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Nat Cardiovasc Res. 2026 Feb 6. doi: 10.1038/s44161-026-00776-9. Online ahead of print.

ABSTRACT

Myocardial injuries lead to cardiomyocyte loss and heart failure. Endogenous glucocorticoids, via the glucocorticoid receptor (GR), limit cardiomyocyte regeneration. Here we show that glucocorticoids suppress mammalian (murine) cardiomyocyte proliferative response to regenerative growth factors and cytokines. GR activation in neonatal cardiomyocytes upregulated MAPK-ERK inhibitors ERRFI1 and DUSP1. Using neuregulin 1 as a model, we demonstrated that glucocorticoids inhibit growth-factor-induced ERK activation, nuclear translocation and transcriptional output. Errfi1 and Dusp1 knockdown restored growth-factor-induced proliferation of glucocorticoid-exposed cardiomyocytes. Cardiac expression of DUSP1 and ERRFI1 increased postnatally, coinciding with regenerative capacity decline. In juvenile and adult cardiomyocytes, regenerative growth factors failed to induce the MAPK-ERK pathway and proliferation; however, DUSP1 inhibition restored these responses. GR antagonism enhanced growth-factor-induced cardiomyocyte protection, proliferation and cardiac function after adult myocardial injury. These findings reveal the emergence of a postnatal systemic brake on cardiomyocyte proliferative response to growth factors and support GR inhibition as a strategy to enhance growth-factor-based regenerative therapies.

PMID:41652035 | DOI:10.1038/s44161-026-00776-9

Nat Cardiovasc Res. 2026 Feb 6. doi: 10.1038/s44161-026-00776-9. Online ahead of print.

ABSTRACT

Myocardial injuries lead to cardiomyocyte loss and heart failure. Endogenous glucocorticoids, via the glucocorticoid receptor (GR), limit cardiomyocyte regeneration. Here we show that glucocorticoids suppress mammalian (murine) cardiomyocyte proliferative response to regenerative growth factors and cytokines. GR activation in neonatal cardiomyocytes upregulated MAPK-ERK inhibitors ERRFI1 and DUSP1. Using neuregulin 1 as a model, we demonstrated that glucocorticoids inhibit growth-factor-induced ERK activation, nuclear translocation and transcriptional output. Errfi1 and Dusp1 knockdown restored growth-factor-induced proliferation of glucocorticoid-exposed cardiomyocytes. Cardiac expression of DUSP1 and ERRFI1 increased postnatally, coinciding with regenerative capacity decline. In juvenile and adult cardiomyocytes, regenerative growth factors failed to induce the MAPK-ERK pathway and proliferation; however, DUSP1 inhibition restored these responses. GR antagonism enhanced growth-factor-induced cardiomyocyte protection, proliferation and cardiac function after adult myocardial injury. These findings reveal the emergence of a postnatal systemic brake on cardiomyocyte proliferative response to growth factors and support GR inhibition as a strategy to enhance growth-factor-based regenerative therapies.

PMID:41652035 | DOI:10.1038/s44161-026-00776-9

Cureus. 2026 Jan 5;18(1):e100833. doi: 10.7759/cureus.100833. eCollection 2026 Jan.

ABSTRACT

Circulating tumor DNA (ctDNA), the tumor-derived fraction of cell-free DNA, has emerged as a valuable biomarker for monitoring treatment response, detecting minimal residual disease (MRD), and identifying early cancer recurrence. While histologic tissue diagnosis remains the gold standard for confirming malignancy, guidelines from organizations such as the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) acknowledge that ctDNA may serve as a supplemental tool in rare instances where tissue is unobtainable. In such cases, results should be interpreted alongside clinical and radiologic findings, with tissue confirmation pursued whenever possible. This case series presents three distinct breast cancer cases in which ctDNA-based MRD detection was instrumental in identifying recurrence and guiding precision therapy based on actionable genomic alterations when biopsy was not feasible or inconclusive.

PMID:41646612 | PMC:PMC12871081 | DOI:10.7759/cureus.100833

BMJ Open. 2026 Feb 5;16(2):e103984. doi: 10.1136/bmjopen-2025-103984.

ABSTRACT

OBJECTIVES: The study aimed to determine the prevalence and identify the associated factors of undernutrition among children under 5 years of age living in riverbank erosion areas in Bangladesh.

STUDY DESIGN: A community-based cross-sectional study.

SETTING: The study was carried out in riverbank erosion-prone areas of the Tangail and Kushtia districts of Bangladesh, which were selected because they are highly vulnerable to riverbank erosion and related livelihood disruptions.

PARTICIPANTS: Participants were selected using a two-stage cluster sampling technique based on the criterion that mothers had at least one child under the age of 5 years.

OUTCOMES: Stunting, wasting and underweight were considered independently as outcome variables to assess nutritional status.

METHODS: Descriptive analysis was performed to determine the prevalence of undernutrition, while the χ² test and multivariable Poisson regression model were used to identify significantly associated factors with undernutrition among children under 5 years of age in riverbank erosion areas.

RESULTS: The average prevalence of stunting, wasting and underweight was 37.74%, 22.64% and 9.81%, respectively. Results from the Poisson regression model showed that children who were average or large in size at birth had a much lower prevalence of all forms of undernutrition compared with those born very small. Female children had a 30% lower prevalence of stunting compared with male children. In addition, having educated parents, receiving four or more antenatal care visits and household livestock ownership were each associated with a lower prevalence of undernutrition.

CONCLUSION: The prevalence of stunting in this study was higher than that reported in the most recent Bangladesh Demographic and Health Survey 2022. Child size at birth, sex, parental education, antenatal care visits and household livestock ownership were identified as significantly associated factors with undernutrition in riverbank erosion areas of Bangladesh.

PMID:41644157 | DOI:10.1136/bmjopen-2025-103984

Science. 2026 Feb 5;391(6785):553-554. doi: 10.1126/science.aee5778. Epub 2026 Feb 5.

ABSTRACT

DNA origami scaffolds displaying HIV antigens stimulate focused antibody responses in mice.

PMID:41643031 | DOI:10.1126/science.aee5778

Science. 2026 Feb 5;391(6785):553-554. doi: 10.1126/science.aee5778. Epub 2026 Feb 5.

ABSTRACT

DNA origami scaffolds displaying HIV antigens stimulate focused antibody responses in mice.

PMID:41643031 | DOI:10.1126/science.aee5778

ACS Appl Bio Mater. 2026 Feb 4. doi: 10.1021/acsabm.5c02239. Online ahead of print.

ABSTRACT

Reconfigurable intelligent surfaces (RISs) are key enabling technologies for next-generation wireless telecommunication systems, offering dynamic control over electromagnetic (EM) wave propagation. However, most existing RIS demonstrations rely on conventional electronic or metallic platforms, raising concerns about resource availability, recyclability, and environmental sustainability. In this study, hybrid nanostructured RIS prototypes (Prototypes I-III) were designed and fabricated using sustainable, wood-derived materials, namely, cellulose nanofibers (CNFs), suberin, and biocarbon, in combination with thermoresponsive vanadium dioxide (VO2) nanoparticles. The EM performance of these RIS architectures was first optimized through full-wave simulations and then validated experimentally by the cast-layer deposition of VO2/CNF-suberin functional layers onto printed circuit board (PCB) substrates. Among the tested designs, Prototype I, comprising a functional layer of 95 wt % VO2, 2.5 wt % nonderivatized CNF, and 2.5 wt % suberin, exhibited the most pronounced thermal response, showing resonance frequency shifts of up to 19 MHz at a 5 GHz center frequency and phase shifts of 83° with temperature variation. Prototype II, containing cationic CNFs, demonstrated improved mechanical stability but reduced electrical continuity due to microstructural cracking, whereas Prototype III, modified with biocarbon, displayed diminished conductivity arising from its lower VO2 content. Degree of linear polarization (DOLP) analysis revealed early stage phase transitions that occurred prior to complete conductive pathway formation. Overall, the hybrid RIS architectures developed from VO2 and wood-derived materials through a sustainable processing route exhibited highly tunable, temperature-triggered EM modulation, with sensitivity ranging from low to high, depending on the material composition and assembly configuration.

PMID:41636383 | DOI:10.1021/acsabm.5c02239

Eur J Vasc Endovasc Surg. 2026 Feb 1:S1078-5884(26)00093-6. doi: 10.1016/j.ejvs.2026.01.056. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare high ligation and stripping (HLS), endovenous laser ablation (EVLA), and ultrasound guided foam sclerotherapy (UGFS) for symptomatic great saphenous vein (GSV) reflux in the long term, given the limited comparative data beyond ten years.

METHODS: Patients with symptomatic GSV reflux were randomised (1:1:1) to undergo HLS, EVLA, or UGFS. One hundred and ninety-six patients treated at Helsinki University Hospital were invited to 14 year follow up. Primary outcomes were above knee GSV reflux and GSV re-intervention rates. Secondary outcomes included quality of life.

RESULTS: Of 233 randomised patients, 214 were included. UGFS increased the risk of GSV reflux recurrence compared with both HLS (risk ratio [RR] 11.7, 95% confidence interval [CI] 1.6 - 85.6) and EVLA (RR 5.0, 95% CI 1.5 - 16.6; 30.8% [12 of 39] after UGFS vs. 2.6% [1 of 38] and 6.1% [3 of 49] after HLS and EVLA, respectively; overall p < .001). UGFS was associated with a higher risk of GSV re-interventions compared with HLS (RR 4.3, 95% CI 1.8 - 10.2) and EVLA (RR 6.9, 95% CI 2.6 - 18.4; 56.4% for UGFS vs. 13.2% for HLS and 8.2% for EVLA; overall p < .001). Neovascularisation rates did not differ between the treatments (29.0%, 22.5%, and 23.1% for HLS, EVLA, and UGFS, respectively; overall p = .76). Aberdeen Varicose Vein Questionnaire scores were comparable across the groups (median [interquartile range] 8.9 [3.7, 13.3] in HLS, 6.1 [0.8, 12.2] in EVLA, and 8.8 [4.1, 13.4] in UGFS, with median differences of +2.8 [HLS vs. EVLA], +0.1 [HLS vs. UGFS], and -2.7 [EVLA vs. UGFS]; overall p = .21).

CONCLUSION: UGFS demonstrated inferior outcomes in terms of GSV recurrent reflux and re-intervention rates compared with both HLS and EVLA, whereas HLS and EVLA showed comparable performance across these outcomes. Long term quality of life was comparable across all groups.

PMID:41633433 | DOI:10.1016/j.ejvs.2026.01.056

Arch Microbiol. 2026 Feb 2;208(4):175. doi: 10.1007/s00203-026-04735-7.

NO ABSTRACT

PMID:41627457 | DOI:10.1007/s00203-026-04735-7

Bioinformation. 2025 Oct 31;21(10):3703-3709. doi: 10.6026/973206300213703. eCollection 2025.

ABSTRACT

The diagnostic performance of the BARD scoring system in detecting significant fibrosis (≥F2) among Bangladeshi patients with biopsy-proven NAFLD is of interest. A cross-sectional study was conducted on 40 adult NAFLD patients at Bangladesh Medical University, Dhaka. Liver fibrosis was staged histologically from biopsy specimens. The BARD score was calculated for each patient and its diagnostic accuracy was evaluated using sensitivity, specificity, predictive values and ROC curve analysis. Clinical and biochemical predictors of fibrosis were also assessed. Among the cohort, 45% had significant fibrosis (F2-F4). The BARD score demonstrated a sensitivity of 83.3%, specificity of 86.4%, positive predictive value of 83.3%, negative predictive value of 86.4% and an AUROC of 0.908 (p < 0.001). A strong positive correlation was observed between BARD score and fibrosis stage (r = 0.736). Multivariate analysis identified BMI ≥28 kg/m2 as an independent predictor of significant fibrosis (OR 17.53, p = 0.022). The BARD score is a reliable noninvasive tool for identifying significant liver fibrosis in Bangladeshi NAFLD patients, facilitating early risk stratification and management in resource-limited settings.

PMID:41623788 | PMC:PMC12859260 | DOI:10.6026/973206300213703

Plant Sci. 2026 Jan 29:113010. doi: 10.1016/j.plantsci.2026.113010. Online ahead of print.

ABSTRACT

The Venus flytrap (Dionaea muscipula) closes its trap only after two touches of its sensory hairs within approximately twenty seconds, reflecting a temporally gated threshold mechanism. Using a quantitative reinterpretation of published electrophysiological and mechanical measurements, this correspondence demonstrates that the bistable, memory-dependent closure of the Venus flytrap conforms to a multiplicative threshold framework (ARCH × Φ), in which four readiness domains, architecture (A), drive (D), context (C), and phase (Φ), jointly determine activation. The framework accounts for the two-trigger rule, refractory gating, and the all-or-none nature of trap closure, capturing the plant's energy-efficient bistability.

PMID:41619979 | DOI:10.1016/j.plantsci.2026.113010

J Neurosurg Spine. 2026 Jan 30:1-9. doi: 10.3171/2025.9.SPINE25604. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the impact of four-rod (4R) constructs and interbody cages (IBCs) on pseudarthrosis and rod breakage (PA/RB) in patients with adult spinal deformity (ASD) who had undergone surgery with pelvic fixation and Schwab grade 2 osteotomies, using a combined finite element model (FEM) and clinical data analysis.

METHODS: A validated FEM simulated Schwab grade 2 osteotomies at the L4-5 level in two-rod and 4R configurations, with or without IBCs at L4-5 and L5-S1. Rod strain and range of motion were calculated under a 7.5-Nm moment. Clinical analysis was conducted on ASD patients with pelvic fixation and Schwab grade 2 osteotomies and ≥ 2 years of follow-up. Patients were classified into 2 groups depending on the presence or absence of PA/RB. Demographic, surgical, radiographic, and patient-reported outcome measure (PROM) data were compared.

RESULTS: The FEM analysis revealed maximal rod strain of 399 MPa at the osteotomy site in flexion. The 4R constructs and IBCs reduced strain to 114 MPa at L4-5 and 80 MPa at L5-S1. Among the 213 patients included in the study, PA/RB occurred in 61 (28.6%). Multivariate analysis revealed the use of 4R constructs (OR 0.331, 95% CI 0.16-0.71, p = 0.004) and IBCs (OR 0.46, 95% CI 0.23-0.94, p = 0.033) as protective factors. Patients with PA/RB experienced more unplanned reinterventions, worse scores on PROMs, and greater loss of sagittal alignment at 2 years postoperatively.

CONCLUSIONS: Constructs with 4Rs and IBCs in ASD surgeries with pelvic fixation and Schwab grade 2 osteotomies significantly reduced rod strain and decreased the risk of PA/RB, leading to better scores on PROMs and decreasing unplanned reinterventions and loss of alignment.

PMID:41616294 | DOI:10.3171/2025.9.SPINE25604

Blood. 2026 Jan 29:blood.2025031266. doi: 10.1182/blood.2025031266. Online ahead of print.

ABSTRACT

Acute myeloid leukemia (AML) is a complex hematological malignancy with multiple disease sub-groups defined by somatic mutations and heterogeneous outcomes. Although genome-wide association studies (GWAS) have identified a small number of common genetic variants influencing AML risk, the heritable component of this disease outside of familial susceptibility remains largely undefined. Here we perform a meta-analysis of four published GWAS plus two new GWAS, totalling 4710 AML cases and 12938 controls. We identify a new genome-wide significant risk locus for pan-AML at 2p23.3 (rs4665765; P=1.35x10-8; EFR3B, POMC, DNMT3A, DNAJC27) which also significantly associates with patient survival (P=6.09x10-3). Our analysis also identifies three new genome-wide significant risk loci for disease sub-groups, including AML with deletions of chromosome 5 and/or 7 at 1q23.3 (rs12078864; P=7.0x10-10; DUSP23) and cytogenetically complex AML at 2q33.3 (rs12988876; P=3.28x10-8; PARD3B) and 2p21 (rs79918355; P=1.60x10-9; EPCAM). We also investigated loci previously associated with risk of clonal hematopoiesis (CH) or clonal hematopoiesis of indeterminate potential (CHIP) and identified several variants associated with risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease sub-group specific risk loci.

PMID:41610418 | DOI:10.1182/blood.2025031266

Nat Commun. 2026 Jan 28;17(1):605. doi: 10.1038/s41467-025-67787-1.

ABSTRACT

A discrete time crystal (DTC) is an out-of-equilibrium phase of matter that spontaneously breaks discrete time-translation symmetry. Previous studies have been limited to a set of models with Ising-like couplings - and mostly only in one dimension - thus precluding our understanding of the existence (or not) of DTCs in models with more realistic interactions. In this work, by combining the latest generation of IBM quantum processors with state-of-the-art tensor network methods, we demonstrate the existence of a DTC in a two-dimensional system governed by anisotropic Heisenberg interactions. We uncover a rich phase diagram encompassing spin-glass, ergodic, and time-crystalline phases, and identify the interplay of initialization, interaction anisotropy, and driving protocols in stabilizing the DTC phase. By extending the study of Floquet matter beyond simplified models, we lay the groundwork for exploring how driven systems bridge the gap between quantum coherence and emergent non-equilibrium thermodynamics.

PMID:41605888 | DOI:10.1038/s41467-025-67787-1

PLoS One. 2026 Jan 28;21(1):e0328745. doi: 10.1371/journal.pone.0328745. eCollection 2026.

ABSTRACT

Cancer remains the second leading cause of death worldwide, with cases rising at an alarming rate. While the causes of cancer are complex and varied, certain risk factors - such as exposure to environmental pollutants and specific lifestyle choices - are modifiable and can be addressed. A case-control study was conducted in Bangladesh from 25 August 2023 to 18 April 2024 to examine the association between cancer risk and a range of lifestyle and environmental factors. The study specifically focused on six common cancer types: breast, hematological, oral, cervical, colorectal, and lung cancer. This study identified several lifestyle and environmental factors positively associated with cancer risk. Individuals using wood or kerosene for cooking had higher odds of cancer compared to those using supplied gas (AOR = 3.886). Consumption of overcooked or poorly cooked food was associated with an increased risk of cancer compared to the consumption of well-cooked food (AOR = 2.478). Oral hygiene also showed a relationship, with participants brushing their teeth only 2-3 times a week having a higher chance of cancer compared to those who brush regularly (AOR = 3.103). In addition, frequent exposure to mosquito repellent was positively associated with cancer risk (AOR = 1.569), and exposure to inorganic dust showed a similar association (AOR = 1.673). These findings highlight modifiable lifestyle and environmental factors that could inform future cancer prevention strategies in Bangladesh.

PMID:41604443 | DOI:10.1371/journal.pone.0328745

Ann Bot. 2026 Jan 28:mcag013. doi: 10.1093/aob/mcag013. Online ahead of print.

ABSTRACT

BACKGROUND: Primed acclimation (PA) is a phenomenon where an abiotic stressor early in a plant's vegetative stage primes defense pathways to the same stressor at later developmental stages. Similarly, cross-stress tolerance is a response where an exposure to one abiotic stressor creates a 'stress memory' that can more quickly respond to a later, different abiotic stressor. Cross-priming is a phenomenon where an early abiotic stressor confers defense to a late season biotic stressor. Peanut (Arachis hypogaea L.), an economically important crop in the United States, has exhibited beneficial primed acclimation responses in previous studies. Sclerotium rolfsii, the causal agent of southern blight, can inflict significant economic damage to peanut operations. The purpose of this study was therefore to test for cross-priming against southern blight in two peanut cultivars.

METHODS: In this factorial greenhouse study, we instituted four sequential treatments each with two levels: (1) cv. Florun 331/cv. Georgia-06G, (2) Primary Water Stress (P-50FC)/Primary Well-Watered (P-100FC), (3) Inoculated/Control, and (4) Secondary Water Stress (S-0FC)/Secondary Well-Watered (S-100FC), yielding a total of 16 treatments. The primary water stress (PWS) consisted of irrigating plants to 50% field capacity for 35 days and the secondary water stress (SWS) was the withholding of any water for seven days.

KEY RESULTS: We documented the absence of a beneficial cross-priming result as we did not see reduced southern blight progression among plants exposed to the PWS. Crucially, we observed a three-way interaction between cultivar, PWS, and SWS in inoculated plants, whereby the treatment combinations "Georgia-06G→P-50FC→S-0FC" and "Florun331→P-50FC→S-100FC" had substantially greater disease severity than their P-100FC counterparts. Serendipitously, we observed reduced secondary transmission of southern blight in P-50FC treated plants. Overall, our results caution that drought acclimation may not only fail to deliver crop production benefits but could even have an adverse influence on peanut yields and disease severity.

PMID:41601275 | DOI:10.1093/aob/mcag013

Diagnostics (Basel). 2026 Jan 21;16(2):338. doi: 10.3390/diagnostics16020338.

ABSTRACT

Background/Objectives: Stool-based GeneXpert testing has become a useful approach for diagnosing pediatric pulmonary tuberculosis (PTB). This study compared two stool-processing methods, centrifugation-based processing (CBP) and simple one-step (SOS), for detecting PTB in children using Xpert MTB/RIF Ultra (Ultra). Methods: Children with presumptive PTB were screened cross-sectionally, and stool samples were collected and tested with Ultra using the CBP method from March 2022 to December 2024 across seven divisions of Bangladesh. A subset of stool samples (n = 281) that tested positive (n = 191) and negative (n = 90) by the CBP method were re-tested again with the same sample by Ultra using the SOS method. The results of the Ultra with SOS-processed stool were compared with the CBP method to evaluate overall agreement and detection efficiency across different bacterial burdens. Results: The SOS method detected 97 of 191 CBP-positive samples, resulting in a positive percentage agreement of 50.8% (95% CI: 43.5-58.1). All 90 Ultra-negative stool were also negative by the SOS method, yielding a negative percentage agreement of 100% (95% CI: 96.0-100.0). Overall agreement between the methods was 66.6% (Kappa: 0.398). The SOS method detected 100% of high- (4/4) and medium- (7/7), 97.3% (36/37) of low-, and 83.3% (35/42) of very-low-bacterial-burden samples, but only 14.9% (15/101) of the trace-detected samples that were identified by the CBP method. Conclusions: Stool testing with Ultra using the SOS processing method missed a significant number of the most prevalent form of child TB-the 'trace-detected' category identified by the CBP method. For increased detection of childhood TB nationwide, the national program should prioritize the use of Ultra on stool samples processed by the CBP method.

PMID:41594314 | DOI:10.3390/diagnostics16020338

Eur J Vasc Endovasc Surg. 2026 Jan 22:S1078-5884(26)00065-1. doi: 10.1016/j.ejvs.2026.01.029. Online ahead of print.

ABSTRACT

OBJECTIVE: Simultaneous treatment of tributaries alongside saphenous trunk ablation is considered the standard practice for managing symptomatic varicose disease. Nevertheless, uncertainty persists regarding the optimal timing of tributary treatment. This study aimed to compare early outcomes of concomitant vs. staged tributary treatment performed as an adjunct to saphenous trunk endovenous laser ablation (EVLA).

METHODS: This was a multicentre, non-blinded, parallel arm, randomised controlled trial (NCT04774939). Patients with symptomatic varicose disease and great, small, or anterior saphenous vein reflux requiring treatment were randomised to isolated laser ablation (ILA) or laser ablation with foam sclerotherapy (LA+FS). Patients randomised to ILA received isolated EVLA of the saphenous trunk, and those randomised to LA+FS received saphenous trunk EVLA with concomitant ultrasound guided foam sclerotherapy (UGFS) of tributaries. The primary outcome was the need for additional tributary intervention at 3 months, as determined by the patient. A power analysis, set to detect a 29.8% difference in additional intervention rates, allowing a 14% dropout rate (α = 0.05, β = 0.20), indicated a required sample size of 66 patients.

RESULTS: At 3 months, 20.7% of patients post ILA compared with 0.0% post LA+FS pursued additional UGFS of tributaries (p < .001). The median (interquartile range [IQR]) procedure time was shorter for ILA compared with LA+FS (median 46 minutes [IQR 41, 55] vs. 55 minutes [49, 63]; p < .001), with a higher 3 month Venous Clinical Severity Score following ILA (median 2.0 [IQR 1.0, 3.0] vs. 1.0 [IQR 0.0, 2.0]; p <.001). Complication rates and 3 month quality of life were similar across the groups.

CONCLUSION: Despite some early clinical advantages seen with concomitant tributary treatment, isolated EVLA met the main therapeutic objectives in most patients, thereby representing an acceptable but slightly less effective alternative to concomitant tributary treatment in the short term. Extended follow up is needed to assess the durability of these results.

PMID:41580273 | DOI:10.1016/j.ejvs.2026.01.029

Bioconjug Chem. 2026 Jan 24. doi: 10.1021/acs.bioconjchem.5c00519. Online ahead of print.

ABSTRACT

Cell-surface conjugation has enormous therapeutic and research potential. Existing technologies for cell-surface modification are usually reversible, nonspecific, or rely on genetic editing of target cells. Here, we present the NanoBondy, a nanobody modified for covalent ligation to an unmodified protein target at the cell surface. The NanoBondy utilizes the 20 naturally occurring amino acids, harnessing NeissLock chemistry engineered from Neisseria meningitidis. We evaluated the binding and specificity of a panel of nanobodies to CD45, a long-lived surface marker of nucleated hematopoietic cells. We demonstrated the conversion of existing nanobodies to covalently reacting NanoBondies using a disulfide clamp to position the self-processing module of FrpA close to the nanobody antigen-binding site. The addition of calcium induces anhydride formation at the NanoBondy C-terminus, enabling proximity-directed ligation to surface amines on CD45. We optimized the NanoBondy reaction by fine-tuning linkers and disulfide clamp sites to modulate anhydride positioning. Tandem mass spectrometry mapped reaction sites between NanoBondy and CD45. NanoBondy ligation was robust to buffer, pH, and temperature and was detected within 2 minutes. We established the reaction specificity of NanoBondies to endogenous CD45 at the surface of NK cells and T cells. NanoBondy technology provides a modular approach for targeted, inducible, and covalent cell-surface modification of immune cells without their genetic modification.

PMID:41578972 | DOI:10.1021/acs.bioconjchem.5c00519

Bioconjug Chem. 2026 Jan 24. doi: 10.1021/acs.bioconjchem.5c00519. Online ahead of print.

ABSTRACT

Cell-surface conjugation has enormous therapeutic and research potential. Existing technologies for cell-surface modification are usually reversible, nonspecific, or rely on genetic editing of target cells. Here, we present the NanoBondy, a nanobody modified for covalent ligation to an unmodified protein target at the cell surface. The NanoBondy utilizes the 20 naturally occurring amino acids, harnessing NeissLock chemistry engineered from Neisseria meningitidis. We evaluated the binding and specificity of a panel of nanobodies to CD45, a long-lived surface marker of nucleated hematopoietic cells. We demonstrated the conversion of existing nanobodies to covalently reacting NanoBondies using a disulfide clamp to position the self-processing module of FrpA close to the nanobody antigen-binding site. The addition of calcium induces anhydride formation at the NanoBondy C-terminus, enabling proximity-directed ligation to surface amines on CD45. We optimized the NanoBondy reaction by fine-tuning linkers and disulfide clamp sites to modulate anhydride positioning. Tandem mass spectrometry mapped reaction sites between NanoBondy and CD45. NanoBondy ligation was robust to buffer, pH, and temperature and was detected within 2 minutes. We established the reaction specificity of NanoBondies to endogenous CD45 at the surface of NK cells and T cells. NanoBondy technology provides a modular approach for targeted, inducible, and covalent cell-surface modification of immune cells without their genetic modification.

PMID:41578972 | DOI:10.1021/acs.bioconjchem.5c00519