. * * window.aa needs to exist and be usable by ANY module's script, * however early it runs - main-nav's script, for one, runs near * the top of

91探花

, well before the real search-insights.js * so the download * begins as early as before. Repeat calls share the same downloads, a * failed load is retried on the next call, and the versions / SRI * hashes live only here. * * Algolia Insights is unaffected: window.aa above is still created in * on every page and queues events until search-insights loads. * * window.loadAlgoliaLibs({ priority: 'high' }) (Oct 2026): used by the * /search page, where the first results wait on these libraries. Chrome * gives async scripts low priority, behind images and fonts; this asks * for high instead (fetchpriority). Only the first call for a library * sets its priority - later calls share that download. */ (function (win, doc) { var LIBS = [ { ready: function () { return !!win['algoliasearch/lite']; }, src: 'https://cdn.jsdelivr.net/npm/algoliasearch@5.52.1/dist/lite/builds/browser.umd.js', integrity: 'sha256-I2oYUIvhx1g6l4lTP+yoERbzLIHKzw4AKaBRQPwIeDY=' }, { ready: function () { return !!win.instantsearch; }, src: 'https://cdn.jsdelivr.net/npm/instantsearch.js@4.98.0/dist/instantsearch.production.min.js', integrity: 'sha256-ngmqZk4WBxUw257aMYZayyNBd983INngagv0jI6Ecfs=' } ]; function loadOne(lib, options) { if (lib.ready()) return Promise.resolve(); // One download per library, shared by every caller; reset on // failure so the next call retries just the library that failed. if (lib.pending) return lib.pending; lib.pending = new Promise(function (resolve, reject) { var script = doc.createElement('script'); script.src = lib.src; script.integrity = lib.integrity; script.crossOrigin = 'anonymous'; script.async = true; if (options && options.priority === 'high') script.setAttribute('fetchpriority', 'high'); script.onload = function () { lib.ready() ? resolve() : reject(new Error('Loaded but not available: ' + lib.src)); }; script.onerror = function () { script.remove(); reject(new Error('Could not load ' + lib.src)); }; doc.head.appendChild(script); }); lib.pending.catch(function () { lib.pending = null; }); return lib.pending; } win.loadAlgoliaLibs = function (options) { return Promise.all(LIBS.map(function (lib) { return loadOne(lib, options); })); }; })(window, document); . */ window.hsConversationsSettings = window.hsConversationsSettings || {}; window.hsConversationsSettings.loadImmediately = false; (function (win) { var EVENTS = ['pointerdown', 'keydown', 'touchstart', 'scroll', 'mousemove', 'wheel']; var done = false; /* 19 Oct 2026 - chat widget layout shift (field CLS). Phones fail Core Web Vitals on CLS (p75 ~0.2 site-wide in CrUX for months). Biggest cause found: HubSpot's chat container is fixed to the bottom-right corner and changes size - 100x96 launcher to 282x253 when the welcome message pops up (~5 s after load), and to full screen when a visitor opens the chat. Its top-left corner moves, so Chrome scores it as a layout shift: 0.088 per page view at 360x640 (0.044 at 412x850), on every page. Taps happen inside the chat iframe, so the parent page never sees the input and the open/close shifts count too. Fix: whenever the container's size changes it is made transparent for 400 ms (Chrome doesn't score shifts of invisible elements), then shown again at its new size. Tested on live io1001 at 360x640 in a cookie-less frame: the 0.088 shift no longer appears. The chat itself is unchanged - it just appears 0.4 s later at each resize. Relies on HubSpot's container id; if that changes this does nothing (no error). */ function cloakChatResizes() { var ID = 'hubspot-messages-iframe-container'; function watch(c) { if (c.getAttribute('data-bb-cloak')) return; c.setAttribute('data-bb-cloak', '1'); var last = c.offsetWidth + 'x' + c.offsetHeight, timer = null; new MutationObserver(function () { var size = c.offsetWidth + 'x' + c.offsetHeight; if (size === last) return; last = size; c.style.setProperty('opacity', '0', 'important'); clearTimeout(timer); timer = setTimeout(function () { c.style.removeProperty('opacity'); }, 400); }).observe(c, { attributes: true, attributeFilter: ['style', 'class'], subtree: true, childList: true }); } var found = document.getElementById(ID); if (found) { watch(found); return; } if (!document.body || !('MutationObserver' in win)) return; var mo = new MutationObserver(function () { var c = document.getElementById(ID); if (c) { mo.disconnect(); watch(c); } }); mo.observe(document.body, { childList: true }); setTimeout(function () { mo.disconnect(); }, 30000); } function loadWidget() { var api = win.HubSpotConversations; if (api && api.widget && api.widget.status && api.widget.status().loaded) return; try { cloakChatResizes(); } catch (e) {} if (api && api.widget) api.widget.load(); } function onFirstInteraction() { if (done) return; done = true; EVENTS.forEach(function (type) { win.removeEventListener(type, onFirstInteraction, { passive: true }); }); var start = function () { if (win.HubSpotConversations) loadWidget(); else (win.hsConversationsOnReady = win.hsConversationsOnReady || []).push(loadWidget); }; if ('requestIdleCallback' in win) win.requestIdleCallback(start, { timeout: 1500 }); else setTimeout(start, 200); } EVENTS.forEach(function (type) { win.addEventListener(type, onFirstInteraction, { passive: true }); }); })(window);

91探花

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Liver cells

Human iPSC-derived liver cells

Consistent human iPSC-derived liver cells for predictive toxicology, drug metabolism, and disease modelling

The liver is one of the most critical organs in the human body, acting as the primary metabolic regulator.

The liver performs multiple functions, including bile acid formation, protein catabolism, and drug metabolism, through the coordinated activity of parenchymal cells, primarily hepatocytes, and non-parenchymal support cells, like Kupffer and hepatic stellate cells.

This makes in vitro human liver models critical for drug development and toxicology assays, especially as animal models often fail to predict human-specific hepatotoxicity. While primary human hepatocytes (PHHs) are the historical gold standard, applying them into scalable, long-term studies has limitations. In 2D culture, PHHs rapidly de-differentiate and lose metabolic activity within days. In addition to this short functional window, PHHs have inherent donor-to-donor variability, meaning that scientists often compromise and rely on immortalised carcinoma cell lines that fail to capture human metabolic biology.

91探花鈥檚 opti-ox deterministic cell programming technology enables the generation of functional human iPSC-derived ioHepatocytes with unmatched lot-to-lot consistency at scale that exhibit sustained albumin secretion and mature phenotype for over two weeks. By overcoming the donor variability and the short functional window associated with PHHs, ioHepatocytes provide a physiologically relevant, functional human cell model for in vitro ADME-Tox profiling and drug-induced liver injury (DILI) screening in the drug discovery pipeline.

Frequently Asked Questions (FAQs)

Why are physiologically relevant human liver cell models critical for drug discovery?

The liver acts as the body's primary metabolic engine, meaning in vitro physiologically-relevant human liver cells are essential for assessing drug metabolism and safety. Animal models often fail to accurately predict human-specific hepatotoxicity, so there is demand for highly predictive human hepatic cells in preclinical workflows.

 

What are the challenges of using primary human hepatic cells in vitro?

While primary human hepatocytes (PHHs) are the historical gold standard, they rapidly de-differentiate and lose function within days in traditional 2D culture. This short functional window, combined with high donor-to-donor variability, limits the use of PHHs in long-term ADME-Tox profiling and DILI screening workflows.

 

What functional advantages do ioHepatocytes offer for toxicity screening?

ioHepatocytes provide a stable functional experimental window of over 17 days, allowing scientists to accurately assess chronic drug exposure. The cells recapitulate complex human liver cell biology, including robust albumin secretion and critical Phase I, II, III, and CYP activity.

 

Where do ioHepatocytes fit within the drug development pipeline?

ioHepatocytes are ideal for early-stage hit-to-lead optimisation and in vitro ADME-Tox profiling. By incorporating a highly reproducible human liver cell model earlier in the pipeline, scientists benefit from higher throughput, faster safety decisions, and reduced downstream clinical risk.

 

References

  1. Godoy P, et al. "Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME." Arch Toxicol, 2013; 87(8):1315-1530. doi: 10.1007/s00204-013-1078-5.

  2. Zeilinger K, Freyer N, Damm G, Seehofer D, Kn枚spel F. "Cell sources for in vitro human liver cell culture models." Experimental Biology and Medicine. 2016; 241(15): 1684-1698. doi: 10.1177/1535370216657448.  

  3. Khetani SR, et al. "Microengineered liver tissues for drug testing." Journal of Laboratory Automation (Later transitioned/related to work often cited in Drug Discovery contexts). 2015; 20(3): 216-250. doi: 10.1177/2211068214566939.  

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