Ensitrelvir cuts household COVID-19 risk when given after exposure

Ensitrelvir COVID-19 Prevention Background

The coronavirus disease 2019 (COVID-19) pandemic caused millions of deaths worldwide. Although its acute phase has waned, it continues to cause illness and death, especially in high-risk groups. This is partly due to its high mutation rate, waning immunity, and high household transmission rates of 32%-48%.

Since the use of masks and social distancing measures is not enough to completely prevent transmission, there is a need for effective preventive drugs, at least for those at increased risk. Earlier trials of nirmatrelvir-ritonavir and molnupiravir did not show significant protection against COVID-19 in exposed household contacts.

Ensitrelvir showed potent in vitro activity against multiple SARS-CoV-2 variants, including omicron. It is approved in Japan for the treatment of mild-to-moderate COVID-19 in patients aged 12 years or older. Currently, it has been approved in Japan for post-exposure prophylaxis in contacts aged 12 years or older, based on the findings of this study.

In the phase 3 SCORPIO-SR trial, it reduced COVID-19 symptoms when initiated within 72 hours of symptom onset. The phase 3 SCORPIO-HR trial demonstrated the drug's antiviral efficacy but failed to show a significant difference in time to symptom resolution.

This motivated the current phase 3 SCORPIO-PEP trial. It was conducted as a double-blind randomized controlled trial involving 2387 randomized household contacts, of whom 2041 were included in the modified intention-to-treat population. The mean age of the population was 42.4 years.

SCORPIO-PEP Trial Study Design

At baseline, all participants had a history of contact with someone with COVID-19, the index patient. All had nasopharyngeal swabs submitted on days 1, 3, 6, 10, 15, 21, and 28 for reverse transcriptase-polymerase chain reaction (RT-PCR) detection of SARS-CoV-2.

Those who were test-negative and asymptomatic at baseline were randomly assigned to receive either ensitrelvir (1,030 participants) or placebo (1,011 participants) for 5 days beginning within 72 hours after symptom onset in the index patient. The primary endpoint was symptomatic RT-PCR-confirmed COVID-19 by day 10.

This required symptomatic RT-PCR positivity within ten days of trial-drug or placebo administration. This included the appearance of one or more symptoms from a panel of 14, lasting at least 48 hours, or worsening in the case of preexisting symptoms.

Approximately 71% of participants were randomized within 48 hours of the index patient's onset of symptoms. About 37% had one or more risk factors for severe COVID-19, including obesity, smoking, and age above 65 years. Nearly 19% of index patients received antiviral therapy, mostly with ensitrelvir. Approximately 85% or more of those in each group completed the regimen.

Over 98% had antibodies to the SARS-CoV-2 nucleocapsid or spike antigens.

COVID-19 Prevention Efficacy Findings

Compared with the ensitrelvir group, the placebo group had a significantly higher rate of new COVID-19 cases (9% vs. 2.9%). The risk ratio in favor of the ensitrelvir group was 0.33, indicating a 67% reduction in relative risk in ensitrelvir recipients post-exposure, compared to placebo.

The observed reduction appears larger than reported in previous household contact PEP studies. However, comparisons of efficacy across trials should be interpreted cautiously in light of differences between trials, definitions of illness, and shorter time limits for delineating primary infection rates. Notably, these differences persisted even when adjusting for differences in the definition of COVID-19.

By day 2, the placebo group showed a rapid rise in symptomatic infections, which was both smaller and spread out over 12 days in the ensitrelvir group. The benefit appeared to be generally consistent across participants with and without risk factors, although subgroup analyses were not adjusted for multiplicity. Across the participating countries, COVID-19 incidence among household contacts was lower in the US than in Japan.

In this study, the drug maintained plasma concentrations above the estimated target concentration, compared to estimates derived from nonclinical studies. This might indicate the persistence of effective prophylaxis beyond the five-day regimen.

Viral Load and Safety Findings

RT-PCR-confirmed SARS-CoV-2 infection rates were also lower with ensitrelvir than with placebo. Among participants with baseline-positive RT-PCR, viral loads were lower, as were those among those who developed infection or symptomatic COVID-19 while on ensitrelvir.

Adverse events were similar in both groups, and neither group reported hospitalizations or deaths from COVID-19. Ensitrelvir was associated with reversible reductions in HDL cholesterol, and its use requires attention to potential drug-drug interactions because it is a moderately strong CYP3A inhibitor.

The researchers did not have data on other measures used to limit household transmission or on the difference in outcomes due to antiviral administration, which is common in Japan and was offered to 38% of patients versus 6% in the US. The risk of selecting for viral mutations associated with resistance following ensitrelvir administration could not be completely excluded due to missing viral sample data from index patients treated with ensitrelvir. Participants using contraindicated medications were also excluded, which may limit real-world generalizability in patients at risk of CYP3A-mediated drug interactions.

Ensitrelvir Post-Exposure Prophylaxis Implications

The findings suggest that when administered within 72 hours of symptom onset in a COVID-19 index patient, ensitrelvir effectively prevented symptomatic illness in household contacts and reduced the relative risk of the illness up to day 10 by 67% among participants who received at least one dose of the drug. Among high-risk participants, about 2.4% of those who received ensitrelvir developed COVID-19, compared with 10% in the placebo group.

https://en.wikipedia.org/wiki/Ensitrelvir

Ensitrelvir cuts household COVID-19 risk when given after exposure

US FDA & Japan’s MHLW accept Bayer’s FXIa inhibitor, asundexian for prevention of ischemic stroke

Bayer announced that the US Food and Drug Administration (FDA) and Japan’s Ministry of Health, Labour and Welfare (MHLW) have accepted the company’s New Drug Applications (NDA) for its investigational Factor XIa (FXIa) inhibitor, asundexian, for the prevention of  ischemic stroke in patients after a non-cardioembolic ischemic stroke or transient ischemic attack (TIA). In addition, the US FDA granted asundexian Priority Review designation.

Approximately 12 million people experience a stroke every year. Of those who survive a stroke, approximately 1 in 10 will have another stroke within 1 year, even with available secondary stroke prevention strategies.

“The acceptances of submissions in key markets represent another milestone in the development of asundexian and in our commitment to secondary stroke care. More than 90 million people worldwide are living with the consequences of a stroke, highlighting its significant impact on public health,” said Christian Rommel, Ph.D., head of research and development at Bayer`s Pharmaceuticals Division. “We are collaborating with health authorities to advance the approval process.”

Bayer is continuing to submit applications for marketing authorization for asundexian to other health authorities globally. China’s Center of Drug Evaluation has also recently accepted Bayer’s marketing authorization application for asundexian and granted it Priority Review designation.

The phase III OCEANIC-STROKE study investigated the efficacy and safety of the oral Factor XIa inhibitor asundexian 50 mg once-daily compared to placebo, for prevention of ischemic stroke in patients after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) in combination with antiplatelet therapy. It is a multicenter, international, randomized, placebo-controlled, double-blind, parallel group and event-driven study, that randomized 12,327 participants worldwide. The primary efficacy endpoint was time to ischemic stroke; the primary safety endpoint was ISTH major bleeding. The full results from OCEANIC-STROKE have recently been published in The New England Journal of Medicine.

The applications to the US FDA and to Japan’s Ministry of Health, Labour and Welfare are based on positive data from the phase III OCEANIC-STROKE study. The study found that asundexian 50 mg, significantly reduced ischemic stroke by 26 per cent in patients after a non-cardioembolic ischemic stroke or high-risk TIA compared to placebo, both in combination with antiplatelet therapy, with no increase in ISTH (International Society on Thrombosis and Hemostasis) major bleeding.

Factor XIa (FXIa) is a protein in the blood coagulation pathway with different roles in hemostasis and thrombosis. FXIa is thought to contribute to the formation of pathological thrombus growth and vessel blockage. However, FXIa has a minor role in the formation of a hemostatic plug that seals the leak at the site of vessel injury.

Asundexian is an investigational compound and has not been approved by any health authority for use in any country for any indication.

Bayer is a leader in cardiology and is advancing a portfolio of innovative treatments in cardiovascular (CV) and cerebrovascular diseases of high unmet medical need. The company has set a clear focus on developing therapies to treat such diseases (e.g., stroke, heart failure, cardiomyopathies, and chronic kidney disease) and it is our ambition to take a leading role in the care of patients with these diseases. Bayer is actively shaping the future of cardiology and neurology with a robust and diversified pipeline, strategically positioned to address critical unmet needs and drive significant long-term value. Bayer’s portfolio already includes several innovative products and compounds in various stages of preclinical and clinical development.

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses.

https://en.wikipedia.org/wiki/Asundexian

https://en.wikipedia.org/wiki/Asundexian

US FDA & Japan’s MHLW accept Bayer’s FXIa inhibitor, asundexian for prevention of ischemic stroke

Breakthrough drug reverses aging in skin and dramatically speeds healing

A drug designed to eliminate worn out, aging cells may help older skin recover from injury much faster, according to research published in Aging (Aging-US). The work, titled "Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing," suggests that targeting "zombie cells" in the skin could one day improve healing after surgery, injury, or chronic wounds in older adults.

The research team included Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Joy Ha, Jannat Dhillon, Grace H. Shin, Jack Crouch, Adam C. Gower, Sami Gritli, and Daniel S. Roh from Boston University Aram V. Chobanian and Edward Avedisian School of Medicine.

Clearing Out Aging Cells

As skin gets older, damaged cells can accumulate instead of dying off. These cells, known as senescent cells, no longer work normally, but they remain active enough to interfere with nearby tissue. Over time, they can release inflammatory signals and other molecules that weaken the skin's ability to repair itself.

The researchers tested whether ABT-263, a senolytic drug, could reduce this burden when applied directly to aged skin. Senolytic drugs are designed to selectively remove senescent cells, which have been linked to aging, inflammation, and slower tissue repair.

In the study, aged mice received ABT-263 on their skin for five days. After treatment, the skin showed fewer signs of cellular aging. When the researchers then created small wounds, the treated mice healed more quickly than untreated mice.

By day 24, 80% of the mice treated with ABT-263 had fully healed wounds, compared with 56% of untreated mice.

A Surprising Healing Boost

One of the more unexpected findings was that ABT-263 briefly increased inflammation in the skin. In many cases, inflammation is seen as harmful, especially when it becomes chronic. But in this case, the short burst appeared to help prepare the skin for repair.

The treatment seemed to wake up healing pathways that are normally sluggish in older tissue. Gene activity increased in areas tied to wound repair, including collagen production, blood vessel growth, tissue remodeling, and other processes needed to close and strengthen damaged skin.

This matters because aging skin does not just wrinkle or thin. It also becomes less responsive after injury. That slower response can increase the risk of prolonged recovery after surgery, delayed closure of wounds, and complications in people with chronic skin injuries.

Why Topical Treatment Matters

ABT-263 has drawn interest because it can target senescent cells, but oral senolytic drugs may cause side effects because they circulate through the body. Applying the drug directly to the skin could offer a more focused approach.

In this study, topical ABT-263 reduced signs of senescence in aged mice, but it did not appear to have the same effect in young mice. That suggests the treatment may be most active in older tissue, where senescent cells have built up.

The researchers believe this targeted approach could be especially useful before surgery or in people at risk for poor wound healing. Instead of waiting for a wound to struggle, a treatment might one day help prepare older skin in advance.

"Our study underscores the potential of topical senolytic treatments to enhance wound healing in aging skin, presenting a potentially promising strategy for preoperative care."

Newer Research Points in the Same Direction

Since this 2024 work, the broader field has continued moving toward localized senolytic strategies for skin repair. A 2025 review in Ageing Research Reviews described cellular senescence as a key contributor to skin aging and skin disease, while noting that senolytics and related therapies could become useful tools for targeting harmful senescent cells in the skin.

A 2026 study took the idea further in diabetic wound healing, a major medical challenge often marked by chronic inflammation, poor blood vessel growth, and cellular senescence. Researchers developed a localized wound dressing carrying ABT-263 and reported that it reduced senescent cell burden, improved healing in diabetic mice, and showed no detectable systemic toxicity in that model.

At the same time, scientists are careful not to portray senescent cells as purely bad. A 2024 Frontiers in Immunology review emphasized that senescence can play a helpful role during normal wound repair, but persistent senescent cells may contribute to chronic wounds, fibrosis, and abnormal healing. The challenge is timing and precision: removing the harmful lingering cells without disrupting the useful early repair signals.

Promise With Important Caution

The findings are exciting, but they are still early. The ABT-263 skin study was done in mice, and more work is needed before scientists know whether the treatment is safe or effective in people.

Researchers will also need to answer key questions about dosing, timing, long term safety, and whether the benefits apply to human skin, surgical recovery, diabetic wounds, or other slow healing conditions.

Still, the idea is powerful. By clearing away cells that hold aging skin back, topical senolytic treatments could someday help the body repair itself more quickly and more effectively. For older adults facing surgery or chronic wounds, that could make healing less difficult, less risky, and far faster.

https://en.wikipedia.org/wiki/Navitoclax

https://www.aging-us.com/article/206165/text

Breakthrough drug reverses aging in skin and dramatically speeds healing |

FDA Approves Trimbow (beclomethasone/formoterol/glycopyrrolate) Inhaler for the Maintenance Treatment of Asthma

In continuation of my update on beclomethasone, Formoterol  & Glycopyrrolate

Formoterol

 beclomethasone, 

Glycopyrrolate

Chiesi USA, Inc. (key-A-zee), a global biopharmaceutical company,  announced  the U.S. Food and Drug Administration approval of  Trimbow (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate; or BDP/FF/G; 86 mcg/4.9 mcg/10.6 mcg and 172 mcg/4.9 mcg/10.6 mcg) for the maintenance treatment of asthma in adults. Trimbow delivers three active ingredients in a single device, referred to as a single inhaler triple therapy (SITT), presenting an option for adults whose asthma may require more than one inhaled medicine for daily maintenance treatment. Trimbow was the first treatment approved in the single inhaler triple therapy class outside of the U.S. and is commercialized in nearly 50 countries, including those within the European Union, the United Kingdom, and China.

• Trimbow (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate; or BDP/FF/G) is the first U.S. FDA-approved product from Chiesi’s respiratory portfolio, bringing with it more than four decades of global expertise in respiratory leadership.
• Approval was supported by Phase 3 TRIMARAN and TRIGGER studies, which included lung function as a co-primary endpoint in adults with asthma,1 building on its long-standing use as the first therapy in its class approved outside the U.S.

Approximately 27 million people in the U.S. live with asthma, which remains a significant burden to patients, caregivers, and society.2 Roughly 50% to 91% of people across all asthma disease severities show evidence of Small Airway Disease (SAD), which affects the tiny bronchioles deep within the airway tree.3,4

“The approval of Trimbow marks an important milestone as healthcare professionals continue to expand options for individualized care for the millions of people in the U.S. living with asthma, many of whom still struggle with symptoms,”2 said Nicola Hanania, MD, MS, Director, Airways Clinical Research Center, Professor of Medicine, Baylor College of Medicine and Chief, Section of Pulmonary, Critical Care and Sleep Medicine, Ben Taub Hospital, Houston, Texas. “This treatment has demonstrated improvement in lung function in Phase 3 clinical trials.”1

The FDA approval is supported by data from two Phase 3, double-blind, parallel-group, randomized, active-controlled clinical trials, TRIMARAN and TRIGGER, that evaluated the safety and efficacy of Trimbow in more than 2,200 adults with uncontrolled asthma.1 Across studies, Trimbow demonstrated improvements in lung function compared with BDP/FF, an inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) product. Trimbow demonstrated a safety profile comparable with BDP/FF, with common adverse events, occuring at an incident rate greater than or equal to 1%, including bronchitis, hypertension, back pain, blood pressure increase, dysphonia, upper respiratory tract infection, influenza, anemia, muscle spasms, laryngitis, oropharyngeal pain, and sinusitis.1

“This is an important development for the community at a time when access to treatment and the cost of care remain significant challenges for many individuals living with asthma,” said Lynda Mitchell, MA, CAE, CEO of the Allergy & Asthma Network. “There is no cure for asthma, and the condition presents a major burden to patients, caregivers, and society. Patients benefit when they have more options to treat their asthma – we are eager to see continued progress in innovation to address ongoing unmet needs in asthma care

FDA Approves Trimbow (beclomethasone/formoterol/glycopyrrolate) Inhaler for the Maintenance Treatment of Asthma

Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain."

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

Scientists discover strange link between vitamin D and pain 

Scientists discover strange link between vitamin D and pain

In continuation of my update on Vitamin D 

Women with low vitamin D levels may face a more painful recovery after breast cancer surgery and could require significantly more opioid medication afterward, according to research published online in the journal Regional Anesthesia & Pain Medicine.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) might benefit from taking vitamin D supplements before undergoing a radical mastectomy.

Researchers say growing evidence points to vitamin D playing an important role in how the body senses and regulates pain. Scientists believe this may be connected to the vitamin's anti inflammatory properties and its effects on the immune system. Vitamin D deficiency is also frequently seen in people with breast cancer.

Study Examined Pain After Breast Cancer Surgery

To explore the connection, researchers carried out a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025.

The study included 184 women with breast cancer who were preparing to have surgery to remove one breast. Half of the participants had vitamin D deficiency (below 30 nmol/L), while the other half had vitamin D levels above 30 nmol/L. The two groups were otherwise similar, with average ages of 44 and 42.

Doctors and nurses caring for the patients did not know their vitamin D status. All participants received the hospital's standard treatment before, during, and after surgery.

During the operation, patients were given fentanyl to control acute pain. After surgery, everyone received intravenous paracetamol every eight hours. Patients were also able to self administer tramadol, another opioid pain medication, by pressing a control button.

Patients With Low Vitamin D Needed More Opioids

Pain levels were recorded immediately after surgery and again at 6, 12, 18, and 24 hours later. Researchers also tracked nausea, vomiting, sedation levels, and length of hospital stay.

Patients with vitamin D deficiency were three times more likely to experience moderate to severe pain during the first 24 hours after surgery compared with patients who had adequate vitamin D levels.

Researchers noted that none of the patients in either group reported severe pain of 7 or higher on the standard 0 to 10 pain scale. The difference was entirely related to a higher number of patients experiencing moderate pain levels between 4 and 6.

The vitamin D deficient group also required more opioid medication. On average, these patients received 8 μg more fentanyl during surgery, which researchers described as a modest increase.

However, after surgery, the difference became much larger. Patients with low vitamin D used an average of 112mg more tramadol than those with sufficient vitamin D levels. The medication was patient controlled, with doses capped at 50mg per hour.

Vitamin D and Recovery Complications

Opioid medications can lead to side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependence and addiction.

The study found postoperative nausea occurred more often among patients with vitamin D deficiency. Vomiting was only reported in the deficient group, although researchers said the difference was too small to be considered statistically significant.

The researchers acknowledged several limitations. Because the study was observational and conducted at a single medical center, it cannot prove that low vitamin D directly caused the increase in pain. The team also did not measure inflammatory markers that might explain how vitamin D influences pain. In addition, information about anxiety, depression, cancer stage, previous treatments, and sleep problems before surgery was not collected.

Even with those limitations, the researchers concluded, "Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy."

They added, "Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain.

https://rapm.bmj.com/content/early/2026/05/04/rapm-2025-107495

https://en.wikipedia.org/wiki/Vitamin_D

Scientists discover strange link between vitamin D and pain | ScienceDaily

New chemical kills 95% of termites without harming humans

Drywood termites are experts at staying out of sight. They live inside wooden structures, quietly feeding and expanding their colonies where homeowners may not notice them until damage is already underway. But their hidden lifestyle also depends on a vulnerable biological process: molting.

Researchers at the University of California, Riverside have shown that bistrifluron, a chemical that blocks the formation of new termite exoskeletons, can destroy drywood termite colonies by interfering with the insects' ability to grow. The findings were published in the Journal of Economic Entomology. In laboratory testing, the treatment killed about 95 percent of a colony without the mammal toxicity concerns linked to many traditional termite control methods.

A Safer Way To Target Termites

"This chemical is more environmentally friendly than ones traditionally used for drywood termite infestations," said Nicholas Poulos, corresponding author of the paper and a doctoral student in UCR's Department of Entomology. "It's specific to insects and can't harm humans."

The reason the chemical is so targeted comes down to the termite body plan. Humans have bones inside their bodies. Termites wear their support system on the outside in the form of an exoskeleton. That outer shell is built largely from chitin, a tough natural material also found in fungal cell walls, fish scales, and the beaks of squids and octopi.

For insects, chitin is essential. It gives the exoskeleton strength, helps shield the body, and provides anchoring points for muscles. When termites grow, they must shed their old exoskeleton and build a new one. Drywood termites go through this process about seven times during their lives.

Bistrifluron interrupts that step. Instead of poisoning termites in a broad, fast acting way, it prevents them from making the chitin they need for their next protective shell.

"Once the termites reach a certain stage, they have to molt. They cannot avoid that," said Dong-Hwan Choe, UCR entomology professor and senior paper author. "With a lethal dose of this chemical, they'll try to shed their old exoskeleton but won't have a new one ready to protect them."

Termites Spread the Treatment Themselves

The effect is not instant. The researchers saw that bistrifluron first made the termites less active and reduced their feeding. Over time, the chemical blocked successful molting, and the insects died.

The 2025 study tested three chitin synthesis inhibitors against the western drywood termite, Incisitermes minor. Bistrifluron worked faster than chlorfluazuron and noviflumuron at the tested rates. In one no choice test, bistrifluron produced 99 percent mortality over 60 days. In a choice test using a 0.1 percent rate, it produced 96 percent mortality over the same period.

The most important part may be how the chemical travels. After termites fed on treated wood, they passed material to other members of the colony. In transfer tests, even when only 5 percent of termites had been exposed, the groups reached 100 percent mortality by day 90. The study reported that food material moved from exposed donor termites to unexposed recipients within 24 to 48 hours.

That finding fits with newer UC Riverside work highlighting how western drywood termites share food and essential gut microbes through proctodeal trophallaxis, a mouth to anus feeding behavior that is difficult to observe because the insects live almost entirely inside wood. Those hidden social behaviors can make infestations hard to detect, but they may also help treatments spread once termites contact treated material.

"It's been successfully used on subterranean termites, which are also important structural pests," Choe said. "But native western drywood termites are also important, especially in California."

A Slower Collapse With Big Advantages

Once drywood termites consume the treated wood, the compound can move through the colony as termites interact. Full colony collapse takes roughly two months, making it slower than some conventional methods. But the tradeoff could be worth it: lower toxicity, more targeted action, and the potential for a localized treatment that does not require tenting an entire home.

"We believe this method of spot treatment can kill a larger colony and spread more easily than current termite control methods," Choe said. "You don't have to apply too much to get a very good result. The chitin synthesis inhibitors show promise as localized treatment for drywood termites."

Traditional fumigation remains a major burden for homeowners. It can be toxic, disruptive, and stressful. People often have to bag food, leave the house, and wait before returning. It also does not prevent termites from coming back later.

"Low-impact strategies like this one will become an attractive option in many cases. Furthermore, the chemical may stay active in the wood for some time, potentially providing protection from future infestations," Choe said.
A Chemical Lure Could Make Treatment StroThe UCR team has also explored another clever way to improve termite control: using scent to draw termites toward treated wood. In earlier work, Choe's lab studied pinene, a pleasant smelling chemical released by forest trees. To western drywood termites, pinene can signal food.

When termites follow that scent into insecticide treated wood, the treatment becomes more effective. A 2025 patent application from UCR describes the use of pinenes to improve localized insecticide injections against western drywood termites. It states that adding pinene to localized treatments killed termites more quickly and increased final mortality compared with insecticide alone. The application also suggests that pinene could allow wider spacing between drill holes and may reduce the time, labor, and amount of insecticide needed for treatment.

"We saw significant differences in the death rates using insecticide alone versus the insecticide plus pinene," said Choe. "Without pinene, we got about 70% mortality. When we added it in, it was over 95%."

Making It Practical for Homes

The bistrifluron study used acetone to dissolve the chemical before applying it to wood. That worked for the research, but it is not ideal for real world use because acetone is flammable and has a strong odor.

"We are working to make it more feasible for practical application in real life scenarios," Poulos said.

That next step matters because western drywood termites are a serious structural pest. They are native to northern Mexico and California, and they are especially important in California. The species has also been introduced to other regions, including Hawaii, New York, Florida, Canada, China, Japan, Korea, and Australia, according to the 2025 study. Movement of lumber and other wood products helps transport termites, while their concealed lifestyle inside wood makes them difficult to manageClimate change may add to the problem. As temperatures shift, the termites may be able to expand into places that were once less suitable for them.

"As we move lumber around the world, the termites are constantly transported to new locations. If they find the climate there acceptable, the problem will spread," Choe said. "In areas where these termites are common, it's just a matter of time before homes are infested, so this study is a good initial step toward alternative strategies for controlling them."

https://en.wikipedia.org/wiki/Bistrifluron

New chemical kills 95% of termites without harming humans | ScienceDaily

New drug combination doubles down on Alzheimer's treatments

A new study finds that combining the current medications for Alzheimer’s disease with small molecules derived from micronutrients found in grapes, berries, peanuts and turmeric is a safer and more effective way to treat the disease.

Individuals with Alzheimer’s have a buildup of toxic amyloid proteins in the brain. Researchers from the School of Pharmacy at the University of Waterloo combined amyloid-destroying small molecules with anti-amyloid antibodies that are already used in Alzheimer’s treatment. They found that it neutralized the clumping of proteins that accumulate in the brain, leading to better outcomes.

Alzheimer’s is the major cause of dementia. Dementia affects nearly 750,000 people in Canada, with a million cases expected by 2030. Alzheimer’s has no cure and current medications only relieve a patient’s symptoms. Anti-amyloid antibody therapies on their own can slow the disease, but they also come with risks that can be fatal, including brain swelling and bleeding.

“We already know the small molecules resveratrol or curcumin, which are found in some common foods, block the buildup of amyloid,” said Dr. Praveen Nekkar Rao, a professor in the School of Pharmacy at Waterloo. “What’s new and exciting is our combination of these molecules with the anti-amyloid antibodies. This approach could allow clinicians to use lower doses of antibodies, potentially reducing the risk of serious treatment-related side effects.”

Since there are few effective treatments for Alzheimer’s, researchers at Waterloo studied whether using two treatments together could work better than using just one. They chose resveratrol and curcumin because they are natural compounds known to reduce amyloid buildup and inflammation.

curcumin

Resveratrol

“I was inspired by chemotherapy, which involves taking multiple medications for effective treatment,” Nekkar Rao said. “Alzheimer’s is a complex disease, but there are very few combination therapy approaches. Our results show that the way forward is definitely combination therapy.”

The researchers emphasize that the study does not suggest that people should start consuming resveratrol or curcumin to prevent or treat dementia. You would have to consume an unsafe amount in order to reach the brain. The next phase of the research will focus on designing next-generation drugs that can reach the brain more effectively, interact favourably with amyloids and pair seamlessly with antibody treatments.

https://en.wikipedia.org/wiki/Curcumin

https://en.wikipedia.org/wiki/Resveratrol

New drug combination doubles down on Alzheimer's treatments

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate

Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced the publication of work describing the large-scale synthesis of enlicitide decanoate, the company’s investigational oral PCSK9 inhibitor, using a tailored suite of enzymes in the latest issue of the peer reviewed journal Science.

• Publication in Science magazine outlines blueprint for the scalable
•  synthesis of complex orally available macrocyclic peptides
• Enlicitide, a novel macrocyclic peptide, has the potential to be the first approved oral PCSK9 inhibitor

“Macrocyclic peptides have the potential to unlock new opportunities to develop oral treatment options for challenging therapeutic targets and broaden patient access,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “The scalable production process for enlicitide described in this publication showcases Merck’s scientific capabilities and underscores our sustained commitment to helping address the global cardiovascular epidemic.”

In this publication, Merck scientists detail the biocatalytic assembly of enlicitide using a suite of enzymes that catalyze selective peptide fragment formation, coupling, and macrocyclization. Together with efficient purifications using crystallization, this strategy enabled the manufacture of a product that would not be possible with traditional synthetic methods. The method described offers a sustainable blueprint for the scalable development of complex macrocyclic peptide therapeutics, environmental advantages and manufacturing efficiencies that support efforts to expand patient access.

About biocatalysis

Biocatalysis describes the process of using enzymes to conduct chemical synthesis. Biocatalysis offers environmental sustainability advantages over chemical catalyst methods. For more than 25 years Merck has invested in the development of biocatalysis including the generation of novel enzymes for the synthesis and novel manufacturing of pharmaceutical products at scale.

About macrocyclic peptides

Over a decade ago, an interdisciplinary team of Merck scientists were challenged to create a type of medicine that may provide the potency and selectivity of a biologic therapy but in the form of a pill. Macrocyclic peptides are intricate ring-shaped molecules with the ability to target and disrupt protein-protein interactions while retaining oral bioavailability. For more information regarding our approach to macrocyclic peptides, visit merck.com

About enlicitide and PCSK9

Enlicitide has the potential to be the first approved oral PCSK9 inhibitor. It is designed to lower LDL-C via the same biological mechanism as currently approved monoclonal antibody, injectable PCSK9 inhibitors but in a daily pill form. Enlicitide is a novel macrocyclic peptide candidate that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.

PCSK9 plays a key role in cholesterol homeostasis by regulating levels of the LDL receptor, which is responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 is designed to prevent the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.

About the CV epidemic and atherosclerotic cardiovascular disease

The silent CV epidemic is the leading cause of deaths globally, contributing to the majority of heart attacks and strokes, and deaths related to CV continue to rise. ASCVD accounts for 85% of CV deaths. It is caused by the buildup of plaque within the arteries, leading to narrowed or blocked blood vessels that can result in serious CV events such as heart attacks and strokes as well as coronary artery disease, peripheral artery disease and cerebrovascular disease.

https://en.wikipedia.org/wiki/Enlicitide_decanoate

Merck Scientists Publish Landmark Paper on Novel Method for Large-Scale Biocatalytic Synthesis of Investigational Oral PCSK9 Inhibitor, Enlicitide Decanoate 

Vitamin D Deficiency Linked to Fatigue, Studies Show

In continuation of my update on Vitamin D

Prevalence and Link to Fatigue

Approximately 40% to 75% of the teen and adult population in the United States is deficient in vitamin D, according to Raymond Francis in “The Great American Health Hoax.” ^[1] Low energy and occasional fatigue are commonly reported among individuals with low vitamin D status, according to a report on the silent epidemic of nutrient deficiencies. ^[2] The scale of the problem is vast, with estimates suggesting that nearly half of all adults may have insufficient levels, the report stated.

Vitamin D deficiency is not confined to a single demographic. Factors such as limited sun exposure, darker skin pigmentation, and indoor lifestyles contribute to widespread insufficiency, researchers said. The link between low vitamin D and fatigue has been documented in multiple studies, though many individuals remain unaware of their own deficiency status.

Mechanism: Vitamin D and Cellular Energy

Vitamin D supports mitochondrial function, which is responsible for cellular energy production, according to research cited in an article on fatigue and mitochondria. ^[3] The mitochondria act as the powerhouses of the cell, generating adenosine triphosphate (ATP) from nutrients. A deficiency may disrupt mitochondrial efficiency, contributing to feelings of lethargy, experts said. ^[4]

The role of mitochondria in energy production is central to understanding why vitamin D insufficiency can lead to persistent tiredness. As noted in the book “Dissolving Illusions,” proper mitochondrial metabolism is essential for normal cellular function, and any disruption can manifest as weakness or apathy. ^[5] Although that text focuses on vitamin C, the principle applies broadly to nutrients that support mitochondrial health, including vitamin D.

Supporting Studies

Multiple studies have reported a connection between low vitamin D levels and fatigue. A 2016 study of 200 female nurses in Iran found that low vitamin D levels accounted for 13% to 18% of reported prolonged tiredness, according to a review of nutrient deficiencies. ^[2] A 2019 study published in Nutrients similarly found that older adults with occasional fatigue had a significantly worse vitamin D status than those without fatigue, the review added. ^[2]

Other research has reinforced these findings. In a broader analysis, researchers noted that individuals frequently reporting low energy were more likely to have suboptimal vitamin D levels compared to their peers, according to an article on fatigue and mitochondrial function. ^[4] The consistency of the association across different populations suggests a robust relationship, though causation requires further investigation, scientists said.

Other Health Impacts

Beyond fatigue, vitamin D deficiency has been linked to several other health issues. Vitamin D directly modulates the body’s innate and adaptive immune responses, according to a review of the critical role of vitamin D in immune function. ^[6] Immune cells require adequate vitamin D to respond efficiently to threats, the review stated. Low levels have also been associated with increased susceptibility to infections and longer recovery times.

Vitamin D also influences bone health and cellular aging. Raymond Francis wrote that vitamin D is essential for calcium metabolism, supports bone health, helps control blood sugar, and protects against cancer. ^[1] The nutrient significantly increases the production of telomerase, an enzyme that repairs telomeres and slows aging, according to the same source. ^[1] These wide-ranging effects underscore the importance of maintaining optimal levels.

Solutions: Increasing Vitamin D Levels

Optimal vitamin D levels are considered to be above 50 nanograms per milliliter, and supplementation with 5,000 IU daily is recommended by some nutritionists, according to an interview on health testing and supplementation. ^[7] At-home blood tests can help individuals assess their current levels, the interview stated. ^[7] Testing allows for personalized dosing rather than generic recommendations.

The safety of higher vitamin D doses has been affirmed by recent reassessments. A news report noted that a “schoolboy error” in earlier guidelines led to overly cautious upper limits, and the Academy of Medicine has since acknowledged that higher intakes are not toxic for most people. ^[8] Dietary sources such as fatty fish, egg yolks, and fortified foods can also contribute, though supplementation is often the most reliable way to correct a deficiency, experts said.

Conclusion

Individuals experiencing unexplained fatigue may consider testing their vitamin D levels, clinicians advised. ^[7] Supplementation and dietary changes can help restore levels to the optimal range, though consulting a healthcare provider is recommended before starting any regimen, according to the interview. ^[7]

The evidence linking vitamin D deficiency to fatigue is supported by prevalence data, mechanistic studies, and clinical observations. Given the high rates of insufficiency in the general population, testing and appropriate supplementation offer a straightforward strategy for addressing a common but often overlooked contributor to low energy, researchers concluded.

https://en.wikipedia.org/wiki/Vitamin_D

Vitamin D Deficiency Linked to Fatigue, Studies Show