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Strongly chiral V2O3 NPs with optical responsiveness achieve targeted and precise cleavage of the RSV pre-fusion protein through photoinduction, thereby inhibiting respiratory syncytial virus.

Abstract

Respiratory syncytial virus (RSV) poses a significant threat to the health of infants, children, and the elderly, and as of now there is a lack of effective therapeutic drugs. To tackle this challenge, chiral vanadium trioxide nanoparticles (V2O3 NPs) with a particle size of 2.56 ± 0.34 nm are successfully synthesized, exhibiting a g-factor value of 0.048 at 874 nm in terms of circular dichroism. Under 808 nm light irradiation, these chiral V2O3 NPs demonstrated selective cleavage of the RSV pre-fusion protein (RSV protein), effectively blocking its conformational rearrangement and preventing RSV infection both in vitro and in vivo. Experimental analysis revealed that the chiral V2O3 NPs specifically bind to the functional domain spanning from aspartate200 (D200) to asparagine208 (N208) in the primary sequence of the RSV protein. Notably, L-V2O3 NPs exhibited a higher affinity, which is 4.06 times that of D-V2O3 NPs and 13.55 times that of DL-V2O3 NPs. The precise cutting site is located between amino acid residues leucine204 (L204) and proline205 (P205), attributed to the reactive oxygen species (ROS) generated by photoinduced nanoparticles. In addition, L-V2O3 NPs inhibited RSV infection by 99.6% in nasal epithelial cells and 99.2% in Vero cells. In the RSV-infected mouse model, intranasal administration of L-V₂O₃ NPs effectively controlled the viral load in the lungs of mice, reducing it by 92.43%. The hematoxylin and eosin staining of mouse organs and serum biochemical indicators are similar to those of the wild-type group, indicating the biosafety of L-V₂O₃ NPs. The findings suggest that chiral nanoparticles hold great potential in controlling RSV and provide new directions and ideas for drug development against viruses.

This study develops a library of lipopeptide-based organ-specific targeting (POST) lipid nanoparticles (LNPs). The POST LNPs, screened in vitro and in vivo, demonstrate high efficiency and specificity in delivering mRNA and siRNA to the lung, liver, and spleen, respectively. Structure-activity relationship analysis indicates that various lipid systems prefer specific lipopeptide structures for enhanced RNA delivery efficacy.

Abstract

Lipid nanoparticles (LNPs) with highly efficient and specific extrahepatic targeting abilities are promising in gene delivery, and the lipopeptides (LPs) with excellent designability and functionality are expected to empower the construction of functional LNPs. This study aims to develop highly efficient ionizable components that accurately match different targeting lipid systems through the modular design of LPs. Based on this, a lipopeptide-based organ-specific targeting (POST) LNP screening strategy is constructed, in which lysine-histidine-based lipopeptides (KH-LPs) are designed as highly efficient ionizable components. The optimal KH-LP LNP screened in vitro shows excellent siRNA/mRNA transfecting ability in various hard-to-transfect cell lines. Compared to the classic LNPs, the POST LNPs screened in vivo achieve even higher (or at least comparable) efficiency and specificity in delivering mRNA and siRNA to the lung, liver, and spleen, respectively. The structure-activity relationship (SAR) proves that the modular regulation of LP structures can accurately provide the optimal ionizable components for different targeting lipid systems, demonstrating the potential of this strategy in developing efficient and selective targeting systems, which is expected to open up more possibilities for gene therapy.

The basic principles of constructing chiral nanomaterials along with the latest research progress are comprehensively summarized and the challenges and future development of chiral nanomaterials for the treatment of NDDs are deeply expected.

Abstract

Chiral nanomaterials are widely investigated over recent decades due to their biocompatibility and unique chiral effects. These key properties have significantly promoted the rapid development of chiral nanomaterials in bioengineering and medicine. In this review, the basic principles of constructing chiral nanomaterials along with the latest progress in research are comprehensively summarized. Then, the application of chiral nanomaterials for the diagnosis of neurodegenerative diseases (NDDs) is systematically described. In addition, the significant potential and broad prospects of chiral nanomaterials in the treatment of NDDs are highlighted from several aspects, including the disaggregation of neurofibrils, the scavenging of reactive oxygen species, regulation of the microbial–gut–brain axis, the elimination of senescent cells, and the promotion of directed differentiation in neural stem cells. Finally, a perspective of the challenges and future development of chiral nanomaterials for the treatment of NDDs is provided.

A spatiotemporal segmentation immunotherapy strategy uses modular microneedles to modulate paradoxical postoperative immunization microenvironments. The modular microneedles load a personalized antitumor vaccine and demonstrate broad antitumor activities in postoperative immunotherapy, reducing recurrence and the incidence of perioperative wound complications.

Abstract

The perioperative period is crucial for determining postoperative tumor recurrence and metastasis. Various factors in postoperative lesions can diminish the therapeutic effect of conventional chemoradiotherapy, while emerging immunotherapy is restricted. The combination use of inflammatory inhibitors during treatment is also controversial. Here, a modular microneedle prepared from engineered keratin proteins is reported, which spatially and temporally differentiates the microenvironment of immune cell activation required for immunotherapy from that of wound healing. The recombinant keratin-84-T-based needle root layer, mainly retained in the epidermis, facilitated dendritic cell recruitment to achieve maximum antigen presentation of loaded vaccines. Meanwhile, the recombinant keratin-81-1Aα-based needle tip layer, located within the dermis, rapidly mitigated inflammatory responses while promoting tissue repair and regeneration. Unlike simply mixing immunotherapy and wound treatment, this spatiotemporal segmentation approach maximized the efficacy of immune therapeutics while promoting wound healing, making it suitable for application throughout the perioperative period.

Nature Energy, Published online: 10 February 2025; doi:10.1038/s41560-025-01705-z

The performance of kesterite solar cells is limited by poor extraction of electrons and holes and their recombination. Researchers have now discovered that annealing the device in a hydrogen-containing atmosphere can promote efficient charge extraction by redistributing certain elements like sodium and oxygen.

Nature Energy, Published online: 10 February 2025; doi:10.1038/s41560-025-01713-z

Jennifer Danis, expert in environmental and energy law and Federal Energy Policy Director at the Institute for Policy Integrity (New York University School of Law), talks to Nature Energy about shifts in the gas infrastructure landscape of the United States, highlighting gaps and opportunities for research and policy to be better aligned for positive change.

Nature Energy, Published online: 10 February 2025; doi:10.1038/s41560-025-01723-x

Author Correction: Scalable fabrication of wide-bandgap perovskites using green solvents for tandem solar cells

Nature Materials, Published online: 10 February 2025; doi:10.1038/s41563-025-02139-4

An advance in fabricating superconducting contacts to germanium leads to new tools for controlling the quantum state of electrons in quantum dots.

Nature Materials, Published online: 10 February 2025; doi:10.1038/s41563-024-02095-5

The authors achieve gate-controlled proximitization of a quantum dot in a planar germanium heterostructure, an isotopically purifiable group IV material. A patterned Pt germanosilicide superconductor is introduced via a thermally activated reaction.

Nature Materials, Published online: 10 February 2025; doi:10.1038/s41563-025-02126-9

Synthesis of millimetre-sized hexagonal diamond has been demonstrated, facilitated by the formation of intermediate post-graphite phases and temperature gradients.

Nature Nanotechnology, Published online: 10 February 2025; doi:10.1038/s41565-024-01839-3

Two decades after the exfoliation of graphene, the focus is shifting to ‘reassembling’ graphite to uncover new insights into interacting electrons.

Nature Nanotechnology, Published online: 10 February 2025; doi:10.1038/s41565-024-01851-7

This paper reports a customizable CRISPR ribonucleoprotein delivery tool, dubbed RIDE, for the treatment of Huntington’s disease in mice, non-human primates and patients’ iPSC neurons.

Nature Nanotechnology, Published online: 10 February 2025; doi:10.1038/s41565-025-01864-w

Here the authors show that Mycobacterium smegmatis porin A modified with nitrilotriacetic acid achieves direct and simultaneous discrimination of rare earth elements, suggesting the potential use of nanopore sensing in geological exploration.

Nature Nanotechnology, Published online: 10 February 2025; doi:10.1038/s41565-025-01858-8

A tunable quantum dot device in Bernal bilayer graphene possesses a spin–valley relaxation time of 38 s at millikelvin temperatures.

Eve's Byte of the Apple

Abstract:

In “Eve’s Byte of the Apple”, Sandi Toksvig will be taking an alternative look at the evolution of information, at how the knowledge of women and about women is encoded, and what comes from those codes. Since 2023 Sandi has been a Bye-Fellow at Christ’s College, Cambridge working on The Mappa Mundi Project, creating a global interactive digital platform telling women’s stories worldwide. In this lecture, she considers how the evolution of information technology has been historically biased against women, continuing that bias to the present day. Most importantly, she asks what might be done about it.

Biography:

Sandi Toksvig was born in Copenhagen, Denmark but grew up travelling the world. After graduating with a first-class degree from Cambridge, Sandi began a career on stage, television and radio. As a political and women’s rights activist, she was co-founder of the Women’s Equality Party in 2015. Sandi has written stage plays, journalism and over 25 books including fact and fiction for both children and adults. Her latest novel Friends of Dorothy was published in 2024.

• Speaker: Sandi Toksvig OBE
• Friday 21 February 2025, 17:30-18:30
• Venue: Lady Mitchell Hall, Sidgwick Avenue.
• Series: Darwin College Lecture Series; organiser: Janet Gibson.

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Title to be confirmed

Abstract not available

• Speaker: Bruno Uchoa, University of Oklahoma
• Thursday 17 April 2025, 14:00-15:30
• Venue: TCM Seminar Room.
• Series: Theory of Condensed Matter; organiser: Gaurav.

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Algebraising foundations of elliptic curves

Elliptic curves are one of the simplest non-trivial objects in algebraic geometry, which are pervasive in modern number theory, but also see applications in point counting algorithms and public key cryptography. Due to their geometric nature, formalising a working definition typically requires a lot of technical machinery, let alone any non-trivial results. Yet, the Lean community has managed to formalise two of the most fundamental theorems in the theory of elliptic curves, with scope for many more projects. In this talk, I will explain these theorems, and how we inadvertently discovered new proofs in our formalisation attempts. Elliptic curves are one of the simplest non-trivial objects in algebraic geometry, which are pervasive in modern number theory, but also see applications in point counting algorithms and public key cryptography. Due to their geometric nature, formalising a working definition typically requires a lot of technical machinery, let alone any non-trivial results. Yet, the Lean community has managed to formalise two of the most fundamental theorems in the theory of elliptic curves, with scope for many more projects. In this talk, I will explain these theorems, and how we inadvertently discovered new proofs in our formalisation attempts.

=== Hybrid talk ===

Join Zoom Meeting https://cam-ac-uk.zoom.us/j/87143365195?pwd=SELTNkOcfVrIE1IppYCsbooOVqenzI.1

Meeting ID: 871 4336 5195

Passcode: 541180

• Speaker: David Angdinata (University College London)
• Thursday 13 February 2025, 17:00-18:00
• Venue: MR14 Centre for Mathematical Sciences.
• Series: Formalisation of mathematics with interactive theorem provers ; organiser: Anand Rao Tadipatri.

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Can kernel machines be a viable alternative to deep neural networks?

Deep learning remains an art with several heuristics that do not always translate across application domains. Kernel machines, a classical model in ML, have received renewed attention following the discovery of the Neural Tangent Kernel and its equivalence to wide neural networks. I will present 2 results which show the promise of kernel machines for modern large scale applications. 1. Data-dependent supervised kernels: https://www.science.org/stoken/author-tokens/ST-1738/full 2. Fast scalable training algorithms for kernel machines: https://arxiv.org/abs/2411.16658

Bio: Parthe Pandit is the Thakur Family Chair Assistant Professor at the Center for Machine Intelligence and Data Science at IIT Bombay. He was a Simons Postdoctoral Fellow at UC San Diego. He obtained his PhD from UCLA and his undergraduate education from IIT Bombay. In 2024, he was awarded the AI2050 Early Career Fellowship by Schmidt Sciences. He has also been the recipient of the 2019 Jack K Wolf Student paper award by the IEEE Information Theory Society.

• Speaker: Dr Parthe Pandit, Indian Institute of Technology, Bombay
• Tuesday 25 February 2025, 14:00-15:00
• Venue: JDB Seminar Room, CUED.
• Series: Signal Processing and Communications Lab Seminars; organiser: Prof. Ramji Venkataramanan.

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Title to be confirmed

Abstract not available

• Speaker: Dr Parthe Pandit, Indian Institute of Technology, Bombay
• Tuesday 25 February 2025, 14:00-15:00
• Venue: JDB Seminar Room, CUED.
• Series: Signal Processing and Communications Lab Seminars; organiser: Prof. Ramji Venkataramanan.

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• Speaker: Vincenzo di Bartholo, University of Cambridge
• Wednesday 19 February 2025, 16:30-17:30
• Venue: MR12.
• Series: Algebra and Representation Theory Seminar; organiser: Adam Jones.

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