Articles

Corvis <sup>ST</sup> biomechanical indices in the diagnosis of corneal stromal and endothelial disorders: an artificial intelligence-based comparative study
- Borderie Vincent Michel
- Georgeon Cristina
- Louissi Nassim
- Memmi Benjamin
- Hamrani Malika
- Bouheraoua Nacim
- Chessel Anatole
British Journal of Ophthalmology, BMJ Publishing Group , 2025, pp.bjo-2025-327855 . <div>Aims<p>To analyse the value of the Corvis ST indices in diagnosing corneal stromal and endothelial disorders (CSEDs). Methods This institutional retrospective case-control study included 903 eyes with a CSED and 597 normal eyes (controls), assessed with Corvis ST and MS39. Main outcome measures: Corvis ST indices. The collected data were divided into a training set (70%) and a test set (30%). Artificial intelligence frameworks were used to distinguish each disorder from controls and to classify corneas into seven groups: keratoconus, highrisk corneas for keratoconus, laser corneal refractive surgery (LCRS), endothelial disorders, stromal opacities, glaucoma corneas and normal corneas. Results Stress-strain index (SSI) significantly increased with age in the control group. Compared with controls matched for age/sex, keratoconus was associated with Corvis Biomechanical Index (CBI) >0.51 (area under the curve, 0.99), Ambrósio's relational thickness horizontal (ARTh) <425.5 (0.97), deflection amplitude at the time of the first applanation (SPA-A1) <96.3 (0.97) and Pachy<522.4 µm (0.91); high-risk corneas with a difference in CBI between fellow eyes (CBI SYM) >0.14 (0.98), (L2) <1.95 (0.83) and Pachy<549.7 µm (0.71); LCRS with ARTh<455.1 (0.93) and CBI>0.35 (0.83); corneal endothelial disorders with Pachy SYM>19.7 µm (0.83), Pachy>569.1 µm (0.82) and CBI SYM>0.14 (0.77); stromal opacities with SPA-A1 SYM>11.8 (0.92), ARTh<569.9 (0.89), SSI SYM>0.14 (0.89) and CBI>0.22 (0.86). A logistic regression function using all indices reached an area under the receiver operating characteristic curve of 0.81 for glaucoma diagnosis. The TabPFN model provided the best accuracy (88.7%) for diagnosing the seven corneal conditions. SSI, SPA-A1, CBI and Pachy correlated with keratoconus grade. Keratoplasty for keratoconus improved but failed to restore normal corneal biomechanics. Conclusions Corvis ST indices are relevant for diagnosing CESDs and distinguishing various disorders from each other.</p></div> (10.1136/bjo-2025-327855)
DOI : 10.1136/bjo-2025-327855
Heatwave Intensification in the Cameroonian Sahelian Zones: Biodiversity Survival Index, Required Vegetation Cover Standards in Human-Settled Environments, and Community Resilience Capacities
- Dzokom Alexis
- Kodji Ezechiel
Sahel Nature Consulting Revue, Sahel Nature Consulting Revue (March 2025) , 2025, 08 (21), pp.1-37 . <div><p>Recent extreme heatwaves in the Sahel, with maximum temperatures exceeding 45 °C, are exposing biodiversity, human populations, and agricultural systems to severe thermal stress. This article synthesizes recent climatic evidence demonstrating the intensification of heatwaves in the region. It proposes a methodological framework combining in situ observations, remote sensing, and modeling to estimate a Biodiversity Survival Index (BSI) under 35-45 °C temperature scenarios. The results indicate that operational vegetation cover standards for human-inhabited environments (defined through minimum thresholds and desirable target levels) can significantly reduce urban and periurban heat island effects and enhance overall resilience. Practical and policy-oriented recommendations are provided to strengthen community resilience, including agroforestry practices, water resource management, climate-sensitive urban planning, and early warning systems. The evidence further suggests that the intensity and frequency of recent heat extremes would not have occurred without anthropogenic climate forcing, and that substantial gains in local heat mitigation can be achieved through vegetationbased strategies and strengthened local governance.</p></div>
Deciphering the intermolecular interactions between G-quadruplex (G4)-forming sequences
- Xia Jianjun
- Zhou Jiahang
- Zhuang Xinzhe
- Ju Huangxian
- Monchaud David
- Chaires Jonathan B
- Šponer Jiří
- Mergny Jean-Louis
- Zhou Jun
Nucleic Acids Research, Oxford University Press , 2025, 53 (22) . <div><p>Interactions between biomolecules govern cellular biology. While protein/protein and protein/nucleic acid (DNA, RNA) interactions-and, to a lesser extent, RNA/RNA and RNA/DNA interactions-ha v e been e xtensiv ely described, a question remains as to whether and how non-canonical DNA str uct ures might interact with each other. This is of particular interest for guanine (G)-rich sequences that can fold into G-quadruplex (G4) str uct ures: Individual G4s are currently studied for their involvement in a myriad of cellular events (mostly pertaining to the control of gene expression), and, more recently, the interactions between two G4s have been scrutinized as being part of a novel gene expression regulatory mechanism in v olving chromatin remodeling through G4-mediated loop f ormation. T he question that needs to be answered is whether G4s or their corresponding G-rich sequences are in v olv ed. We present here a series of results collected using a combination of sequences, experimental conditions, and tec hniques, whic h led us to the conclusion that G4/G4 intermolecular interactions are mostly go v erned b y primary sequence interactions in vitro.</p></div> (10.1093/nar/gkaf1288)
DOI : 10.1093/nar/gkaf1288
Hausses caniculaires en zones sahéliennes camerounaises : indice de survie de la biodiversité, normes requises du couvert végétal en milieux habités et capacités de résilience communautaire
- Dzokom Alexis
- Kodji Ezechiel
Sahel Nature Consulting Revue, Sahel Nature Consulting Revue (March 2025) , 2025, 08 (21), pp.1-37 . Les récentes vagues de chaleur extrême dans le Sahel, avec des maxima dépassant 45 °C, exposent la biodiversité, les habitants et les systèmes agricoles à des stress thermiques sévères. Cet article propose une synthèse des preuves climatiques récentes montrant l’intensification des canicules dans la région. Un protocole méthodologique combinant observations in situ, télédétection et modélisation pour estimer un Indice de Survie de la Biodiversité (ISB) face à des scénarii 35–45 °C. Les résultats montrent que des normes opérationnelles de couvert végétal pour milieux habités (seuils minimaux et cibles souhaitables) permettent de réduire l’îlot de chaleur et d’améliorer la résilience Des recommandations pratiques et politiques pour renforcer la résilience communautaire (agroforesterie, gestion de l’eau, aménagements urbains et systèmes d’alerte). Les preuves montrent que l’intensité et la fréquence des épisodes chauds récents ne seraient pas survenues sans le forçage climatique anthropique, et que des gains substantiels en atténuation locale de la chaleur peuvent être obtenus par des stratégies basées sur la végétation et la gouvernance locale.
Label-free nonlinear microscopy probes cellular metabolism and myelin dynamics in live tissue
- Asadipour Bahar
- Morizet Josephine
- Ronzano Remi
- Zhang Xingjian
- Aigrot Marie-Stephane
- Mahou Pierre
- Solinas Xavier
- Phan Minh Son
- Chessel Anatole
- Stankoff Bruno
- Desmazieres Anne
- Beaurepaire Emmanuel
- Stringari Chiara
Communications Biology, Nature Publishing Group , 2025 . Metabolic coupling between neurons and glial cells plays a critical role in brain activity and myelin plasticity. Understanding its role in physiological and pathological contexts requires advanced methods to map metabolism and myelin in live tissue with high spatiotemporal resolution. Here, we present a label-free, multimodal, nonlinear optical microscopy platform integrated with an advanced image processing framework that simultaneously maps cellular metabolism and myelin distribution in organotypic cerebellar cultures. We combine third-harmonic generation microscopy for high-resolution myelin imaging with single axon precision with two-photon fluorescence lifetime microscopy of NAD(P)H metabolic biomarker to assess redox states with single-cell resolution. We introduce automated image analysis methods for cell segmentation and myelinated axon detection, enabling quantitative metabolic and myelin assessment in intact tissue during experimental myelination, demyelination and remyelination. Using this framework, we map the 3D myelin distribution in cerebellar folia and identify distinct metabolic signatures in neurons, oligodendrocytes, and microglia. Furthermore, we measure a metabolic shift in microglia along with myelin distribution changes during experimental demyelination. In conclusion, we establish label-free optical imaging as a powerful tool for the non-invasive characterization of neuro-glial metabolic coupling and myelin organization in living brain tissue, opening new perspectives for research in neuroinflammation and neurodegeneration. (10.1038/s42003-025-09192-4)
DOI : 10.1038/s42003-025-09192-4
Genome-wide ribonucleotide detection in <i>Archaea</i>
- Moalic Yann
- Reveil Maurane
- Kundnani Deepali L
- Balachander Sathya
- Yang Taehwan
- Gombolay Alli
- Ranjbarian Farahnaz
- Brizard Raphael
- Durand Patrick
- Myllykallio Hannu
- Jebbar Mohamed
- Hofer Anders
- Storici Francesca
- Henneke Ghislaine
Nucleic Acids Research, Oxford University Press , 2025, 53 (21) . <div><p>Genome integrity is constantly challenged by the incorporation of ribonucleotides ribonucleoside monophosphates (rNMPs) during DNA synthesis. Co v alently link ed single and se v eral consecutiv e rNMPs occur in the genome of a number of organisms. T he y are mainly introduced by DNA polymerases during DNA replication and repair. In general, cells evolved ribonucleases H (RNases H) specialized in the removal of rN-MPs from DNA to a v oid an y detrimental consequences on genome st abilit y. Here, we describe the in v olv ement of types 1 and/or 2 RNases H in processing embedded rNMPs in the genome of two archaeal species Haloferax volcanii and Thermococcus barophilus . Genome-wide, nucleotide-resolution maps of embedded rNMPs re v eal oriC -centered strand-switching profiles in H. volcanii rnhB , indicating origin firing in native cells, while their absence in T. barophilus reflects low origin usage. The data also define archaeal sequence-context rules for rNMP embedment, confirm the predominant role of RNase HII in rNMP remo v al with e vidence of compensatory repair pathw a y s, and link incorporation patterns to measured rNTP/dNTP pools. Together, these findings unco v er archaeal-specific mechanisms of rNMP incorporation and repair with implications for replication and genome st abilit y.</p></div> (10.1093/nar/gkaf1231)
DOI : 10.1093/nar/gkaf1231
Consensus guidelines for cellular label-free optical metabolic imaging: ensuring accuracy and reproducibility in metabolic profiling
- Georgakoudi Irene
- Skala Melissa
- Quinn Kyle
- Stringari Chiara
- Sorrells Janet
- Heikal Ahmed
- Li Lin
- Xu He
- You Sixian
- Walsh Alex
- Datta Rupsa
- Samimi Kayvan
- Gillette Amani
- Eliceiri Kevin
- Balu Mihaela
- Boppart Stephen
- Digman Michelle
- Dunning Kylie
- Evans Conor
- Garcia Alba Alfonso
- Houston Jessica
- Hwang Wonsang
- Lindley Matthew
- Li Xingde
- Liu Zhiyi
- Marcu Laura
- Murugkar Sangeeta
- Nichols Michael
- Niesner Raluca
- Parekh Sapun
- Rajaram Narasimhan
- Ranjit Suman
- Shen Keyue
- Shi Lingyan
- Torrado Belén
- Vallmitjana Alexander
- Wang-Evers Michael
- Zemp Roger
Journal of Biomedical Optics, Society of Photo-optical Instrumentation Engineers , 2025, 30 (S2), pp.S23901 . Significance: Cellular metabolism plays a central role in health and disease, making its study critical for advancing diagnostics and therapies. Label-free optical metabolic imaging using endogenous fluorescence from reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) provides nondestructive, high-resolution insights into metabolic function and heterogeneity from the sub-cellular to the tissue level. Standardized approaches are essential to ensure reproducibility and comparability across studies. Aim: We aim to establish a consensus framework for the acquisition, calibration, and reporting of microscopic imaging metabolic function assessments based on fluorescence intensity and lifetime measurements of NAD(P)H and FAD. Approach: We present best practices for calibrating, analyzing, and reporting fluorescence intensity-based optical redox ratios and fluorescence lifetime data using multiexponential fitting and phasor analysis. Guidelines for validation experiments and cross-system standardization are provided to improve accuracy and reproducibility. Results: We demonstrate the importance of calibration procedures and normalization strategies for intensity-based optical redox measurements. We highlight needed calibration, signal-to-noise ratio considerations, and the impact of distinct analytical approaches on fluorescence lifetime-based metabolic function metrics. Conclusion: We recommend a consistent, practical framework for reproducible, label-free, optical metabolic imaging, facilitating robust comparisons across studies and supporting the broader adoption of optical metabolic imaging technologies for biomedical research and clinical translation. (10.1117/1.JBO.30.S2.S23901)
DOI : 10.1117/1.JBO.30.S2.S23901
Ultrafast photooxidation of semireduced flavin in fatty acid photodecarboxylase
- Vos Marten
- Balduzzi Elsa
- Sorigué Damien
- Aleksandrov Alexey
Science Advances, American Association for the Advancement of Science (AAAS) , 2025, 11 (38) . The initial photoproduct of the natural photoenzyme fatty acid photodecarboxylase involves the flavin anion radical flavin adenine dinucleotide (FAD •– ). Using spectrally resolved ultrafast transient absorption spectroscopy, we demonstrate that FAD •– photoexcitation in the absence of substrate leads to the formation of the oxidized flavin FAD ox (the resting state in the catalytic cycle) within 100 femtoseconds. While this feature is similar to that occurring in flavoprotein oxidases, the ensuing photocycle is more complex. Upon excitation at the lowest-energy transition, the ejected electron is initially captured as a hydrated electron ( e – H ) before transferring to a secondary acceptor in 2.5 picoseconds and returning to the flavin in 37 picoseconds. This implies that e – H can be generated within a protein environment, an unprecedented finding. This assessment is supported by molecular dynamics simulations showing an expansion of the flavin-binding pocket without substrate, allowing water molecules to fill the void. Our results may pave the way to developing unconventional photocatalytic processes. (10.1126/sciadv.adz1904)
DOI : 10.1126/sciadv.adz1904
A Selective and Sensitive Method for Colistin Detection by G-Quadruplex Ligand Competition
- Wei Shijiong
- Qiu Dehui
- Yan Xinrong
- Liu Bin
- Mergny Jean-Louis
- Monchaud David
- Ju Huangxian
- Zhou Jun
Analytical Chemistry, American Chemical Society , 2025, 97 (31), pp.16805 . Colistin (COL) is a widely used antibiotic and is quite often used as a last-resort treatment option for treating multidrug-resistant Gram-negative bacterial infections. Due to its widespread use, COL accumulates in nature, which represents a novel ecological and health threat. However, there is currently no rapid and specific method available for titrating COL levels in collected samples. Herein, we report a simple chemiluminescence detection method based on the specific interaction between COL and a parallel G-quadruplex (G4). To this end, we exploit the catalytic properties of the G4/hemin DNAzyme, which is able to oxidize substrates to provide a readily monitored readout. The stronger affinity of G4 for COL versus hemin allows for the inactivation of the G4/hemin DNAzyme, which is used herein to quantify COL in solution. Through a series of optimizations, we identified the best G4 sequence (F3TC), oxidation substrate (luminol), and experimental conditions, which allow for the detection of COL over a broad concentration window, from 0.5 to 2,500 ng/mL, with a detection limit of 0.4 ng/mL and excellent selectivity against other antibiotics. Compared with existing methods, the proposed approach provides a simpler and label-free quantification of COL, which might serve as a valuable standard method for antibiotic detection, whose use was validated under real conditions herein (10.1021/acs.analchem.5c01733)
DOI : 10.1021/acs.analchem.5c01733
Design, synthesis, biophysical and biological evaluation of original condensed pyrrolopyrimidine and pyrrolopyridine ligands as anti-SARS-CoV-2 agents targeting G4
- Guillon Jean
- Savrimoutou Solène
- da Rocha Nicolas
- Albenque-Rubio Sandra
- Helynck Olivier
- Durand Cyrielle
- Chiaravalli Jeanne
- Pinaud Noël
- Ronga Luisa
- Moreau Stéphane
- Chirold Simon
- Zangmo Tshering
- Arab Melika
- Lari Lindita
- Mergny Jean‐louis
- Munier-Lehmann Hélène
- Lavigne Marc
European Journal of Medicinal Chemistry, Elsevier , 2025, 292, pp.117655 . The design and synthesis of novel bis[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines, pyrrolopyridines, pyrazolopyrimidines, imidazopyrimidines, and tris[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines are reported here. These original G-quadruplex (G4) ligands have been then subjected to a screening on SARS-CoV-2 using a competition HTRF assay by targeting the SUD-NM/TRF2 RNA G4 interaction. The more promising derivatives have been evaluated in vitro to determine their potential antiviral effect on two different cell lines infected by two SARS-CoV-2 strains. This study revealed a clear correlation between their antiviral property and their efficacy to prevent the SUD/G4 interaction. This correlation supports the choice of SUD/RNA G4 complexes formed during SARS-CoV-2 infection as new antiviral targets (10.1016/j.ejmech.2025.117655)
DOI : 10.1016/j.ejmech.2025.117655
Chromium‐Doped Zinc Gallate Nanoparticles for Enhanced Enzyme‐Linked Immunosorbent Assay Sensitivity: Optimization of Synthesis and Functionalization Strategies for Ultra‐Low IgG Detection
- Ferjaoui Zied
- Liu Jianhua
- Matuszewska Celina
- Chanéac Corinne
- Viana Bruno
- Bouzigues Cédric
- Scherman Daniel
- Mignet Nathalie
- Richard Cyrille
Small Science, Wiley , 2025, 5 (10) . The use of zinc gallate nanoparticles (ZnGa 2 O 4 :Cr 3+ ) (ZGO‐NPs) presents significant potential for improving the sensitivity in enzyme‐linked immunosorbent assays (ELISA). The persistent luminescence signal increase of these nanoparticles in the presence of hydrogen peroxide (H 2 O 2 ) offers advantages for the sensitive detection of biomolecules. Herein, different conditions of ZGO synthesis have been investigated by varying the hydrothermal reaction duration (6, 12, and 24 h) and examining its impact in the presence of H 2 O 2 . These nanoparticles have been integrated into ELISA assays, using as target antigen IgG. The lowest limit of detection (LOD) of 0.2 pg mL −1 is observed for ZGO‐NPs prepared during 12 h (ZGO2), and with a detection range from 1 to 1000 pg mL −1 . The impact of covalently functionalizing these nanoparticles has then been assessed. First using glucose oxidase (GOx) and the detection antibody (Ab D ) linked to PEGylated ZGO‐NPs, named ZGO‐GOx‐Ab D . Alternatively, only the detection antibody is linked to the PEG ZGO‐NPs, named ZGO‐Ab D . The results show a significant lowering of the LOD when using the functionalized ZGO2 NPs and also highlight the impact of the signal amplification by H 2 O 2 . Specifically, when using ZGO2‐GOx‐Ab D incubated with glucose to produce H 2 O 2 , or with ZGO2‐Ab D to which H 2 O 2 was added, the LODs are ≈98 and 56 fg mL −1 respectively, with detection ranges from 0.01 to 100 pg mL −1 . (10.1002/smsc.202500177)
DOI : 10.1002/smsc.202500177
Machine Learning Model for Predicting Visual Acuity Improvement After Intrastromal Corneal Ring Surgery in Patients With Keratoconus
- Perez Eva
- Louissi Nassim
- Kallel Sofiene
- Hays Quentin
- Bouheraoua Nacim
- Hamrani Malika
- Chessel Anatole
- Borderie Vincent
Cornea, Lippincott, Williams & Wilkins , 2025 . Background: Keratoconus is a progressive, degenerative corneal disease that can lead to significant visual impairment. The intrastromal ring segment implantation procedure is effective in reshaping the cornea and improving vision. However, vision does not improve postoperatively in all operated eyes, and the results vary widely among patients, making it challenging to predict postoperative visual gain. Purpose: This study investigated the potential of machine learning in predicting postoperative visual acuity in keratoconus patients undergoing intrastromal ring segment implantation with the aim of enhancing surgical decision-making. Methods: This retrospective study analyzed 120 eyes of 102 patients with keratoconus who underwent ring segment implantation (1 symmetric or asymmetric segment, 150-300 mm thick, 150 degrees, or 160 degrees-arc). Preoperative and postoperative refraction, corneal topography, and tomographic data were collected. Various models were trained to predict postoperative visual acuity improvements. Results: The models demonstrated excellent performance, with XGBoost achieving perfect results in predicting whether vision will improve after surgery (R 2 = 1.0, Youden Index = 1.0; all test observations being correctly classified). The CatBoost model achieved an R 2 of 0.59 [0.7-line mean absolute error (MAE)] for predicting postoperative visual acuity, an R 2 of 0.76 (MAE, 1.08 D) for predicting keratometry, and an R 2 of 0.54 (MAE, 0.29) for predicting corneal asphericity. Key features for accurate predictions included preoperative keratometry values (K1, K2, Kmax), corneal asphericity, and visual acuity, whereas segment characteristics featured low importance. Conclusions: This study shows the strong potential of machine learning for selecting candidates for surgery and predicting postoperative visual improvements after ring segment implantation in keratoconus eyes. (10.1097/ICO.0000000000003933)
DOI : 10.1097/ICO.0000000000003933
In situ determination and matching of the refractive index of the Human cornea to improve polarization-resolved SHG imaging in depth
- Nyembo Kasongo Poncia
- Mahou Pierre
- Sintès Jean-Marc
- Latour Gaël
- Schanne-Klein Marie-Claire
Biomedical optics express, Optical Society of America - OSA Publishing , 2025, 16 (8), pp.3270-3282 . <div><p>The human cornea is a highly organized tissue, which comprises hundreds of 1-3 µm thick stacked collagen lamellae. However, this microstructure is poorly characterized and requires further investigation. Polarization-resolved second harmonic generation (pSHG) microscopy is a powerful technique for this purpose because of its specificity for collagen and its sensitivity to its orientation. However, pSHG is prone to spatial resolution degradation with depth unless the immersion refractive index is matched to that of the sample, which is critical for corneas that are approximately 600 µm thick. In the absence of experimental data on the refractive index along the entire cornea, we propose a measurement method that applies to the entire cornea directly under the microscope objective. We then use an iodixanol solution to match the refractive index of the immersion medium to that of the cornea. Finally, we carefully characterize the pSHG orientation data obtained under these optimal conditions, and we show that they provide a better resolution along the entire thickness of the cornea and a better determination of the lamellae orientation.</p></div> (10.1364/boe.564209)
DOI : 10.1364/boe.564209
Multiscale characterization of myelin distribution with polarized THG microscopy
- Morizet Josephine
- Olivier Nicolas
- Aigrot Marie-Stephane
- Mahou Pierre
- Martin Elodie
- Desmazieres Anne
- Stankoff Bruno
- Stringari Chiara
- Beaurepaire Emmanuel
Optica, Optical Society of America - OSA Publishing , 2025, 12 (7), pp.1122 . Myelin is essential for axonal conduction and metabolic support. To better understand its role in health and disease, it is necessary to establish accurate methods for in situ mapping of myelin at scales ranging from submicrometer to centimeters. Third-harmonic generation (THG) microscopy has recently been proposed as an efficient label-free method to visualize myelin in thick and living tissue. However, the contrast mechanism of THG from myelinated axons is complex and poorly described, which has limited the development of THG as a quantitative probe of myelin distribution. Here, we present a systematic characterization and modeling of polarization-resolved THG (pTHG) signals from individual axons as a function of their diameter and myelin thickness, and we show that pTHG can be used to derive myelin scores in several biological systems. First, we confirm the sensitivity and specificity of the THG contrast for myelinated axons in mouse brain tissue and its ability to detect isolated micrometer-sized axons oriented both in-plane and out-of-plane. We then present a detailed characterization of the pTHG contrast of small and large axons in live zebrafish larvae at different developmental stages, and we demonstrate that pTHG detects early axon development in vivo. We show that classical models of coherent multiphoton microscopy fail to reproduce pTHG profiles of axons because they neglect myelin-induced optical aberrations, and we establish a numerical strategy based on finite-difference time-domain calculations that can accurately relate pTHG signal profiles to axonal diameter and myelin thickness. Finally, we illustrate the relevance of pTHG microscopy for characterizing myelin distribution at different scales in fixed mouse and human brain tissue. (10.1364/optica.562091)
DOI : 10.1364/optica.562091
Editorial: The metabolic pathways of archaea
- Myllykallio Hannu
- Qin Wei
- Berg Ivan
Frontiers in Microbiology, Frontiers Media , 2025, 16 . (10.3389/fmicb.2025.1648560)
DOI : 10.3389/fmicb.2025.1648560
Time Delay Distribution and Laser Stability in Arbitrary Detuning Asynchronous Optical Sampling
- Antonucci Laura
- Bonvalet A.
- Solinas X.
- Joffre M.
Journal of Physical Chemistry A, American Chemical Society , 2025, 129 (27), pp.6121-6132 . Arbitrary Detuning ASynchronous OPtical Sampling (ADA-SOPS) is an emerging technique for extending standard pump−probe experiments performed with two femtosecond lasers to multitimescale experiments, which are of great interest for the study of complex systems. Although no specific requirements are needed for laser repetition rates, their ratio determines the achievable delay distribution and therefore is strongly related to the temporal resolution of the technique. We report a detailed theoretical analysis of measurement performances with respect to laser repetition rates, and we validate our model with experimental data. In the case of amplified laser systems, we demonstrate that achieved delays are inherently correlated to the time interval between amplified pulses, which affects the pulse energy and can generate artifacts. Nevertheless, a deep understanding of the origin of such artifacts allows to suggest several compensation strategies, either during data analysis or at the conception of the experimental setup. Finally we present a new algorithm integrated into the ADASOPS device: by selecting pairs of probe pulses having the same elapsed time with respect to the previous pulse, it automatically compensates any effect of energy fluctuation. (10.1021/acs.jpca.5c01853)
DOI : 10.1021/acs.jpca.5c01853
IgG detection in human serum employing non-functionalized chromium doped zinc gallate nanoparticles
- Ferjaoui Zied
- Zimmer Capucine
- Matuszewska Celina
- Chanéac Corinne
- Viana Bruno
- Bouzigues Cédric
- Scherman Daniel
- Mignet Nathalie
- Richard Cyrille
Next Nanotechnology, Elsevier , 2025, 8, pp.100199 . Chromium-doped zinc gallate (ZnGa2O4:Cr3 +) nanoparticles (ZGO) show promising potential for antigen immunodetection using persistent luminescence, thereby reducing autofluorescence interference. Recently, we have shown that ZGO prepared by hydrothermal treatment at 120°C for 24 h can be used for in vitro biodetection in simple media such as phosphate-buffered saline. In this study, we investigated the effect of the protocol used to synthesize these ZGO nanoparticles, using a hydrothermal treatment at 220°C for different durations (6 h, 12 h, and 24 h), followed by calcination at 500°C. The nanoparticle size determined by transmission electron microscopy after grinding and centrifugation was found to be around 15 nm. The persistent luminescence signal of the ZGO nanoparticles varied with the hydrothermal synthesis conditions. Moreover, in the presence of H2O2, these nanoparticles show a signal enhancement dependent on the hydrothermal duration, with a 12 h treatment showing the highest 8-fold luminescence increase in the presence of H2O2 produced by glucose oxidase mediated glucose degradation. Based on these results, these non-functionalized nanoparticles were successfully used to develop a persistent luminescence-based sandwich immunoassay for autofluorescence-free detection of antigens in undiluted human serum samples, using rabbit IgG as a model antigen. This study highlights the promising potential for biosensing applications of persistent ZGO nanophosphors for IgG detection in a complex medium (undiluted human serum), with a linear range from 1 ng mL−1 to 104 ng mL−1 and a limit of detection of 0.01 ng mL−1. The present optimization of ZGO nanophosphor synthesis offers promising prospects for medical diagnostics due to their increased sensitivity and ability to eliminate autofluorescence interference, as well as their ease of use, since no functionalization of the ZGO NPs is required before use. (10.1016/j.nxnano.2025.100199)
DOI : 10.1016/j.nxnano.2025.100199
Laser driven FLASH radiobiology using a high dose and ultra high dose rate single pulse proton source
- Flacco A
- Bayart E.
- Romagnani L
- Cavallone M.
- de Marzi L.
- Fouillade C
- Giaccaglia C.
- Heinrich S.
- Lamarre-Jouenne I.
- Monzac J.
- Parodi K.
- Patriarca A
- Rösch T
- Schreiber J
- Tischendorf L
Scientific Reports, Nature Publishing Group , 2025, 15, pp.16511 . Laser-driven proton sources have long been developed with an eye on their potential for medical application to radiation therapy. These sources are compact, versatile, and show peculiar characteristics such as extreme instantaneous dose rates, short duration and broad energy spectrum. Typical temporal modality of laser-driven irradiation, the so-called fast-fractionation, results from the composition of multiple, temporally separated, ultra-short dose fractions. In this paper we present the use of a high-energy laser system for delivering the target dose in a single nanosecond pulse, for ultra-fast irradiation of biological samples. A transport line composed by two permanent-magnet quadrupoles and a scattering system is used to improve the dose profile and to control the delivered dose-per-pulse. A single-shot dosimetry protocol for the broad-spectrum proton source using Monte Carlo simulations was developed. Doses as high as 20 Gy could be delivered in a single shot, lasting less than 10 ns over a 1 cm diameter biological sample, at a dose-rate exceeding 10 9 Gy s -1 . Exploratory application of extreme laser-driven irradiation conditions, falling within the FLASH irradiation protocol, are presented for irradiation in vitro and in vivo. A reduction of radiation-induced oxidative stress in vitro and radiation-induced developmental damage compatible with the onset of FLASH effect were observed in vivo, whereas anti-tumoral efficacy was confirmed by cell survival assay. (10.1038/s41598-025-01105-z)
DOI : 10.1038/s41598-025-01105-z
Two-dimensional infrared spectroscopy using a fast-scanning interferometer and chirped pulse up-conversion at 100 kHz
- Jonušas Mindaugas
- Bournet Quentin
- Bonvalet Adeline
- Natile Michele
- Ersen Andrei-Ovidiu
- Guichard Florent
- Zaouter Yoann
- Georges Patrick
- Druon Frédéric
- Hanna Marc
- Joffre Manuel
The Journal of Chemical Physics, American Institute of Physics , 2025, 162 (17), pp.174201 . We report on a 100-kHz two-dimensional infrared (2DIR) spectrometer in the pump-probe geometry, which we apply to the measurement of the 2DIR spectrum of carboxy-hemoglobin. The probe pulses are spectrally resolved by chirped-pulse upconversion (CPU) using a fast 2048-pixel linescan CMOS camera. The two-pulse pump sequence is generated using a conventional interferometer with a fast-scanning mechanical delay line allowing to achieve a scanning frequency of 2 Hz. The resulting modulation frequency of 3.1 kHz is large enough to shift the relevant signal away from the low-frequency noise of the laser source. The combined use of an interferometer on the pump side and of CPU on the probe side opens the way to an improved spectral resolution in both pump and probe dimensions, as compared to currently-available 100-kHz 2DIR spectrometers based on pulse shapers and Mercury-Cadmium Telluride (MCT) detector arrays. (10.1063/5.0261494)
DOI : 10.1063/5.0261494
Genome wide analyses reveal the role of mutator phenotypes in Mycobacterium tuberculosis drug resistance emergence
- Zein-Eddine R.
- Le Meur Adrien
- Skouloubris S.
- Jelsbak L.
- Refrégier Guislaine
- Myllykallio Hannu Hannu
npj Antimicrobials and Resistance, Springer Nature , 2025, 3 (1), pp.35 . Antimicrobial combination therapy is widely used to combat Mycobacterium tuberculosis (Mtb), yet resistance rates continue to rise. Mutator strains, with defects in DNA repair genes, drive resistance in other bacterial infections, but their role in Mtb remains unclear. Here, we study the contribution of single nucleotide polymorphisms (SNPs) in DNA Repair, Replication, and Recombination (3 R) genes to Mtb resistance. Through large-scale bioinformatics analysis of 53,589 whole-genomes, we identified 18 novel SNPs in lineages 2 and 4 linked to genotypic drug resistance in 3 R genes, covering 12.5% of clinical isolates with available genome sequences. Notably, a number of the detected SNPs were positively selected during Mtb evolution. Experimental tests showed that mutM, fpgg2, xthA, and nucS mutants had increased the mutation frequency compared to the wild type. Our findings highlight the role of 3 R gene mutations in resistance, emphasizing the need for surveillance to improve early detection and control strategies. (10.1038/s44259-025-00107-1)
DOI : 10.1038/s44259-025-00107-1
Ultra-Specific G-Quadruplex–Colistin Interaction for Efficient Transcriptome-Wide G4 Mapping
- Wei Shijiong
- Zhang Xiaobo
- Feng Yilong
- Tao Shentong
- Qiu Dehui
- Yan Xinrong
- Li Guangming
- Guittat Lionel
- Zhang Wenli
- Monchaud David
- Mergny Jean-Louis
- Ju Huangxian
- Zhou Jun
Journal of the American Chemical Society, American Chemical Society , 2025, 147, pp.9962 - 9971 . G-quadruplexes (G4s) are challenging targets for chemical biology interventions, notably because of their dynamic topological polymorphism. We found that the antibiotic smallmolecule colistin (COL) interacts specifically with a single subtype of G4 structures, the so-called parallel G4s. This interaction triggers the aggregation of the G4/COL complexes in a structure-specific manner, which can thus be separated from the bulk solution by centrifugation. This unprecedented mode of affinity-precipitation was exploited here to design the COL-induced RNA G4 precipitation and sequencing (CoRP-seq) protocol, which allows for the assessment of the prevalence of RNA G4s in the transcriptome of human cells in a straightforward manner. CoRP-seq shines by its ultraspecificity, simplicity, and practical convenience, which thus advances G4 mapping further and addresses unmet needs in the field of G4omics. (10.1021/jacs.5c01172)
DOI : 10.1021/jacs.5c01172
Increasing the Accuracy and Robustness of the CHARMM General Force Field with an Expanded Training Set
- Croitoru Anastasia
- Kumar Anmol
- Lambry Jean-Christophe
- Lee Jihyeon
- Sharif Suliman
- Yu Wenbo
- Mackerell Alexander
- Aleksandrov Alexey
Journal of Chemical Theory and Computation, American Chemical Society , 2025, 21 (6), pp.3044-3065 . <div><p>Small molecule empirical force fields (FFs), including the CHARMM General Force Field (CGenFF), are designed to have wide coverage of organic molecules and to rapidly assign parameters to molecules not explicitly included in the FF. Assignment of parameters to new molecules in CGenFF is based on a trained bond-angledihedral charge increment linear interpolation scheme for the partial atomic charges along with bonded parameters assigned based on analogy using a rules-based penalty score scheme associated with atom types and chemical connectivity. Accordingly, the accuracy of CGenFF is related to the extent of the training set of available parameters. In the present study that training set is extended by 1,390 molecules selected to represent connectivities new to CGenFF training compounds. Quantum mechanical (QM) data for optimized geometries, bond, valence angle, and dihedral angle potential energy scans, interactions with water, molecular dipole moments, and electrostatic potentials were used as target data. The resultant bonded parameters and partial atomic charges were used to train a new version of the CGenFF program, v5.0, which was used to generate parameters for a validation set of molecules, including drug-like molecules approved by the FDA, which were then benchmarked against both experimental and QM data. CGenFF v5.0 shows overall improvements with respect to QM intramolecular geometries, vibrations, dihedral potential energy scans, dipole moments and interactions with water. Tests of pure solvent properties of 216 molecules show small improvements versus the previous release of CGenFF v2.5.1 reflecting the high quality of the Lennard-Jones parameters that were explicitly optimized during the initial optimization of both the CGenFF and the CHARMM36 force field. CGenFF v5.0 represents an improvement that is anticipated to more accurately model intramolecular geometries and strain energies as well as non-covalent interactions of drug-like and other organic molecules.</p></div> (10.1021/acs.jctc.5c00046)
DOI : 10.1021/acs.jctc.5c00046
Nance-Horan-Syndrome-like 1b controls mesodermal cell migration by regulating protrusion and actin dynamics during zebrafish gastrulation.
- Escot Sophie
- Hassanein Yara
- Elouin Amélie
- Torres-Paz Jorge
- Mellottee Lucille
- Ignace Amandine
- David Nicolas B
Communications Biology, Nature Publishing Group , 2025, 8 (1), pp.328 . Cell migrations are crucial for embryonic development, wound healing, the immune response, as well as for cancer progression. In most cells, the RAC1/Arp2/3/WAVE signalling pathway induces branched actin polymerisation, which protrudes the membrane and allows migration. Fine-tuning the activity of the RAC1/Arp2/3/WAVE complex modulates protrusion lifetime and migration persistence. Recently, NHSL1, a novel interactor in this complex has been identified as a negative regulator of cell migration in vitro. We here analysed its function in vivo, during zebrafish gastrulation, as nhsl1b is specifically expressed in migrating mesodermal cells. Loss and gain of function experiments revealed that nhsl1b is required for the proper migration of the mesoderm, controlling cell speed and migration persistence. Consistent with a role in regulating actin dynamics, Nhsl1b localises to the tip of actin-rich protrusions. However, in contrast to the in vitro situation, it appears to be a positive regulator of migration, with its loss of function reducing the length and lifetime of protrusions, whereas overexpression has the opposite effect. These results reveal that the effects of actin modulators depend on the cellular context, and highlight the importance of analysing their function in physiological contexts. (10.1101/2023.01.28.526006)
DOI : 10.1101/2023.01.28.526006
Fast and Efficient Red‐absorbing Photoswitching Proteins Based on Flavin–Ligand Charge Transfer Complexes
- Zhuang Bo
- Liebl Ursula
- Vos Marten
- Sliwa Michel
ChemPhotoChem, Wiley , 2025 . Recently a novel class of reversible protein photoswitches has been discovered that is based on a charge transfer (CT) complex composed of the flavin cofactor and a substrate‐analogue inhibitor molecule in the family of sarcosine oxidase flavoproteins. Here, excitation of the CT band results in barrierless dissociation of the CT complex on the femtosecond timescale followed by its thermally activated reformation, on the timescale of a few nanoseconds at ambient temperature. The photoreaction is thought to involve a well‐defined isomerization of the inhibitor without its dissociation from the protein. This reaction occurs with an unusually high quantum yield (~80%), is initiated by absorption in the red part of the visible absorption spectrum, and leads to a photoproduct absorbing in the blue spectral region (negative photochromism). Therefore, this class of photoswitches can be considered a promising template for developing a new class of fast negative photochromic compounds for Life Science applications provided the lifetime of the photoproducts (‘light state’) can be prolonged. Potential future developments will be discussed. (10.1002/cptc.202500012)
DOI : 10.1002/cptc.202500012
Understanding the key challenges in tuberculosis drug discovery: what does the future hold?
- Zein-Eddine Rima
- Ramuz Masoud
- Refrégier Guislaine
- Lutzeyer Johannes F
- Aleksandrov Alexey
- Myllykallio Hannu
Expert Opinion on Drug Discovery, Informa Healthcare , 2025, 20 (9), pp.1115-1130 . Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern. It spreads through airborne droplets and has a high mortality rate, particularly without treatment. Drug resistance is rising, with treatments against multidrug-resistant TB (MDR-TB) showing poor treatment success rates. The thick, lipid-rich wall of Mtb and its slow growth reduce antibiotic effectiveness, requiring long treatment courses of 4-6 months. Current therapies often fail against drugresistant strains, highlighting the urgent need for new, short-course treatment, affordable, and combination-friendly drugs. Areas covered: Within this perspective, the authors review and comment on the following topics regarding Mtb resistance emergence and treatment strategies: i) Existing treatment ii) Resistance evolution in Mtb; iii) Key challenges in drug discovery targeting Mtb; iv) emerging strategies and recent advances in Mtb drug discovery, and v) Next-generation approaches. Literature was identified through a search of PubMed, google scholar, and web of science, from January 2010 to March 2025. Expert opinion: AI is accelerating the discovery of bioavailable and safe preclinical drug candidates for TB, though data limitations and biological complexity remain challenging. Future progress requires multi-modal models, open-access datasets, and interdisciplinary collaboration. (10.1080/17460441.2025.2531229)
DOI : 10.1080/17460441.2025.2531229