On Saturday, Al-Qassam Brigades, the armed wing of the Islamic Resistance Movement (Hamas), launched a large-scale surprise attack on Israel, resulting in a significant number of casualties and penetrating multiple military bases and Israeli settlements. Israel immediately declared that Israel is now "at war" and vowed to "take revenge" on the Hamas militants. This event is undoubtedly the most serious conflict between Israel and Palestine in over a decade, with both sides trapped in a vicious cycle of violence, jeopardizing the fragile geopolitical stability in the Middle East.
The re-eruption of the Israel-Palestine conflict is regrettable, and both sides bear responsibility. Israel's illegal occupation of Palestinian territories and its refusal to accept the "two-state solution" serve as the root causes of the conflict. However, new dynamics in the Palestinian, regional and international situation have acted as the trigger for this latest outbreak.
Firstly, Hamas launched the attack in retaliation for the hardline policies and extremist actions of Israel's far-right government against the Palestinians. Since the Netanyahu government came to power, it has consistently challenged the Palestinian redline and ultimately fueled Palestinian anger. Hamas named this military operation the "Al-Aqsa Flood," highlighting its religious significance and revengeful intent.
Secondly, Hamas sought to counter the marginalization of the Palestinian issue. Recently, Saudi Arabia has been negotiating a "normalization" deal with Israel and has come close to an agreement brokered by the US. Saudi Arabia holds a prominent position in both the Arab and Islamic worlds, and once it establishes diplomatic relations with Israel, the Palestinian cause is likely to be greatly impacted.
Furthermore, Hamas aimed to maintain its leadership position in the armed resistance movement of Palestine. In recent years, Palestinian armed resistance has been led primarily by emerging small-scale militant groups like the "Lions' Den" in the West Bank, challenging Hamas' leadership among Palestinians. It was necessary for Hamas to defend its leadership position through a major, attention-grabbing attack.
Lastly, the economic situation in the Gaza Strip was on the brink of collapse, motivating Hamas to seek a way out for survival.
Judging from the background of the incident, it is clear that the US also has a looming presence and certain responsibility in the bloody conflict.
First of all, the US abandoned justice by supporting Israel in its conflict with Palestine and condoning Israel's behaviors, which eventually led to this tragedy. Since the beginning of this year, the US, which claims to be the mediator for peace in the Middle East and the most important ally of Israel, has not fulfilled its obligation to promote justice and prevent tensions from escalating. Instead, it has become an accomplice in stirring up the conflict between Palestine and Israel.
Second, the Biden administration has chosen a time like this to desperately push for the normalization of relations between Saudi Arabia and Israel, with the main purpose of boosting Biden's votes in next year's election. It has been acting poorly in Middle East affairs. Therefore, the Biden administration is trying to expand the results of the Abraham Accords to highlight the "fruits of peace" in the Middle East. However, such a "peace in the Middle East" that the US has been showing off has led to an unprecedented threat to the survival of the Palestinians and ultimately led to a bloody conflict. The current escalation of tensions and violence proves that a Middle East peace plan without the two-state solution will only intensify conflicts and hinder peace.
Finally, the US has its own intentions by pushing to improve relations between the Arab countries and Israel - to establish a new political and military alliance against Iran, enhance its ability to control the situation in the Middle East, and, take a longer view, to try to create a coterie to marginalize China's influence in the Middle East.
The "peace" promoted by the US in the Middle East is likely to bring more divergences, contradictions and conflicts to the region. If the US continues to have a bias toward Israel, it will lead the peace process in the Middle East astray, and the Israel-Palestine conflict will recur once and again, while peace in the Middle East will become only castles in the air.
Three of China's science and technology (S&T) clusters are among the world's five biggest S&T clusters as announced by the World Intellectual Property Organization (WIPO).
Wang Wenbin, spokesperson of the Foreign Ministry, said on Monday during a routine press conference that the achievement showed the success of China's measures to encourage relevant regions to leverage their strength as reservoirs of innovation factors and increase their ability to innovate and boost economic growth.
On September 20, the WIPO released the Global Innovation Index 2023, which showed that three Chinese S&T clusters - Shenzhen-Hong Kong-Guangzhou, Beijing as well as Shanghai-Suzhou - were among the world's top five.
In addition, the GII identified 24 S&T clusters in China, up from 21 in 2022, as the country is now home to the greatest number of S&T clusters, said the WIPO.
Wang said that the achievement showed that relevant regions have used their advantages of innovative factors, and this is having a positive effect.
"Since the first edition of the GII was released in 2007, China has been on the list at various ranks more and more frequently, reflecting the continuous improvement of China's innovation-driven development," said Wang.
Data from the National Bureau of Statistics showed that China's innovation-driven index reached 336.3 in 2022, up 15.5 percent year-on-year, and social research and development investment surpassed 3 trillion yuan ($410.37 billion) for the first time, ranking second worldwide, said Wang.
Daren Tang, director-general of the WIPO, said that China has become a major contributor to international intellectual property work, and has successfully transformed itself into a global center of innovation, creativity and technology.
Wang reaffirmed that innovation is attached with international cooperation, openness and sharing. "China will keep implementing win-win strategy of opening-up, improving openness, promoting international communication and cooperation in science and technology, and building an open, fair, just and non-discriminatory environment for development," he noted.
Shares of the heavily indebted Evergrande Group closed up about 28 percent on Tuesday as the company resumed its trade on the Hong Kong Stock Exchange, several days after its founder Hui Kai Yan has been subject to mandatory measures in accordance with the law due to suspicion of violating law and committing crimes.
Shares of Evergrande jumped as much as 42 percent during Tuesday’s trading. Another Evergrande stock, Evergrande Property Services Group, closed down about 3 percent.
Real estate and property management services stocks fell on Tuesday’s closing, with Zhenro Properties Group dropping about 9 percent and Country Garden Services Holdings Co falling about 7 percent.
Last week, China Evergrande said it received notification from relevant authorities that Hui Ka Yan, an executive director of the company and chairman of the board of directors of the company, has been subject to mandatory measures in accordance with the law due to suspicion of criminal wrongdoing.
"There is currently no other inside information in relation to the company that needs to be disclosed," Evergrande said in a statement to the Hong Kong Stock Exchange on Monday.
In September, several staff working in the wealth management unit of the crisis-hit property developer were placed under a criminal probe.
“The resumption of trading of two Evergrande stocks today has attracted much attention, on the one hand, because investors are concerned about Evergrande's current operating conditions and capital market performance, on the other hand, there is no trading in the A-share market due to holidays, and the Hong Kong stock market is more able to see the market performance of real estate stocks,” Yan Yuejin, a research director at Shanghai-based E-house China R&D Institute, told the Global Times on Tuesday.
Yan noted that Evergrande shares had better-than-expected performance, which was in line with the laws of the capital market. Investors will continue to pay close attention to the situation of Evergrande's real estate projects, the expansion of its property services sector and the development direction of new-energy vehicles, he added.
Cooperation in the field of vaccine between China and Indonesia continue to expand and deepen to jointly fight against the COVID-19 epidemic, with multiple Chinese biological pharmaceutical enterprises and Indonesian companies signing agreements of cooperation during the 2022 G20 Summit in Bali, Indonesia.
During the summit, Indonesian biological pharmaceutical company PT Etana Biotechnologies Indonesia (Etana) signed agreements with three Chinese companies including CanSino Biologics Inc, Walvax Biotechnology Co, and Abogen Biosciences.
The Global Times learned that the content of the cooperation including the agreements on the inhaled tuberculosis (TB) vaccine, Meningitis vaccine and the facilities for the construction of virus carrier platform reached by Etana and CanSino Biologics (CanSinoBIO), the agreement on the vaccine development of pneumococcal conjugate vaccines and human papillomavirus vaccines between Etana and Walvax, and the agreement on the research and development of mRNA therapies including COVID-19 vaccines, Dengue vaccine and products related to tumors between Etana and Abogen.
According to Nathan Tirtana, founder and CEO of Etana, the company hope to take advantage of this opportunity to help the Indonesian Ministry of Health achieve its goals and ensure the fair distribution of vaccines, medicines and medical devices among different countries, especially the developing countries.
The Global Times learned from CanSinoBIO that the two companies will promote joint development and commercialization of innovative vaccine products based on their respective advantages and help Indonesia build a regional vaccine production center.
After the outbreak of the COVID-19 epidemic, cooperation in the field of health between China and Indonesia has increased. Particularly, the cooperation in vaccine has always been at the forefront of the world.
China was the first country to cooperate with Indonesia in the research and development of vaccines and specific medicines for COVID-19. China has also supported Indonesia in establishing a regional vaccine production center and is one of the largest suppliers of COVID-19 vaccines to Indonesia. Meanwhile, Indonesia was also one of the first countries to provide material assistance to China after the COVID-19 outbreak.
So far, COVID-19 vaccines of multiple Chinese companies including Sinovac Biotech, China National Biotec Group (CNBG), CanSinoBIO and BioKangtai have been approved for use in Indonesia.
Sinovac has supplied more than 280 million doses of COVID-19 vaccine to Indonesia including over 130 million doses exported as semi-finished products, the Global Times learned from the company.
BioKangtai started production of the adenovirus vector vaccine for COVID-19 in February of 2021, and the vaccine was approved for emergency use in Indonesia on October 31, 2021. The company signed a purchase agreement on the vaccine with an Indonesian partner in November 2021. Over 30 million doses of the company's adenovirus vector vaccine were exported to Indonesia in 2021.
In March this year, CanSinoBIO's adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) was approved by BPOM Indonesia as booster shots following inactivated vaccine, while CNBG's inactivated vaccine, which had previously been approved as emergency use in Indonesia, was also approved there in March as a heterologous booster.
Apart from the cooperation in the combat against COVID-19 between the two countries, Chinese and Indonesian experts and scientists of TB and respiratory infectious diseases also discussed and shared their latest research results on the elimination of TB with innovative vaccine technologies during a forum in Bali on Wednesday.
The technology used in CanSinoBio's adenovirus vector vaccine can also be used in the TB vaccine, the company said at the forum.
Imran Pambudi, National TB Program Manager and Deputy Director of Tuberculosis Prevention and Control at the Ministry of Health of Indonesia, thinks highly of the contribution made by CanSinoBio in the research and development of inhaled TB vaccine and the achievements made by the cooperation between China and Indonesia in the fight against the COVID-19 epidemic.
Chinese researchers have successfully proven the existence of the very massive first-generation stars, which are the oldest stars in the universe. After years of work, they have discovered the chemical signature of these stars for the first time, a breakthrough that holds significant importance for understanding the origins and evolution of stars.
The research findings were published online in the international scientific journal Nature on Wednesday, providing an answer to the longstanding question in the scientific community regarding the existence of the very massive first-generation stars during the early stages of the universe, approximately 13.8 billion years ago.
The researchers from the National Astronomical Observatory of China analyzed over 5 million stellar spectra obtained from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) in North China's Hebei Province. Through this analysis, they identified a star located in the halo of the Milky Way, approximately 3,327 light-years away from Earth, with a mass approximately half that of the Sun.
This star exhibited a metal-poor characteristic, indicating its alignment with the characteristics of second-generation stars formed after the demise of the first-generation stars.
The first-generation stars were supermassive stars with masses ranging from 140 to 260 times that of the Sun, making them the oldest stars in the universe. These stars existed over 13 billion years ago but had short lifespans of only 3 million years before undergoing supernova explosions, giving rise to the second-generation stars observed by the researchers.
By observing and studying the second-generation star, the researchers will be able to infer the mass and characteristics of its preceding generation of stars, said Xing Qianfan, a deputy researcher from National Astronomical Observatory of China.
Xing said that the research team will utilize the massive dataset from LAMOST to deduce the distribution of stars with different masses in the earliest first-generation stars. This will enable them to explore the evolutionary history of the entire universe and the evolution of stars.
Members of a post-disaster reconstruction working group recently walked into the flooded Xinle village, located in Wuchang city of Northeast China's Heilongjiang Province, to investigate and identify flood-hit houses. According to estimates, review of all the homes in 24 townships will complete in three to four days.
In the aftermath of Typhoon Doksuri, Heilongjiang and multiple other regions in China, including Beijing and North China's Hebei Province, have ramped up efforts to restore order for people living in inundated areas.
In Guyu village, Wuchang city, more than 2,000 mu (133 hectares) of corn has been soaked in water. The local emergency department has transferred large-scale pumping facilities to carry out 24-hour drainage of farmland water. Wuchang has mobilized six post-disaster technical guidance groups to provide technical guidance for villagers in 24 towns and villages for draining field water and spraying pesticides to prevent and control pests and diseases.
At Sunday midnight, a train carrying 690 tons of Wuchang rice left the local train station. This was the first train of food supplies transported from Wuchang station after the resumption of the railway, which was cut off by flooding.
People wearing protective gear for disinfection in Shangzhi, one of the seriously stricken cities in Heilongjiang, have completed three rounds of disinfection across more than 320,000 square meters of flood-affected areas.
In response to the flooding of farmland, Hebei Province organized experts and technicians to head to the front lines of the disaster resistance to guide post-disaster agricultural production. At the same time, the province promptly redirected 1.06 million kilograms of seeds of short-growth crops such as cabbage and spinach to prepare for replanting to minimize farmers' losses.
In Zhuozhou, Hebei, four shopping malls and 29 supermarket chains have resumed operation and schools are also stepping up efforts to clean up sludge and disinfect areas to ensure the timely return of students to campus in September. Hebei officials had said earlier that it plans to complete the reconstruction in two years and will take efforts to ensure affected residents are able to return to their homes prior to the approach of winter.
In Beijing, the lives of local people have gradually resumed. Most recently, six A-level scenic spots in the Fangshan district have reopened. The Fangshan district has labeled regions into three colors based on the severity of flood impact - red, yellow and green - serving as a more efficient method to solve disaster relief work. Officials from Beijing said they have mapped out a plan to improve the city's disaster relief capabilities and the development of flooded regions over the next three years.
Not only have local departments in flood-stricken regions moved quickly to deal with disaster relief, the Ministry of Agriculture and Rural Affairs urged agricultural departments at all levels to make efforts to alleviate disaster and promote vegetable production.
Meanwhile, to deal with future emergent heavy rainfall and floods and improve the adaptability of urban infrastructure to withstand extreme weather, observers have suggested that the impact infrastructure in some high-risk areas may face from extreme rainstorms brought by climate change be re-evaluated to determine whether the existing level of defense needs to be upgraded, as well as to improve the vigilance and preparedness of local departments and strengthen resilience in the face of a changing climate.
Some water control experts said this round of heavy rainfall reminded some places to make up for the shortcomings of local flood control projects. They pointed out some northern cities in recent years have relaxed their vigilance and constructed flood storage areas in a disorderly manner, such as when building houses, locals may take soil from earth dams, which weakens the flood control capacity of levees.
Sun Shao, a senior researcher at Chinese Academy of Meteorological Sciences, told the Global Times that challenges encountered by cities in northern China due to deficient drainage systems, limited river networks, and inadequate urban green space planning, makes them highly vulnerable to flooding during unexpected heavy rainfall.
Cheng Xiaotao, a deputy chief engineer from the China Institute of Water Resources and Hydropower Research (IWHR), told the Global Times that besides flood control projects, effective communication about the severity of extreme weather among meteorological, hydrological and water conservancy departments is crucial. For instance, emergency command departments can compile data about the specific precipitation and flow rate of rivers and inform the public in detail.
As heavy rainfall events intensify, there is a higher probability of sudden flash floods, mudslides, and other disasters, Sun said. He explained that reviewing historical patterns, during the 1950s to 1970s, the main rain belt was concentrated in northern China, which later shifted to southern China in the 1980s and 1990s. Since the beginning of the 21st century, the main rain belt has gradually moved northward again.
China is considering holding degree holders who use artificial intelligence (AI) to ghostwrite their theses legally responsible. The draft of the Degree Law was submitted to the Standing Committee of the 14th National People's Congress, China's top legislature, for deliberation on Monday.
The draft lays out legal responsibilities for actions such as degree holders using or impersonating another's identity to gain admission qualifications, employing artificial intelligence to author thesis papers, and institutions granting degrees unlawfully, as reported by the media on Monday.
Academic misconduct includes plagiarism, forgery, data falsification, using artificial intelligence to produce a thesis, impersonating another's identity to obtain admission qualifications, and securing admission qualifications and graduation certificates through illicit means like favoritism and cheating. The draft also addresses other illegal or irregular behaviors that, when exhibited during the study period, should prevent the awarding of a degree.
The draft states that if an individual who has already obtained a degree is found to have used illegal means to do so, the degree-granting institution must revoke the degree certificate. This decision should be made following a review by the degree evaluation committee.
House dust mites surround us. Burrowing cheerfully into our pillowcases, rugs and furniture, the mites feast on our dead skin cells, breaking them down into small particles they can digest.
Now that your skin is crawling, relax. If you’re like most people, you will never know they are there.
An unlucky minority, however, is very aware of dust mites. Some of these unfortunate folks have a simple dust allergy. But others have an additional condition called atopic dermatitis, often referred to as eczema. They react to the presence of dust — or rather, dust mites — with hideous itching and redness. It wasn’t totally clear what, exactly, caused people with dermatitis to react so badly to dust mites.
It turns out that these people react not to the dust mite, but to its dinner — to the breakdown products of the person’s own skin. The finding helps explain why people with atopic dermatitis react so badly to dust mites, and it provides several new options to help treat the itch. It also resolves a decade-long debate in dermatology — why people with dermatitis are scratching in the first place.
Inside out vs. outside in Atopic dermatitis is known for producing red, cracked and dry skin and, of course, the itching. People usually get diagnosed in childhood. Sometimes it goes away as kids get older, but it still affects between 9 and 30 percent of adults in the United States. Patients with dermatitis who react to dust are told to avoid dusty places and use special pillowcases. For the worst outbreaks, they are often prescribed a steroid cream. In some cases, they can end up in the hospital.
But what causes the itch in the first place? For the past 10 years, scientists have been scratching away at two hypotheses — one called “inside out,” and the other called “outside in.”
The “inside out” hypothesis came first, explains Graham Ogg, a dermatologist with the Medical Research Council Human Immunology Unit at the University of Oxford. The idea was that the immune system was overreacting to normal things: Dermatitis was an inside problem with the immune system itself.
In 2006, however, researchers reported in Nature Genetics that deficiencies in a protein called filaggrin were associated with atopic dermatitis. Now, it’s estimated that 20 to 30 percent of people with atopic dermatitis are also deficient in filaggrin, a protein in the outermost layer of the skin.
“It’s important for moisturizing the skin, keeping the skin hydrated,” explains Ogg. If people with dermatitis are deficient in filaggrin, then “the primary problem isn’t the immune system, it’s the barrier function in the skin.” If the barrier breaks down, more irritants can get in, prompting the immune response and the intolerable itch. So, the “outside in” hypothesis was born. In this view, the immune system wasn’t overreacting; instead it was reacting properly to the avalanche of aggravations it was faced with.
But what if these two hypotheses weren’t at odds, Ogg wondered, and instead were two sides of the same coin? To find out, Ogg and his group began by looking at a molecule called CD1a. This molecule is produced in the skin, and specializes in presenting bits of foreign matter to T cells — the immune system responders that mount attacks against foreign invaders.
It turns out that the CD1a molecules responded to extract-of-house-dust-mite — the delightful concoction that people get scratched with when they are tested for a dust allergy. And when they react, it’s because of CD1a molecules.
To find out if people with dermatitis had more CD1a than people without the condition, the scientists used suction to give eczema sufferers and healthy volunteers large blisters on their arms. The blisters were harvested for their skin and blood cells. And in patients with atopic dermatitis, those skin and blood cells were stuffed with CD1a, far more than in healthy controls.
But what was the CD1a reacting to? Usually CD1a senses fat molecules, presenting bits of them to the immune system to prep it for attack. Ogg and his group assumed that if they analyzed house dust mites, they would find the lipid or fat responsible. Not quite. Instead, they found a protein called phospholipase A2. Phospholipase is an enzyme that dust mites produce that breaks down skin cells, producing fat molecules the mites can digest. CD1a, it turns out, responds to those lipids — reacting to the house dust mite’s dinner. Reacting, really, to the breakdown products of human skin.
This seems like support for the “inside out” hypothesis. CD1a is part of the immune system, and the immune system does seem to be over-reacting.
Filaggrin also had a role to play. The protein doesn’t just create a barrier to keep the skin moisturized — it’s also anti-inflammatory, Ogg’s group showed. If a skin sample was challenged with essence of dust mite, adding filaggrin could damp down the immune response. But eczema patients with low or no filaggrin had no defense. Their skin was more permeable, and there was nothing to stop the inflammation. The “outside in” hypothesis —the idea that the barrier function is the broken part of the system – is true too. Ogg and his colleagues report their findings February 10 in Science Translational Medicine.
“It links together the observations very nicely,” says Muzalifah Haniffa, a dermatologist at Newcastle University in England. It never was a matter of “inside out” or “outside in.” The two are inextricably linked.
Eat like a dust mite, sting like a bee? So, to recap: As dust mites chow down on human skin, they cause damage to the cells. People with dermatitis have immune systems that detect the products of the damage and react, causing itching and pain. Filaggrin, when present, can tamp down the response. But when absent, nothing stops the itch.
The study shows filaggrin is far more than a simple barrier protein. Instead it directly affects immune responses in the skin, something that’s never been seen before, Haniffa notes.
This isn’t the first time that Ogg’s group has come across phospholipase A2. “Bee venom also contains phospholipase. In fact it contains massive amounts,” Ogg explains. Knowing that bee venom and dust mites have something in common helps scientists to understand one of the ways that the immune system senses damage to skin — and gives them another option to consider for treatment.
Right now, clinical trials are focused on stopping the inflammatory proteins produced further down the line. But, Haniffa says, scientists might try methods to increase the amount of filaggrin in the skin — beefing up the barrier against dust mite incursions and reducing the immune response at the same time. Other drugs or creams could target phospholipase A2, inactivating it. Without phospholipase, dust mites wouldn’t be able to break down skin cells, halting any immune reaction.
And that means we can hope for a new day. One with, hopefully, no itch.
A conspicuous “chirp” heralded the first detection of gravitational waves. But some future measurements could be more like hushed murmurs.
Scientists may soon be able to tease out a faint signal of gravitational waves from black hole collisions too distant to be detected directly, scientists with LIGO, the Advanced Laser Interferometer Gravitational-Wave Observatory, report in the April 1 Physical Review Letters. A detection could come in as few as three years — considerably faster than scientists had dreamed possible, the new analysis suggests. When LIGO detected the stretching and squeezing of spacegenerated by a pair of merging black holes, scientists were wowed (SN: 03/05/16, p. 6). The signal stood out well above spurious bumps and wiggles in the data, which are ever-present in LIGO’s extremely sensitive detectors. It rose swiftly in frequency — when converted to sound waves, it was reminiscent of a bird’s chirp — a hallmark of the black holes’ inward-spiraling cosmic dance.
But such obvious swells are outnumbered by a sea of smaller ripples. With these ripples, “you’re looking at black holes which are much farther away,” says LIGO spokesperson Gabriela González of Louisiana State University in Baton Rouge.
LIGO is not sensitive enough to detect these waves outright, but by comparing the data recorded by LIGO’s separate detectors — one in Louisiana and one in Washington state — scientists could identify patterns revealing the presence of the background waves. Such a measurement would allow scientists to compare black hole populations of different ages and could help nail down the conditions under which black hole pairs form.
“My honest opinion was, ‘I’m going to be lucky if we see this result in my lifetime,’” says physicist Emanuele Berti of the University of Mississippi in Oxford, who is not involved with LIGO. He has changed his tune. “Nature was good to us, and now we think that we’re going to be able to see them pretty soon.”
That’s because new estimates of the rate of such black hole mergers are higher than many scientists expected. Using models of binary black hole populations combined with LIGO data, scientists find that LIGO could be sensitive to nearly 2,000 such black hole mergers a year, meeting their most optimistic predictions.
The possibility shows LIGO’s versatility, González says. “There are good prospects of all kinds — it’s not just detections of single events.”
For centuries, the mouth and the body have been disconnected — at least when it comes to health care. Through the Middle Ages and beyond, teeth fell under the care of barbers, who could shave a customer and pull a molar with equal skill. In the 1700s, French surgeon Pierre Fauchard published the Treatise on Teeth, establishing dentistry as its own science.
Across the channel in England, as physicians gained stature in the 19th century, surgeons and dentists engaged in a power struggle. In the modern United States, after medicine became linked to employer insurance and Medicare, the fissure between medicine and dentistry widened. Insurance coverage began at the throat. So when Salomon Amar, a periodontal specialist at Boston University, began exploring links between oral bacteria and heart disease in animal studies in the late 1990s, reactions were lukewarm. “Many cardiologists thought we were a bit crazy,” he says. Skepticism still abounds, but the same molecular tools that have dramatically changed understanding of the gut microbiome are now allowing scientists to track and examine bacteria in the mouth. Advocates of a connection between the artery disease atherosclerosis and microbes are hoping to find convincing proof of their suspicions, while exploring links between ailing gums and other conditions, including cancer, arthritis, diabetes and even Alzheimer’s disease.
The work has profound implications for public health, given that more than 65 million American adults are thought to have periodontal disease, which occurs when bacterial overgrowth inflames the gums and can lead to erosion of gums and bone. If it turns out that periodontal decay drives other diseases, doctors would have a new, and relatively simple, means of prevention.
Wenche Borgnakke, a dental researcher at the University of Michigan in Ann Arbor, has been making this case for years, citing “solid evidence that periodontal treatment has an effect on systemic disease.” She points to a study published last year in the journal Medicine comparing patients on dialysis who received periodontal treatment with those who did not. Those getting treatment had an almost 30 percent lower risk of pneumonia and hospitalization from infections. Another study published earlier this year found that gum disease is associated with a roughly 10 percent higher mortality over 10 years among patients with kidney problems. Researchers working in the field often point out that about half of all deaths from atherosclerosis occur in people who do not have any classic risk factors, such as high cholesterol or obesity. Something else — something as yet unknown — is also contributing to heart disease. Even the root cause of many cancers is largely unexplained. Most women with breast cancer, for instance, have no risk factors other than older age. Says Jean Wactawski-Wende, a cancer epidemiologist at the State University of New York at Buffalo: “The more I work on oral health and cancer, the more I think, ‘Oh my gosh, I’ve got to keep my teeth clean.’ ”
Foul mouth To date, more than 500 scientific papers have weighed in on the connection between atherosclerosis and gum disease. Officially, the theory remains “biologically plausible,” but unproven, according to the American Heart Association’s formal position. Some concepts are undisputed: For one, the microbes that live in the mouth don’t stay in the mouth. The simple act of brushing allows bacteria clinging to the teeth and gums to leak into the bloodstream.
As the posters at the dentist’s office attest, neglected oral hygiene encourages bacterial growth, allowing the microbes to breed on and between teeth, as well as under the gums. What the illustrations don’t show is that these microorganisms form a biofilm, a tough microbial community bound together with sugar molecules in a thin coating. This is the plaque your dentist warns you about.
“If you do not brush your teeth, it will sit there and accumulate. As that plaque gets thicker and thicker, there is less and less oxygen in the deepest layers,” Borgnakke says. Safely sheltered, the innermost plaque starts to favor anaerobic bacteria, which, when they escape into the blood, can survive in the oxygen-starved nooks and crannies deep inside the body.
As plaque builds up, gums get irritated, swell and draw more blood into the distressed tissue. Eventually, chemicals produced by the biofilm break down the thin layer of cells that form a boundary between the gums and the blood vessels. Periodontitis officially occurs when gum and bone tissue starts to deteriorate. The space between the tooth and gums forms a pocket; dentists measure the depth of the pockets to determine the severity of infection. “We usually think of an infection as some bug from the outside that attacks the body,” says Borgnakke. “In this case, it’s an internal infection.”
It was once thought that only a handful of microbial species were involved in the development of periodontitis, but the latest studies have revealed that many of the microbes responsible for gum disease come from “previously underappreciated species,” according to a 2015 report in Advances in Experimental Medicine and Biology. Because many bacteria resist growth in a laboratory, only a small portion of some 500 to 700 species of oral microbes have been well characterized.
One aggressive pathogen, an organism called Porphyromonas gingivalis, has antennae that stick out and can pry open the space between two cells, Borgnakke says. “This is a really, really nasty bug.” Within minutes of invading blood vessels, P. gingivalis and its gang of accomplices are ferried to distant sites, where they can set up outposts. “Bacteria that normally live in the mouth are found in every organ in the body, and even muscle cells,” she says.
The body doesn’t take this assault lying down. The immune system gets agitated and tends to stay in a state of slow simmer. But the bacteria that cause periodontal disease have a knack for turning the body’s defense on its head, according to a 2015 review in Nature Reviews Immunology. Case in point: Common white blood cells called neutrophils are deployed to the failing gums — where they not only fail to control the infection, but also end up releasing enzymes that further destroy tissue. The immune system also releases an avalanche of chemicals designed to help control the infection. For example, the liver starts producing C-reactive protein, a molecule that has such an important role in signaling the rise of heart disease that it is considered a risk factor by some researchers.
Smoking gums Even after two decades of study, it has been hard to directly link periodontal dynamics to blocked arteries, despite hundreds of studies that have tried. There are seemingly smoking guns. Among them, P. gingivalis is commonly found lodged inside arteries, and the development of plaque in the arteries is driven by many of the same inflammatory chemicals triggered by periodontal disease. Many researchers also point to C-reactive protein, which is probably present long before atherosclerosis develops. But people with periodontitis also tend to share well-known risk factors for heart disease, such as high cholesterol, smoking and obesity. A sugar-sweetened diet that promotes oral decay is no friend to your arteries. The relationship is also hard to study because both atherosclerosis and periodontitis unfold slowly over time, so epidemiologists must rely on indirect measures of disease.
Experts line up on both sides. “If there is an association, it’s a very weak one,” says Peter Lockhart, former chairman of oral medicine at Carolinas HealthCare System in Charlotte, N.C. An expert on heart valve infections, Lockhart was one of the leaders of an American Heart Association panel that reviewed the evidence before releasing an official statement in 2012. “I think the question has been answered for now,” he says. For cardiologists, the threat from periodontal disease “pales by comparison to the known risk factors that need to be focused on.”
Others aren’t ready to abandon the hypothesis. In 2015 in the journal Atherosclerosis, a team of German researchers reviewed studies released since the AHA statement. They pointed out that a large body of work published in the previous three years, using more refined tools and study design, shows that a connection between the two “cannot be ruled out.” One study, published in PLOS ONE in 2014 from researchers at the University of Florida in Gainesville, Meharry Medical College in Nashville and elsewhere, claims to have found a causal relationship, at least in mice. A significant portion of animals that drank water containing P. gingivalis experienced inflammation and bacterial accumulation in their hearts and blood vessels. Very few unexposed animals did.
Into the brain While the artery studies carry on, new research is finding oral bacteria in surprising places. The brain, for one. In 2013, a team of researchers from Florida and the United Kingdom compared brain tissue samples from 10 people who had died from Alzheimer’s disease with samples from 10 people who had died from other causes. Signs of P. gingivalis infection showed up in four Alzheimer’s patients but in none of the comparison patients, the researchers reported in the Journal of Alzheimer’s Disease. In a follow-up experiment published in the same journal, the researchers inoculated P. gingivalis into the mouths of 12 mice genetically protected from Alzheimer’s. Six months later, evidence of the same bacteria appeared in the brains of three-fourths of the animals. Another type of oral bacteria, spirochetes called Treponema denticola , “are already known to enter the brain,” says neuroscientist Sim Singhrao of the University of Central Lancashire in England. Traveling along the nerves that connect to the jaw, “they are a bit like jellyfish, crawling up into neurological tissue.” Once nestled inside the brain, oral bacteria could trigger an inflammatory chain reaction that eventually destroys certain nerve cells and leads to Alzheimer’s disease, says StJohn Crean , Lancashire’s executive dean of the College of Clinical and Biomedical Sciences. He points out that Chinese researchers, writing last year in the Journal of Periodontal Research, found that people carrying certain versions of APOE, a gene linked to Alzheimer’s, were also more likely to suffer aggressive periodontal infection. Finally, a study published in March in PLOS ONE found that among 59 people with hallmarks of Alzheimer’s disease followed for six months, those with periodontitis experienced cognitive decline at more than six times the rate as those without gum disease.
“We’ve moved on from that ‘this-can’t-be-right’ feeling,” Crean says. He is hoping to get funding for a study that would compare progression of Alzheimer’s among people who receive intensive oral hygiene, such as frequent dental-office–style cleanings, compared with those who brush and floss regularly. But he also notes that the arrow connecting gum disease and Alzheimer’s could point in both directions. “When your memory goes, you’re not going to remember to brush your teeth.”
Teeth and tumors Providing still more reason to invest in dental floss, new research is raising questions about cancer’s link to gum health. Aside from oral cancers, the cancer connection was barely on the scientific radar before 2008, when a study appeared in Lancet Oncology. Some research had suggested that gum disease is associated with higher cancer mortality, but questions remained about the influence of smoking. In the study in Lancet Oncology, researchers from Imperial College London, Harvard Medical School and elsewhere reviewed data for almost 50,000 men enrolled in the Harvard Health Professionals Follow-Up Study. That study found a small increased risk of cancer mortality in men with periodontal disease.
A second study, published in February in Annals of Oncology, found that men with advanced periodontal disease who had never smoked nonetheless had a 2.5 times higher risk of cancers associated with smoking, such as lung, bladder and esophageal tumors. The researchers hypothesize that gum disease might trigger the same sort of immune response that tobacco does. Another study examined data from more than 73,000 participants of the Women’s Health Initiative, which gathered health information from volunteers over 15 years. Participants diagnosed with periodontal disease had a 14 percent increased risk of breast cancer compared with women with healthy gums. “It’s a modest increase, but when 50 percent of adults are diagnosed with periodontal disease, you could see this becoming a very important factor for prevention,” says Buffalo’s Wactawski-Wende, who led the study, published in January’s Cancer Epidemiology, Biomarkers & Prevention.
Laboratory studies are also offering compelling evidence of associations with certain cancers. Almost a dozen studies conducted over the last five years have found one particular species of mouth bacteria, Fusobacterium nucleatum, living in seeming abundance in colorectal tumors. Like P. gingivalis, F. nucleatum thrives in diseased gums and in low-oxygen areas. Wactawski-Wende is studying samples of various tumors to look for oral organisms. Burning questions
Given that periodontal disease causes the immune system to remain in a state of irritation, other lines of research have tried to tie diseased gums to inflammatory diseases like rheumatoid arthritis and diabetes. Writing last year in the journal Mediators of Inflammation, researchers from the University of Ceará in Brazil reviewed published studies on rheumatoid arthritis, concluding that “the majority of the articles have confirmed that there is a correlation,” especially among women. Both gum disease and arthritis, they wrote, could even feed off one another, amplifying a hyperactive immune system that makes both conditions worse.
A long line of research has also examined the relationship between diabetes and periodontal disease. In 2013, Borgnakke and an international team reviewed the evidence in the Journal of Clinical Periodontology. Of the 17 studies they found to have sufficient quality, the evidence suggests that people with poor periodontal health have a greater chance of developing early symptoms of diabetes and having greater complications from the disease once it develops. But she acknowledges that diabetes, and in fact all conditions under study, have multiple causes, making the role of any one culprit difficult to determine.
It’s also hard to account for the role of genetics. “You could have two patients with the same amount of plaque. One patient will have really deep pockets [between teeth and gums], and the other one will have no consequences,” she says. “That’s why it’s so hard to say anything in general.”
Even as research continues, those involved concede that they may never satisfy skeptics, given the slim chance of ever having a long-term prospective study. That research would need to monitor the cardiac health of a large population over an extended time, half with gum disease and half without, to determine if those with periodontal problems experienced worse cardiac health. But given the length of time it takes for both gum disease and systemic disease to reveal themselves, a study would need to involve thousands of participants over many years to be definitive, Amar says. “It would be financially prohibitive.” And he points out that pharmaceutical companies, which often help fund large clinical trials, would not back a study that has no product for them to eventually sell.
“Causality may not ever be demonstrated,” he says. To most doctors, the mouth will probably remain unconnected to the body. Amar and others will nonetheless continue, in hopes their work may one day give health professionals a little more to chew on.
