The Innovation最新文献

The remarkable morphological diversity and species abundance of teleost fishes offer a valuable resource for understanding vertebrate evolution. In phase I of the Fish10K project, genomes of 110 teleost species were sequenced and assembled, filling gaps in 3 previously unrepresented orders, and integrated with existing data to generate a 464 species whole-genome alignment spanning all teleost orders-the largest such resource beyond mammals and birds. Comparative analyses reveal distinctive genomic features, including progressive genome compaction with shortened intron lengths relative to non-teleost ray-finned fishes. Analysis of the transposable element (TE) landscape suggests a potential association between TE expansion in teleost genomes and different habitats, as well as the uniqueness of teleosts' DNA-dominated transposon composition among vertebrates. Genome-wide phylogenetic analyses refute the widely accepted monophyly of "Siluriphysi" hypothesis and support the hypothesis of a single origin of electroreception followed by secondary loss in Characiformes. A refined evolutionary timeline of teleosts by whole-genome alignment resource placed teleosts at ∼253 million years ago, predating the Permian-Triassic extinction, and delineates three diversification phases punctuated by mass extinctions, challenging continuous post-Cretaceous-Palaeogene acceleration models. This study establishes a large-scale genomic database and a foundational whole-genome alignment resource, advancing insights into the landscape of teleost genomic architecture and macroevolution.

Tidal disruption events (TDEs), which occur when stars enter the tidal radii of supermassive black holes (SMBHs) and are subsequently torn apart by their tidal forces, represent intriguing phenomena that stimulate growing research interest and pose an increasing number of puzzles in the era of time-domain astronomy. Here, we report an unusual X-ray transient, XID 935, discovered in the 7 Ms Chandra Deep Field-South, the deepest X-ray survey ever. XID 935 experienced an overall X-ray dimming by a factor of more than 40 between 1999 and 2016. Not monotonically decreasing during this period, its X-ray luminosity increased by a factor $>27$ within 2 months, from $L_{0.5-7\text{keV}}<{10}^{40.87}$ erg s^-1 (October 10, 2014-January 4, 2015) to $L_{0.5-7\text{keV}}={10}^{42.31\pm 0.20}$ erg s^-1 (March 16, 2015). The X-ray position of XID 935 is located at the center of its host galaxy with a spectroscopic redshift of 0.251, whose optical spectra do not display emission characteristics associated with an active galactic nucleus. The peak 0.5-2.0 keV flux is the faintest among all the X-ray-selected TDE candidates to date. Thanks to a total exposure of $\sim 9.5$ Ms in the X-ray bands, we manage to secure relatively well-sampled, 20-year-long X-ray light curves of this deepest X-ray-selected TDE candidate. We find that a partial TDE model could not explain the main declining trend. An SMBH binary TDE model is in acceptable accordance with the light curves of XID 935; however, it fails to match short-timescale fluctuations exactly. Therefore, the exceptional observational features of XID 935 provide a key benchmark for refining quantitative TDE models and simulations.

Programmable epigenetic editors (EEs) that achieve long-term gene expression modulation without altering the DNA sequence hold immense therapeutic potential. However, the clinical translation of current CRISPR-based epigenome editors is impeded by substantial challenges, particularly their large molecular size, which limits efficient in vivo delivery. Here, we report the rational design and engineering of compact, mRNA-delivered EEs (CRISPR OFF-EE) using Streptococcus pyogenes Cas9 (SpCas9), intein-split-SpCas9, or the smaller Cas-SF01 (a Cas12i3 variant). Combined with optimized mRNA architecture and lipid nanoparticle (LNP) delivery, a single intravenous LNP administration of the optimized OFF-EE V2 mRNA, along with selected guide RNAs (gRNAs) targeting Pcsk9 in mice, resulted in an ∼83.2% reduction in circulating PCSK9 levels and a corresponding ∼51.4% reduction in low-density lipoprotein cholesterol (LDL-C) levels, persisting for at least 180 days. SF01-based EEs showed higher specificity with fewer off-target methylation events than SpCas9-based counterparts. Our optimized LNP formulation also demonstrated a favorable safety profile with predominantly liver-tropic activity. These findings establish a robust and versatile platform for advancing in vivo therapeutics based on precise and durable epigenetic silencing using transiently delivered, engineered mRNA editors.

Small-scale soft robots with high morphological flexibility show significant potential for precise operation and sensing in confined environments. However, due to the coupled driving mechanism and the influence of environmental disturbances, the highly adaptable and stable navigation across diverse terrains through multimodal motion, which involves morphing shape and maintaining the reshaped configuration, still presents a major challenge for soft millirobots. Here, we develop a multi-stimuli-responsive millirobot with a multimodal locomotion adaptive control method, enhancing environmentally synergistic interactions and tasking capabilities. Constructed from materials responsive to temperature, humidity, and magnetic fields, the millirobot precisely navigates unstructured environments and independently controls deformation and locomotion. Theoretical models guide its polymorphic locomotion with optimal actuating parameters, such as bipedal walking in the two-leg mode and rolling in the wheel mode. A hierarchical dual-layer path-following controller manages path information and adjusts movement patterns. Experiments demonstrate the millirobot's environmental adaptability, morphological complementarity, and functional diversity. With various locomotion modes across different morphologies, the millirobot can traverse slopes, curved surfaces, stairs, slits, and gaps. It also performs tasks, such as cargo capture and transport, through morphological transformation. The proposed multimodal motion strategy based on polymorphism makes the soft millirobot a promising candidate for applications in micro-object manipulation and crevice inspection at confined, varied, and unstructured terrains.

Younger donors are preferred in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but this preference may limit access for patients whose only available donors are older. This study evaluated whether donor leukocyte telomere length (LTL), in conjunction with donor age, refines donor selection strategies to improve outcomes in recipients with acute leukemia. The discovery analysis included 1,049 acute leukemia patients who underwent allo-HSCT at the First Affiliated Hospital of Zhejiang University School of Medicine, while the replication cohort included 153 recipients from three additional centers. Donor LTL was measured using real-time quantitative PCR and categorized into quartiles: short (Q1) and long (Q2-Q4). Donor age was prespecified as <40 (younger) vs. ≥40 (older) years based on clinical practice. Long donor LTL was associated with a lower cumulative incidence of relapse (CIR), improved overall survival (OS), and better relapse-free survival (RFS) in allo-HSCT recipients. Recipients of grafts from donors aged ≥40 years with short LTL had higher CIR (adjusted hazard ratio [aHR] = 1.51; 95% confidence interval [CI], 1.04-2.19), worse OS (aHR = 1.76; 95% CI, 1.20-2.58), and worse RFS (aHR = 1.53; 95% CI, 1.06-2.20) compared with recipients of grafts from donors <40 years. Immune cell profiling showed that older donors with short LTL had more CD8⁺CD57⁺HLA-DR^- cells. In the replication cohort, recipients of grafts from older donors with long LTL had outcomes comparable with those of recipients with younger donors, while those with older donors and short LTL had inferior outcomes. These findings support considering donor LTL as a supplemental factor during donor evaluation, especially when younger donors are not available.

Despite many efforts and financial support, globally successful eutrophication restoration cases are rare, particularly in subtropical shallow lakes. Proposal and implementation of restoration strategy is hindered by lack of evidence in the long-term. Based on 2,000 years of management history and the recently successful recovery achievement in West Lake, a typical subtropical shallow urban lake in Hangzhou, China's first lake-related world cultural heritage site listing, we highlight the origin, eutrophication, restoration, and management processes. Its management and restoration was undertaken using five crucial procedures that included paludification prevention, external nutrient loading reduction, internal nutrient control, recovery of submerged macrophytes, and stable system regulation. We found a vital factor and successfully reestablished a stable aquatic system dominated by submerged macrophytes for more than 15 years based on a long-term synergistic technique, which not only inhibits phytoplankton propagation but also improves the self-purification capacity of the water body and landscape function. Our study highlights challenges and objectives of management and protection in West Lake at the next stage, and the strategy and methods regarding ecological restoration for similar subtropical shallow urban lakes on account of cross-century scale evidence.