Out of options. Illustration: Liu Rui/GT

The 23rd China International Industry Fair, which drew to a close on Saturday in Shanghai, attracted over 200,500 visitors from more than 2,800 enterprises across 30 countries and regions, offering a unique platform for domestic and foreign manufacturing companies.

As a window and platform to promote global industrial economic exchange, the fair, which has now been run for 22 years, has attracted higher attendances and publicity. 

The proportion of international brands participating in the exhibition has increased to 30 percent, the organizer said, according to Xinhua. 

Alongside companies from traditional manufacturing powers such as the US, Germany, Japan, and Italy, there were also first-time exhibitors from Kazakhstan, Azerbaijan and Cuba. In addition, the companies from Italy have further expanded its scale, with the number of exhibitors increasing to 65, an increase of 30 percent over the same period of the previous session.

As the process of industrial digitization accelerates, technologies such as artificial intelligence and industrial Internet are reshaping the global production system.

Zhejiang Sineva Intelligent Technology Co, a tech company aiming to provide mobile robot solutions, displayed the SIBOT series of composite robots that have been recognized by customers in the semiconductor industry.

In 2023, the company has launched a variety of products such as SIBOT series composite robots and W series water tank robots, focusing on the core capabilities of precise handling, connection and transportation, and automatic loading and unloading, to help partners further improve logistics performance and production efficiency.

"We are helping customers improve the digitalization and intelligence level of production and operation links to realize 'Chinese speed'," Liu Changlun, CEO of Zhejiang Sineva, said. 

At the exhibition, Schneider Electric released a white paper on the highly integrated 5G+PLC solutions together with the China Academy of Information and Communications Technology and the China United Network Communications Group Co, which are designed to explore the value arising from the connection between 5G networks and controls. 

It also signed a strategic cooperation agreement with Sunshine Pumps (Tianjin) Co Under the agreement, the two parties will focus on the production and operation of high-end smart devices to explore opportunities for collaboration on digital and software solutions. 

Pang Xingjian, senior vice president and head of industrial automation China of Schneider Electric, said that digital acceleration and sustainable development have become two long-term strategies that are both inseparable and complementary to each other for industrial enterprises: digital solutions underpin sustainable development, whereas sustainable development provides new stages and drivers for digital solutions. 

Xin Guobin, vice minister of industry and information technology said at the opening ceremony on Tuesday that the ministry will work with other parties to foster a world-class business environment that is market-oriented, law-based, and internationalized, continuously deepen international innovation cooperation, and safeguard the security and stability of global industrial and supply chains.

Cambodia highly appreciated the current development of economic and trade cooperation with China, Cambodian Deputy Prime Minister Aun Pornmoniroth told Xinhua in an interview on Friday.

Pornmoniroth, who is also the minister of economy and finance, said many infrastructure projects, technology transfer, and investments in Cambodia, which are a crucial source of economic growth, have been promoted under the Cambodia-China financial cooperation and the Belt and Road Initiative.

The trade volume between the two countries is increasing yearly, even with the impacts of the COVID-19 pandemic, he said. "It is believed to increase further in upcoming years."

Cambodia can export agricultural products to China directly, including bananas, mango, and longan, just to name a few, he added.

Besides, the Cambodia-China Free Trade Agreement (CCFTA) and the Regional Comprehensive Economic Partnership (RCEP) agreement, which took effect in 2022, demonstrate the commitment of participating countries to safeguarding the multilateral trading system, maintaining economic openness, and upholding a spirit of cooperation, which will, in turn, enhance socio-economic development.

"Undoubtedly, the two agreements will largely contribute to Cambodia's graduation from its status as a least-developed country in the next five years and an achievement of Cambodia's vision to become an upper-middle-income country by 2030 and a high-income country by 2050," Pornmoniroth said.

He added that the bilateral economic and trade cooperation reached another significant level during the official visit of Cambodian Prime Minister Hun Manet to China, resulting in the signing of a crucial document, namely, the action plan on building a Cambodia-China community with a shared future in the new era (2024-2028).

Also, he said both countries agreed to enhance trade facilitation to promote high-quality development of bilateral economic and trade cooperation, including making full use of the CCFTA and RCEP, promoting e-commerce cooperation, China International Import Expo, China Import and Export Fair, China-ASEAN Expo, China International Consumer Products Expo, and China International Small and Medium Enterprises Fair, among others.

Pornmoniroth said the signed action plan emphasizes the key priority areas of cooperation, such as politics, production capacity, agriculture, energy, security, and people-to-people exchanges, called the Cambodia-China Diamond Hexagon cooperation framework.

He added that the action plan clearly reflects the two countries' commitment to deepening the building of a high quality, high level, and high standard Cambodia-China community with a shared future in the new era.

Chinese technology giant Huawei has successfully replaced internal software management systems it once sourced from US vendors with its own in-house version in 88 overseas subsidiaries, as the company continues to reduce foreign reliance amid prolonged US curbs.

According to an article published on Huawei's online community for its employees Xinsheng.huawei.com, the 88 overseas units in 75 countries were the first batch of Huawei's global branches to complete the switch to its self-developed MetaERP, covering business sectors including cloud computing, devices, and information and communication technology. 

Huawei said it plans to accomplish the switchover in all of its more than 200 overseas units within the year.

ERP software is used by companies to manage key business operations ranging from accounting to supply chain management. It is widely seen as the most critical enterprise management IT system.

"The global switchover to MetaERP, and its ability to support the normal operations of Huawei's diverse lines of business worldwide, will prove to be an all-around victory," said the company.

In May 2019, the US Commerce Department added Huawei to a trade blacklist over alleged security concerns. The move has cut it off from a range of services and products, including ERP tools it largely purchased from US vendors.

Since then, the company has launched a transformation project to guarantee ERP continuity. After three years of efforts, the company successfully piloted the MetaERP system in Malaysia in September 2021, and applied it to key subsidiaries including Huawei Technologies in July 2022. 

In January 2023, MetaERP successfully supported the company's yearly settlements, representing a key victory for the system.

In late April, Huawei held an internal ceremony to celebrate the switch in Dongguan, South China, attended by the company's rotating Chairperson Meng Wanzhou.

"We were cut off from our old ERP system and other core operation and management systems more than three years ago. Since then, we have been able not only to build our own MetaERP, but also to manage the switch and prove its capabilities. Today we are proud to announce that we have broken through the blockade. We have survived!" Tao Jingwen, a Huawei board member and president of the quality, business process and IT management department, said during the ceremony.

In a study of pregnant women in Brazil, nearly 30 percent of those infected with Zika virus had babies with fetal abnormalities, researchers report March 4 in the New England Journal of Medicine.

Zika virus is the leading suspect for what’s causing a spike in certain birth defects reported in Brazil. Scientists have previously found traces of Zika in the brains of fetuses with microcephaly (a birth defect that leaves babies with smaller-than-normal heads). And one study has reported that the virus can infect and kill a cell type crucial to developing brains (SN Online: 3/4/16).

The new study enrolled 88 pregnant women from Rio de Janeiro who had developed a rash (a sign of Zika infection). They tracked the women throughout their pregnancies; so far, eight have given birth. Of the 42 women who both tested positive for Zika and received fetal ultrasounds, 12 of the women’s babies had abnormalities (including small heads, damaged brain tissue, and low levels of amniotic fluid).

Despite mild clinical symptoms, Zika infection during pregnancy appears to be linked with grave outcomes, the authors write.

Bacteria is back, baby. After decades of gobbling antibiotics and overzealous hand sanitizing, it’s now clear that the bacteria that live in and on our bodies can help keep us healthy. That realization is what led scientists to rub brand-spanking-new babies with fluid from the mothers’ vaginas.

Like about a third of babies born in the United States, these babies were born by C-section, and so missed out on a trip through the birth canal, where their bodies would have been propelled with viselike pressure through a channel coated with microbe-laden fluid. This crushing, juicy journey coats babies with their mothers’ vaginal microbes. Babies born by C-section are instead colonized with bacteria that live on skin (possibly picked up from the dust in the hospital operating room).

That difference may have important implications for future health, some scientists think. Studies have hinted that microbes picked up during a vaginal birth can sculpt newborns’ immune systems in ways that combat disorders including obesity, asthma and allergies. So it follows that replacing those missing vaginal microbes might be a good thing.

Scientists led by Maria Dominguez-Bello of New York University and the University of Puerto Rico in San Juan took a first step in testing that idea with the vaginal wipe-down experiment. An hour before a C-section, doctors inserted a square of wet, folded gauze into four women’s vaginas to slurp up the fluid. This microbe-laden gauze came out right before the C-sections began. Within a minute of birth, the newborns were swabbed with the gauze, first on their lips, then their faces, trunks, arms and legs, genitals, anuses and, finally, their backs. The whole-body rubdown took about 15 seconds.

Those 15 seconds led to bacterial changes that lasted through the newborns’ first month, the researchers reported February 1 in Nature Medicine. Compared with babies born via C-section who didn’t get swabbed, the four swabbed babies had bacterial species on their mouths, skin and guts that were more similar to those in their mothers’ vaginas. That resemblance suggests that swabbing could transform the newborns’ microbes in a way that might ultimately be beneficial.

The study gives some much-needed heft to the idea that microbes matter. By showing that newborns’ bacteria can be manipulated in a pretty simple way, the study opens the door for other tests of whether this microbial rehab is a good thing.

But the study is preliminary, the authors stress in their paper. The results come from four babies, with only a month of follow-up. It’s possible that these changes don’t stick around. It’s also possible that these microbes don’t actually improve health.

Those outstanding questions haven’t deterred some intrepid parents of babies born by C-section who want to try “vaginal seeding,” says pediatric infectious disease expert Aubrey Cunnington of Imperial College London. Over the last several years, news reports have raised interest, prompting some parents to request the procedure. On neonatal infection rounds last summer, a fellow doctor brought up a troubling story. “She described a recent situation where she had needed to stop a midwife from performing seeding, because the mother had a genital herpes infection,” Cunnington says.

That situation raised an important issue — fluid from a mother’s vagina may carry beneficial microbes, but it could also hold bacteria and viruses that could harm a newborn, Cunnington and colleagues wrote in an editorial published February 23 in BMJ. “Demand has outstripped both professional awareness and professional guidance on this practice,” he and his colleagues wrote in their editorial.

A lack of guidance is worrisome, he argues, because the procedure could unknowingly expose newborns to dangerous bugs, pathogens that babies born by C-section usually avoid. Group B streptococcus, which is carried by about 30 percent of women, can trigger meningitis and fatal septicemia, he says. Herpes simplex virus can lead to death and disability in newborns. And chlamydia and gonorrhea can cause severe eye infections.

Cunnington argues that those potential risks, coupled with unproven and potentially slim benefits, makes the procedure a no-go for now. “On balance, I don’t think the potential benefit outweighs the risk,” he says. Health practitioners at his hospital have been advised not to perform the procedure. (But because the swabbing is so simple, they can’t stop parents, or more realistically, another helper, from performing it themselves.) Staff at other hospitals vary in their willingness to help.

In the swabbing study, the protocol came with built-in safeguards. The women were tested for pathogens, and showed no signs of viral or bacterial infections. And the gauze was handled carefully so that it didn’t pick up new germs. Those precautions should be followed by any hospital or DIYer.

Like any decision — particularly those related to pregnancy and children — choosing whether to swab a baby born by C-section comes with a murky risk assessment. Some of that risk can be lowered by ruling out pathogens such as group B strep and STDs, tests that are usually offered to pregnant women in the United States. Cunnington points out that group B strep test results aren’t always reliable, and that STDs can be picked up after the tests. As a result, looking for those pathogens close to the time of delivery can make microbe swabbing less risky.

If you don’t feel like an adventurous self-experimenter, you can tend to your newborn’s microbes in other ways. Breastfeeding and avoiding unnecessary antibiotics may both encourage good microbes to flourish, no swabbing necessary.

In a galaxy far, far away, Chewbacca is a 7.5-foot-tall Wookiee. On Earth, he’s a small furry beetle.

Researchers discovered four new species of weevils on an island off the coast of Papua New Guinea, one of which they named after the lofty Star Wars character. Trigonopterus chewbacca is a black, flightless beetle about 3 millimeters long that thrives in the tropical forests of New Britain. Although T. chewbacca doesn’t resemble its namesake in size, the dense hairlike scales covering its head and legs reminded the researchers of Chewbacca’s fur.

Before these finds, Trigonopterus beetles hadn’t been spotted on New Britain. The discovery of T. chewbacca and its three relatives, T. obsidianus, T. puncticollis and T. silaliensis, suggests that the genus colonized the island at least four separate times, the team reports April 21 in ZooKeys.

T. chewbacca joins the ranks of other insects with a Star Wars moniker. Among its peers: a furry moth also named after the heroic Wookiee, a wasp named for Yoda and a Darth Vader slime-mold beetle.

Vultures are the birds everyone loves to hate. Even though you have nothing to fear from them — unless you’re dead — vultures’ steady diet of carrion will gross most people out. That diet may also be responsible for the birds’ quick and steep declines around the globe, a new study shows.

It’s not the dead bodies that are killing vultures, though. It’s the poisons with which humans have laced those meals, both intentionally and inadvertently, Evan Buechley and Çağan Şekercioğlu of the University of Utah in Salt Lake City conclude in the June Biological Conservation.

The team went searching for an explanation to something Şekercioğlu had reported in 2004 and is still true today — that vultures are the most threatened group of birds. Of the 22 species of vultures, nine are now critically endangered, three are endangered and four are near threatened, according to the International Union for Conservation of Nature, which tallies endangered species.

Buechley and Şekercioğlu were looking for an explanation of why these scavenging species (called “obligate scavengers” because they depend almost entirely on carrion for survival) are doing so poorly but “facultative scavengers” — birds such as storks, gulls and crows that can also eat things other than carrion and trash — tend to be doing well and even increasing in numbers in many cases. The researchers collected ecological information and population trend data on the 22 species of vultures and other avian scavengers and then tried to figure out what made the vultures so vulnerable.

Some aspects of biology do contribute to the vulture declines, the team found. These are large animals that live long and don’t produce a lot of offspring. That means that populations can take a long time to recover from bird deaths. But the ultimate cause of those deaths is what is disturbing — dietary toxins, which are the primary cause of declines in 14 of the 16 threatened and near-threatened vulture species, the team found.

Those toxins come in various forms. In India and Southeast Asia, it’s the cattle drug diclofenac, which causes kidney failure in any vulture unlucky enough to come across a cow that didn’t survive its medical treatment. Diclofenac is a problem for vultures in Africa, too, (and now Spain), but there the birds have also fallen victim to the poisons used to kill hyenas, jackals and lions in response to dead livestock. Wildlife poachers have also deliberately poisoned their prey in an effort to get rid of the circling vultures that can alert authorities to their crime. (Buechley and Şekercioğlu discovered a 2007 incident in Namibia in which a poisoned elephant carcass killed as many as 600 birds.) And in Europe and the Americas, carcasses laced with rodenticides, insecticides and lead from ammunition are also killing vulture species.

Without vultures, some of these ecosystems are already having problems. Other scavenging species aren’t quite able to fit into the vulture niche. They can’t eat as much and they don’t have stomachs equipped to kill deadly microbes, like vultures do. That means anything that does eat carrion could potentially spread disease. Populations of scavenging pests, like rats and feral dogs, have already skyrocketed in some places as these animals feast on what vultures would have once dealt with. Perhaps not surprisingly, that has led to problems, such as an increase in dog bites in India that has resulted in thousands of human deaths from rabies.

Much of the vulture declines could be easily solved by banning the chemicals that kill them, the researchers note. Because while vultures may be more inherently vulnerable to extinction than other bird species, due to their biology, their importance to the global ecosystem — and our own health — makes them too valuable to let slip away.

DNA from an ancient woman who lived in what’s now Romania indicates that people in Asia trekked to Africa starting between 45,000 and 40,000 years ago.

Evidence for this back-to-Africa trip comes from the partial remains of a 35,000-year-old Homo sapiens discovered in a Romanian cave more than 60 years ago. A distinctive pattern of alterations to mitochondrial DNA extracted from two of the teeth are similar to alterations seen in mitochondrial DNA of present-day North Africans, signaling an evolutionary connection, the team proposes May 19 in Scientific Reports.

After evolving in Africa around 200,000 years ago, human populations spread out of the continent by 50,000 years ago. The ancient Romanian woman’s DNA came from a maternal line that originated in West Asia after humans initially left Africa but then ended up in North Africa, the scientists propose.

Careening through the bloodstream, a single nanoparticle is dwarfed by red blood cells whizzing by that are 100 times larger. But when specially designed nanoparticles bump into an atherosclerotic plaque — a fatty clog narrowing a blood vessel — the tiny particles can play an outsized role. They can cling to the plaque and begin to break it down, clearing the path for those big blood cells to flow more easily and calming the angry inflammation in the vicinity.

By finding and busting apart plaques in the arteries, nanoparticles may offer a new, non-surgical way to reduce a patient’s risk for heart attack and stroke.

Nanoparticles measure less than 100 nanometers across — a thousandth the thickness of a dollar bill. Despite being tiny, they can be engineered to haul a mix of molecules — such as tags that make them stick to a plaque, drugs that block inflammation or dyes that let scientists track their movements. Over the last two decades, scientists have exploited these strategies to fight cancer, designing nanoparticles that deliver drugs (SN Online: 1/3/14) or dyes for imaging deep into the core of a tumor. The U.S. Food and Drug Administration has approved a few dozen cancer-focused nanomedicines.
Now researchers have begun engineering nanoparticles to target cardiovascular disease, which kills even more people each year than cancer. Nanosized compounds have been built that can sweep into clogged arteries to shrink the plaques that threaten to block blood flow. Some nanoparticles home in on the plaques by binding to immune cells in the area, some do so by mimicking natural cholesterol molecules and others search for collagen exposed in damaged vessel walls. Once at the location of a plaque, either the nanoparticles themselves or a piggybacked drug can do the cleanup work.

The aim of all these approaches is to prevent strokes and heart attacks in people with cardiovascular disease, either before surgery becomes necessary or after surgery to prevent a second event. Today, cardiovascular nanoparticles are still far from pharmacy shelves. Most have not reached safety testing in patients. But in mice, rats and pigs, nanodrugs have slowed the growth of the plaques that build up on vessel walls, and in some cases have been able to shrink or clear them.

“I think the effect we can have with these nanoparticles on cardiovascular disease is even more pronounced and direct than what we’ve seen in cancer,” says Prabhas Moghe, a biomedical engineer at Rutgers University in Piscataway, N.J.
Every minute, more than a gallon of blood pumps through the human heart, pushing through miles of blood vessels to deliver oxygen and nutrients to organs and extremities. In a healthy person, the trip is as smooth as a drive on a freshly paved highway. But in the more than 10 percent of U.S. adults who have cardiovascular disease, the route might be more like a pothole-filled road squeezed by Jersey barriers.

Waxy globs, or plaques, of fat and cholesterol line the blood vessels, thickening and hardening the walls, impeding blood flow. As fat builds up inside the vessels, it also leaks into the vessel walls, swelling them and signaling the body to send immune cells to the area. The congregation of immune cells aggravates the blockage, the way emergency vehicles surrounding the site of a multi-car pileup further slow traffic on a highway.

“The inflammation and the accumulation of fat in the walls of the blood vessel sort of feed off each other and exacerbate each other,” Moghe says.

If the plaques grow large enough, or pieces chip off and travel to smaller vessels, they can block a vessel. If oxygen-filled blood can’t reach the brain or heart, a stroke or heart attack results.

The drugs most often prescribed to prevent or treat atherosclerosis — plaque buildup on the inner walls of the arteries — are statins (SN: 5/5/12, p. 30). This highly successful and effective class of drugs, available since 1987, slows the growth of the fatty plaques by lowering the amount of cholesterol circulating in the blood. But taking statins is akin to limiting the number of cars on a damaged road rather than repairing potholes, some argue. And the drugs can boost a person’s risk of diabetes and liver damage. In many cases, patients don’t begin taking statins until they already have severe atherosclerosis, and the drugs do little to reverse the buildup of plaques that already exist.

“Heart disease is still the number one killer in the U.S.,” says endocrinologist and biochemist Ira Tabas of Columbia University Medical Center. Drug-carrying nanoparticles that can shrink existing atherosclerotic plaques and eliminate the accompanying inflammation could change that, Tabas and others say.
Going places
To treat atherosclerotic plaques with nano­particles, researchers have devised a variety of ways to send circulating particles directly to the fatty clogs. In each approach below, a molecule that’s part of the nanoparticle binds to a molecule in or near the plaques.

Click the black dots in the interactive image below to learn about different types of nanoparticles.
Macrophage magnet
To make nanoparticles congregate at the dangerous plaques, researchers need to identify something that makes the blockage stand out from the rest of the body. The crowds of immune cells near plaques act as a signpost that a plaque exists.

Many of the immune cells involved in atherosclerosis are macrophages, white blood cells that gulp pathogens, dead cells or debris in the body. At the site of a plaque, macrophages become swollen with fats and transform into what are called “foam cells” because of their foamy appearance. As they digest fats, foam cells send out chemical signals to recruit more inflammation-causing cells and molecules to the area. Because they’re so intimately involved in the formation of plaques, macrophages and foam cells are a prime target for nanoparticles.

Moghe’s group has designed nanoparticles that bind to molecules on the surface of macrophages, preventing them from gobbling fats and becoming foam cells. The researchers made the nanoparticles specifically target a subtype of macrophage that’s involved in atherosclerosis, not the macro-phages that might respond to other injuries in the body. When nanoparticles were injected into mice with narrowed arteries, the blockages decreased by 37 percent, Moghe’s group reported last year in the Proceedings of the National Academy of Sciences.

Others are using cholesterol-like molecules as nanoparticle taxis to carry drugs to plaques and subdue the immune reaction. Statins aim to lower the form of cholesterol called low-density lipoprotein, which earned the name “bad cholesterol” for accumulating in plaques. High-density lipoprotein, or “good cholesterol,” shuttles LDL away from these clogs to the liver, where it can be broken down. HDL also prevents macro-phages from turning into foam cells and producing inflammatory molecules. So Shanta Dhar, a chemist at the University of Georgia in Athens, developed nanoparticles that mimic HDL. She presented the work in March in San Diego at a meeting of the American Chemical Society.

“HDL is our body’s natural cholesterol-removing nanomaterial,” she says. In animal tests, the HDL-based nanoparticle can bind to free-floating macro-phages circulating in the blood, just as HDL does, and follow them to a plaque, she explains. The nanoparticles can also bind to macrophages already glommed on to a plaque, and, mimicking the activities of natural HDL, carry the cells away.

Plaque buster
Willem Mulder, a nanomedicine researcher at the University of Amsterdam and the Icahn School of Medicine at Mount Sinai in New York City, has also designed HDL-mimicking nanoparticles. His particles deliver statins that make a beeline for macrophages and plaques, letting him administer the drug at lower-than-usual doses. He was inspired by earlier studies that showed how extremely high doses of statins, given to mice, could lower LDL levels while also packing anti-inflammatory properties. Of course, in humans, such high doses would probably cause liver or kidney damage. Mulder’s solution: tack the statins to a nanoparticle to send them, missile-like, to the plaques. That way, a low dose of the drug could achieve the high concentration needed at the site of the atherosclerosis.
“We’re exploiting the inherent targeting properties of HDL,” he says. “And it works well with statins, which are small molecules.”

In 2014 in Nature Communications, Mulder’s group reported that plaque-filled arteries in mice given the nanoparticle were 16 percent more open than arteries in mice with no treatment, and 12 percent more open than in mice given a systemic statin. More work is needed to show whether these modest gains would translate to a reduced risk of heart attacks and strokes.

Others are using plaque-targeting nanoparticles to deliver anti-inflammatory drugs similar to methotrexate, which is used as a treatment for rheumatoid arthritis. The side effects of drugs like this, given systemically, are generally severe: vomiting, hair loss and “brain fog,” to name a few.

“If someone with rheumatoid arthritis comes into your office completely crippled, it’s worth all the side effects to put them on an anti-inflammatory drug,” Tabas says. “But imagine someone with some risk factors for heart disease who feels great. They’re not going to put up with these side effects.”

Tabas thinks that drugs that work distinctly from traditional anti-inflammatory drugs and promote resolution of inflammation and healing, known as pro-resolving drugs, could be perfect candidates to tack on to nanoparticles because they would make possible lower doses with fewer side effects.

He’s awaiting the results of two large clinical trials testing non-nano-versions of the drugs methotrexate and anti-IL1 beta. It remains to be seen whether they’re effective at clearing plaques and how severe the side effect are. If the drugs are effective, even with some side effects, Tabas says, it will give weight to his approach: Activating pro-resolving pathways using targeted nanoparticles.

Tabas and his collaborator Omid Farokhzad at Harvard University encapsulate their nanoparticles with a small section of a protein called annexin A1, which helps resolve inflammation and promote healing. His hope is that delivered only to an atherosclerotic plaque, the drug won’t have the host of side effects that other immune blockers have.

Destination: vessel wall
The inflamed vessel wall around an atherosclerotic plaque goes through several changes in addition to the accumulation of belligerent immune molecules. As vessel walls are stretched and inflamed, the structural protein collagen, meant to keep the vessels taut and tubular, becomes exposed the way the threads of a tire begin to appear as it wears down. Scientists are using the exposed collagen to their advantage. Nanoparticles with a tag recognizing the collagen end up at plaques. But it’s not as easy as affixing a GPS destination to the particles, says vascular surgeon Melina Kibbe of Northwestern University Feinberg School of Medicine in Chicago.

“It took us over a year of trying to find the right targeting [molecule] that would work,” Kibbe says. Her nanoparticle combines a collagen-binding protein with nitric oxide, a molecule that stimulates the growth of new cells at wounds. To maximize the surface area of the drug that contacts the vessel wall, Kibbe’s team arranged the molecules in a line, forming a nanofiber, rather than a sphere. As the fiber is swept through the bloodstream, it binds to exposed collagen, anchoring the nitric oxide in place to spur healing of the artery.

Kibbe and colleagues added fluorescent tags to the nanofibers and showed that the fibers congregated at injured spots on mouse arteries within an hour of injection. The tagged particles remained there for three days and the treated vessels ended up 41 percent more open, the researchers reported in the March Antioxidants & Redox Signaling.
Tabas also uses a collagen-binding protein, one that is organized in a more spherical shape, to get the piece of annexin A1 to atherosclerotic plaques. In mice, the particles stayed in the plaques up to five days after treatment, shrinking the plaque by more than a third, his team reported in Science Translational Medicine in 2015. By comparison, some circulating statins last less than a day in the blood.

Rather than targeting proteins or immune cells, scientists at Harvard’s Wyss Institute for Biologically Inspired Engineering have designed nanoparticles that are activated by the physical squeeze that comes with being swept through a narrowed artery. When the shear force around them increases, a cue that a plaque is present, the nanoparticles release their payload: a clot-dissolving drug called tissue plasminogen activator. The researchers reported late last year in Stroke that the nanoparticle, coupled with a stentlike device placed in the artery, increased the survival rate to more than 80 percent in mice that normally die of a clot entering their lungs.

Pathway to patients
Nanoparticles currently in development for cardio-vascular disease are still in animal testing. While no one has seen major side effects or toxicity in the animal trials so far, it remains a concern with a class of medicines that is so new.

“We sometimes get so wrapped up in exuding only the good stuff about nanomedicine that we forget we also have to look at the side effects,” Dhar says.
Another challenge for atherosclerosis drugs is determining who would benefit from treatment. Kibbe imagines her particles being used first in patients with severe atherosclerosis who receive stents or other invasive procedures to clear their plaques. The procedures are intended to help, she says, “but they actually are so traumatic that they cause injury to the vessel wall.” Due in part to this renewed buildup in the arteries, people who have had one heart attack are at higher risk for a second. Even among people who have a permanent stent put in, which is designed to keep part of an artery clear, up to 20 percent become reblocked. Giving these patients nanoparticle-based drugs could keep them healthy, Kibbe says.

Taken to the next level, nanomedicines “certainly might be able to prevent plaques,” she adds. Tabas imagines his nanoparticles given as a once-a-month injection, but that’s speculation.

Moving to test nanoparticles as a preventive — in the huge percentage of the population at risk for athero-sclerosis — is probably a long way off, Mulder says. According to the U.S. Centers for Disease Control and Prevention, around half of all adult Americans have one of the top risk factors for cardiovascular disease.

“I really don’t foresee that you would start preventively treating patients who don’t have symptoms with nanoparticles,” Mulder says. “But to take a person who’s hospitalized after a heart attack and stick a needle in their arm and infuse nanoparticles, that’s not hard.”

Once a few drugs have been validated as working in clinical trials, researchers expect progress to speed up, since the drug cargo on a nanoparticle engineered to target a plaque could easily be switched out for other drugs. Designing the particles, says Moghe, “is almost like building with pieces of Lego.”

This article appears in the June 11, 2016, issue of Science News with the headline, “Nano for the heart.”

Editor’s Note (revised): This article was edited on July 1 and again on July 2, 2016. Due to a misunderstanding by the writer, a quote in the original article mistakenly implied that researcher Ira Tabas of Columbia University was referring to problems with statins. He was, in fact, referring to problems with anti-inflammatories. He is not a critic of statins. Additional changes were made to clarify the activity of annexin A1. It is not a traditional anti-inflammatory agent, as was stated in the article, but what is called a pro-resolving molecule. Tabas did not develop the nanoparticles he works with, as was implied in the original. We now credit the researcher who developed those nanoparticles.