![]() ![]() ![]() In 2012, Garcia co-founded the production company Seven Bucks Productions, for which she has since produced several films starring Johnson, including Baywatch, Jumanji: Welcome to the Jungle (both 2017), Shazam!, Hobbs & Shaw, Jumanji: The Next Level (all 2019), Jungle Cruise, Red Notice (both 2021), DC League of Super-Pets, and Black Adam (both 2022). In 2008, she began managing her ex-husband Dwayne Johnson's career. įollowing her graduation from the University of Miami's School of Business, she began her career in finance at Merrill Lynch in 1992. She is the founder of GSTQ, and the CEO and chair of The Garcia Companies and TGC Management, overseeing a portfolio of brands in business, entertainment, and food, including TGC Management, Teremana Tequila, Athleticon, and the Project Rock Collection at Under Armour, VOSS, Atom Tickets, Salt & Straw, ZOA Energy, Acorns, and the XFL. Acura TSX 2.Dany Garcia Rienzi (born November 29, 1967) is an American film producer and businesswoman. Honda Accord Euro R H22A red top engine for 1299Ġ1-05 Honda Civic 1.7L sohc vtec engine for 349ĩ8-02 Honda Accord 2.3L sohc vtec engine for 275ġJZGTE non vvti front sump auto trans for 1249 rear sump is 1299ģSGE beams dual vvti engine and 6 speed trans for 999 Jdm Orlando 2008 Toyota FJ Cruiser Base 4x4 4dr SUV 5A 2009 Scion tC Base 2dr Hatchback 4A 2006 BMW 3 Series 325i 4dr Sedan 2007 Subaru Impreza WRX STI AWD. Subaru Impreza wrx EJ205 turbo engine for 999Īll front end conversions are 399 I have the following front endsĪcura TSX 04-05 front end with clear headlights oem H.I.DĪlso have Jdm doors also all for 300 I have the following doors complete with door panels LEXUS GS430 LS430 SC430 ENGINE 4.3L V8 MOTOR AUTOMATIC TRANS JDM 3UZ-FE VVT-I. Original LOW MILES and PERFORMANCE GUARANTEE Engines. JDM Engine Depot is direct importer and supplier of used JDM Engines, Transmissions and Parts. Free Shipping, No Sales Tax, No Down Payment and Free Expert Support Live. We are proud to be the largest supplier of JDM Engines, having more than 5000 JDM Motors in stock. Realtime driving directions to JDM Orlando, Inc, 1343 W Michigan St, Orlando, based on live traffic updates and road conditions from Waze fellow drivers. JDM Engine is the reliable and cost-effective way for your Japanese Car Engine replacement. Toyota Supra Subaru Impreza wrx Sti bugeye JDM Engines and Transmissions comes with average 45000 to. Honda Integra DC5 Type R Evo 8 and Subaru Forester Sti doors with panels SF9įor more information please message me or give us a call 40 we are located at 1343 W Michigan st Orlando Fl 32805 everything is plus tax and limited one per customer for all items and engines on sale thank you! N.1 IN ORLANDO JDM REW JDM IMPORTS Current Inventory eBay Parts Store 'WHERE JDM ISNT JUST A BUSINESS. The perfect choice for engine replacement. WE BREATH, EAT AND DRIVE JDM.' 'What drives your mind, is your life.' ENGINE All of our engines are handpicked by our staff at REW JDM. HIGH QUALITY INSPECTED & TESTED JAPAN IMPORTED LOW MILES 40-60K ENGINES & TRANSMISSIONS. JDM Engine Depot supplies JDM Engines, JDM Transmissions and JDM Parts from its warehouse and store-front located in Belleville, New Jersey. 06 07 08 09 10 Subaru Forester Outback Impreza Engine. Honda Accord Civic CRV Odyssey Element Prelude Integra Stream NSX Legend Delsol CRX Ascot, d17a, b20b, b20z. 1 Montgomery St, Belleville NJ 07109 Phone: (201) 955-9556 Email: email protected Learn More. We put in that extra attention to detail to make sure we fulfill your needs and assure top quality. Ok everyone so made a list of stuff that's going to be on our BLACK FRIDAY SPECIAL!!! Here we goĪcura TSX 04-05 front end with clear headlights oem H.I. ![]()
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![]() ![]() Monday, you’ll see the actual competition begin.” “On Monday, when we get the pads on it’ll be the first day kicking in front of the team where every kick is charted and timed, make or miss. “I didn’t want them to have to kick in front of the team and be evaluated until they got a couple of kicking opportunities just working out the operations,” Fassel said. As a result, Monday will be the official beginning of the face-off. Through two practices and Friday’s walk-through, special teams coordinator John Fassel has taken a slow approach to thrusting either guy into a competition. It’s time to figure out who’ll be the next kicker for the Dallas Cowboys. ![]() ![]() Kicker competition set to kick off Monday - Nick Harris, The Detroit Lions are the only other NFC team in the top 10 of Super Bowl odds (+2200). The 49ers are second at +1000, followed by the Cowboys at +1400. These are certainly the three teams most fans and analysts would list as the best in the NFC, though the order will depend on each individual.īased on the current betting odds from DraftKings Sportsbook, the Eagles are the top team in the conference at +650 to win the Super Bowl (bet $100 to win $650). When you talked about years playing together- years of experience- I think we’re up there to be that better team.” We didn’t lose a (former Eagle and now 49ers’ defensive tackle) Javon Hargrave, and then draft somebody. I think we’re the only team that gained players. I think we are the top team when you talk about numbers and experience- guys we got back. We beat ourselves with mistakes and things like that. “You look at our game last year, that’s a game we could have won. Parsons is not afraid of anyone in the NFC.Īppearing on 105.3 The Fan’s GBag Nation, Parsons said he believes the Cowboys are the “top team” over the Philadelphia Eagles and San Francisco 49ers in the NFC hierarchy entering the 2023 season: We will miss him greatly.” Micah Parsons Names Cowboys NFC’s ‘Top Team’ Over Eagles, 49ers Entering 2023 Season - Adam Wells, Bleacher Report He was an amazing ambassador for the Cowboys and a great friend and docent for our art program and the purpose of connecting with children and inspiring them to enjoy art. Few people have generated such widespread goodwill and respect like Phil did over the years. We have such wonderful memories with him, just as so many others do. “The loss of Phil Whitfield leaves us all heartbroken. In a statement posted by AT&T Stadium, Gene Jones said: He quickly caught the eye of the Jones family who tapped Whitfield to oversee the installation of the works of art. Whitfield was born a Cowboys fan and became a stadium security guard in the early 90s. NBC 5 talked to Whitfield in 2014 about his part in the installation of works from 58 world-class artists at Jerry World in Arlington. The Dallas Cowboys are remembering longtime security guard turned AT&T Stadium art ambassador Phil Whitfield who died this week at the age of 62. Our thoughts and condolences go out to the entire Whitfield family. Cowboys ‘heartbroken’ over passing of AT&T Stadium art ambassador Phil Whitfield - Elvira Sakmari, He says he has been playing in the guard position for the first few days of camp.īut overall, this camp has fewer growing pains and more of a chance to refine and tighten things up for him compared to his rookie season. Tyler Smith described that last season’s quick adjustments were a “pre-curser” to his current work. He also said that in Martin’s absence, everyone has stepped up to keep the standards high, including Tyron Smith, the longest-standing veteran with the Cowboys. Smith said on Thursday that Martin texted the group to “set the tone” and that he would “be there soon.” Meanwhile, they are all in full support of Martin’s decision during this time. His ability to adapt and adjust to playing both guard and tackle helped create the versatility the line needed, especially after multiple injuries occurred. Tyler Smith was one of the Cowboys’ most underrated rookies last season. Tyler Smith Helping Dallas Cowboys Offensive Line During Zack Martin’s Holdout Zack Martin told the boys to hold down the fort until he gets back. ![]() How the Dallas Cowboys’ Offensive Line Is Keeping the Bar High Amid Zack Martin’s Holdout - Jess Nevarez, Pro Football Network ![]() ![]() ![]() There are countless products on the market that claim they can help you “burn calories, boost metabolism, and increase energy levels.” Claim 4: “Burn calories, boost metabolism, increase energy levels” You might lose fat if you’re eating a healthier diet and exercising whilst drinking the teas, but the results would mostly be due to your change in lifestyle over the teas.įor more information on this, please read my articles on healthy body fat and permanent fat loss. Mainly in the form of water and feces.Ĭan Skinny Teatox cause you to “lose fat?” Unlikely. Unfortunately, the bathroom scale gives you absolutely no indication if you’re losing fat, muscle, water, or anything else for that matter.īottom line: Can Skinny Teatox cause you to “lose weight?” Yes. However, for many people that want to “lose weight,” their expectation is that they would like to reduce body fat from those trouble spots like the hips, thighs, belly, and arms.Īnd one of the quickest methods to check for “weight loss” is the woefully misleading bathroom scale. I don’t think there is any question that you will “lose weight” if you are drinking teas loaded with laxatives and diuretics. I believe this claim is truthful, but it deviates from what consumers expectations might actually be. If your body’s bowel and bladder movements are normal, then you are naturally “detoxing” and “cleansing” yourself without the need of teas. It’s also important to note that many of the ingredients in Skinny Teatox teas are both laxatives and diuretics. Check out this SBS article on detoxing to read more. Unless you’re eating a steady diet of heavy metals and other known pollutants, probably not. Remember there is no legal or standardised definition for “detox” or “cleanse” in a marketing context, so they can be used any which way a company pleases.Īnd for all this “detox” talk out there, remember your body has its own built-in filters your, liver, lungs, spleen, and kidneys.īut wait, don’t my body’s filters get gunked up with “toxins” and need a good “cleansing?” To me, this sounds like similar marketing jargon that goes hand in hand with “detox.” If you don’t know specifically which toxins were talking about, how much or how many are in your body before you start drinking the tea, and you don’t have a measure after you’ve drunk the tea, then how do you know it’s “detoxifying” you? Claim 2: “Cleanse”įollowing on from “detox” above, Skinny Teatox claims their teas will “cleanse” you too. ![]() How can you KNOW if the tea is actually working? Are we talking about hexavalent chromium? Lead? Mercury? What’s the story? “Detox” is the primary marketing claim found across the Skinny Teatox website. But nowhere on the website did I find any mention of specifically WHICH “toxins” the tea actually “detoxifies.” Skinny Teatox makes explicit claims on its website that the product can not only “detoxify” and “cleanse” you but will also cause you to “lose weight, burn calories, increase your energy levels, and keep your appetite in check.”īut are these claims truthful and can the product actually deliver? Claim 1: “Detoxify” Drugs used for real detoxification are not ingredients in a smoothie. Real detoxification is provided in hospitals under life-threatening circumstances - usually when there are dangerous levels of drugs, alcohol, or other poisons in the body. Real detoxification isn’t ordered from a menu at a juice bar, or assembled from supplies in your pantry. It is a fake treatment for a fake condition. “Detox” is a legitimate medical term that has been co-opted to sell useless products and services. Scott Gavura eloquently provides a real definition for detox in a recent article on Science-Based Medicine: Popularised by questionable internet personalities such as self-styled toxin-hunter Vani Hari (aka Food Babe), the term “detox” has been recklessly bandied around with little consideration for accuracy of use – and frankly, it’s terrifying consumers.īut if you buy into the hype, then you are fat, tired, and unhealthy because “dangerous toxins” have accumulated in your body. What is “detox” and why is it plastered all over different products these days? Before we get into Skinny Teatox’s specific marketing claims, it’s important to look at the marketing juggernaut that is the word “detox.” ![]() ![]() If you haven’t done so already, please follow the Getting Started instructions that came with your Kindle and plug in your Kindle to charge the battery. Please look at the Getting Started iĬongratulations! You are reading on your new Kindle DX. If your Kindle was a gift, you will need to register your device. To turn to the next page, press on the Next Page button. You can leave this guide at any time by pressing the Home button on your Kindle. This section provides an overview of Kindle DX and highlights a few basic features so you can start reading as quickly as possible. You are reading the Welcome section of the Kindle DX User’s Guide. ![]() Welcome to Thank you for purchasing Amazon Kindle DX. 123 10.3 Transferring Personal Documents. 122 10.2 Transferring Periodical Subscriptions. ĬHAPTERđ0: MigratingĜontent to Your New Kindle 122 10.1 Transferring Books. ĬHAPTERĘ: Kindle and YourĜomputer 110 8.1 Getting Started. ĬHAPTERĖ: Accessing the Web 94 6.1 Using Basic Web. ĬHAPTERĔ: Searching on Kindle 73 4.1 Introduction to Search. ĬHAPTERē: Reading on Kindle 42 3.1 Types of Content. Table of Contents WELCOME 8 CHAPTERđ: Getting Started with Your Kindle 18 1.1 Views of Kindle DX. ![]() ![]() ![]() But if the NYC fire hydrant doesn’t have this red painted curb, the 15-foot rule still applies. Generally, a fire hydrant is followed by a red painted curb that designates a no parking zone. However, between sunrise and sunset, a passenger vehicle may stand alongside a fire hydrant as long as the licensed operator remains behind the wheel and is ready to move the vehicle if required to do so.Īfter sunset, you cannot park within 15 feet of a fire hydrant at all. The car was parked so close to the hydrant that firemen dented it while hooking up and then the hose kinked up. Firefighters and bystanders got together to move the car.įire Hydrant Regulations Code 40 says you cannot stop, stand, or park within 15 feet of a NYC fire hydrant, on either side. 3 Do not park by a broken hydrant, you will still get a parking ticket. 2 If you receive a fire hydrant parking ticket, the fine will cost you a steep 115. Which is exactly what happened to the hose stuck through the vehicle. Why you should never Park by a fire hydrant in NYC Why You Should Never Park By A Fire Hydrant 1 Drivers should never stop, stand, or park within 15 feet of an NYC fire hydrant. Firefighters can’t thread the hose under or around the car because it’s not very flexible and tends to kink reducing the flow of water. They were trying to put out a fire at three apartment houses nearby. So, firefighters smashed two windows and fed the hose through the car. If you think getting a ticket is the worst thing that can happen, then you should read this story. ![]() One minute turns into ten minutes and before you know it you forgot where you parked. Even if you think you’ll just be a minute. So if you park directly in front of one, are your breaking the law? YES ! We’re not supposed to park in front of fire hydrants period. ![]() Its pretty easy to remember, you cannot park within 15 feet of a fire hydrant. We all know the Fire hydrant regulations. ![]() ![]() ![]() You can choose the type of source that is connected if available and you can also edit the gain. Now you can edit the external source in CasaSetup as well. They are the 3.5mm jack inputs on the back of the Music Server: There are also 1-2 external sources on the Music Server which can have CD players or AM/FM tuners connected to. ![]() If you don’t want to show all the sources you can hide them by ticking the ‚Hide Source‘ box. For example one could be Jazz Playlist, and another could be Dad’s Favourites. These sources allow you to setup different music on them and then you choose which source to play in which room. There will be 8 or 12 inbuilt sources depending on which Music Server you have bought. Next up is the Sources, in this menu you can give the sources names. Then in Control Type select ‚Enable third party control using TCP/IP (telnet) communication‘. Tick the box next to ‚Enable third party control of CasaTunes’ under the Settings. Once in CasaSetup you need to change the Third party Control settings to allow the Miniserver to control the Music Server. The trigger inputs require a voltage to trigger them. ![]() This option allows you to use the trigger inputs to play a doorbell sound or mute pages. You will be on the Select Controller page of the menu and here the controller type should be CasaTunes CT.įor the option ‚Enable muting or paging when triggered?‘ you can set this to Disable. You can change the language with the drop down list in the top right hand corner. Once you are connected to CasaSetup you will be greeted with the screen below. To find the IP of the Music Server look at the connected devices in your router by going to your router setup on your browser (usually the IP address 192.168.1.1 or 192.168.0.1 you can find this in the information that comes with your router).Ĭlick on the below menu options to see how to configure each part of CasaSetup for your Music Server. To directly connect to CasaSetup from the Music System itself the address is: For Windows the addresses to enter into your browser are: You can remotely run CasaSetup on any computer that is connected to the LAN. You also need to run a CAT cable from the Music Server to your router. We are looking to provide installation boxes that suit our speakers via our webshop soon.īelow is a diagram of how speakers would be connected either in mono or stereo setup. ![]() Speaker installation boxes for cast concrete ceilings should have a volume of 7-10l as well as suitable options for mounting the speaker. If the cable length is more than 50m, the cross-section rule must be adapted accordingly. For example, the user name of „userold“ changed to „usernew“, so the directory C:\Users\userold\Music\CasaTunes must be changed to C:\Users\usernew\Music\CasaTunes.Ĭable cross-section between a speaker and the music server: up to 20m should be 1.5 mm², from 20 to 50m should be 2.5mm². If the user name for logging on to the server is changed, this must be taken into account in the path statement.If you change the username or password the computer may reboot specifying the new login information is required.Nevertheless, should a new username be used the following points should be noted: We recommend that these are not changed, as home networks are usually protected by the router and the Music Server is not a big security risk. If you log on to the actual Loxone Music Server using a screen and keyboard the username is „Loxone“ (no password) and the computer name is „MusicServer“. In this guide you can find all the information for setting up your Loxone Music Server and how to set it up with Loxone Config so you can use the apps to control the music! General information At the time of review, all components must be installed and fully functional.Configure your Loxone Music Server which runs CasaTunes software to allow control from the Miniserver. – Loxone Water Sensors in appropriate roomsĪ Loxone Partner Consultant will review each project you submit for the Smart Home Bonus. – Loxone Smoke Detector in designated rooms* – Loxone Touch/Touch Pure/Touch Surface for control in each room – Loxone Valve Actuators for zoned heating control for each room/zone – The shading should be controlled either by a Geiger motor, our Shading Actuator or our Relay Extension – A Motion Sensor Tree in each room (unless using our Ceiling Light with inbuilt motion sensor) – A minimum of 80% of the lighting should be Loxone Tree. The following hardware must be included in a Loxone Smart Home project: To qualify, the following functions must be commissioned: The 3% bonus will be in the form of a credit note on your account. The Smart Home Bonus is available on projects where the components were purchased after. Have you commissioned a true Loxone Smart Home? If so, you’ll effectively receive an addition 3% discount off the list price of all the Loxone components you’ve used in this project. ![]() ![]() ![]() Give your drivers and customers the Google Maps experience they know and love with routes that cover 40 million miles of roads in over 200 countries and territories. Shell Ultimate Road Trips Gas Station Near Me Shell Motorsport The Shell App Together we are a force for good Mobile Payment at Shell via third-party apps. Whether you’re expanding your ridesharing operations into Australia or deploying a two-wheeler service in India, we’ve got you covered with detailed, high-quality data for urban areas and cities around the globe. Plan your route and nd a Shell gas station close to your location. Looking for a place to eat? It's all in Google Maps: browse nearby restaurants, find one you like, check out the dining environment, and even make reservations.īy tracking real-time traffic information, Google Maps can help you find the best route to your destination.ĭeliver great experiences all over the globe Type Shell gas stations in the search bar at the top of the screen. You can access Google Maps on a desktop computer or a mobile device. To find Shell gas stations using Google Maps, follow these steps: Open Google Maps on your device. ![]() The wonderful world is all around you, waiting for you to discover. How to Find the Closest Shell Gas Station Near Me. Or even better, join a local guide program to share your favorite stores. Torn between two businesses? You can start by looking at comments and photos shared by locals to make a more informed decision. Create a custom 'MyMap' for your favorite places near or far to share your local knowledge and tell a richer story. El municipio de Fawn Creek se encuentra ubicado en las coordenadas Según la Oficina del Censo de los Estados Unidos, el municipio tiene una superficie total de 178. ![]() ![]() ![]() I'm sure this resonates with other people too. I can't tell you the amount of times I've eaten at a takeaway or function where my heart is about to explode from the salt content in a salt fish dish. Let's not forget boiling the sodium off is subjective. According to the Canadian Forces National Investigation Service 100g of boiled salt fish contains 400mg of sodium. Soaking and boiling the salt fish doesn't significantly change the sodium content. Therefore the actual processing alone renders it high in sodium. Plus if you look at the quantity of salt being used during the curing process it exceeds the daily amount. ![]() That's a long period of time for salt to fully absorb the fish in its entirety. If you examine the process of how salt fish is made - it is fish fillets that have been dried in refined processed salt for several days. That's the million dollar question and one which would probably have people divided. Does soaking and boiling salt fish eliminate the salt? I know most of us are used to purchasing saltfish because it is the cultural norm, but times are changing, diseases are becoming more prevalent and prevention is better than cure - as the elders would say. ![]() I want my post to open up the idea to change and for you to hopefully explore your options outside of the norm. Unfortunately, we also know someone who has died of complications associated with diabetes or renal failure. In the Caribbean community, we all know someone who has "sugar" (type 2 diabetes) as we refer to it. Thankfully, these diseases are preventable with a bit of awareness and modification to ones diet. It forces the body to work much harder which results in an extra strain on the heart, kidney and brain. The bodies blood pressure is raised when extra water from sodium is stored. I think most of us are already aware of the health adversities caused by salt and sugar. The above cardiovascular diseases are in some way or another related to highly refined sodium consumption (think table salt). I grew up on the stuff myself but.with African Caribbean people leading with some of the highest figures for I know how passionate Caribbean people are about salt fish. I've been wondering do I write this post or don't I. I've been going back and fourth in my mind. In the Latin American countries it is called bacalao. Salt fish is used for savoury foods such as - stews, fritters, fish cakes or cooked up with other foods. The whole concept of this was to increase the flavour and extend the shelf life. The fish would usually be left out in the sunshine for several days to completely dry. Any of the aforementioned fish is cured and dry salted with white table salt. In short, salt fish is typically made with cod, flounder, haddock or even pollock. ![]() Growing up I would search the cupboards in search of snacks and stumble upon copious amounts of packaged salt fish. Similar to rice, saltfish is one of those dietary staples that you will find in most Islanders cupboard. Like most Caribbean people I grew up eating salt fish, it plays a crucial role in Caribbean/ Latino recipes. There is a very good reason for that which I will explain in full shortly. I have yet to post a Caribbean recipe which includes salt fish. If you have been following my blog from the beginning then you may have noticed something. ![]() ![]() ![]() Once the new page is opened, your connection credentials are generated for you but make note of the following information: To view the OpenVPN credentials that are generated for you on the configuration dashboard, press ' View Configuration'. Once the desired parameters are chosen, save them with « Save Configuration » ![]() Choose this version, if you have recurrent connection issues such as sudden disconnections. TCP allows more stable connections than the UDP version but is a bit slower. UDP allows higher speed than the TCP version but can result in broken downloads in some cases. Server group: Choose the server group and the OpenVPN protocol (UDP or TCP) you want to use:.Country: Since native protocol connections may only be used with exactly one server you now have to choose the country you want to surf from the server to be used in this country will be chosen by CyberGhost automatically.You can download all the configuration files after creating them.Ĭhoose OpenVPNand your preferred C ountry and S erver Grou p, as described below.Īlso, type in a Device nameto assign to your device, then configure the parameters for the new device. Each server has a configuration file that you will need to create in order to connect to the VPN server. Click on section 'VPN' from the left-side menu, scroll down the page and click ' Configure Device'.ģ. Visit your CyberGhost VPN online account and login with your CyberGhost Username and Password.Ģ. Your first VPN Connection Download OpenVPN configuration filesġ. Install Tunnelblick and VPN configuration Then you’re reay to hit the Start OpenVPN Client button.Tunneblick app is an alternative method of connecting to CyberGhost VPN servers that will be useful if the CyberGhost application cannot be installed on your Mac or if it does not work as expected. And so I wrote a Mac OpenVPN client and merge it in the same app as the one that enables the Server. Use the same OpenVPN Enabler app in the targetted client Mac, but use the Client tab. Drag the exported mobileconfig file onto a “well” just below the Start OpenVPN Client button.Once the file is dropped on the well, the OpenVPN Client app will extract out the client parameters from the profile ands set up the VPN client config. The OpenVPN app for MacOS is very Windows-centric. If the client is a Mac - now we need an app. Then watch if the VPN button shows it’s connected. You launch the mobileconfig profile the usual way, by launching it from Settings or hitting the VPN button in Settings. You just need to have it sitting on your iOS device. ( ) You don’t even need to open it or look at it. For iOS, I didn’t write an OpenVPN client app because the one provided by OpenVPN suffices. The extra step is that we need an app on the iOS device. Copy the above profile to the iOS device and install it in Settings. If the client is an iOS device - except for one extra step, connecting to an OpenVPN Server from an iOS device is almost like what we did with the old Mojave VPN Server. ![]() ovpn file with any other OpenVPN client.ġ. ![]() mobileconfig file, in the selected directory. Note: from version 1.0.5 onwards, OpenVPN Enabler is also able to export a. Copy this profile to the Mac or iOS device, either through AirDrop or through email or any other means. ![]() ![]() ![]() Therefore, there remains a need for effective biomarkers and potential targets to improve the diagnosis and treatment of patients with brain metastasis.Īccumulating evidence, including our work on multi-omics subtyping analysis, suggests that the tumor environment (TME) plays a major role in brain metastasis patients’ responses to stereotactic radiosurgery and whole-brain radiation therapy 9. Unfortunately, the mortality rate and the recurrence of brain metastasis remain high 8. Substantial advances have been made in the diagnosis and treatment of patients with metastatic brain tumors, including targeted therapies that penetrate blood brain barrier and stereotactic radiosurgery as primary strategies of therapy 7. Brain metastasis are 10 times more common than primary brain tumors 6 and is associated with poor survival outcomes 6. The majority of brain metastases are from primary cancers such as lung, breast, and melanoma 5. It is estimated that brain metastasis occurs in at least 6% of all newly diagnosed cancer cases 1, 2, 3, and is a devastating cancer complication for the 200,000 patients each year diagnosed in the US 4. These discoveries provide potential biomarkers for effective therapeutic targets and intervention strategies.īrain metastasis refers to the malignant tumors that metastasize to the brain. Taken together, our comprehensive analyses identify type I collagen-secreting tumor-associated fibroblasts as key mediators in metastatic brain tumors and uncover tumor receptors that are potentially associated with patient survival. ![]() Furthermore, tumor cell-specific receptors exhibit a significant association with patient survival in both brain metastasis and native glioblastoma cases. ![]() Additionally, we observe M1 activation in native microglial cells and infiltrated macrophages, which may contribute to a proinflammatory TME and the upregulation of collagen type I expression in fibroblasts. These fibroblasts exhibit high expression of type I collagen genes, dominate cell-cell interactions within the TME via the type I collagen signaling axis, and facilitate the remodeling of the TME to a collagen-I-rich extracellular matrix similar to the original TME at primary sites. Importantly, we identify tumor-associated fibroblasts in both our in-house dataset and external scRNA-seq datasets. Interestingly, distinct cellular compositions are observed across different samples, indicating the influence of diverse cellular interactions on the infiltration patterns within the TME. Our analysis reveals the presence of various intratumoral components, including tumor cells, fibroblasts, myeloid cells, stromal cells expressing neural stem cell markers, as well as minor populations of oligodendrocytes and T cells. In this study, we have applied scRNA-seq and profiled 10,896 cells collected from five brain tumor tissue samples originating from breast and lung cancers. Recently, the remarkable breakthroughs in single-cell RNA-sequencing (scRNA-seq) technology have advanced our insights into the tumor microenvironment (TME) at single-cell resolution, which offers the potential to unravel the metastasis-related cellular crosstalk and provides the potential for improving therapeutic effects mediated by multifaceted cellular interactions within TME. Therefore, there is a critical need to identify effective biomarkers that can support frequent surveillance and promote efficient drug guidance in brain metastasis. ![]() It is a leading cause of death in advanced-stage cancer, resulting in a five-year overall survival rate below 10%. Brain metastases is the most common intracranial tumor and account for approximately 20% of all systematic cancer cases. ![]() |
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