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Abstract Polymer nanoparticles that can sharply sense and detect biological signals in cells are promising candidates for biomedical and theranostic nanomaterials. However, the response ability of current polymer assemblies poorly matches the requirement of trace concentration level (10−6 ~ 10−9 mol/L) of cellular biosignals due to their linear signal input-to-function output mode, which impedes their practical applications in vivo. Here we report a kind of nanobowl system with pH-tunable invaginated morphology that can nonlinearly amplify the response abilities toward biosignals by modulating the surface concavity. Compared to conventional spherical nanoparticles, nonspherical nanobowls with a specific concave structure reduce the critical response threshold of polymers by up to 5 orders of magnitude, from millimole to nanomole level, covering most of biosignal concentration windows. Moreover, we find that this nonlinear signal gain effect is originated from the collective impact of a single signal on transitioning the polymer chain aggregation state of individual assemblies, rather than just altering a certain unit or chain. This nonlinear signal-to-response mechanism is potential to solve the tricky problems of probing and sensing endogenous signals with trace physiological concentration.

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Abstract Selective ion transport underpins fundamental biological processes for efficient energy conversion and signal propagation. Mimicking these ‘ionics’ in synthetic nanofluidic channels has been increasingly promising for realizing self-sustained systems by harvesting clean energy from diverse environments, such as light, moisture, salinity gradient, etc. Here, we report a spatially nanoconfined ion separation strategy that enables harvesting electricity from CO2 adsorption. This breakthrough relies on the development of Nanosheet-Agarose Hydrogel (NAH) composite-based generators, wherein the oppositely charged ions are released in water-filled hydrogel channels upon adsorbing CO2. By tuning the ion size and ion-channel interactions, the released cations at the hundred-nanometer scale are spatially confined within the hydrogel network, while ångström-scale anions pass through unhindered. This leads to near-perfect anion/cation separation across the generator with a selectivity (D-/D+) of up to 1.8 × 106, allowing conversion into external electricity. With amplification by connecting multiple as-designed generators, the ion separation-induced electricity reaching 5 V is used to power electronic devices. This study introduces an effective spatial nanoconfinement strategy for widely demanded high-precision ion separation, encouraging a carbon-negative technique with simultaneous CO2 adsorption and energy generation.

Abstract The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

Abstract Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Top-down exfoliation is one of the most promising approaches for the scalable production of 2D materials, but the current techniques are limited by low yield of monolayers. Here, the authors report the exfoliation of graphene and other layered materials via viscous-polymer-assisted ball-milling, leading to a production of graphene products with monolayer percentage up to 97.9% at a yield of 78.3%.

The location and timing of metastasis are still fundamentally unpredictable. Here the authors present the Metastatic Network model, a machine learning framework that integrates clinical data and DNA alterations to predict the risk of metastasis to specific organs as well as clinical outcomes

Abstract Among today’s nonvolatile memories, ferroelectric-based capacitors, tunnel junctions and field-effect transistors (FET) are already industrially integrated and/or intensively investigated to improve their performances. Concurrently, because of the tremendous development of artificial intelligence and big-data issues, there is an urgent need to realize high-density crossbar arrays, a prerequisite for the future of memories and emerging computing algorithms. Here, a two-terminal ferroelectric fin diode (FFD) in which a ferroelectric capacitor and a fin-like semiconductor channel are combined to share both top and bottom electrodes is designed. Such a device not only shows both digital and analog memory functionalities but is also robust and universal as it works using two very different ferroelectric materials. When compared to all current nonvolatile memories, it cumulatively demonstrates an endurance up to 1010 cycles, an ON/OFF ratio of ~102, a feature size of 30 nm, an operating energy of ~20 fJ and an operation speed of 100 ns. Beyond these superior performances, the simple two-terminal structure and their self-rectifying ratio of ~ 104 permit to consider them as new electronic building blocks for designing passive crossbar arrays which are crucial for the future in-memory computing.

Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China. Here, the authors carry out multi-region sampling of Chinese ESCC samples, and find recurrent ERBB4 mutations, BRCA1/2 variants, and amplification of CD274; together with high levels of genomic and T-cell receptor heterogeneity.

The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.