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By Vijay Kumar Malesu Mar 7 2024 Reviewed by Lily Ramsey, LLM

In a recent study published in Science Immunology, a group of researchers investigated how sensory nerve sprouting and mast cell activity, driven by nerve growth factor (NGF), contribute to persistent bladder pain and dysfunction in recurrent urinary tract infection (rUTI) cases.

Study:  Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity . Image Credit: Rabizo Anatolii/Shutterstock.com Background 

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), lead to numerous clinical visits annually due to their high recurrence rate, especially in women.

Recurrences are often attributed to UPEC persisting within the urinary tract's epithelial cells, causing rUTIs even in individuals with intact immune systems.

Standard UTI treatment involves a short course of antibiotics, with longer prophylactic use in cases of frequent recurrences.

rUTI patients frequently experience symptoms like pelvic pain and increased urination frequency, often treated with antibiotics despite negative urine cultures.

Further research is needed to develop targeted therapies that address the underlying neuro-immunological mechanisms contributing to chronic pelvic pain and bladder dysfunction in rUTI patients. About the study 

In the present study, researchers employed a rUTI mouse model to mimic symptoms and phenotypes observed in human clinical settings.

They evaluated voiding behavior, pain-like responses, and nerve anatomy through various techniques such as cystometry, histology, and three-dimensional (3D) model reconstruction.

Additionally, enzyme-linked immunosorbent assay (ELISA) and flow cytometry were utilized to identify proteins and cell types relevant to rUTI pathology.

To validate their findings, the team implemented multiple targeting strategies, including receptor antagonists and neutralizing antibodies against NGF, as well as genetically modified mice lacking specific immune cell receptors or cells. Related StoriesCellectricons expertise in pain research recognized by second EU research grantLow back pain? Theres good and bad newsNew drug targets key mechanism in ALS, protects motor neurons

To further establish the connection between their observations in mice and human patients, the researchers administered NGF, histamine, and bradykinin to naive mice.

This replicated the primary observations from the rUTI model, suggesting a possible translational significance of their findings.

Human bladder biopsies and urine samples were collected from control individuals and rUTI patients experiencing pain to confirm the animal model data with human clinical observations.

These human samples underwent similar analysis protocols to those applied in animal studies, ensuring that the insights gained from the research were grounded in both preclinical and clinical realities.

The study explored nerve growth in rUTI through various methods. Researchers collected dorsal root ganglia (DRGs) from mice, treated them with enzymes for dissociation, and then cultured the cells on coated coverslips. Adding NGF or its antagonist revealed NGF's role in neurite outgrowth.

This was paralleled by in vivo experiments where NGF was instilled into mouse bladders to induce nerve sprouting, contrasting with treatments that neutralized NGF or blocked its receptor, which prevented such growth.

Additionally, monocytes and mast cells were cultured with neurons to demonstrate further NGF's influence on nerve development.

Various techniques were employed to assess pelvic sensitivity and bladder innervation effects, underscoring NGF's central role in sensory nerve sprouting associated with rUTI symptoms. Study results 

Patients experiencing rUTI often report persistent symptoms such as pelvic sensitivity and urinary frequency, even after bacterial cultures show no signs of infection. This observation led researchers to investigate the role of bladder sensory nerves and their connection to rUTI symptoms.

Upon examining bladder biopsies from rUTI patients, an increase in Substance P (SP+), a marker for nociceptive sensory nerves, was observed, suggesting alterations in nociceptive activity.

A mouse model of rUTI was employed to explore these clinical findings further, revealing similar symptoms of increased pelvic sensitivity and urinary frequency alongside significant sensory nerve sprouting in the lamina propria.

The investigation into the underlying mechanisms of these observations pointed towards the role of NGF, a key mediator in nerve sprouting and sensitization. Elevated levels of NGF, but not brain-derived neurotrophic factor (BDNF), were identified in the bladders of rUTI mice.

Targeting NGF signaling through the administration of native NGF to naive mice or utilizing NGF-neutralizing strategies replicated the rUTI phenotype or alleviated symptoms, respectively, confirming NGF's pivotal role.

The cellular source of NGF was traced back to recruited monocytes and bladder-resident mast cells, which were identified as primary contributors to the elevated NGF levels during rUTI.

These findings were further confirmed by in vitro experiments showing that monocytes and mast cells induced nerve growth. This process could be blocked by Tropomyosin receptor kinase A (TrkA) antagonism, indicating the specificity of NGF from these immune cells in inducing sensory nerve sprouting.

Exploring the link between sensory nerve sprouting, sensitization, and the observed rUTI symptoms, researchers discovered that the sustained release of NGF-sensitized nociceptors leads to pain-like responses and urinary frequency.

This process involved the activation of Transient Receptor Potential Vanilloid 1 Positive (TRPV1+) nerves, with mast cell products such as histamine and bradykinin playing significant roles in mediating these symptoms.

Interestingly, the administration of histamine or bradykinin directly into the bladder of naive mice induced similar symptoms to those observed in rUTI, suggesting a role for these mast cell products in the pathological process. Journal reference:

Byron W. Hayes et al. Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity. Sci. Immunol. (2024). doi:10.1126/sciimmunol.adi5578. https://www.science.org/doi/10.1126/sciimmunol.adi5578 

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Not enough: Corvette concept falls 1,000 hp short of Chinese hypercar hype [video]

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Not enough: Corvette concept falls 1,000 hp short of Chinese hypercar hype [video]

The Corvette CX making its debut at this weekend’s The Quail, a Motorsports Gathering, generates more than 2,000 combined hp from its four, individually controlled and torque-vectoring electric motors. It’s staggering power, draped in beautiful bodywork, at a point in time when Corvette is rapidly climbing through the supercar ranks. There’s only one problem with this latest rendition of America’s motorsports icon: China’s has 1,000 more hp.

The specs for the Yangwang U9 Track Edition that leaked last week in BYD filings with the Ministry of Industry and Information Technology (MIIT) read like something out a middle schooler’s journal. 3,000 hp. 0-60 in one second. An electric motor for each wheel. A top speed approaching 300 mph. If it’s real (and there is absolutely zero reason to believe that it isn’t), the BYD will be the performance car benchmark against which all others are measured, like the Ferrari F40 of the 1980s, McLaren F1 of the 1990s, or Bugattis of the twenty-first century.

And that 3,000 hp BYD? That’s a production car, if limited. Meanwhile, the latest no production intent, pie-in-the-sky, no-holds-barred, you can just say shit and no one will ever question it electric hypercar concept from GM falls more than 1,000 hp short, at “just” 2,000 hp.

But don’t count the Corvette out.

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More grease, bigger hammer


Callaway Sledgehammer, via Mecum Auctions.

Whatever you may think of poster-era supercars like the Lamborghini Diablo, Porsche Carerra GT, or Pagani Huayra – or even modern electric hypercars like the Tesla Model S Plaid and Xiaomi SU7 – the one thing they all have in common is that they are all objectively slower than the 255 mph Callaway Corvette Sledgehammer from 1988, above.

I won’t go into the specs of that car (this isn’t that kind of car blog), but the point is that while the Corvette is often overlooked, there is a reason GM’s top-shelf sporty car carries that “King of the Hill” nickname – and the new Corvette CX concept is similarly, undoubtedly, more than just a list of specs in a magazine.

And those specs are seriously impressive. The new Corvette CX concept packs four independent electric motors putting out a combined 2,000 hp and some ungoldy amount of Earth-moving torque under advanced software controls that enable four-wheel torque vectoring for maximum grip and cornering performance, as well as precise steering control under even the heaviest of braking.

Power to those motors comes from the Corvette CX’ 90 kWh lithium-ion battery that’s centrally mounted low in the chassis, giving the car a low center of gravity and, crucially, ideal 50/50 front-rear weight distribution.

Plus: it’s gorgeous


The Corvette team says the CX concept draws from more more than seventy (!) years of Corvette heritage while being a forward looking concept, not a retro piece. Stylistically, the concept seems more visually mature and subdued than its in-production C8 cousin, and seems to promise a return to the C3-5 eras’ cleaner, less busy aesthetics.

Phil Zak, executive design director for Chevrolet, is very rightly proud of the CX’ design. “While the shape of a Corvette has always been expressive and forward-looking, each crease and line has its roots in the generations that came before it. It is aspirational, it is cultural, it is the reason people want to come and work at Chevrolet,” says, Zak. “The CX … demonstrate(s) our design teams stepping away from the constraints of production vehicles and unleashing their creativity. Through this exercise, we’ve added to Corvette and defined the design direction for Corvette moving forward.”

The rest of the official GM press release copy highlights the aviation-inspired canopy, jet-age interior, and an underbody fan system not entirely unlike the system leaked in Tesla patent filings earlier this week. You can see that here:

Aggressively futuristic, yet unquestionably a Corvette, the CX concept shows what an uncompromised future sports car can be. The athletic exterior design, highlighted by the fighter-jet-inspired cockpit canopy, isn’t just about looking powerful – it was shaped in collaboration with the GM Motorsports Aero Group. Every angle was designed with ultimate performance in mind.

On the inside, every aspect of the CX concept was designed to provide an unmatched driving experience. The forward-opening fighter-jet-style canopy automatically raises as you approach. Driver and passenger settle into seating finished in Inferno Red ballistic textile, bolstered to help hold occupants in place during high-g cornering maneuvers. Premium silicone leather, milled aluminum, and low-gloss forged carbon fiber accents give an elevated feel to the driver-focused cabin.

The digital windscreen transforms the windshield into an immersive surround display with real-time performance data. Every major control is elegantly integrated into the steering wheel, keeping the driver’s focus on the road ahead.

The innovations continue underneath the skin with the Vacuum Fan System. Built-in fans draw air through the open-channel bodywork, generating massive downforce and adjusting the airflow over the rear diffuser to refine aerodynamic balance in real-time. The front diffuser and rear wing are both active, adjusting automatically in response to the driver’s inputs to generate maximum grip. The integrated understructure of the CX concept is visible through the aero channels in the bodywork, and the suspension A-arms are wing-shaped to enhance airflow and reduce front-end lift.

CHEVROLET

All in all, the new Corvette CX concept is an impressive piece of engineering and rolling art. It’s also a statement from GM that, while the Corvette may very well be going all-electric in its next iteration, it won’t be going any slower. In fact, the first electric Corvette might even be the best one ever – but don’t say that one too loud (you’ll upset the New Balance crowd).

That said, as a pure concept that almost no one will ever drive and which might never get publicly strapped on to a dyno, it is absolutely baffling that Chevy wouldn’t have just claimed 3,000 hp. Even if it was just to match BYD’s claims and continue to build on a century of hype for American exceptionalism, you know?

That’s my take, anyway – what’s yours? Watch the Corvette CX Concept hype video from Chevrolet, below, then let us know what you think of the latest GM concept in the comments.

Electric Corvette CX concept


SOURCE | IMAGES: GM, Mecum.


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Trump warned by top Senate Democrats to rethink advanced AI chip sales to China

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Trump warned by top Senate Democrats to rethink advanced AI chip sales to China

Nvidia CEO Jensen Huang, right, speaks alongside President Donald Trump about investing in America, at the White House in Washington, on April 30, 2025.

Jim Watson | AFP | Getty Images

Six Senate Democrats on Friday released an open letter asking President Donald Trump to reconsider his decision to allow tech giants Nvidia and Advanced Micro Devices to sell AI semiconductor chips to China in exchange for 15% of revenue from the sales.

The letter — signed by Senators Chuck Schumer, D-N.Y.; Mark Warner, D-Va.; Jack Reed, D-R.I.; Jeanne Shaheen, D-N.H.; Christopher Coons, D-Del.; and Elizabeth Warren, D-Mass. — was in response to an Aug. 11 announcement by Trump that Nvidia and AMD would pay the U.S. government a 15% cut of revenue from chip sales to China in exchange for export licenses.

“Our national security and military readiness relies upon American innovators inventing and producing the best technology in the world, and in maintaining that qualitative advantage in sensitive domains. The United States has historically been successful in maintaining and building that advantage because of, in part, our ability to deny adversaries access to those technologies,” the letter states.

“The willingness displayed in this arrangement to ‘negotiate’ away America’s competitive edge that is key to our national security in exchange for what is, in effect, a commission on a sale of AI-enabling technology to our main global competitor, is cause for serious alarm,” the letter continues.

Senators also warned that selling advanced AI chips — specifically Nvidia’s H20 and AMD’s MI308 chips — to China could help strengthen its military systems, a claim that Nvidia denies.

In a statement to CNBC, a Nvidia spokesperson said: “The H20 would not enhance anyone’s military capabilities, but would have helped America attract the support of developers worldwide and win the AI race. Banning the H20 cost American taxpayers billions of dollars, without any benefit.”

Dylan Patel on China’s Catch-22 in securing advanced chips amid U.S. restrictions

The letter from Senate Democrats also requests a detailed response from the administration by Friday, Aug. 22, regarding the current deal involving Nvidia and AMD, as well as any similar arrangements being made with other companies.

“We again urge your administration to quickly reverse course and abandon this reckless plan to trade away U.S. technology leadership,” the letter states.

A request for comment from the White House and AMD was not immediately returned.

Despite Trump allowing chip sales to resume, it has already become clear that China isn’t welcoming Nvidia back with open arms, instead urging tech companies to avoid buying U.S. companies’ chips, according to a Bloomberg report.

“We’re hearing that this is a hard mandate, and that [authorities are actually] stopping additional orders of H20s for some companies,” Qingyuan Lin, a senior analyst covering China semiconductors at Bernstein, told CNBC.

In a separate report, The Information said regulators in China have ordered major tech companies, including ByteDance, Alibaba, and Tencent, to suspend Nvidia chip purchases until a national security review is complete.

CNBC’s Kristina Partsinevelos contributed to this report

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Tesla raises Model S/X prices, but bundles ‘Full Self-Driving’ and brings back free Supercharging

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Tesla raises Model S/X prices, but bundles 'Full Self-Driving' and brings back free Supercharging

Tesla has raised Model S and Model X prices by $10,000, but it decided to include its ‘Full Self-Driving’ package, free Supercharging for life, ‘Premium Connectivity’, and a new ‘Premium Service’ for 4 years.

For the last few years, Model S and Model X have been in a free fall, and the latest mild update to the two flagship vehicles doesn’t appear to be helping much.

The automaker is now updating pricing and included features to try to shake things up.

Tesla is now making a new ‘Luxe Package’ standard on all Model S and Model X vehicles:

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Full Self-Driving (FSD), previously priced at $8,000, is now included in all Model S and Model X vehicles. The automaker claims that FSD will eventually result in unsupervised autonomous driving, but for the meantime, it is a level 2 driver assistance system.

Tesla is also introducing a new “Four-year Premium Service”:

Includes tire and windshield protection plan plus maintenance. Covers scheduled services including wheel alignment, tire rotations, front camera cleaning and replacement of HEPA filter, cabin filter and wiper blades.

The automaker is also bringing back included Supercharging for life.

Tesla used to offer free Supercharging for life as a perk on Model S and Model X vehicles.

In 2018, Tesla discontinued the perk after claiming it was unsustainable – although it temporarily reinstated it as a sales incentive at times. For example, it was offered as recently as December as an end-of-year incentive.

In the new terms, Tesla mentioned that it can’t be used for commercial purposes, such as if you use the vehicle as an Uber, and it is not transferable to a new owner if you sell the vehicle:

Charge for free at 70,000+ Superchargers worldwide. You are still responsible for Supercharger fees, like idle and congestion fees, when applicable. May only be redeemed at Tesla-owned Superchargers. Cannot be used for commercial purposes (e.g., taxi, rideshare or delivery services). If Tesla determines in good faith at its sole discretion that the vehicle is being used for commercial purposes, Tesla may remove the free Supercharging from the vehicle. The vehicle will then default to Pay Per Use Supercharging. Not transferable to subsequent vehicle owners or to another vehicle.

Initially, free Supercharging was tied to the vehicle rather than the owner, but this was later changed.

Finally, Tesla is also including ‘Premium Connectivity’, which enables Tesla owners to use some features that require more bandwidth, such as live traffic visualization, satellite-view maps, and video streaming, amongst other things.

It usually is $10 per month or $100 per year.

All of that comes with a significant price increase. The Model S now starts at $94,990 and $109,990 for the Plaid version.

Model X now starts at $99,990 and goes up to $114,990 if you want the quicker Plaid version.

Electrek’s Take

As the name implies, this looks like Tesla is trying to position Model S and Model X more as luxury vehicles.

A $10,000 price increase is significant, but the added features offer considerable potential value, depending on whether you plan to utilize them.

FSD sells for $8,000, but it only has an impact if you want FSD. If you don’t, Model S and Model X likely became a bad deal for you.

Free Supercharging is hard to value because it depends on how often you need to fast charge on the road.

Personally, I do it a couple of times a month, a little more when I go on road trips. It can take a while to accumulate $1,000 in Supercharger costs like that, but if you are someone who relies more on Supercharger, you can make it worth it fairly quickly.

However, you should take into account that this doesn’t add any resell value to your vehicle as you can transfer the inlcuded Supercharging.

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