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AppYea expands its SleepX patent commercialization portfolio with a non-diluting agreement.

Appyea

AppYea (OTC: APYP) announced that its subsidiary SleepX, which focuses on the development of accurate wearable monitoring solutions to treat sleep apnea and snoring – has signed new commercialization agreement for two additional patents by Ben-Gurion University. The new patented technology enables the innovative detection of sleep apnea and hypopnea through speech analysis using only a smartphone and with no physical contact. This is compared to traditional technologies that use physical sensors to detect apnea in overnight sleep labs. "In recent years we see a growing number of major players taking development efforts in the field of sleep monitoring and sleep apnea”, said Boris (Bary) Molchadsky, chairman & CEO of AppYea. “We are developing our own products that cater to this market while increasing our patent portfolio and examining synergistic technologies as part of our strategy to become a leading player in the sleep health market while also offering licensing agreements for leading smartphone manufacturers.” SleepX is a research and development company recently acquired by AppYea. The company had developed a unique product for monitoring and treating sleep apnea and snoring. The technology is protected by several international patents and the company plans to start serial production in 2022. SleepX focuses its activities on the development and commercialization of its flagship product SleepX PRO solution which is designed to diagnose sleep apnea using only a smartphone and with no physical contact. The company recently announced that it has applied to the Helsinki Committee for approval to begin its planned clinical trial on the SleepX PRO application. This trial is intended to take place at a hospital sleep lab as the first step toward applying for an FDA approval under the first-of-its-kind medical device category for “contactless detection of sleep apnea to be performed through the Artificial Intelligence (AI) analysis of breathing during sleep”. As far as SleepX is aware, the global sleep apnea devices market size is valued at USD 3.7 billion as of 2020 with a 6.2% CAGR, reaching USD 6.1 billion by 2028, according to Grand View Research’s report. Safe Harbor and Forward-Looking Statements This release includes forward-looking statements. Such statements involve risks and uncertainties which could cause actual results to differ materially from those set forth herein. No statement herein should be considered an offer or a solicitation of an offer for the purchase or sale of any securities. Although APYP believes that the expectations reflected in the forward-looking statements and the assumptions upon which they are based are reasonable, it can give no assurance that such expectations and assumptions will prove to have been correct. Although we believe that our plans, intentions and expectations reflected in or suggested by the forward-looking statements in this report are reasonable, we cannot assure stockholders and potential investors that these plans, intentions or expectations will be achieved. These forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties, and other factors, some of which are beyond our control and difficult to predict and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements. The reader is cautioned not to put undue reliance on these forward-looking statements, as these statements are subject to numerous factors and uncertainties, including but not limited to our ability to raise capital needed to develop and market our products, the effectiveness of the Registration Statement, our ability to manage the business post acquisition, economic conditions, intense competition, entry of new competitors and products, adverse federal, state and local government regulation, inadequate capital, unexpected costs and operating deficits, increases in general and administrative costs, unanticipated losses, financial condition and stock price, inability to carry out research, development and commercialization plans and other specific risks. APYP does not undertake any obligation to publicly update any forward-looking statement. Neither APYP nor SLEEPX are subject to the reporting requirements of the Securities and Exchange Commission. Contact Details Asaf Porat +1 800-674-3561 info@appyea.com Company Website http://www.appyea.com

May 16, 2022 07:00 AM Eastern Daylight Time

Funding update: Marquee tech founders and investors join Ultrahuman’s Series A

Ultrahuman

Several prolific tech investors and founders have come together to invest in Ultrahuman, a leading metabolic fitness platform that uses glucose biomarkers to help people optimize their lifestyle. Balaji Srinivasan (ex-Coinbase), Nithin Kamath (founder of Zerodha via Rainmatter) and Preethi Kasireddy (ex-a16z) along with several others have invested in Ultrahuman, the world’s most advanced metabolic fitness platform, in an undisclosed funding amount which will be in addition to their recent series A round. Others influential leaders include Groww founders (Harsh Jain, Lalit Keshre, Neeraj Singh and Ishan Bansal), Razorpay founder, Harshil Mathur and RazorpayX GM - Shashank Mehta, Akshay BD (founding team Uber India) and Tanmay Bhat (celebrity content creator and investor) as they support Ultrahuman, a metabolic fitness platform that helps people optimize their metabolism via real-time biomarkers like glucose in combination with HRV, sleep and activity insights. The metabolic health crisis is unarguably one of the largest healthcare crises that exist today. Over a billion people in the world suffer from a metabolic health disorder which contributes to almost 85% of all chronic diseases in the world. By helping people understand how food and exercise affect their metabolic health, people would be able to make informed choices about what they eat and their activity levels. The approach is a geography/diet agnostic way to help people eat and exercise better. Measuring a powerful biomarker like glucose can reveal so much about how a particular food item affects the user’s metabolic health by measuring the glucose response. This response is unique to an individual and it depends on various factors like their gut microbiome, stress levels, time of the day, food ingredient quality, etc. Ultrahuman launched with Ultrahuman M1 - a metabolic health tracking platform that provides intelligent nudges based on glucose biomarkers. This helps people optimize their exercise, sleep and nutrition based on deep insights from the platform. The M1 tracks the wearer’s metabolism as they go about their day using a continuous glucose monitoring device. It triggers timely personalized nudges to the user such as alerts to high glucose variability events leading to oxidative stress and suggestions to optimize it via lifestyle interventions. Nithin Kamath, founder of Zerodha, added: “A big part of living healthier is tracking your diet and eating right, but the problem is doing this accurately is tricky. The approach that Ultrahuman is taking to tackle this problem of improving metabolic fitness by using biomarkers is really interesting. We're excited to join Mohit and Vatsal on their journey.” Ultrahuman has raised over $25M to date. Existing investors include Alpha Wave, Steadview Capital, Nexus Venture Partners, Blume Ventures and Utsav Somani’s iSeed fund, and a range of other angel investors including Tiger Global’s Scott Schleifer. “We’re super excited to welcome some of the world’s foremost founders, investors and biohackers to join our Series A round. The most inspiring aspect of this investment is that most of them are long term users of the platform as well and that strengthens our mission holistically”. said Mohit Kumar, Founder and CEO, Ultrahuman. Ultrahuman was started by Mohit Kumar and Vatsal Singhal who were also co-founders at Runnr which later merged with India’s largest food delivery service Zomato. Mohit is an avid cyclist, biohacker and Brazilian Jiu-Jitsu enthusiast. Vatsal is a cross-fit enthusiast and a biohacker. Mohit was training at one of the largest MMA Camps in the world (Tiger Muay Thai in Thailand). During his training, he observed athletes train smartly via the usage of data, recovery tools and protocols. About Ultrahuman Ultrahuman is the world's most advanced metabolic fitness platform. By using glucose and other biomarkers, Ultrahuman is helping people improve their energy levels, lose fat and avoid metabolic disorders. For more information and updates on Ultrahuman, please visit ultrahuman.com or follow us on Facebook, Instagram, Twitter, LinkedIn, and YouTube. Contact Details Ultrahuman Bilal Mahmood +44 7714 007257 b.mahmood@stockwoodstrategy.com Company Website https://ultrahuman.com/

May 12, 2022 06:30 AM Eastern Daylight Time

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CoorsTek Recognized as a US Best Managed Company

CoorsTek

CoorsTek is proud to announce it has been selected as a 2022 US Best Managed Company. Sponsored by Deloitte Private and The Wall Street Journal, the program recognizes outstanding U.S. private companies and the achievements of their management teams. The 2022 designees are U.S. private companies that have demonstrated excellence in strategic planning and execution, a commitment to their people and fostering a dynamic, resilient culture, as well as strong financials. This year’s designees continued to propel their businesses forward by prioritizing purpose, investing in their workforces, and demonstrating their commitment to diversity, equity and inclusion. “We are honored to be recognized as a best managed company again this year,” said Jonathan Coors, CEO of CoorsTek. “This award is a tribute to the dedication and resiliency of our CoorsTek team members across the globe over the past several years. It also speaks to the strong values that guide our daily activities and actions, and our focus on delivering essential products and services to the marketplace.” Applicants are evaluated and selected by a panel of external judges focused on assessing hallmarks of excellence in four key areas: strategy, ability to execute, corporate culture and governance/financial performance. They join a global ecosystem of honorees from more than 40 countries recognized by the Best Managed Companies program. About The Best Managed Companies Program The Best Managed Companies program is a mark of excellence for private companies. U.S. designees have revenues of at least $250 million. Hundreds of private companies around the world have competed for this designation in their respective countries through a rigorous and independent process that evaluates four key criteria in their management skills and practices — strategy, execution, culture and governance/financials. U.S. program sponsors are Deloitte Private and The Wall Street Journal. For more information, visit www.usbestmanagedcompanies.com. Please see www.deloitte.com/us/about for a detailed description of our legal structure. About CoorsTek Founded in 1910 and headquartered in Golden, Colorado, CoorsTek is a fifth-generation, family owned and operated global manufacturer of engineered ceramics. By utilizing over half of the world’s known elements in our material formulations, we deliver unique solutions to our diverse customer base by leveraging ceramic properties. With more than 30 facilities across three continents, five million square feet in manufacturing space, and more than 6,000 team members, we are the partner of choice in engineered ceramics. CoorsTek makes the world measurably better by providing customers with amazing solutions, serving customers in numerous industries including semiconductor, aerospace, automotive, medical, energy and many others around the world. For more information about the company and its products please visit our website at www.coorstek.com. Contact Details CoorsTek Nancy Fullerton +1 517-304-4695 nfullerton@coorstek.com Company Website https://www.coorstek.com

May 11, 2022 03:52 PM Eastern Daylight Time

DermTech Helps Detect Skin Cancer Through a Smart Sticker Instead of a Scalpel

YourUpdateTV

A video accompanying this announcement is available at: https://youtu.be/9SD9aKn3328 Would it surprise you to know that one in five Americans develop skin cancer by the age of 70? In fact, more than two people die of skin cancer in the U.S. every hour. It is one of the deadliest forms of skin cancer and one of the most common cancers diagnosed in the U.S. Because of the nation-wide closures of dermatology offices during the pandemic, there was a significant delay in routine cancer screening which impaired referrals for preliminary cancer diagnoses. This means there is a potential backlog of undiagnosed skin cancers. Even prior to the pandemic, only 16 percent of Americans ages 18-29 surveyed in a 2018 study stated that they visited a dermatologist’s office in the past 12 months. What if there were an innovative and painless ways to get your moles checked at home via a telehealth appointment and under clinician supervision? DermTech’s reliable and patient-friendly test, the DermTech Melanoma Test, enhances early melanoma detection by accurately ruling out melanoma. It uses a non-invasive Smart Sticker to gently lift skin cells from the surface of the skin, which are tested for the presence of genomic markers associated with melanoma. A negative test result means there is greater than 99% probability that the mole is not melanoma. The Smart Sticker is simply pressed onto the spot, lifted off and then sent to DermTech’s lab. Patients can access the DermTech Melanoma Test at dermatologists’ offices, through certain primary care providers or remotely via telehealth in 44 states. For more information visit: https://dermtech.com/ Contact Details YourUpdateTV +1 212-736-2727 yourupdatetv@gmail.com

May 10, 2022 01:30 PM Eastern Daylight Time

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Dartmouth Innovation & Technology Festival Celebrates Completion of Dartmouth’s West End District Focused on Solving the World’s “Wicked Problems”

Dartmouth

With $500 Million in capital and programming investments, expanded district combines Dartmouth’s liberal arts focus with entrepreneurial spirit, technological and scientific expertise to create future leaders; Festival program will include a range of speakers and topics focused on creating a sustainable, equitable future Former Dartmouth president, John Sloan Dickey, famously implored students to apply their education for the benefit of humankind—because “there is nothing wrong with the world that better human beings cannot fix.” That’s the spirit behind the recently completed West End District at Dartmouth, which will be celebrated at the Dartmouth Innovation & Technology Festival, May 12-14, 2022. The festival will gather leading alumni, global technology experts, public policy leaders, faculty, and students for provocative discussions about innovation, collaboration, and the art of the possible. Dartmouth President Philip J. Hanlon said of the West End District, “Solving society’s greatest challenges requires that students, faculty, and staff have the necessary cutting-edge infrastructure to do their best work." Dartmouth’s West End began with the idea that organizing scholarship by research areas, rather than by departments, works better to break down the silos that have kept scientists, business leaders, and innovators looking at complex problems only from within their own disciplines. Interdisciplinary, inter-school, and intergenerational collaboration will prepare future leaders to tackle the world’s most wicked issues. The West End District includes the Tuck School of Business, Thayer School of Engineering, and two new state-of-the-art buildings, the Arthur L. Irving Institute for Energy and Society and the Class of 1982 Engineering and Computer Science Center, which houses the Department of Computer Science, Magnuson Center for Entrepreneurship, and the Digital Applied Learning and Innovation Lab. Key Points The West End District changes the way teaching and learning happens. It allows faculty and students to think systemically and holistically about society’s challenges—and is where big ideas become bold realities at the intersections of science, technology, business, and the liberal arts. The West End was a top priority of Dartmouth’s The Call to Lead campaign and is the largest building project in Dartmouth’s 253-year history. The Dartmouth Innovation & Technology Festival will feature a range of events, including: The presentation of the first annual McGuire Family Prize for Societal Impact, awarded to Jason McLellan, a structural biologist whose groundbreaking coronavirus research conducted at the Geisel School of Medicine laid the foundation for COVID-19 vaccines that have saved countless lives. Keynote and panel conversations about a range of topics, including sustainability, whether crypto currency can deliver long-term value, women’s health, artificial intelligence, transportation, and increasing diversity in STEM. Interactive experiences in makerspaces led by faculty and Dartmouth students. About Dartmouth Founded in 1769, Dartmouth is a member of the Ivy League and consistently ranks among the world’s greatest academic institutions. Dartmouth has forged a singular identity for combining its deep commitment to outstanding undergraduate liberal arts and graduate education with distinguished research and scholarship in the Arts and Sciences and its four leading graduate schools—the Geisel School of Medicine, the Guarini School of Graduate and Advanced Studies, Thayer School of Engineering, and the Tuck School of Business. Contact Details Racepoint Global Madison Everts dartmouth@racepointglobal.com

May 10, 2022 01:22 PM Eastern Daylight Time

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The Hidden Cost of Debt on Your Mental Health

YourUpdateTV

May is Mental Health Awareness Month, and with 80% of Americans in debt amid inflation and rising interest rates one of the biggest factors impacting our mental health that not enough people are talking about is financial debt. Recently, licensed clinical psychologist and National Debt Relief Financial Wellness Board Member, Dr. Regine Muradian conducted a satellite media tour to discuss why self-care is important during challenging financial times. A video accompanying this announcement is available at: https://youtu.be/h_cczQ9fKS8 A recent survey by National Debt Relief sought to uncover “The Hidden Cost of Debt” to understand the spiraling impact of debt on mental and physical health. The national survey of two thousand Americans revealed a hunger to have a game plan in place so they feel confident in their ability to tackle debt while living their life mentally, physically and financially well. National Debt Relief has helped over 450,000 clients settle their debt by working with creditors and banks to negotiate down the total amount owed in as little as 24-48 months. What’s more, 95% of clients are in a better financial situation, and they are 4x more likely to reach their financial goals and save after one month of completing National Debt Relief’s program. Some of the survey findings include: 7 in 10 people feel like a black cloud hangs over them when they have to pay a bill or loan People lose 200 hours of sleep per year over their debt & have 3 debt nightmares a week 3 in 5 Americans have considered putting off marriage to avoid inheriting their partner’s debt 54% believe having a partner who is in debt is a major reason to get a divorce 69% of respondents said being in debt has made them withdraw from the things they love Continuing to look at the future, 3 in 4 want to pay off all debt so their children won’t have to suffer Nearly three-quarters of those polled wish there were tools and resources available to help them when they were at their worst in debt ( 73% ). While it is very important to deal with the monetary side of debt, it’s also critical to understand how our finances can have a toll on mental health and relationships with friends, relatives, and spouses. Dr. Muradian shares her tips and insights on the best ways to cope with and overcome the hidden costs and burden of debt: Establishing a plan for getting out of debt and get back in control Prioritizing self-care practices through the journey to support mental health, such as: Reframing thoughts by shifting from “I’m in debt” to “I have a plan to get out of debt”. Doing one activity each day for oneself like exercising or reading Having transparent conversations with loved ones (partner, spouse, family or friends) to avoid feelings of isolation. To get started on the path to financial stability, visit nationaldebtrelief.com or call 800-927-6955 for a free consultation. About Dr. Regine Muradian: Dr. Regine Muradian is a licensed clinical psychologist, children’s author, speaker, consultant and mental health advocate. In her clinical practice, Dr. Muradian works with children, adolescents, and adults who present with a wide range of emotional stressors. She specializes in Anxiety and is a Certified Clinical Anxiety Treatment Professional (CCATP), ADHD, Depression, Eating Disorders/Body Image and Executive Functioning and Leadership Training. Dr. Muradian is also a specialist in Psychological, Personality and Neuropsychological Assessments. Dr. Muradian is fluent in French, Romanian, and incorporates her multicultural background and experiences in her clinical practice and trainings. Her focus is on helping people find their passion through exploring their inner strengths and bring these to the surface. There is no age limit to success as it all starts with an idea. How you generate and create that idea is the path to ultimate success. Dr. Muradian has been featured as a national renowned parent expert in outlets not limited to: Good Day LA, UK Talk Radio, WFLA Channel 8, Architectural Digest, FabFitFun, Huffington Post, MSN, CV Weekly, Thrive Global, and Healthline. About National Debt Relief: National Debt Relief (NDR), a BBB A+ Accredited business that helps consumers get out of debt and is committed to empowering people on their financial journey, bringing them back to living their lives and away from focusing on debt. NDR offers a successful alternative to bankruptcy, credit counseling or taking on new loans. As a top-rated debt relief company in the U.S., NDR is proud to have positively impacted the lives of hundreds of thousands of people on their journey to become debt-free. NDR wants to make sure clients succeed and have the best chance to regain control of their finances. Founded in 2009, NDR is values-centric; built on integrity, growth and connection. Contact Details YourUpdateTV +1 212-736-2727 yourupdatetv@gmail.com

May 09, 2022 01:00 PM Eastern Daylight Time

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Telos “Mission” NFT Challenge - 175,000 in Crypto Prizes!

Telos Foundation

Telos Blockchain (ticker: TLOS) presents its “Mission NFT Challenge” for digital graphic creators, offering a very attractive prize pool to be shared among contest winners. Telos believes that NFTs are both an art form and a pivoting technology that should be easily and affordably accessible to the masses. As such, Telos strives to facilitate the lowest barrier of entry into the emerging field of NFTs. Utilizing Byt.io, the latest leading NFT marketplace to integrate Telos, end-users will mint and trade their NFTs at unprecedented fast speeds while enjoying industry-low gas fees. The Telos EVM will also offer a congestion-free minting experience that leaves no carbon footprint or any of the front running / MEV that constantly plagues Ethereum users. Furthermore, contract deployment is a fraction of the cost and significantly faster on Telos when compared to virtually every other network, making it a far superior ecosystem to build on. Transactions are instant on Telos! Some Contest Details: The contest opens for registration on Monday May 9th, 12:00 pm EST and participants can submit their projects by Friday, June 24th, 12:00 pm EST. Public Voting on the submissions will take place between Monday May 23rd, 12:00 pm EST to Thursday, June 30th, at 12:00 pm EST. Twenty finalists will be announced on Friday July 1st, 12:00 pm EST and the top five winners will be selected and announced on Tuesday July 5th at 11:00 am EST. Telos encourages all digital artists and aspiring NFT projects to compete in this contest to win one of 5 prizes worth 25,000 TLOS each. Furthermore, an honorable pick by The Big Gooey, Telos’ in-house NFT curator, will award one winner with an additional 50,000 TLOS. The contest and voting will be hosted on the Taikai platform (also built on telos), which recently completed a very successful hackathon for the Telos Ignite contest. The public will vote on all submissions to select the top 20 projects after which a panel of judges will decide on the top five. This maiden NFT contest is inviting artists to bring their NFT projects (ERC 721) and deploy them on the tEVM where they can be minted to be sold on the Byt marketplace or other secondary markets. All additional details and criteria can be found on the Taikai platform through the following link: https://taikai.network/en/telos-foundation/hackathons/nftp-slug/overview About Telos Live since 2018, Telos Blockchain (ticker: TLOS) is a third-generation smart contract platform that offers compatibility with Solidity, Vyper, and Native C++ smart contracts. Telos provides full EVM/Solidity support with fixed low-cost gas fees and no front running and, more uniquely, offers a path to fee-less transactions via its robust native C++ smart contract support. Even while operating as a Net Zero Blockchain, Telos still sustainably supports hundreds of millions of transactions per day, produces blocks in 0.5 second intervals (on a first-in-first-out basis, eliminating front running on the network), and securely validates transactions via a credibly neutral and globally decentralized block producer network. As a result, the Telos blockchain has the throughput needed to facilitate and scale the thriving Metaverse / Web 3.0 landscape better than any other blockchain in existence. Its performance is unrivaled in the industry and was purpose-built to offer speed, scalability, cost-effectiveness, credible decentralization, and end-user fairness. Telos harnesses its power by utilizing tight C++ on the frontend and a custom WASM runtime environment on the backend. About The Foundation The Telos Foundation is a Decentralized Autonomous Organization established as a promotional and funding body to advance the Telos Blockchain Network and provide support to network applications. Contact Details The Team hello@telosfoundation.io Telos NFT Curator The Big Gooey thebiggooey@telosfoundation.io Byt Co-founder Will Perkins will@byt.io Company Website https://www.telos.net/

May 09, 2022 11:06 AM Eastern Daylight Time

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Web3 Solidity Engine, tEVM 2.0 - Ahead of Schedule

Telos Foundation

As the Goliaths of crypto continuously crash ( Solana ), fail to deliver ( Ethereum ), or live in their white papers ( Cardano ), David ( Telos ) continues to defy them all and over-deliver. The Telos story is very much a David vs. Goliath story. Why? Because Telos is tens and even hundreds of billions of dollars smaller than its peers in market cap, yet still manages to significantly lead them in speed, costs, true capacity, credible neutrality, front running protection, fair governance, and energy efficiency ( Net Zero ). The tEVM Version 1.0's capabilities are already a quantum leap ahead of its peers and are clearly demonstrated in this video. Now, less than a year later, version 2.0 is set to elevate the tEVM's performance further. Jesse Schulman (Lead Architect and TCO), alongside Kersten Wirth (Program Manager), will be providing detailed insights into the development of Telos EVM 2.0. This hybrid "Super-Node" solution will be even easier to operate and integrate than the previous version, offer top-notch history management, and tie in with the best available Ethereum clients. The dev-duo will also be discussing the many benefits and successes of the existing tEVM Version 1. Since its launch, the tEVM’s ecosystem is closing on six months of strategic growth. On the DeFi side, it has already launched multiple Dex/AMMs, Price Oracles, Farming dApps, multi-Chain bridges, Lending dApps, and everything else that a vibrant DeFi ecosystem requires to level up its TVL and end-user occupancy. Telos’ TVL is now where the market cap leading chains were not long ago but with far superior governance, no front running, credible neutrality, true decentralization, and an ESG compliant EVM that is several multiples faster. In utopian fashion, Telos’ ecosystem is now ready to scale its occupants and its TVL simultaneously. About Telos Live since 2018, Telos Blockchain (ticker: TLOS) is a third-generation smart contract platform that offers compatibility with Solidity, Vyper, and Native C++ smart contracts. Telos provides full EVM/Solidity support with fixed low-cost gas fees and no front running and, more uniquely, offers a path to fee-less transactions via its robust native C++ smart contract support. Even while operating as a Net Zero Blockchain, Telos still sustainably supports hundreds of millions of transactions per day, produces blocks in 0.5 second intervals (on a first-in-first-out basis, eliminating front running on the network), and securely validates transactions via a credibly neutral and globally decentralized block producer network. As a result, the Telos blockchain has the throughput needed to facilitate and scale the thriving Metaverse / Web 3.0 landscape better than any other blockchain in existence. Its performance is unrivaled in the industry and was purpose-built to offer speed, scalability, cost-effectiveness, credible decentralization, and end-user fairness. Telos harnesses its power by utilizing tight C++ on the frontend and a custom WASM runtime environment on the backend. About The Foundation The Telos Foundation is a Decentralized Autonomous Organization established as a promotional and funding body to advance the Telos Blockchain Network and provide support to network applications. Not investing advice. Contact Details The Team hello@telosfoundation.io Company Website https://www.telos.net/

May 04, 2022 01:00 PM Eastern Daylight Time

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Hong Kong Baptist University joint research reveals that gut microbial enzymes reactivate triclosan which induces colitis

Hong Kong Baptist University

HONG KONG SAR - Media OutReach - 3 May 2022 - A Hong Kong Baptist University (HKBU) collaborative research study has revealed that certain gut microbial enzymes mediate the reactivation of triclosan (TCS) from its inactive glucuronide metabolite. TCS is an antimicrobial agent commonly used in a wide range of consumer products, and it is associated with the development of colitis. Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis at HKBU, points out that according to the research results specific gut microbial enzymes drive the conversion of TCS metabolites to TCS which increases the chance of developing colitis. The research results have been published in Nature Communications, an international scientific journal. Mechanism of TCS exposure leading to colitis previously unclear TCS is widely used as an antimicrobial agent in consumer products such as toothpaste, mouthwash, hand sanitisers, cosmetics and toys. It is a major environmental contaminant, and it has been shown that TCS exposure increases the risk of colitis. Once TCS enters the human body, it is rapidly metabolised to form the biologically inactivemetabolite TCS-glucuronide (TCS-G), which is easily eliminated from the body. Due to this characteristic, the mechanism of how environmental exposure to TCS leads to gut toxicity in the human body has previously remained unclear. To answer this question, a research team co-led by Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis at HKBU; Professor Matthew R Redinbo from the University of North Carolina at Chapel Hill; and Professor Zhang Guodong from the University of Massachusetts Amherst conducted a research study based on the hypothesis that certain gut microbial enzymes act on TCS-G in the gut, leading to the reactivation of TCS and the subsequent development of colitis. TCS concentration uniquely high in the gut To begin with, the research team sought to determine whether the gut has a different TCS metabolic profile compared to other body tissues. A group of mice were fed food that contained TCS. After four weeks, it was found that the biologically inactive TCS-G was dominant in their liver, bile, heart and small intestine, while the colitis-inducing TCS was dominant in the gut (cecum and colon). The results showed that the gut has a uniquely high concentration of TCS compared to other body tissues. The research team then analysed the relationship between TCS-containing products and the concentration of TCS in the human body. In a group of human subjects who used TCS-containing personal care products for four months, both TCS and TCS-G were detected in their stool and urine samples, with TCS being dominant in stool and TCS-G being dominant in urine. However, TCS and TCS-G were not detected in the control group who used TCS-free personal care products. The results showed that the use of TCS-containing products leads to a high level of TCS, specifically in the human gut. Gut microbiota significant in TCS-G conversion The question remains why the human gut has a uniquely high TCS concentration. To answer this, the research team put forth the hypothesis that gut microbiota participate in the conversion of TCS-G to TCS, leading to the accumulation of TCS in the gut. To test this hypothesis, the researchers observed that in an in vitro setting, cultured gut bacteria from both mice and humans were able to catalyse the conversion of TCS-G to TCS. To investigate whether the same phenomenon appears in an in vivo setting, the research team found that the inhibition of gut bacteria from mice by applying an antibiotic treatment almost reduced the concentration of TCS in their guts by half, and it increased the concentration of TCS-G by six-fold. The results affirmed that gut microbiota play a significant role in the conversion of TCS-G to TCS in the gut. Specific enzymes catalyse TCS-G conversion To investigate the mechanism by which gut microbiota catalyse TCS-G conversion, the research team focused on the intestinal β - glucuronidase (GUS) enzymes produced by gut bacteria in both mice and humans, because they have been shown to catalyse a wide range of metabolite conversions. Using a series of screening techniques, two types of GUS, namely “Loop 1” and “flavin mononucleotide (FMN)-binding” GUSs, were found to be most effective at converting TCS-G to TCS in vitro. The research team then applied a GUS inhibitor, a drug that inhibits the function of Loop 1 and FMN-binding GUSs, to TCS-exposed and TCS-free mice. It was found that the GUS inhibitor could curb the conversion of TCS-G to TCS by the GUS enzymes. Colitis in TCS-exposed mice was also relieved after the application of the GUS inhibitor. The results support the notion that specific microbial GUS enzymes drive the conversion of TCS-G to TCS, and as a result, the chance of developing colitis is increased. More stringent TCS controls needed Professor Cai said: “Our research results clearly defined the mechanism by which gut microbiota are involved in the metabolism and toxicology of TCS, and the study offers a way to prevent the development of colitis following environmental exposure to chemicals. “Regulatory bodies should consider imposing more stringent controls on the use of TCS. Although the US Food and Drug Administration (FDA) banned the marketing of TCS in over-the-counter antiseptic products in 2016, the chemical remains approved for use in a wide range of products. Transparency on TCS ingredients in product labelling and illustrations should also be improved so that consumers can be aware of the potential risks and make informed choices.” #HongKongBaptistUniversity #HKBU Contact Details Winnie Shum of the Communication and Public Relations Office +852 3411 5262 hkbunews@hkbu.edu.hk Company Website https://www.hkbu.edu.hk/

May 03, 2022 09:00 AM Eastern Daylight Time

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