{"id":55692,"date":"2026-01-14T08:00:10","date_gmt":"2026-01-14T16:00:10","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&p=55692"},"modified":"2026-01-14T13:14:08","modified_gmt":"2026-01-14T21:14:08","slug":"should-younger-and-older-people-receive-different-treatments-for-the-same-infection","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/","title":{"rendered":"\u540c\u6837\u7684\u611f\u67d3\uff0c\u5e74\u8f7b\u4eba\u548c\u8001\u5e74\u4eba\u5e94\u8be5\u63a5\u53d7\u4e0d\u540c\u7684\u6cbb\u7597\u5417\uff1f"},"content":{"rendered":"

\u6d1b\u6749\u77f6-\u5e94\u5bf9\u611f\u67d3\u5e76\u4e0d\u50cf\u6740\u6b7b\u75c5\u539f\u4f53\u90a3\u4e48\u7b80\u5355\u3002\u4eba\u4f53\u8fd8\u9700\u8981\u4ed4\u7ec6\u5f15\u5bfc\u548c\u76d1\u63a7\u5176\u514d\u75ab\u53cd\u5e94\uff0c\u4ee5\u9632\u6b62\u9644\u5e26\u635f\u5bb3\u3002\u8fd9\u79cd\u88ab\u79f0\u4e3a\u75be\u75c5\u8010\u53d7\u6027\u7684\u8c03\u8282\u5bf9\u4e8e\u5728\u514d\u75ab\u7cfb\u7edf\u6b63\u9762\u5e94\u5bf9\u611f\u67d3\u65f6\u4fdd\u62a4\u6211\u4eec\u7684\u7ec4\u7ec7\u81f3\u5173\u91cd\u8981\u3002.<\/p>\n

To survive an infection, your body must activate a tolerance mechanism that is compatible with the specific progression of your disease. So, if your body is changing over the course of your lifetime, does that mean the specific mechanisms it uses to survive an immune onslaught change, too?<\/p>\n

\"From<\/a>
From left: Karina Sanchez and Janelle Ayres.
Click here<\/a> for a high-resolution image.
Credit: Jake Terry<\/figcaption><\/figure>\n

Salk scientist Janelle Ayres<\/a>, PhD, has spent the past two decades studying disease tolerance, and this question is the latest to cross her lab bench. The answer, published in Nature <\/em><\/a>on January 14, 2026, is that younger and older mice with sepsis\u2014a life-threatening exaggerated response to infection\u2014have distinct disease courses and tolerance mechanisms. What\u2019s more, the genes and proteins that protected young survivors from sepsis-induced multi-organ damage and death had the opposite<\/em> effect in older survivors.<\/p>\n

The mechanisms young mice used to survive sepsis were the very same mechanisms that caused older mice to die, suggesting that future therapies may be more effective if tailored to the patient\u2019s age. New sepsis treatments are especially needed as the antibiotic resistance crisis continues to threaten current care strategies.<\/p>\n

\u201cThere are many cases where a patient\u2019s body successfully kills the infectious pathogen, but the patient still dies\u2014I want to understand why,<\/em>\u201d says Ayres, senior author of the study, Howard Hughes Medical Institute Investigator, and professor and holder of the Salk Institute Legacy Chair at Salk. \u201cIt\u2019s not just the pathogen that can hurt us; it\u2019s our own responses to those pathogens. The focus of my lab has been to elucidate the disease tolerance strategies our bodies use to manage that self-inflicted damage. Dissecting those strategies may lead us to more effective therapies and a way around the antimicrobial resistance crisis.\u201d<\/p>\n

What is sepsis?<\/strong><\/h2>\n

The immune system is a powerful ally. Many organs, cells, and molecules combine to form a united front against invaders like the flu or dysfunctions like cancer. Sometimes, however, the immune system focuses too tightly on eliminating the threat and forgets that its attacks have repercussions on the rest of the body as well.<\/p>\n

Sepsis is an extreme example of the damage the immune system can do when it overreacts. In this condition, the immune system sets out to attack a bacterial, fungal, viral, or parasitic infection, but that protective response quickly spirals out of control. So <\/em>out of control, in fact, that sepsis can cause multi-organ failure and death.<\/p>\n

The threat of sepsis is enormous\u2014anyone can get it, and sepsis-related deaths make up 20 percent of all global deaths. So, how do we treat it?<\/p>\n

Antibiotics are the first medication deployed. However, the patient\u2019s immune response is doing so much more damage than the pathogen those antibiotics are targeting, and the growing threat of antibiotic resistance also adds concern about the overuse of antibiotics as the primary treatment for sepsis.<\/p>\n

Anti-inflammatory medications are sometimes used in addition to antibiotics, but they come with their own shortcomings. First is timing<\/em>, as the damage is usually done by the time they\u2019re administered. Second is lack of specificity<\/em>, as silencing the entire immune response can immunocompromise the patient and put them at even greater risk.<\/p>\n

The search for novel solutions beyond the antibiotics we know is also more urgent than ever, in the face of an escalating antibiotic resistance crisis, which has been named one of the top 10 global threats to humanity by the World Health Organization<\/a>. Global antibiotic resistance deaths outnumber deaths from HIV, tuberculosis, and malaria combined.<\/p>\n

Ayres says disease tolerance mechanisms may be more precise targets for controlling infection-generated damage\u2014offering a powerful alternative to the current antibiotic and anti-inflammatory duo. The challenge is figuring out what those exact disease tolerance mechanisms are, and accounting for the fact that the ones that are important for survival may be changing as an individual ages.<\/p>\n

“While host disease tolerance mechanisms are a great alternative to treating bacterial infections, they are difficult to identify,\u201d says co-first author Karina Sanchez, a research scientist in Ayres\u2019 lab. \u201cThankfully, Ayres\u2019 lab developed a novel model to help with that identification, which we could pair with a sepsis model in mice to explore age-related differences in disease tolerance mechanisms.\u201d<\/p>\n

Does sepsis affect younger and older people differently?<\/strong><\/h2>\n

To determine if and how disease tolerance mechanisms change with age, the researchers started with two groups of mice\u2014one younger, one older. They dosed both groups using the\u00a0strategy Sanchez mentioned, called LD50, that the lab developed in 2018<\/a>,\u00a0which allows the researchers to easily compare mice that do and don\u2019t recover from infection.<\/p>\n

When the researchers observed the mice that did not survive, they noticed the younger mice died faster than the older mice, demonstrating two distinct disease trajectories. But for the younger and older mice that survived, did their disease tolerance mechanisms also differ?<\/p>\n

The researchers discovered that young survivors were protected by a protein called Foxo1 and a gene it regulates, called Trim63. When Foxo1 turns on Trim63 expression, it stimulates the production of the protein MuRF1, which then promotes the breakdown of larger molecules into usable energy in cardiac and skeletal muscle cells.<\/p>\n

In young survivors, increased expression of Foxo1 and Trim63 created a cardioprotective effect, blocking multi-organ damage and preventing the cardiac remodeling seen in their deceased counterparts. Surprisingly, Foxo1, Trim63, and MuRF1 had the opposite<\/em> effect on older survivors.<\/p>\n

The researchers saw that Foxo1 deletion improved survival of older mice and decreased survival of younger mice. And in normal conditions, older survivors recovered with enlarged hearts, showing that the very same mechanism causing younger mice\u2019s demise had enabled their survival.<\/p>\n

\u201cOur findings reveal that young and aged hosts can have distinct disease trajectories when exposed to the same pathogens,\u201d says co-first author Justin McCarville, a former postdoctoral researcher in Ayres\u2019 lab. \u201cDespite this difference, we show that involvement of the same molecular pathway determines survival, but it leads to opposite outcomes, depending on age. This raises broader questions about how disease may manifest differently across age groups and underscores the potential need for therapies that are tailored to the unique physiology of different ages.\u201d<\/p>\n

Creating age-specific therapies for sepsis<\/strong><\/h2>\n

The concept of antagonistic pleiotropy <\/em>helps make sense of these seemingly surprising findings. Antagonistic pleiotropy is a theory first proposed in evolutionary biology that suggests some traits that are beneficial in youth can incur costs later in life. Getting through the reproductive years of youth is the evolutionary priority, so biology will often optimize those years at the expense of an organism\u2019s health down the line.<\/p>\n

\u201cWe aren\u2019t doomed, though\u2014this doesn\u2019t mean as we get older our bodies completely betray us,\u201d says Ayres. \u201cOur work demonstrates that aged mice are capable of mounting the appropriate disease tolerance response, and we have initiated lines of investigation in our lab to figure those mechanisms out.\u201d<\/p>\n

These findings may guide the development of more effective treatments for sepsis, and potentially other infections, diseases, and disorders. Medications could be developed that are age-specific, targeting different disease tolerance mechanisms in younger and older patients. This strategy would improve outcomes for both age groups, ushering in an exciting new era of tailored therapeutics that pathogens will not evolve resistance to, helping to overcome the global crisis of antibiotic resistance.<\/p>\n

Other authors and funding<\/strong><\/h2>\n

Other authors include Justin McCarville, Sarah Stengel, and April Williams of Salk, and Jessica Snyder of the University of Washington.<\/p>\n

The work was supported by the Howard Hughes Medical Institute, National Institutes of Health (DP1 AI144249, R01AI114929, P30 014915), Keck Foundation, Canadian Institutes of Health, NOMIS Foundation, and Helmsley Trust.<\/p>","protected":false},"featured_media":55696,"template":"","faculty":[79],"disease-research":[146,122],"class_list":["post-55692","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-janelle-ayres","disease-research-aging-and-regenerative-medicine","disease-research-immune-system-biology"],"acf":[],"yoast_head":"\nShould younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Should younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Dealing with an infection isn\u2019t as straightforward as simply killing the pathogen. The body also needs to carefully steer and monitor its immune response to prevent collateral damage. This regulation, called disease tolerance, is crucial to protecting our tissues while the immune system tackles the infection head-on.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/zh\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2026-01-14T21:14:08+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/01\/260114-pr-Ayres-homepage.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"767\" \/>\n\t<meta property=\"og:image:height\" content=\"767\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"7 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/\",\"name\":\"Should younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2026\\\/01\\\/260114-pr-Ayres-homepage.jpg\",\"datePublished\":\"2026-01-14T16:00:10+00:00\",\"dateModified\":\"2026-01-14T21:14:08+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/#breadcrumb\"},\"inLanguage\":\"zh-CN\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2026\\\/01\\\/260114-pr-Ayres-homepage.jpg\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2026\\\/01\\\/260114-pr-Ayres-homepage.jpg\",\"width\":767,\"height\":767},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Should younger and older people receive different treatments for the same infection?\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"zh-CN\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Should younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/zh\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/","og_locale":"zh_CN","og_type":"article","og_title":"Should younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies","og_description":"LA JOLLA\u2014Dealing with an infection isn\u2019t as straightforward as simply killing the pathogen. The body also needs to carefully steer and monitor its immune response to prevent collateral damage. This regulation, called disease tolerance, is crucial to protecting our tissues while the immune system tackles the infection head-on.","og_url":"https:\/\/www.salk.edu\/zh\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2026-01-14T21:14:08+00:00","og_image":[{"width":767,"height":767,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/01\/260114-pr-Ayres-homepage.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"7 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/","url":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/","name":"Should younger and older people receive different treatments for the same infection? - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/01\/260114-pr-Ayres-homepage.jpg","datePublished":"2026-01-14T16:00:10+00:00","dateModified":"2026-01-14T21:14:08+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/#breadcrumb"},"inLanguage":"zh-CN","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/"]}]},{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/01\/260114-pr-Ayres-homepage.jpg","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/01\/260114-pr-Ayres-homepage.jpg","width":767,"height":767},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/should-younger-and-older-people-receive-different-treatments-for-the-same-infection\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Should younger and older people receive different treatments for the same infection?"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"zh-CN"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"hero":false,"line_1":"Should younger and older people receive different treatments for the same infection?","line_2":"Salk Institute scientists find the mechanisms young mice use to fight sepsis become disadvantageous in older age, suggesting age-specific treatments may be necessary in ongoing antibiotic resistance crisis","poster_quote":"","gallery":false,"paper_url":"https:\/\/www.nature.com\/articles\/s41586-025-09923-x","journal_title":"Nature","paper_author_list":"Karina K. Sanchez, Justin L. McCarville, Sarah J. Stengel, Jessica M. Snyder, April E. Williams, and Janelle S. Ayres","doi":"10.1038\/s41586-025-09923-x","paper_title":"Disease tolerance and infection pathogenesis age-related tradeoffs in mice","subhead":"Salk Institute scientists find the mechanisms young mice use to fight sepsis become disadvantageous in older age, suggesting age-specific treatments may be necessary in ongoing antibiotic resistance crisis","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"","descriptive_blurb":"","has_journal_cover":false,"og_image_override":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/55692","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":10,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/55692\/revisions"}],"predecessor-version":[{"id":55735,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/55692\/revisions\/55735"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media\/55696"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media?parent=55692"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/faculty?post=55692"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disease-research?post=55692"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}