扩大科研人员的研究思路、进行科研选题很有意义，这些知识点可能对科研工作有所启发，获得新的科研视角和思路，但还需要科研人员进行科学验证。

知识发现与科学发现  http://blog.sciencenet.cn/blog-280034-713521.html

这里可以看到自1986年以来，国外情报专家的很多知识发现，被科研人员得到了证实。但我国的科研人员对知识发现的方法和应用不太熟悉，还没有很好地利用这种知识挖掘和信息分析的好方法。

知识发现平台 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi

 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi?refresh=T&ID=11546

科学杂志1月2日发表此文，迅速被国际同行关注。

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http://www.sciencemag.org/articleusage?gca=sci;347/6217/67

这种由皮肤脂肪组织分泌的抗菌肽名叫Cathelicidin，这种防御性多肽有着非常漫长的演化历史，在人类和其他动物的自体免疫中发挥着重要作用。“在感染发生后，我们的细胞会迅速合成抗菌肽Cathelicidin来抑制病原菌的传播。Cathelicidin的碳端带有正电荷，能够与携带负电荷的细菌细胞膜结合，并造成细菌细胞裂解。”文章的第一作者张凌娟（Dr. Ling-juan Zhang）向果壳网科学人介绍道，“与抗生素不同的是，Cathelicidin还具有免疫调控功能，它能够募集免疫细胞并协同增强与抵抗感染相关的免疫应答。”

张凌娟对果壳网科学人说，“基于抗菌肽研发的类抗生素药物也许会比目前的抗生素在对抗感染方面更为有效——对那些产生耐药性的病原菌所引起的疾病尤其如此。”关于抗菌肽的研究迈出了可喜的一步，但人们与病原微生物的战斗，还有很长的路要走。

原文检索：

Ling-juan Zhang, Christian F. Guerrero-Juarez, Tissa Hata, Sagar P. Bapat, Raul Ramos,Maksim V. Plikus, and Richard L. Gallo. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 2 January 2015; DOI:10.1126/science.1260972

http://www.bio360.net/news/show/12796.html

A-query: chronic inflammation
C-query: cathelicidin

The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 40 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here. The results of this search are saved under id # 19680 and can be accessed from the start page after you leave this session. There are 466 terms on the current B-list (127 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin.

To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms.

http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi

job id # 19680 started Wed Jan 7 19:12:11 2015
Max_citations: 50000
Stoplist: /var/www/arrowsmith_uic/data/stopwords_pubmed
Ngram_max: 3
A_query_raw: chronic inflammationWed Jan 7 19:12:20 2015

A query = chronic inflammation started Wed Jan 7 19:12:21 2015
A query resulted in 50000 titles
C_query_raw: cathelicidin Wed Jan 7 19:12:45 2015

C: cathelicidin 1594

A: chronic inflammation 74982

AC: ( chronic inflammation ) AND ( cathelicidin ) 40

C_query_raw: cathelicidin Wed Jan 7 19:12:51 2015

C: cathelicidin 1594

A: chronic inflammation 74982

AC: ( chronic inflammation ) AND ( cathelicidin ) 40

C query = cathelicidin started Wed Jan 7 19:12:52 2015
C query resulted in 1594 titles
A AND C query resulted in 40 titles
6071 B-terms ready on Wed Jan 7 19:21:40 2015

Sem_filter:
Genes & Molecular Sequences, and Gene & Protein Names
466 B-terms left after filter executed Wed Jan 7 19:22:22 2015

B-list on Wed Jan 7 19:23:10 2015
1 nod2
2 toll receptor
3 card15
4 tlr4
5 formyl peptide receptor
6 cd14
7 tlr9
8 il-18
9 map kinase
10 vegf
11 trem-1
12 tlr2
13 cytokine gene
14 signal regulated kinase
15 lipopolysaccharide binding protein
16 caspase
17 defensin
18 beta defensin
19 hepcidin
20 vegf c
21 mrsa
22 tlr7
23 p2x7
24 il-8
25 cytokine production
26 tlr-2
27 cxcl10
28 vitamin d receptor
29 th1
30 fpr2
31 tlr
32 hif-1alpha
33 stat3
34 gelsolin
35 p38
36 nf kappab
37 c jun n
38 anca
39 blt1
40 p2x
41 il-1beta
42 myd88
43 ppargamma
44 il-13
45 histone deacetylase
46 il-6
47 cxcr2
48 nod1
49 il-1
50 il-15
51 gp130
52 il-10
53 pi3k
54 cpg
55 inflammatory bowel disease
56 aryl hydrocarbon receptor
57 visfatin
58 egfr
59 autophagy
60 erk
61 chemokine
62 s100a7
63 toll
64 nadph oxidase
65 ifn gamma
66 heparan sulfate proteoglycan
67 il-4
68 oncostatin m
69 thymic stromal lymphopoietin
70 ccr6
71 copd
72 mek1
73 peptide gene
74 il-22
75 macrophage activation
76 cd34
77 fgf23
78 tnf alpha
79 c jun
80 tlr3
81 c ebp
82 genome wide
83 high mobility group
84 th2
85 apolipoprotein a i
86 cd8
87 ap-1
88 ifn
89 activin
90 hmgb1
91 serum amyloid a
92 cdna
93 lyn
94 lps
95 npc2
96 psgl-1
97 tnf
98 tgf beta1
99 cd40l
100 cytokine
101 integrin
102 sdf-1
103 muc1
104 nf
105 apolipoprotein a
106 ccl26
107 hiv
108 egfr transactivation
109 tie2
110 mek
111 nk
112 differentially expressed gene
113 interferon gamma
114 transcription factor
115 adenoviral gene
116 muc2
117 ccr2
118 gene coding
119 bone morphogenetic protein
120 pthrp
121 cathepsin
122 inflammatory gene
123 mediterranean fever
124 expression gene
125 bax
126 phoq
127 p2y

http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/view_b_txt.cgi?ID=19680

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6: Expression patterns of beta-defensin and cathelicidin genes in parenchyma of bovine mammary gland infected with coagulase-positive or coagulase-negative Staphylococci. 2014
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16: Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. 2012
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21: Effects of Bacterial Infection on Airway Antimicrobial Peptides and Proteins in Chronic Obstructive Pulmonary Disease. 2011
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22: The Epithelia-Specific Membrane Trafficking Factor AP-1B Controls Gut Immune Homeostasis in Mice. 2011
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23: Differential suppression of epidermal antimicrobial protein expression in atopic dermatitis and in EFAD mice by pimecrolimus compared to corticosteroids. 2011
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24: Peptidylarginine Deiminases Present in the Airways During Tobacco Smoking and Inflammation can Citrullinate the Host Defense Peptide LL-37 Resulting in Altered Activities. 2011
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26: Vitamin D, innate immunity, and sarcoidosis granulomatous inflammation: insights from mycobacterial research. 2010
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27: Antimicrobial peptide hCAP-18/LL-37 protein and mRNA expressions in different periodontal diseases. 2010
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28: Enhanced expression of the antimicrobial peptide LL-37 in lesional skin of adults with atopic eczema. 2009
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29: Gingival crevicular fluid levels of cathelicidin LL-37 and interleukin-18 in patients with chronic periodontitis. 2009
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30: Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages. 2009
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31: Cathelicidin antimicrobial peptides inhibit hyaluronan-induced cytokine release and modulate chronic allergic dermatitis. 2008
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32: IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. 2008
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33: The role of cathelicidin and defensins in pulmonary inflammatory diseases. 2007
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34: Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation. 2005
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35: The expression of human antimicrobial peptide LL-37 in the human nasal mucosa. 2004
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36: The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. 2003
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37: Antimicrobial peptide LL-37 is upregulated in chronic nasal inflammatory disease. 2003
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38: Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. 2003
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39: SMAP-29: a potent antibacterial and antifungal peptide from sheep leukocytes. 1999
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40: Epithelial antimicrobial peptides: review and significance for oral applications. 1998
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