BackgroundCompound liquorice tablets is a cough-suppressing compound formulation containing opium powder and liquorice. With the strict regulation of traditional opioids, this medication has emerged as a novel alternative for substance abuse due to its easy accessibility and low cost; however, its addiction potential and severe adverse complications remain underrecognized and insufficiently addressed in clinical practice.Case summaryThe patient is a 29-year-old male who began self-medicating with compound liquorice tablets for a dry cough after COVID-19 infection. His daily dosage gradually escalated to 200–600 tablets within two years, resulting in established drug dependence. Two days after discontinuing the medication, he developed delirium manifested as confusion, disorientation, visual hallucinations and psychomotor agitation, accompanied by palpitations, hypertension, tremors, rhinorrhea, vomiting, severe hypokalemia, and bilateral lower limb edema. Organic brain diseases were excluded by systematic examinations. According to the ICD-10 diagnostic criteria, he was diagnosed with opioid-induced mental and behavioral disorders, hypokalemia and hypertension. We implemented a benzodiazepine tapering regimen to control delirium and sympathetic excitation associated with withdrawal symptoms, combined with antidepressants and antipsychotics to improve mood, anxiety, and psychotic symptoms, Under the guidance of a cardiologist, we actively managing hypertension and correcting internal environmental disturbances. Following comprehensive management, the patient’s withdrawal symptoms and delirium resolved, with stable emotional state and blood pressure, resulting in successful withdrawal.ConclusionThis is the first reported case of delirium caused by withdrawal from compound liquorice tablets. It provides preliminary insights for clinical identification, diagnosis, and multidisciplinary management of dependence on compound liquorice tablets, as well as related withdrawal symptoms and complications. This case also alerts to the emerging risk of abuse associated with new substances such as compound liquorice tablets and underscores the need for stricter prescription controls and patient education regarding the risks of abuse.
Structural Biology Reveals New Drug Targets for Rare Neuromuscular Disease
Researchers at the University of California San Diego have uncovered the structural mechanisms that cause congenital myasthenic syndromes (CMS), revealing mutation-specific treatment strategies and identifying an existing antidepressant as a promising candidate for drug repurposing.
The study, published in Nature, explains how disease-causing mutations alter the human acetylcholine receptor (AChR), the protein responsible for converting nerve signals into muscle contraction. The findings also provide a framework for developing precision medicines tailored to the specific mutation carried by individual patients.
CMS is a rare inherited group of neuromuscular disorders that typically appears at birth or early childhood. Mutations in the AChR impair communication between nerves and muscles, leading to muscle weakness, difficulty walking, breathing problems, and, in severe cases, paralysis or death. Although more than 50 disease-causing mutations have been identified, the molecular mechanisms underlying these disorders have remained largely unknown.
To address this question, the investigators determined 12 high-resolution structures of representative mutant AChRs with and without therapeutic compounds. By combining these structural data with functional studies, they identified common mechanisms that explain the two major forms of CMS.
Fast-channel CMS is caused by loss-of-function mutations that reduce receptor opening and weaken neuromuscular transmission. The researchers discovered a previously unknown allosteric binding pocket that can be targeted by positive allosteric modulators (PAMs), compounds that enhance receptor activity without directly activating the channel.
Notably, different PAMs restored receptor function in different patient mutations rather than producing a universal effect. The authors write that this “mutation-specific activity underscores the capability and necessity of tailoring therapies to individual patient genotypes.”
The study also showed that the newly identified drug-binding pocket is largely absent until a PAM binds, creating an opportunity to design more effective compounds that stabilize receptor function. The authors conclude that these findings point to “a new class of allosteric drugs” with potential applications not only in fast-channel CMS but also in disorders such as myasthenia gravis, in which acetylcholine receptor function is compromised.
The team also investigated slow-channel CMS, a gain-of-function disorder in which receptors remain open too long, causing excessive calcium influx and progressive damage at the neuromuscular junction.
Structural analyses revealed that the current therapies quinidine and fluoxetine act through a shared mechanism, blocking the receptor pore despite their distinct chemical structures.
The investigators also evaluated reboxetine, an antidepressant already approved in several countries. Unlike the existing drugs, reboxetine selectively inhibited abnormal receptor activity across multiple slow-channel mutations while largely sparing normal receptor function.
The authors believe that reboxetine’s ability to suppress pathological receptor activity, together with its established clinical safety profile, “positions it as a potential candidate for slow-channel CMS therapy,” although they caution that its known adverse effects warrant careful evaluation in future clinical studies.
Beyond identifying therapeutic opportunities, the study establishes unifying principles of CMS pathogenesis. The researchers found that fast-channel mutations weaken the coupling between acetylcholine binding and channel opening, whereas slow-channel mutations stabilize an abnormally widened, desensitized-like pore. These shared structural mechanisms explain why genetically diverse mutations produce similar clinical symptoms while requiring different therapeutic strategies.
The work also revises understanding of receptor biology. The authors write that their findings “overturn the traditional view of the β subunit as merely a structural scaffold,” instead demonstrating that it plays “a central role in the gating cycle.”
Overall, the researchers conclude that their integrated structural and functional analyses define how CMS mutations disrupt receptor gating, reveal the molecular basis of current and candidate therapies, and identify new druggable sites for intervention. They conclude that the work provides “a roadmap towards the development of safer and more effective, mutation-specific treatments for both fast-channel and slow-channel CMS.”
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Why Long, Uninterrupted Sitting May Matter for Cancer Prevention
Public health advice has long emphasized exercise: move more, meet weekly activity targets, reduce time spent sitting. But a growing body of evidence suggests that the pattern of inactivity may also matter. Sitting for long, uninterrupted periods may not carry the same health implications as the same amount of sedentary time broken up by movement.
A new study published in PLOS Medicine adds cancer outcomes to that discussion. Researchers analyzed accelerometer data from 91,292 UK Biobank participants who wore wrist activity monitors for seven days and were then followed for a median of more than 12 years. The study found that prolonged sedentary behavior was associated with higher risk of cancer mortality and cancer incidence, while interrupted sedentary behavior showed the opposite pattern.
Beyond “sit less, move more”
Sedentary behavior includes waking activities such as sitting, reclining, or lying down that require very low energy expenditure. Most guidelines and public health messages focus on total sedentary time. That is understandable: total sitting time is easy to communicate and has been repeatedly linked to poor cardiometabolic outcomes.
But the new study asks a more precise question: does it matter whether sedentary time happens in long blocks or is regularly interrupted?
The researchers defined prolonged sedentary behavior as bouts lasting at least 30 minutes in which at least 90% of the time was sedentary. Interrupted sedentary behavior included shorter bouts or sedentary periods broken up by movement. This distinction allowed the team to examine not only how much time people spent inactive, but how that inactivity was distributed throughout the day.
Long, unbroken sedentary bouts linked to higher risk
Each additional hour per day of prolonged sedentary behavior was associated with a 9% higher risk of cancer death. Prolonged sedentary time was also associated with higher overall cancer incidence, obesity-related cancers, and type 2 diabetes-related cancers.
Interrupted sedentary behavior showed an inverse association across the same outcomes. In other words, sedentary time that was broken up by activity was not linked to the same pattern of risk as long, uninterrupted bouts.
The authors summarize the implication clearly: “These findings suggest that not only the total amount of sedentary time, but also how sedentary time is accumulated, may be important for cancer risk.”
This matters because sedentary behavior is widespread and often built into modern work, transport, and leisure routines. For many people, the practical question is not whether they can avoid sitting altogether, but whether they can interrupt long sitting periods often enough to reduce risk.
Light movement should not be ignored
The study also used substitution models to estimate what might happen if sedentary time were replaced with different types of activity. Replacing one hour per day of prolonged sedentary behavior with light physical activity was associated with a 12% lower risk of cancer death. Replacing 30 minutes per day with moderate physical activity was also associated with lower cancer mortality risk.
That finding is important because light activity is more achievable for many people than structured exercise. Standing up, walking slowly, doing household tasks, or taking brief movement breaks may not feel like “exercise,” but they may still interrupt metabolically harmful patterns of prolonged inactivity.
As the authors note, “light movement shouldn’t be ignored.”
The biological rationale is plausible. Experimental studies have shown that breaking up sitting with short activity bouts can improve glucose and insulin responses compared with uninterrupted sitting. Prolonged sedentary time may also contribute to low-grade inflammation, impaired immune function, insulin dysregulation, and ectopic fat accumulation—pathways that have all been discussed in relation to cancer risk.
A public health signal, not proof of causation
The study has important strengths. It used device-measured activity rather than self-reported sitting time, reducing recall bias. It also followed participants for more than a decade and included multiple cancer outcomes.
Still, the findings should be interpreted carefully. This was an observational study, so it cannot prove that prolonged sitting directly causes cancer or cancer death. UK Biobank participants are also known to be healthier and more physically active than the general UK population, which may limit generalizability. Activity was measured over only seven days, and the monitors could not capture the context of sedentary behavior, such as whether someone was sitting at work, watching television, driving, or resting because of underlying illness.
The authors also note that residual confounding cannot be ruled out. People who sit for long uninterrupted periods may differ from others in ways that are difficult to fully measure, including occupation, frailty, health status, or broader lifestyle patterns.
Rethinking cancer prevention in everyday terms
Cancer prevention is often framed around smoking, alcohol, diet, body weight, vaccination, screening, and exercise. Sedentary behavior is increasingly part of that picture, but this study suggests the message may need to become more specific.
The goal may not only be to reduce total sitting time, but to avoid accumulating that time in long, uninterrupted blocks. For public health, that is a potentially actionable target: movement breaks at work, walk-and-talk meetings, standing transitions, household activity, or brief light-intensity movement after long periods of sitting.
The study does not suggest that movement breaks replace established cancer prevention measures. Nor does it mean that every hour of sitting carries the same risk for every person. But it does support a more nuanced view of inactivity: the body may respond differently to sedentary time that is regularly interrupted than to sedentary time accumulated in prolonged bouts.
As activity monitors become more common and prevention science becomes more personalized, cancer prevention advice may eventually move beyond broad exercise targets toward daily behavior patterns. For now, the message is simple enough: long sitting spells may be worth breaking, even with light movement.
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Chimeric Allergen Receptor Treg Cells Suppress Allergic Asthma in Mice
Genetically engineered CAR T cells expressing artificial receptor proteins are increasingly used in the clinic to boost the immune system’s response against leukemias and other cancers. Researchers at Lausanne University Hospital and University of Lausanne, and at Center for Human Immunology Lausanne, have now adapted this approach to suppress the immune system’s response to a common birch pollen allergen. The investigators developed regulatory T cells (Tregs) armed with chimeric allergen receptors (CAlleR Tregs), which in tests reduced or preventing asthma symptoms in mice sensitized to the allergen. The team suggests that their technique could eventually be used to treat a wide variety of allergies in humans.
“Our study provides proof-of-concept and preclinical evidence that CAlleR Tregs redirected against a birch pollen allergen can downmodulate birch pollen–induced allergic asthma,” said study lead Yannick D. Muller, MD, PhD, an associate professor at Lausanne University Hospital and the University of Lausanne.
Muller and colleagues reported on their study in Journal of Experimental Medicine (JEM) in a paper titled “Chimeric allergen receptor regulatory T cells suppress birch pollen allergic airway inflammation,” concluding “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.”
Asthma affects over 300 million people worldwide, around 60% of whom suffer from allergic asthma. Allergens trigger an immune response in a patient’s airways, causing inflammation, excessive mucus production, and difficulty in breathing. “Allergic asthma is driven by an exacerbated type 2 immune response, characterized by the overproduction of IL-4, IL-5, and IL-13 by Th2 cells,” the authors explained. These cytokines trigger events that ultimately result in airway hyperresponsiveness, and airway mucus plugging, which is the primary cause of death in asthma.
Allergen immunotherapy (AIT), which involves the administration of gradually increasing doses of allergen, is the only treatment that addresses the underlying cause of asthma. Yet, it is not recommended for patients with severe asthma, representing the most vulnerable population at greatest risk of asthma-related morbidities and mortality. “This highlights the need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma,” Muller commented.
Regulatory T cells (Tregs) are immune cells that can dampen the body’s immune responses and prevent excessive inflammation. Tregs are being investigated as potential therapies for a variety of inflammatory and autoimmune disorders. “Importantly, Tregs can be expanded ex vivo and reinfused with multiple clinical trials evaluating their potential in autoimmune and inflammatory disorders,” the team continued. “However, Treg therapy has shown only limited efficacy, which has been mostly attributed to the lack of antigen specificity.”
Muller and colleagues wondered whether they could boost the therapeutic potential of Tregs by genetically engineering them to express receptor proteins that recognize specific allergens. This approach is analogous to the CAR T cell method that is now commonly used to treat cancers: cytotoxic T cells are engineered to express chimeric antigen receptors that specifically recognize proteins on the surface of cancer cells, directing the immune system to attack and kill the tumor cells.
A leading cause of allergic asthma is birch tree pollen, to which 8–16% of the European population are sensitive. The birch allergen Bet v1 is the most abundant allergenic protein, the authors commented. And while AIT for birch pollen–associated rhinitis and asthma has been shown to be effective, it is contraindicated for patients with severe and uncontrolled asthma. “This highlights the unmet need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma.”
Muller’s team constructed chimeric allergen receptors (CAlleRs) that specifically recognize the Bev v1 component of birch tree pollen. These CAlleRs were based on antibodies isolated from a birch-allergic patient, linked to protein signaling domains that can activate Treg cells. “We identified and characterized four novel anti–birch-specific antibodies and generated single-chain variable fragments (scFvs) fused to a CD28-ζ signaling domain,” the investigators noted.
Exposure to the birch pollen allergen, when stabilized by noncompetitive antibodies, boosted the suppressive activity of Tregs expressing these CAlleRs. The researchers found that simultaneous binding by a CAlleR and a non-competing antibody promotes receptor–allergen cross-linking underlying a novel mechanism to induce T cell activation by soluble antigens. “This mechanism opens new avenues not only for rewiring synthetic receptors against any soluble antigens including autoantigens for therapeutic intervention but also for delineating a more global pathway for antigen cross-presentation in allergies.”
Muller and colleagues injected these CAlleR-expressing Tregs into mice that were already allergic to birch pollen. When these treated animals were re-exposed to birch pollen, they showed decreased signs of allergic inflammation, reduced mucus production, and increased lung function. Next, the researchers injected CAlleR-expressing Tregs into mice that had never been exposed to birch pollen. When these animals were subsequently exposed to pollen, they failed to develop any asthma symptoms.
The team concluded, “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.” Muller added, “Future studies should evaluate the persistence and stability of CAlleR Tregs over time and define the optimal modalities for implementing such a therapeutic approach.” CAlleRs could also be developed that specifically suppress the immune response to other common allergens, including house dust mites or certain food allergens.” Future work should evaluate whether such approach could also be suitable to restore tolerance against food allergies,” the investigators said.
The post Chimeric Allergen Receptor Treg Cells Suppress Allergic Asthma in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.
Data rights are the missing pillar for modernizing consent in medicine
Nature Medicine, Published online: 06 July 2026; doi:10.1038/s41591-026-04506-3
Data rights are the missing pillar for modernizing consent in medicine
Author Correction: Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial
Nature Medicine, Published online: 06 July 2026; doi:10.1038/s41591-026-04551-y
Author Correction: Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial
Biomarkers Could Help in Antidepressant Choice
Antidepression treatment based on a person’s individual biomarkers could help determine which of the world’s most popular medications to use, a clinical trial suggests.
The SMART Trial to Predict Anhedonia Response to Antidepressant Treatment results suggest that behavioral, brain, and clinical data could together determine the optimal antidepressant to choose before a person starts treatment.
There were no significant primary endpoint differences in depression outcomes between participants who received bupropion or sertraline based on biomarkers identified in the prior Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study.
But people negative for biomarkers with both drugs had significantly worse depression symptom trajectories than those who had at least one positive biomarker, regardless of the drug they received.
Response rates among participants with both biomarkers were almost double that of those without any biomarkers, with those who had at least one biomarker having an intermediate response.
“Our results suggest that we could boost response rate by using two sets of biomarkers previously identified in the EMBARC study, making an important contribution to advancing the goals of precision psychiatry,” reported Peter Zhukovsky, PhD, from Harvard Medical School, and co-workers in Nature Mental Health.
“Ultimately, we strongly hope these advances will enable personalized treatment guidance to accelerate and boost antidepressant benefits.”
Treatment for depression is often still trial and error, with symptoms improving in only half the people taking an antidepressant. This could be due to treatments not being chosen based on people’s individual characteristics.
Finding markers that predict response to different antidepressants could therefore provide patients and clinicians with valuable information to guide treatment choice.
The trial was among the first to investigate how treatment could be guided using clinical information such as responses to questionnaires, behavioral information such as performance in computerized tasks, and brain data such as magnetic resonance imaging (MRI) scans.
It was carried out as part of the Wellcome Leap Multi-Channel Psych Program effort to double the number of people who respond to the first treatment they try for depression via the integration of multimodal biomarkers.
Firstly, the researchers investigated biomarker models that predicted response to the selective serotonin reuptake inhibitor (SSRI) sertraline or the norepinephrine-dopamine reuptake inhibitor bupropion using the EMBARC study.
The treatment-assignment algorithm that was developed generated two marker-based indications for each patient—one for bupropion and sertraline—with the predictive model achieving a cross-validated area under the curve of 0.86 and 0.66, respectively.
The team then examined whether antidepressant response could be boosted using their created biomarker combination of a functional MRI imaging marker, reward learning and sensitivity, cognitive control, the clinical variables of depression severity and neuroticism, and the demographic variable of employment status.
After analyzing these biomarkers among participants, who had major depressive disorder, the group was randomly assigned to receive a full 8-week course of an SSRI or non-SSRI.
The primary outcome was the change in depression severity from pretreatment baseline to eight weeks after the start of treatment, with no significant differences in treatment outcomes for those assigned a drug consistent versus inconsistent with their biomarkers.
This, the researchers say was possibly due to the limited power to detect moderate effects.
However, significant differences emerged in symptom reduction trajectories for those with positive markers for both medications, with a response rate of 71.4% compared with 65.4% for those with a positive biomarker for either drug and 42.9% for those with two negative markers.
The authors concluded: “We found that, relative to patients with two negative markers, those with one or two markers were characterized by significantly larger reduction in depressive symptoms, showing that biomarker-guided treatment selection can boost efficacy for two of the most widely prescribed antidepressants around the world.”
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Opinion: Stopping doctors from ordering unnecessary diagnostic tests requires a structural fix
American medicine runs more than 14 billion tests a year. While some tests can be lifesaving, many are used at the wrong time or on the wrong patient and are useless or even harmful.
The medical industry has spent enormous effort making more advanced tests but expended little effort learning how to use tests correctly. There is a science for how to better use tests, diagnostic stewardship, but most doctors have never heard of it.
Debriefing Consult for Psychiatric Symptoms After Severe Maternal Morbidity
Conditions: PTSD (Childbirth-Related); Severe Maternal Morbidity; Depression – Major Depressive Disorder; Anxiety
Interventions: Behavioral: Virtual maternal fetal medicine debriefing consult
Sponsors: Cedars-Sinai Medical Center; Cedars Sinai Medical Center, Los Angeles, USA
Not yet recruiting
Interventions: Behavioral: Virtual maternal fetal medicine debriefing consult
Sponsors: Cedars-Sinai Medical Center; Cedars Sinai Medical Center, Los Angeles, USA
Not yet recruiting
Strong Public Support for Embryonic Genome Editing to Eliminate Severe Conditions, European Survey Shows
A European survey launched at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) suggests broad public support for fertility treatment and research, including genome editing in human embryos for specific reasons.
The report, “Fertility, Embryo Research and Genome Editing: Public Attitudes in Europe,” was commissioned by the charity Progress Educational Trust (PET), which aims to improve choices for people affected by infertility and/or genetic conditions, and was supported by ESHRE. It explored public attitudes towards fertility treatment, embryo research, genome editing, surrogacy, and related topics.
The authors say the findings will “inform ESHRE’s ongoing work in Europe, linked to implementation of the European Union’s SoHO (Substances of Human Origin) Regulation and to the ethical considerations that arise in our field.”
The survey included 8688 participants aged 16–75 years across the U.K., Netherlands, Spain and Italy, with more than 2000 respondents in each country.
Across all four countries, a large proportion of respondents supported state-funded fertility treatment for people experiencing infertility and wishing to conceive, ranging from 54% in the Netherlands to 57% in the U.K., 62% in Spain, and 64% in Italy. Support was highest for heterosexual couples (47–59%) and lowest for transgender people (12–18%).
Conversely, most respondents said they did not support people being able to choose the biological sex of their child, based on personal preference. Opposition was strongest in the Netherlands (72%) followed by the U.K. (59%), Italy (55%) and Spain (47%). Nonetheless, there was still a significant minority that expressed support for sex selection. This support was strongest in Spain (32%) followed by the U.K. (26%), Italy (22%) and the Netherlands (18%), and was more common among younger participants than their older counterparts.
The age differential across responses could mean that with time, there will be a shift in views and potential changes in policy, the authors note.
The survey also found public backing for the use of human embryos in research to better understand and develop treatments for congenital diseases. Support ranged from 41% in Italy to 48% in the Netherlands and Spain, substantially exceeding opposition in all four countries (15–24%), including Italy, where research uses of human embryos are currently prohibited.
Respondents were then asked whether they supported or opposed the use of genome editing in human embryos, in three different scenarios:
- For scientific and medical research to help understand or develop treatments for congenital disease, without human implantation.
- In human embryos that will be transferred to a human to establish pregnancy to help eliminate a severe or life-threatening condition, like cystic fibrosis, in the resulting child.
- In human embryos that will be transferred to a human to establish pregnancy to help eliminate a common or medically manageable condition, like asthma, in the resulting child.
In all four of the countries, more respondents supported than opposed all three of the uses of genome editing, with the highest level of support given if the technique helps eliminate a severe or life-threatening condition.
It is important to note that this use of genome editing—which was supported by 55% in the Netherlands, by 53% in Spain, by 52% in the U.K. and by 46% in Italy—is not permitted by law in any of these four countries at present.
PET commented: “It is heartening to see such substantial support for uses of genome editing in human embryos, across all four of the countries surveyed. That said, these findings present an interesting conundrum. Respondents seem to be more ready to countenance the use of genome-edited embryos in treatment—at least, if helps to eliminate a severe or life-threatening condition—than they are to countenance the use of genome-edited embryos in research. Realistically, research must occur first. There is therefore a need for wide-ranging public conversations, where the vital role played by research—in enabling treatment, and ensuring that treatment is safe and effective—can be conveyed.”
Professor Karen Sermon, immediate past chair of ESHRE, said, “Reproductive medicine and embryo research are advancing rapidly, and these findings show the importance of understanding how the public views those developments. It is particularly striking that support for some applications extends beyond what is currently permitted in certain countries. As science advances, it is essential that public awareness keeps pace, so that decisions about future treatments are informed by both evidence and societal values.”
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