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bioRxiv [Preprint]. 2025 Nov 29:2025.11.26.690749. doi: 10.1101/2025.11.26.690749.

ABSTRACT

Small molecule activators of protein phosphatase 2A (PP2A), hereafter SMAPs, have attracted substantial interest, for their potential to inhibit cancer cell proliferation by targeting PR65, the scaffold subunit of the PP2A heterotrimer. PR65 is a uniquely flexible and stable molecule composed of 15 tandem HEAT (Huntingtin, Elongation factor 3-PP2A-TOR1) repeats. We characterized the binding sites and interactions of two SMAPs ATUX-8385 and DT-061 with PR65 and evaluated effects on PR65 structural dynamics using docking and molecular dynamics simulations. We initiated SMAP-bound PR65 simulations starting from two binding sites: S1, determined by cryo-electron microscopy for DT-061 bound to PP2A, on the inner helices of the HEAT repeats 2 and 3 (2 i and 3 i ); and S2, predicted by docking of ATUX-8385 onto PR65, on 4 i and 5 i and outer helices 5 o and 6 o consistent with footprinting experiments. S2 proved to be a stable site for both SMAPs when initiating the simulations at S2. However, neither DT-061 nor ATUX-8385 demonstrated stable binding to S1. DT-061 rapidly dissociated from S1 to settle instead at a neighboring site S4 overlapping with our previously identified S3 for PR65 in extended form, suggesting that binding to S1 may be a 2-step process: an initial binding to PR65 alone, either to S3/S4 or S2, followed by movement to S3/S4, and then an induced relocation to S1 upon complexation with the regulatory and catalytic subunits. Targeted in silico mutagenesis showed that mutations at S2 and S4 destabilized SMAP binding to the PR65 (subunit). Heterotrimeric PP2A simulations showed that S3 and S4 binding were not persistent upon complexation. Together, these results corroborate our findings. Furthermore, preferentially stabilized a relatively extended PR65 conformation that would accommodate, if not promote, the assembly of the catalytic and regulatory subunits to prompt the activation of the trimeric phosphatase.

PMID:41394555 | PMC:PMC12697531 | DOI:10.1101/2025.11.26.690749

Biophys Rev. 2025 Jul 28;17(4):1119-1132. doi: 10.1007/s12551-025-01343-5. eCollection 2025 Aug.

ABSTRACT

The material properties of biomolecular condensates, such as interfacial tension, viscoelasticity, stiffness, and molecular dynamics, are crucial for their biological functions in processes like signal transduction, stress response, and gene regulation. These properties influence both endogenous condensates, like the nucleolus and stress granules, and synthetic condensates engineered for potential drug delivery applications. In vitro studies, using purified components, provide controlled environments to explore the fundamental physics of phase separation, offering high precision in manipulating molecular components and conditions. However, cell-based characterisations are indispensable for understanding the physiological relevance of biomolecular condensates, accounting for molecular crowding, post-translational modifications, and interactions with cellular structures. Light-microscopy techniques offer the potential to bridge in vitro findings with in cellulo behaviour. This review outlines some fundamental challenges of in cellulo studies and discusses the potential of fluorescently labelling biomolecular condensates using the tetracysteine tag/biarsenical dye strategy. We describe how fluorescence-based techniques, including fluorescence recovery after photobleaching (FRAP) and emerging techniques like fluorescence lifetime imaging microscopy (FLIM), flicker spectroscopy, and raster image correlation spectroscopy (RICS), may be used to gain a detailed understanding of the material properties of biomolecular condensates within the cellular environment. Finally, we discuss the potential of Brillouin light scattering (BLS) microscopy, a label-free technique that holds potential for deciphering the cellular biophysics of biomolecular condensates.

PMID:41378109 | PMC:PMC12686230 | DOI:10.1007/s12551-025-01343-5

Biophys Rev. 2025 Jul 28;17(4):1119-1132. doi: 10.1007/s12551-025-01343-5. eCollection 2025 Aug.

ABSTRACT

The material properties of biomolecular condensates, such as interfacial tension, viscoelasticity, stiffness, and molecular dynamics, are crucial for their biological functions in processes like signal transduction, stress response, and gene regulation. These properties influence both endogenous condensates, like the nucleolus and stress granules, and synthetic condensates engineered for potential drug delivery applications. In vitro studies, using purified components, provide controlled environments to explore the fundamental physics of phase separation, offering high precision in manipulating molecular components and conditions. However, cell-based characterisations are indispensable for understanding the physiological relevance of biomolecular condensates, accounting for molecular crowding, post-translational modifications, and interactions with cellular structures. Light-microscopy techniques offer the potential to bridge in vitro findings with in cellulo behaviour. This review outlines some fundamental challenges of in cellulo studies and discusses the potential of fluorescently labelling biomolecular condensates using the tetracysteine tag/biarsenical dye strategy. We describe how fluorescence-based techniques, including fluorescence recovery after photobleaching (FRAP) and emerging techniques like fluorescence lifetime imaging microscopy (FLIM), flicker spectroscopy, and raster image correlation spectroscopy (RICS), may be used to gain a detailed understanding of the material properties of biomolecular condensates within the cellular environment. Finally, we discuss the potential of Brillouin light scattering (BLS) microscopy, a label-free technique that holds potential for deciphering the cellular biophysics of biomolecular condensates.

PMID:41378109 | PMC:PMC12686230 | DOI:10.1007/s12551-025-01343-5

Data Brief. 2025 Nov 14;63:112281. doi: 10.1016/j.dib.2025.112281. eCollection 2025 Dec.

ABSTRACT

The agricultural landscape of Bangladesh is significantly influenced by the cultivation of vegetables, which is directly involved in the nutritional intake of the people, the economy, and the food security of the entire nation. Precise identification of vegetables is essential to efficient cultivation, inventory management, and smart agricultural practices. In our study, we introduce a comprehensive dataset for vegetable detection, consisting of 3534 high-resolution images captured in natural, real-world settings using a Redmi Note 12 from multiple roadside vehicles of local vendors. The dataset encompasses 22 distinct vegetable classes, covering a wide range of appearances, shapes, and natural daylight environments to enhance model robustness and practical applicability. Each image has been meticulously annotated using the Roboflow platform to facilitate object detection tasks, and the resulting dataset is provided in Pascal VOC format. Unlike other imaging datasets, our work emphasizes ground-level perspectives, making it particularly relevant for handheld and low-cost monitoring systems. The primary goal of this dataset is to support the development of computer vision models for accurate vegetable recognition, thereby aiding decision-making in vegetable cultivation and contributing to smarter and sustainable agricultural practices.

PMID:41377183 | PMC:PMC12686877 | DOI:10.1016/j.dib.2025.112281

RSC Adv. 2025 Dec 9;15(57):49063-49073. doi: 10.1039/d5ra07413d. eCollection 2025 Dec 8.

ABSTRACT

Energy loss at the interface between the subcells limits the efficiency of existing tandem solar cells. In this work, we propose a novel two-terminal perovskite/silicon tandem solar cell with vertically aligned silicon (Si) nanowires (NWs) incorporated between the two subcells. The sub-wavelength dimensions of the embedded Si NWs, grown on top of the Si bottom subcell, allow efficient light trapping and lead to guided resonant modes. Finite-difference time-domain (FDTD) analysis shows that, across the entire spectrum, these guided modes effectively couple the incident light between the subcells, reducing reflection losses in the interlayer and enhancing absorption in the underlying bottom c-Si cell. To evaluate the performance of the proposed tandem solar cell, we performed electrical simulations using the enhanced carrier generation profile obtained from the FDTD simulations. The proposed embedded NW tandem configuration yields 22.6% enhancement in short-circuit current density compared to conventional architectures, boosting the power conversion efficiency from 26.98% to 32.11%. These findings offer the necessary theoretical framework for experimentalists, providing a clear pathway towards realizing high-performance perovskite/Si tandem solar cells.

PMID:41377156 | PMC:PMC12687930 | DOI:10.1039/d5ra07413d

BMC Bioinformatics. 2025 Dec 9. doi: 10.1186/s12859-025-06333-8. Online ahead of print.

ABSTRACT

Sequence sketching-a class of techniques aimed at generating compact representations of longer sequences-has become widely used in numerous long read applications, including assembly and mapping. Instead of comparing sequences, sketches allow us to sample from a subspace of k-mers and use those samples for comparison, saving both time and memory in the end application. One of the important metrics that determines the performance of a sketch is the sketch density, which refers to the fraction of the sampled k-mers retained by the sketch. While a lower density is preferable for space considerations, it could also impact the sensitivity of the mapping process. In this work, we visit the problem of reducing sketch density while preserving accuracy in the context of long-read mapping. We present an efficient algorithm called MHsketch that uses Jaccard estimators to reduce sketch density in mapping applications. Starting from an initial ground set of k-mers generated through a sketching method of choice, the approach applies MinHashing to derive a smaller sketch and uses that for mapping. In addition to reducing density, this approach is also easily parallelizable. To demonstrate the efficacy of our method, we modified a recently developed long read mapping tool (JEM-mapper) to adopt different sketching schemes, including Syncmer and Strobemer, and incorporated MHsketch to evaluate the effectiveness of downsampling. Experimental evaluation demonstrates the ability of our approach to significantly reduce density and reap performance benefits from it. In particular, our experiments reveal that MHsketch (syncmers) achieves high-quality mapping while reducing time-to-solution (speedups between [Formula: see text] to [Formula: see text]), and drastically reducing memory usage ([Formula: see text] savings) compared to state-of-the-art tools. Availability: https://github.com/TazinRahman1105050/MHsketch.

PMID:41366730 | DOI:10.1186/s12859-025-06333-8

BMC Gastroenterol. 2025 Dec 8;25(1):855. doi: 10.1186/s12876-025-04526-2.

NO ABSTRACT

PMID:41361773 | DOI:10.1186/s12876-025-04526-2

Public Health Chall. 2025 Nov 29;4(4):e70171. doi: 10.1002/puh2.70171. eCollection 2025 Dec.

ABSTRACT

AIMS: This study explored the knowledge, attitudes, and practices (KAPs) related to water, sanitation, and hygiene (WASH) and food safety among mothers in Noakhali, a coastal district of Bangladesh.

METHODS: A cross-sectional study involving 325 mothers was conducted in the Noakhali district of Bangladesh using purposive sampling. A standard pretested questionnaire was used to assess KAPs regarding WASH practices.

RESULTS: Research findings indicated that although most participants had optimal knowledge, only a smaller percentage displayed positive attitudes and proper hygiene practices. Mothers with higher education and better economic standing were significantly more likely to exhibit favorable WASH behaviors, underscoring the critical role of education and economic empowerment. Importantly, mothers with good knowledge were nearly 10 times (adjusted odds ratio [AOR]: 9.621, 95% confidence interval [CI]: 4.23-21.88) more likely to practice safe hygiene, revealing the transformative potential of informed communities.

CONCLUSION: This study calls for culturally appropriate, community-driven interventions that honor the strength and resilience of rural Bangladeshi women. Promoting education, improving infrastructure, and expanding awareness through schools, media, and grassroots initiatives can pave the way for healthier, more dignified lives. Empowering mothers with knowledge and tools such as educational resources, training programs, and healthcare services is not only a public health necessity but also an investment in the future of rural Bangladesh.

PMID:41323026 | PMC:PMC12664651 | DOI:10.1002/puh2.70171

Nat Cell Biol. 2025 Nov 28. doi: 10.1038/s41556-025-01850-3. Online ahead of print.

NO ABSTRACT

PMID:41315770 | DOI:10.1038/s41556-025-01850-3

Sci Rep. 2025 Nov 28. doi: 10.1038/s41598-025-29919-x. Online ahead of print.

ABSTRACT

Rice blast, caused by Magnaporthe oryzae, is a persistent threat to rice production in Bangladesh, particularly in the haor (wet-land basin) region, where up to 80% yield loss occurs annually. This study aimed to explore the potential of an endophytic bacterium, Bacillus velezensis BDKishJoy-6B, for promoting growth and enhancing blast tolerance in rice cultivars commonly grown in this vulnerable agro-ecosystem. Fifteen isolates of P. oryzae were collected from haor regions and characterized morphologically and for pathogenicity. The most virulent isolate, KSH01 (GenBank: PQ269871.1), was selected for pathogenicity assays. Antagonistic endophytic bacteria were isolated from rice roots and screened for plant growth-promoting traits. The most effective isolate, BDKishJoy-6B, was identified as B. velezensis (GenBank accession: PQ770697.1). This strain was applied to two rice cultivars (US-2 and BRRI Dhan34) via seed priming, seedling priming, and combined treatments. Growth parameters, yield traits, defense gene expression (OsPOD, OsPAL1, OsPR5), and antioxidant enzyme activities (SOD, POD, APX, PPO, MDA) were assessed under artificial disease pressure. B. velezensis BDKishJoy-6B significantly enhanced rice growth and yield under blast stress, especially in BRRI Dhan34. Notably, seedling priming showed the highest upregulation of defense genes and antioxidant activities, correlating with reduced disease symptoms and increased biomass accumulation. Seedling priming with B. velezensis BDKishJoy-6B offers a promising bio-management strategy for controlling rice blast by modulating host antioxidant and defense pathways, with potential application in haor-based rice production systems.

PMID:41315720 | DOI:10.1038/s41598-025-29919-x

Endoscopy. 2025 Nov 28. doi: 10.1055/a-2757-3509. Online ahead of print.

NO ABSTRACT

PMID:41314248 | DOI:10.1055/a-2757-3509

Methods Enzymol. 2025;724:83-97. doi: 10.1016/bs.mie.2025.09.018. Epub 2025 Oct 14.

ABSTRACT

Multidrug transporters are membrane proteins that confer antibiotic resistance on bacterial cells by actively extruding toxic compounds. NorM from Vibrio cholerae (NorM-VC) belongs to the MATE (Multidrug And Toxic compound Extrusion) family and is active as an ion/antibiotic exchanger. With the availability of high-resolution crystal and cryo-EM structures, and mechanistic predictions for NorM proteins, there is a need for convenient activity measurements in non-pathogenic cells and cell mimics. Here, we outline methods for the expression and purification of NorM-VC, protein reconstitution in proteoliposomes, and transport activity measurements in Lactococcus lactis and proteoliposomes using doxorubicin as the substrate. These measurements can easily be adapted for high throughput measurements in multi-well plates and extended to other classes of multidrug transporters that use doxorubicin as a substrate.

PMID:41309185 | DOI:10.1016/bs.mie.2025.09.018

Methods Enzymol. 2025;724:83-97. doi: 10.1016/bs.mie.2025.09.018. Epub 2025 Oct 14.

ABSTRACT

Multidrug transporters are membrane proteins that confer antibiotic resistance on bacterial cells by actively extruding toxic compounds. NorM from Vibrio cholerae (NorM-VC) belongs to the MATE (Multidrug And Toxic compound Extrusion) family and is active as an ion/antibiotic exchanger. With the availability of high-resolution crystal and cryo-EM structures, and mechanistic predictions for NorM proteins, there is a need for convenient activity measurements in non-pathogenic cells and cell mimics. Here, we outline methods for the expression and purification of NorM-VC, protein reconstitution in proteoliposomes, and transport activity measurements in Lactococcus lactis and proteoliposomes using doxorubicin as the substrate. These measurements can easily be adapted for high throughput measurements in multi-well plates and extended to other classes of multidrug transporters that use doxorubicin as a substrate.

PMID:41309185 | DOI:10.1016/bs.mie.2025.09.018

bioRxiv [Preprint]. 2025 Oct 22:2025.10.21.683747. doi: 10.1101/2025.10.21.683747.

ABSTRACT

Global health remains threatened by spillovers of zoonotic SARS-like betacoronaviruses (sarbecoviruses) that could be mitigated by a pan-sarbecovirus vaccine1. We described elicitation of potently neutralizing and cross-reactive anti-sarbecovirus antibodies by mosaic-8 nanoparticles (NPs) displaying eight different sarbecovirus spike receptor-binding domains (RBDs) as 60 copies of eight individual RBDs2-6 (mosaic-8 RBD-NPs) or 30 copies of two "quartets," each presenting four tandemly-arranged RBDs7 (dual quartet RBD-NPs). To facilitate manufacture of a broadly protective mosaic-8 vaccine, we generated membrane-bound RBD quartets that can be genetically encoded and delivered via mRNA: dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, which utilizes ESCRT- and ALIX-binding region (EABR) technology that promotes immunogen presentation on cell surfaces and circulating enveloped virus-like particles (eVLPs)8. Immunization with mRNA immunogens elicited equivalent or improved binding breadths, neutralization potencies, T cell responses, and targeting of conserved RBD epitopes across sarbecoviruses, demonstrating successful conversion of protein-based mosaic-8 RBD vaccines to mRNA formats. Systems serology9 showed that the mRNA vaccines elicited balanced IgG subclass responses with increased Fcγ receptor-binding IgGs, consistent with potentially superior Fc effector functions. A new technique, Systems Serology-Polyclonal Epitope Mapping (SySPEM), revealed distinct IgG-subclass-specific epitope targeting signatures across mRNA and protein-based vaccine modalities. These results demonstrate successful conversion of mosaic-8 RBD-NPs to mRNA or EABR-mRNA vaccines that provide easy manufacturing and enhanced protection from future pandemic sarbecovirus outbreaks.

PMID:41280075 | PMC:PMC12633426 | DOI:10.1101/2025.10.21.683747

bioRxiv [Preprint]. 2025 Oct 22:2025.10.21.683747. doi: 10.1101/2025.10.21.683747.

ABSTRACT

Global health remains threatened by spillovers of zoonotic SARS-like betacoronaviruses (sarbecoviruses) that could be mitigated by a pan-sarbecovirus vaccine 1 . We described elicitation of potently neutralizing and cross-reactive anti-sarbecovirus antibodies by mosaic-8 nanoparticles (NPs) displaying eight different sarbecovirus spike receptor-binding domains (RBDs) as 60 copies of eight individual RBDs 2-6 (mosaic-8 RBD-NPs) or 30 copies of two "quartets," each presenting four tandemly-arranged RBDs 7 (dual quartet RBD-NPs). To facilitate manufacture of a broadly protective mosaic-8 vaccine, we generated membrane-bound RBD quartets that can be genetically encoded and delivered via mRNA: dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, which utilizes ESCRT- and ALIX-binding region (EABR) technology that promotes immunogen presentation on cell surfaces and circulating enveloped virus-like particles (eVLPs) 8 . Immunization with mRNA immunogens elicited equivalent or improved binding breadths, neutralization potencies, T cell responses, and targeting of conserved RBD epitopes across sarbecoviruses, demonstrating successful conversion of protein-based mosaic-8 RBD vaccines to mRNA formats. Systems serology 9 showed that the mRNA vaccines elicited balanced IgG subclass responses with increased Fcγ receptor-binding IgGs, consistent with potentially superior Fc effector functions. A new technique, Systems Serology-Polyclonal Epitope Mapping (SySPEM), revealed distinct IgG-subclass-specific epitope targeting signatures across mRNA and protein-based vaccine modalities. These results demonstrate successful conversion of mosaic-8 RBD-NPs to mRNA or EABR-mRNA vaccines that provide easy manufacturing and enhanced protection from future pandemic sarbecovirus outbreaks.

PMID:41280075 | PMC:PMC12633426 | DOI:10.1101/2025.10.21.683747

Mol Med. 2025 Nov 23. doi: 10.1186/s10020-025-01398-w. Online ahead of print.

NO ABSTRACT

PMID:41276822 | DOI:10.1186/s10020-025-01398-w

Mol Med. 2025 Nov 23. doi: 10.1186/s10020-025-01398-w. Online ahead of print.

NO ABSTRACT

PMID:41276822 | DOI:10.1186/s10020-025-01398-w

BMC Gastroenterol. 2025 Nov 20;25(1):826. doi: 10.1186/s12876-025-04455-0.

ABSTRACT

BACKGROUND: The fecal immunochemical test (FIT) is a diagnostic modality for colorectal cancer (CRC) screening, with the US Multisociety Task Force setting an 80% adherence benchmark for follow-up colonoscopy (FUC). Guidelines recommend that FITs be performed only in the context of CRC screening.

METHODS: Our study is a retrospective review of all patients with positive FIT records from 2018 to 2023. Patient characteristics, FIT ordering practices, and clinical settings were collected. The compliance rates with FUC, colonoscopy diagnostic yield, and adenoma detection were analyzed, and adherent and nonadherent patients were compared via univariate and logistic regression analyses.

RESULTS: A total of 1424 patients had positive FIT results, with ages ranging between 18 and 92 years. Among the 1424 patients, 245 (17.2%) were < 45 years (group 1), 829 (52.9%) were 45-75 years (group 2), and 350 (24.6%) were > 75 years (group 3). In group 2, 241 (16.9%) tests were conducted for CRC screening. Seven hundred and three (49.3%) positive FIT tests, including tests for abdominal pain and anemia, were carried out for diagnostic purposes. Only 618 (43.3%) patients with positive FIT results underwent FUC, of whom 277 (44.8%) had adenomas and 28 (4.5%) were diagnosed with CRC. Bivariate analysis revealed that age, fewer comorbidities, prior colonoscopy, family history of CRC, diagnostic FIT, and outpatient setting increased FUC adherence. Multivariate analysis revealed that age and outpatient setting were predictive factors.

CONCLUSION: Although FITs are used for CRC screening, our study found a discrepancy between guidelines and real-world practice. Compliance with FUC after a positive FIT is below the optimal range, with adherence decreasing with age.

PMID:41267005 | DOI:10.1186/s12876-025-04455-0

Nat Commun. 2025 Nov 20;16(1):10240. doi: 10.1038/s41467-025-65473-w.

ABSTRACT

A major regulator of gastrointestinal physiology is the enteric nervous system. This division of the autonomic nervous system is unique in its extensiveness, with neurons distributed from the esophagus to the rectum, and its capability for local information processing. However, the constant motion of the gut, arising from its relative movements in the peritoneal cavity and the peristaltic movements associated with gut motility, as well as the sparse distribution of the neurons constituting the enteric nervous system, has made access and analysis exceedingly challenging. Here, we present the construction and validation of a bioelectronic implant for accessing neural information from the distal colon. Our bioelectronic monitoring system demonstrates real-time electrophysiological recording in response to chemical and mechanical distension under anesthesia and to feeding and stress in freely-moving animals. Direct access to the communication pathways of the enteric nervous system paves the way for neuromodulation strategies targeting the gut-brain axis.

PMID:41266383 | DOI:10.1038/s41467-025-65473-w

Nat Commun. 2025 Nov 20;16(1):10240. doi: 10.1038/s41467-025-65473-w.

ABSTRACT

A major regulator of gastrointestinal physiology is the enteric nervous system. This division of the autonomic nervous system is unique in its extensiveness, with neurons distributed from the esophagus to the rectum, and its capability for local information processing. However, the constant motion of the gut, arising from its relative movements in the peritoneal cavity and the peristaltic movements associated with gut motility, as well as the sparse distribution of the neurons constituting the enteric nervous system, has made access and analysis exceedingly challenging. Here, we present the construction and validation of a bioelectronic implant for accessing neural information from the distal colon. Our bioelectronic monitoring system demonstrates real-time electrophysiological recording in response to chemical and mechanical distension under anesthesia and to feeding and stress in freely-moving animals. Direct access to the communication pathways of the enteric nervous system paves the way for neuromodulation strategies targeting the gut-brain axis.

PMID:41266383 | DOI:10.1038/s41467-025-65473-w