skip to content

Department of Pharmacology

 

Adapting the BOADICEA breast and ovarian cancer risk models for the ethnically diverse UK population

Thu, 17/07/2025 - 11:00

Br J Cancer. 2025 Jul 17. doi: 10.1038/s41416-025-03117-y. Online ahead of print.

ABSTRACT

BACKGROUND: BOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle, hormonal and reproductive risk factors. However, it has largely been developed using data from White/European individuals, limiting its applicability to other ethnicities. Here, we updated BOADICEA to provide ethnicity-specific risk estimates.

METHODS: We utilised data from multiple sources to derive estimates for the distributions and effect sizes of risk factors in major UK ethnic groups (White, Black, South Asian, East Asian, and Mixed), along with ethnicity-specific population cancer incidences. We also developed a method for deriving adjusted polygenic scores for individuals of mixed genetic ancestry.

RESULTS: The predicted average absolute risks were smaller in all non-White ethnic groups than in Whites, and the risk distributions were narrower. The proportion of women classified as at moderate or high risk of breast or ovarian cancer, according to national guidelines, was considerably smaller in non-Whites.

DISCUSSION: The updated BOADICEA, available in the CanRisk tool ( www.canrisk.org ), is based on more appropriate estimates for non-White women in the UK. Further validation of the model in prospective studies is required. Considering these findings, risk classification guidelines for non-White women may need to be revised.

PMID:40676226 | DOI:10.1038/s41416-025-03117-y

Cluster Analysis of a Database of Surgically Managed Adult Spine Deformity (ASD)Patients: Determining the Minimal Clinically Important Difference for Each Cluster, Comparing Two Clustering Approaches

Wed, 16/07/2025 - 11:00

Spine (Phila Pa 1976). 2025 Jul 16. doi: 10.1097/BRS.0000000000005453. Online ahead of print.

ABSTRACT

STUDY DESIGN: retrospective analysis of prospectively collected data.

OBJECTIVE: to investigate whether two clustering approaches applied to the same database would lead to differences in the minimal clinical important difference (MCID) for health-related quality of life parameters (HRQoL).

SUMMARY OF BACKGROUND DATA: Machine learning approaches are being increasingly employed for the analysis of complex and heterogeneous settings such as that of adult spine deformity (ASD). However, it is not yet clear whether and how the choice of number and type of variables impacts the outcomes of a study.

METHODS: Two previously published clustering approaches (C12 and C16) were applied to a multicentric database of ASD patients who underwent surgery and had a minimum follow-up of one year. After clustering, the MCID for the Oswestry Disability Index, SRS-22, and SF-36 PCS were calculated for all clusters using the ROC method.

RESULTS: Data from 516 patients were available. Both algorithms led to a division of the database in three clusters, which presented similar characteristics both for C12 and C16. In particular, patients in clusters 1 to 3 presented an increasing level of imbalance and disability. The MCID for ODI, SRS-22, and SF-36 for each cluster differed between C12 and C16, but a similar pattern of increase of the MCID from Cluster 1 to Cluster 3 was observed for all HRQoL parameters and in both C12 and C16. The error rate, however, was smaller for C16.

CONCLUSION: Different clustering algorithms applied to the same database allowed to obtain similar clusters of ASD patients. However, the obtained MCIDs for the evaluated HRQoL parameters were different, highlighting the relevance of the choice of variables for the investigation of these parameters. The results suggest that clinically-driven clusters should be used when investigating clinical outcomes, as they allow for a smaller error rate.

PMID:40667701 | DOI:10.1097/BRS.0000000000005453

Nutritional and physiological limitations shape the radiation-use efficiency response to legume proportion in C<sub>4</sub> grass-legume mixtures

Wed, 16/07/2025 - 11:00

AoB Plants. 2025 Jun 26;17(4):plaf036. doi: 10.1093/aobpla/plaf036. eCollection 2025 Aug.

ABSTRACT

Legume introduction is effective for boosting primary productivity in C4-grass-dominated subtropical and tropical grasslands by overcoming nitrogen (N) limitation and consequently improving radiation-use efficiency (RUE), a key metric underlying plant production. However, an excessive proportion of C3 legumes may negatively affect RUE, especially in warm climates. We assessed the relationship between aboveground RUE and legume proportion of Paspalum notatum Flügge (C4 grass) mixtures with a tropical legume (Arachis glabrata Benth.; 0%-80%) under different defoliation and N fertilizer treatments in two studies over 3 years in Florida, USA. Linking the field data to a conceptual model, RUE was optimized at 26%-30% legume proportion across studies and years. When pastures were N-fertilized, RUE plateaued at 26% legume (0.60 g MJ-1) and linearly decreased with higher legume proportions. When pastures were unfertilized, RUE showed a quadratic relationship with legume proportion, being maximized at 30% legume (1.10 g MJ-1), overyielding the RUE in only-grass and legume-dominated sites by 110% and 86%, respectively. These responses suggest that RUE is N-limited when legume is below 30% in unfertilized canopies and is physiologically limited when legume is above 30% due to replacement of the C4 grass with a C3 legume. These findings provide a robust rationale to target low-to-moderate legume proportions in tropical grasslands for optimizing production and other ecosystem services. We empirically demonstrated that optimum legume proportion is ∼30% in a C4-grass-based tropical grassland compared with previous observations of ≥40% in C3-grass-based temperate grasslands, relevant insights for the design and maintenance of grassland ecosystems.

PMID:40667455 | PMC:PMC12260219 | DOI:10.1093/aobpla/plaf036

The SpyBLI cell-free pipeline for the rapid quantification of binding kinetics from crude samples

Mon, 14/07/2025 - 11:00

RSC Chem Biol. 2025 Jun 23. doi: 10.1039/d5cb00079c. Online ahead of print.

ABSTRACT

Accurate measurements of binding kinetics, encompassing equilibrium dissociation constant (K D), association rate (k on), and dissociation rate (k off), are critical for the development and optimisation of high-affinity binding proteins. However, such measurements require highly purified material and precise ligand immobilisation, limiting the number of binders that can be characterised within a reasonable timescale and budget. Here, we present the SpyBLI method, a rapid and cost-effective biolayer interferometry (BLI) pipeline that leverages the SpyCatcher003-SpyTag003 covalent association, eliminating the need for both binder purification and concentration determination. This approach allows for accurate binding-kinetic measurements to be performed directly from crude mammalian-cell supernatants or cell-free expression blends. We also introduce a linear gene fragment design that enables reliable expression in cell-free systems without any PCR or cloning steps, allowing binding kinetics data to be collected in under 24 hours from receiving inexpensive DNA fragments, with minimal hands-on time. We demonstrate the method's broad applicability using a range of nanobodies and single-chain antibody variable fragments (scFvs), with affinity values spanning six orders of magnitude. By minimising sample preparation and employing highly controlled, ordered sensor immobilisation, our workflow delivers reliable kinetic measurements from crude mixtures without sacrificing precision. We expect that the opportunity to carry out rapid and accurate binding measurements in good throughput should prove especially valuable for binder engineering, the screening of next-generation sequencing-derived libraries, and computational protein design, where large numbers of potential binders for the same target must be rapidly and accurately characterised to enable iterative refinement and candidate selection.

PMID:40655043 | PMC:PMC12247212 | DOI:10.1039/d5cb00079c

Correction to "Catalytic Asymmetric Synthesis of β-Amino α-Tertiary Alcohol through Borrowing Hydrogen Amination"

Mon, 14/07/2025 - 11:00

Org Lett. 2025 Jul 14. doi: 10.1021/acs.orglett.5c02795. Online ahead of print.

NO ABSTRACT

PMID:40653978 | DOI:10.1021/acs.orglett.5c02795

Delineating roles of Nb<sup>V</sup> and Zr<sup>IV</sup> oxoclusters in aqueous phase degradation of phosphonate nerve agent simulants

Fri, 11/07/2025 - 11:00

Chem Commun (Camb). 2025 Jul 11. doi: 10.1039/d5cc03483c. Online ahead of print.

ABSTRACT

Nb-polyoxometalates (Nb-POMs) and Zr-metal organic frameworks (Zr-MOFs) are two of the most proven metal-oxide based materials for nerve gas degradation, purported for base and acid hydrolysis mechanisms respectively. We compare nerve-agent simulant degradation between several Nb-POMs plus a Zr-oxyhydroxide cluster, as a soluble surrogate for Zr-MOFs. We conclude that lability of the metal-oxo species and re-hydrolysis of metal fluoride or metal phosphonate bonds is as important, if not more important than acid/base catalysis of the metal-cation.

PMID:40641320 | DOI:10.1039/d5cc03483c

A Pathway to Healthier Aging or an Illusion? A Narrative Review on Deprescribing Protocols for the Elderly

Fri, 04/07/2025 - 11:00

Sage Open Aging. 2025 Jun 9;11:30495334251345091. doi: 10.1177/30495334251345091. eCollection 2025 Jan-Dec.

ABSTRACT

Polypharmacy is the concurrent use of many drugs increasingly prevalent in elderly populations worldwide, with over 50% of older adults taking more than five drugs. The rise in chronic conditions such as diabetes, hypertension, and dementia largely drives this trend. However, polypharmacy poses significant risks, including adverse drug events, falls, cognitive decline, and hospitalizations, particularly due to age-related physiological changes that alter drug metabolism and clearance. Vulnerable populations, especially those with comorbidities, face heightened risks of complications associated with polypharmacy, underscoring the need for effective management strategies. Despite extensive literature on polypharmacy, gaps remain in practical, evidence-based approaches to safely reduce medication burdens. Structured deprescribing protocols are emerging as a critical intervention for reducing inappropriate medication use, improving patient outcomes, and lowering healthcare costs. These protocols involve stepwise algorithms and tools for screening to find potentially inappropriate medications and clinical decision-making frameworks to prioritize deprescribing as it can reduce fall risk, hospitalizations, and healthcare costs while enhancing quality of life. This narrative review examines evidence from trials, cohort studies, and meta-analyses on deprescribing protocols, highlighting challenges like patient resistance and withdrawal effects. It emphasizes tailored approaches, patient engagement, and shared decision-making for safe, effective, patient-centered deprescribing across healthcare settings.

PMID:40611862 | PMC:PMC12220885 | DOI:10.1177/30495334251345091

Harnessing artificial intelligence for sustainable urban development: advancing the three Zeros method through innovation and infrastructure

Wed, 02/07/2025 - 11:00

Sci Rep. 2025 Jul 2;15(1):23673. doi: 10.1038/s41598-025-07436-1.

ABSTRACT

Integrating artificial intelligence (AI) into sustainable urban development presents an innovative pathway for addressing global environmental and socio-economic challenges. This study examines how AI technologies-such as machine learning, the Internet of Things (IoT), and big data analytics-can advance the three zeros method, a sustainability framework proposed by Nobel laureate Muhammad Yunus, which focuses on zero carbon emissions, zero poverty, and zero waste. By analyzing panel data across 50 countries and incorporating case studies, the research highlights AI's role in promoting carbon neutrality, economic inclusivity, and waste reduction. The findings reveal that AI-driven R&D innovation exerts the most decisive influence on sustainability, followed by AI-powered infrastructure, while market advantage plays a comparatively more minor role. Additionally, the study uncovers regional disparities in AI's impact, with the most significant benefits observed in countries at upper-middle levels of sustainable development. Moreover, urbanization serves as a threshold factor, altering AI's effects on sustainability. When urbanization is below a critical level, AI-driven innovation and infrastructure support sustainability, whereas the AI market advantage inhibits it. However, infrastructure may hinder sustainable development beyond this threshold while AI market mechanisms become more influential. These insights underscore the need for policymakers to tailor AI-driven sustainability strategies based on urbanization dynamics and regional development levels.

PMID:40603460 | DOI:10.1038/s41598-025-07436-1

Mixed-methods study to assess delay among patients with tuberculosis in an urban setting of Bangladesh

Tue, 01/07/2025 - 11:00

PLoS One. 2025 Jul 1;20(7):e0327348. doi: 10.1371/journal.pone.0327348. eCollection 2025.

ABSTRACT

BACKGROUND: Tuberculosis (TB) regained its position as the leading cause of death globally from a single infectious disease agent in 2024. Delayed diagnosis and treatment hamper effective TB control. We investigated the duration of diagnostic and treatment delay along with the associated factors among people with pulmonary TB in Bangladesh.

METHODS: A mixed-method study was conducted between December'19 and March'21, at icddr,b TB Screening and Treatment Centres (TBSTCs), Dhaka. We interviewed people with TB (PWTB) seeking care at these TBSTCs using a structured questionnaire to collect data on socio-demographic, clinical and healthcare seeking behaviors. We used established frameworks to define stages of delay and associated factors. Qualitative interviews were conducted among a subset of participants to gain further insight into the factors associated with delay.

RESULTS: We enrolled 895 PWTB with mean (±SD) age 36.6 (±16.1) years; majority of participants were males (69.9%) and living in urban areas (82.3%). The median (IQR) patient delay estimated was 47 (29-72) days, with diagnostic delay 45 (30-70) days and treatment delay 2 (2-4) days. The predictors of delay were those with diabetes (OR 2.0, 95% CI - 1.11, 3.42), who initially self-treated (OR 2.1, 95% CI - 1.09, 3.88), and were bacteriologically diagnosed (OR 3.7, 95% CI - 1.31, 10.46). Qualitative approach supported the quantitative findings and revealed the practice of visiting formal physicians during worsening illness, neglecting to acknowledge signs or symptoms consistent with TB, lack of TB related knowledge, and financial insolvency as major reasons for delay.

CONCLUSION: Our findings showed that improper health-seeking behavior is one of the major drivers of patient delay. Thus, targeted programmatic intervention to raise community awareness on TB and its care services with a special focus on informal providers can help reduce this delay.

PMID:40591627 | DOI:10.1371/journal.pone.0327348

Clinical Implications of Pharmacogenomics of β<sub>1</sub>-Adrenoceptor for Anesthesia

Sat, 28/06/2025 - 11:00

J Cardiothorac Vasc Anesth. 2025 May 8:S1053-0770(25)00363-5. doi: 10.1053/j.jvca.2025.05.006. Online ahead of print.

ABSTRACT

Genetic polymorphisms within the β1-adrenoceptor are common within the population. Although not directly causative of disease, accumulating evidence supports that they have significant molecular and clinical effects, including altering the response to inotropes and β-blockers, as well as altering exercise capacity. Here, we summarize current evidence as relevant to anesthetists who treat patients with heart failure.

PMID:40581538 | DOI:10.1053/j.jvca.2025.05.006

Genomic features and pathogenic potential of <em>Streptococcus agalactiae</em> isolated from bovine clinical mastitis

Thu, 26/06/2025 - 11:00

J Adv Vet Anim Res. 2025 Mar 24;12(1):80-89. doi: 10.5455/javar.2025.l874. eCollection 2025 Mar.

ABSTRACT

OBJECTIVE: The goal of this study is to describe the genome of Streptococcus agalactiae that was found in clinical mastitis in cattle in Bangladesh. This work will show how strong the bacteria are and how important they are for public health.

MATERIALS AND METHODS: Whole genome sequencing (WGS) was performed using the Illumina MiSeq platform, followed by comprehensive analysis with various bioinformatic tools to identify key genomic features.

RESULTS: WGS revealed that the isolates are closely related, belonging to sequence type ST4, a rare type previously identified in both human and animal hosts. The isolates possess 44 virulence-related genes linked to adherence, capsule biogenesis, enzyme production, immunoreactive antigens, protease, and cytolysin production. They also carry two pilus islands (PIs), PI-1 and PI-2b, which are often associated with invasive diseases. PI-2b proteins are key targets for vaccine development against Group B Streptococcus (GBS). The isolates belong to serotype Ia and carry the gbs2018-2 variant, indicating their adaptability to a wide range of hosts, including humans and animals. These virulence factors are critical for understanding S. agalactiae's pathogenicity and developing vaccines against its infections. Additionally, the isolates harbor antimicrobial resistance genes conferring resistance to glycopeptides (vanT, vanY), macrolides (mreA), peptides (mprF), penicillins and β-lactams (pbp), and aminoglycosides. Source tracking via the BacWGSTdb website identified these isolates as closely related to human pathogens, indicating their zoonotic potential.

CONCLUSION: These results suggest that S. agalactiae could be a zoonotic pathogen. This highlights the need for ongoing genomic surveillance to fully understand how it causes disease and come up with effective ways to control it.

PMID:40568491 | PMC:PMC12186781 | DOI:10.5455/javar.2025.l874

Amyloid Forming Human Lysozyme Intermediates are Stabilized by Non-Native Amide-π Interactions

Wed, 25/06/2025 - 11:00

Adv Sci (Weinh). 2025 Jun 25:e03957. doi: 10.1002/advs.202503957. Online ahead of print.

ABSTRACT

Mutational variants of human lysozyme cause a rare but fatal hereditary systemic amyloidosis by populating an intermediate state that self-assembles into amyloid fibrils. However, this intermediate state is recalcitrant to detailed structural investigation, as it is only transiently and sparsely populated. Here, this work investigates the intermediate state of an amyloid-forming human lysozyme variant (I59T) using CEST and CPMG RD NMR at low pH. 15N CEST profiles probe the thermal unfolding of the native state into the denatured ensemble and reveal a distinct intermediate state. Global fitting of 15N CEST and CPMG data provides kinetic and thermodynamic parameters, characterizing the intermediate state populated at 0.6%. 1H CEST data further confirm the presence of the intermediate state displaying unusually high or low 1HN chemical shifts. To investigate the structural details of this intermediate state, this work uses molecular dynamics (MD) simulations, which recapitulate the experimentally observed folding pathway and free energy landscape. This work observes a high-energy intermediate state with a locally disordered β-domain and C-helix, stabilized by non-native hydrogen bonding and amide-π interactions, accounting for its anomalous 1H chemical shifts. Together, these NMR and MD data provide the first direct structural information on the intermediate state, offering insights into targeting lysozyme amyloidosis.

PMID:40557600 | DOI:10.1002/advs.202503957

Association of LEPR Gene Polymorphisms With Youth-Onset Diabetes in Bangladesh

Tue, 24/06/2025 - 11:00

Cureus. 2025 May 23;17(5):e84696. doi: 10.7759/cureus.84696. eCollection 2025 May.

ABSTRACT

Introduction Polymorphisms of the leptin receptor (LEPR) gene are associated with type 2 diabetes mellitus (T2DM), but the association varies among different geographic populations. The present study aims to observe the association of single-nucleotide polymorphisms (SNPs) of the LEPR gene (rs1137100 and rs1137101) with youth-onset T2DM in Bangladesh. Methods This case-control study encompassed 62 individuals with youth-onset T2DM (age range 18-29 years) and an equal number of age-matched controls with normal glucose tolerance (NGT). Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes of both LEPR SNPs were expressed as AA, AG, and GG, where G is considered a risk allele. Results The frequency of G-allele was higher in DM than in NGT for both rs1137100 (55.6% (69/124) vs. 42.7% (53/124); OR 1.7, 95% CI 1.02-2.78; p=0.042) and rs1137101 (59.7% (74/124) vs. 41.9% (52/124); OR 95% CI 1.24-3.40, p=0.005). In the codominant model, the GG genotype was associated with DM (GG vs. AA: rs1137100: OR 3.37; CI 1.11-10.19; p=0.032; rs1137101: OR 4.93; CI 1.62-14.99; p=0.005) but not the AG genotype (AG vs. AA). In the dominant model, the risk variants AG+GG (vs. AA) of rs1137100 did not have an association (p=0.289), but rs1137101 had (OR 2.60; CI 1.07-6.33; p=0.035). In the recessive model, risk variant GG (vs. AG+AA) of both SNPs had an association with DM (rs1137100: OR 2.98; CI 1.19-7.47; p=0.017; rs1137101: OR 3.02; CI 1.25-7.27; p=0.014). No association was significant in any models when adjusted for body mass index (BMI). Conclusion Although the LEPR gene SNPs rs1137100 and rs1137101 show a potential association with an increased risk of youth-onset T2DM in the Bangladeshi population, this association appears to be BMI-dependent.

PMID:40551902 | PMC:PMC12182985 | DOI:10.7759/cureus.84696

Voclosporin: A comprehensive review of its role as a novel calcineurin inhibitor in the management of systemic lupus erythematosus

Mon, 23/06/2025 - 11:00

Medicine (Baltimore). 2025 Jun 20;104(25):e42858. doi: 10.1097/MD.0000000000042858.

ABSTRACT

Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations, including lupus nephritis. Calcineurin inhibitors (CNIs) are a treatment option, but traditional CNIs have limitations. Voclosporin, a novel oral CNI, inhibits calcineurin to modulate T-cell activation and stabilize podocytes in lupus nephritis. This review assesses voclosporin's therapeutic potential in treating SLE (lupus nephritis), examining its mechanism of action, clinical efficacy, safety profile, and advantages over other CNIs. A broad search was conducted to identify studies published from 2009 to 2024 on voclosporin and other CNIs in lupus nephritis, using databases such as PUBMED, SCOPUS, Google Scholar and Cochrane Library. MeSH Keywords included "voclosporin," "lupus nephritis," "systemic lupus erythematosus," and "calcineurin inhibitors." Studies were included if they reported relevant clinical outcomes, evaluated voclosporin in lupus nephritis, or provided comparative data on voclosporin versus other CNIs, focusing on randomized controlled trials, systematic reviews, meta-analyses, retrospective studies and cohort studies. Voclosporin demonstrated higher renal response rates at 52 weeks than standard treatment alone (40.8% vs 22.5%). It has stable pharmacokinetics, reducing the need for individualized dose adjustments and frequent monitoring. Safety outcomes show a lower incidence of adverse effects like hypertension and hyperlipidemia compared to traditional CNIs. Voclosporin offers superior efficacy and safety compared to traditional CNIs for managing lupus nephritis, with predictable dosing and a favorable side effect profile. Continued research is needed to optimize voclosporin's use and support personalized medicine approaches.

PMID:40550096 | DOI:10.1097/MD.0000000000042858

Erratum: Opportunities and challenges for people-centered multi-hazard early warning systems: Perspectives from the Global South

Mon, 23/06/2025 - 11:00

iScience. 2025 Jun 6;28(6):112784. doi: 10.1016/j.isci.2025.112784. eCollection 2025 Jun 20.

ABSTRACT

[This corrects the article DOI: 10.1016/j.isci.2025.112353.].

PMID:40546946 | PMC:PMC12179605 | DOI:10.1016/j.isci.2025.112784

Clinical outcome and deep learning imaging characteristics of patients treated by radio-chemotherapy for a "molecular" glioblastoma

Sat, 21/06/2025 - 11:00

Oncologist. 2025 Jun 4;30(6):oyaf127. doi: 10.1093/oncolo/oyaf127.

ABSTRACT

BACKGROUND: Since 2021, glioblastomas have been classified into two subgroups: classic glioblastomas (histGB), defined as IDH wild-type grade 4 astrocytomas with necrosis and vascular proliferation, showing contrast enhancement (CE) on MRI; and molecular glioblastomas (molGB), characterized by specific alterations (7+/10-, EGFR amplification, TERT mutation). Although not always the case, molGB often lack CE and may mimic low-grade gliomas (LGG), hence complicating the diagnosis. Survival outcomes remain debated. This study aimed to evaluate the response of molGB to standard treatment and assess the ability of machine learning and deep learning to differentiate molGB without CE from LGG on MRI.

METHODS: We retrospectively studied 132 glioblastoma patients treated with radiotherapy and temozolomide, comparing the survival outcomes of histGB and molGB. Artificial intelligence (AI) models were trained using features from MRI FLAIR hypersignal segmentation to distinguish molGB without CE from LGG.

RESULTS: No significant difference in median overall survival (OS) (20.6 vs 18.4 months, P = .2) or progression-free survival (10.1 vs 9.3 months, P = .183) was observed between molGB and histGB. However, molGB without CE demonstrated improved median OS (31.2 vs 18 months, hazard ratios 0.45). Artificial intelligence models distinguished molGB without CE from LGG, achieving a best-performing ROC AUC of 0.85.

CONCLUSIONS: While patients with molGB and histGB have similar overall survival, patients with molGB without CE appear to have better outcomes. Artificial intelligence models effectively differentiate molGB from LGG, supporting their potential diagnostic utility.

PMID:40542584 | DOI:10.1093/oncolo/oyaf127

Click biology highlights the opportunities from reliable biological reactions

Thu, 19/06/2025 - 11:00

Nat Chem Biol. 2025 Jun 19. doi: 10.1038/s41589-025-01944-x. Online ahead of print.

ABSTRACT

Click chemistry is a powerful concept that refers to a set of covalent bond-forming reactions with highly favorable properties. In this Perspective, I outline the analogous concept of click biology as a set of reactions derived from the regular building blocks of living cells, rapidly forming covalent bonds to specific partners under cell-friendly conditions. Click biology using protein components employs canonical amino acids and may react close to the diffusion limit, with selectivity in living cells amid thousands of components generated from the same building blocks. I discuss how the criteria for click chemistry can be applied or modified to fit the extra constraints of click biology and achieve favorable characteristics for biological research. Existing reactions that may be described as click biology include split intein reconstitution, spontaneous isopeptide bond formation by SpyTag and SpyCatcher and suicide enzyme reaction with small-molecule ligands (HaloTag and SNAP-tag). I also describe how click biology has created new possibilities in fields including molecular imaging, mechanobiology, vaccines and engineering cellular intelligence.

PMID:40537536 | DOI:10.1038/s41589-025-01944-x

Severe scoliotic deformities: results of surgical treatment and complications in a multicentric series of children and young adults

Thu, 19/06/2025 - 11:00

Spine Deform. 2025 Jun 19. doi: 10.1007/s43390-025-01122-y. Online ahead of print.

ABSTRACT

PURPOSE: The surgical management of severe spinal deformities (> 80°) in children and young adults remains challenging despite technical advances. Large, stiff curves with a short radius present a high complication rate, also in terms of acute or chronic spinal cord injury. There is a lack of consensus regarding the perioperative management of these curves, also due to the limited evidence available. This study aimed to review the strategies used in different hospitals for the surgical management of severe spinal deformities in young subjects and, in particular, to analyze the complication rate in a large series of patients.

METHODS: Multicentric, retrospective study on surgically treated patients younger than 25 with a coronal or sagittal deformity measuring at least 80°. Perioperative and radiographic data were collected. The rate of mechanical, neurologic, infectious, and other complications was analyzed, along with possible risk factors.

RESULTS: Data from 161 patients were analyzed. After surgery, there was a significant improvement of the deformity both on the coronal and sagittal plane. The overall complication rate was 25%. An increased angular ratio in the first postoperative X-ray was the main risk factor for the development of complications, along with a higher correction of the spinosacral angle. Performing a 3CO was associated with a higher risk of infections but not with a higher risk of mechanical complications. The use of an anterior approach did not increase the complication rate. A higher rate of non-mechanical and non-infectious complications was observed in patients who did not wear a brace or did not undergo halo traction before surgery.

CONCLUSION: While spinal fusion is an effective treatment for the management of severe deformities, the rate of complications is still high.

PMID:40536621 | DOI:10.1007/s43390-025-01122-y

Ammonium Cation-Promoted CO<sub>2</sub> Electroreduction on Au in Acidic Media

Wed, 18/06/2025 - 11:00

J Am Chem Soc. 2025 Jun 18. doi: 10.1021/jacs.5c08017. Online ahead of print.

ABSTRACT

The electrochemical reduction of CO2 in acidic media has received considerable attention, as it can mitigate the carbonate formation issue. However, the available protons in acidic media can boost the hydrogen evolution reaction (HER), so alkali metal cations are generally employed to promote the CO2 reduction reaction (CO2RR) while suppressing the HER. Here we report that NH4+ cations are more effective promoters of CO2 electrolysis on Au in acidic media than Na+ and K+, achieving a 3-fold improvement in the CO2RR activity. The promotional effect of NH4+ cations is mainly attributed to their enhanced electrostatic stabilization of the CO2 adsorption, which is the rate-limiting step for the CO2RR on Au. An estimation of the local pH under relevant conditions indicates that NH4+ can mitigate the interfacial pH swing during the CO2RR compared to Na+ and K+. Further studies on Au nanocatalysts of varying sizes indicate that the cation effect is independent of the catalytic sites. Our work advances the understanding of the cation effect on CO2RR using nonmetal cations and demonstrates a viable cation strategy to enhance CO2 electrolysis.

PMID:40530857 | DOI:10.1021/jacs.5c08017

Corrigendum: An enhanced pattern detection and segmentation of brain tumors in MRI images using deep learning technique

Wed, 18/06/2025 - 11:00

Front Comput Neurosci. 2025 Jun 3;19:1570979. doi: 10.3389/fncom.2025.1570979. eCollection 2025.

ABSTRACT

[This corrects the article DOI: 10.3389/fncom.2024.1418280.].

PMID:40529250 | PMC:PMC12170620 | DOI:10.3389/fncom.2025.1570979