Machine-learning-optimized Cas12a barcoding enables the recovery of single-cell lineages and transcriptional profiles.

The development of CRISPR-based barcoding methods creates an exciting opportunity to understand cellular phylogenies. We present a compact, tunable, high-capacity Cas12a barcoding system called dual acting inverted site array (DAISY). We combined high-throughput screening and machine learning to predict and optimize the 60-bp DAISY barcode sequences. After optimization, top-performing barcodes had ∼10-fold increased capacity relative to the best random-screened designs and performed reliably across diverse cell types. DAISY barcode arrays generated ∼12 bits of entropy and ∼66,000 unique barcodes. Thus, DAISY barcodes-at a fraction of the size of Cas9 barcodes-achieved high-capacity barcoding. We coupled DAISY barcoding with single-cell RNA-seq to recover lineages and gene expression profiles from ∼47,000 human melanoma cells. A single DAISY barcode recovered up to ∼700 lineages from one parental cell. This analysis revealed heritable single-cell gene expression and potential epigenetic modulation of memory gene transcription. Overall, Cas12a DAISY barcoding is an efficient tool for investigating cell-state dynamics.

Characterization of Metabolic Patterns in Mouse Oocytes during Meiotic Maturation.

Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.

Genome evolution of the ancient hexaploid Platanus × acerifolia (London planetree).

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.

The high-quality genome of Cryptotaenia japonica and comparative genomics analysis reveals anthocyanin biosynthesis in Apiaceae.

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, Ks, and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology.

Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for HCC.

BACKGROUND AND AIMS: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. APPROACH AND RESULTS: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 ( LPCAT1 ) and ceramide synthase 5 ( CERS5 ) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. CONCLUSIONS: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.

An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration.

The remodeling and stiffening of the extracellular matrix (ECM) is a well-recognized modulator of breast cancer progression. How changes in the mechanical properties of the ECM are converted into biochemical signals that direct tumor cell migration and metastasis remain poorly characterized. Here, we describe a new role for the autophagy-inducing serine/threonine kinases ULK1 and ULK2 in mechanotransduction. We show that ULK1/2 activity inhibits the assembly of actin stress fibers and focal adhesions (FAs) and as a consequence impedes cell contraction and migration, independent of its role in autophagy. Mechanistically, we identify PXN/paxillin, a key component of the mechanotransducing machinery, as a direct binding partner and substrate of ULK1/2. ULK-mediated phosphorylation of PXN at S32 and S119 weakens homotypic interactions and liquid-liquid phase separation of PXN, impairing FA assembly, which in turn alters the mechanical properties of breast cancer cells and their response to mechanical stimuli. ULK1/2 and the well-characterized PXN regulator, FAK/Src, have opposing functions on mechanotransduction and compete for phosphorylation of adjacent serine and tyrosine residues. Taken together, our study reveals ULK1/2 as important regulator of PXN-dependent mechanotransduction.

Bioinspired Framework Catalysts: From Enzyme Immobilization to Biomimetic Catalysis.

Enzymatic catalysis has fueled considerable interest from chemists due to its high efficiency and selectivity. However, the structural complexity and vulnerability hamper the application potentials of enzymes. Driven by the practical demand for chemical conversion, there is a long-sought quest for bioinspired catalysts reproducing and even surpassing the functions of natural enzymes. As nanoporous materials with high surface areas and crystallinity, metal-organic frameworks (MOFs) represent an exquisite case of how natural enzymes and their active sites are integrated into porous solids, affording bioinspired heterogeneous catalysts with superior stability and customizable structures. In this review, we comprehensively summarize the advances of bioinspired MOFs for catalysis, discuss the design principle of various MOF-based catalysts, such as MOF-enzyme composites and MOFs embedded with active sites, and explore the utility of these catalysts in different reactions. The advantages of MOFs as enzyme mimetics are also highlighted, including confinement, templating effects, and functionality, in comparison with homogeneous supramolecular catalysts. A perspective is provided to discuss potential solutions addressing current challenges in MOF catalysis.

Contributions of repeated learning to memory in humans: insights from single-neuron recordings in the hippocampus and amygdala.

Despite the well-established phenomenon of improved memory performance through repeated learning, studies investigating the associated neural mechanisms have yielded complex and sometimes contradictory findings, and direct evidence from human neuronal recordings has been lacking. This study employs single-neuron recordings with exceptional spatial-temporal resolution, combined with representational similarity analysis, to explore the neural dynamics within the hippocampus and amygdala during repeated learning. Our results demonstrate that in the hippocampus, repetition enhances both representational specificity and fidelity, with these features predicting learning times. Conversely, the amygdala exhibits heightened representational specificity and fidelity during initial learning but does not show improvement with repetition, suggesting functional specialization of the hippocampus and amygdala during different stages of the learning repetition. Specifically, the hippocampus appears to contribute to sustained engagement necessary for benefiting from repeated learning, while the amygdala may play a role in the representation of novel items. These findings contribute to a comprehensive understanding of the intricate interplay between these brain regions in memory processes. Significance statement  For over a century, understanding how repetition contributes to memory enhancement has captivated researchers, yet direct neuronal evidence has been lacking, with a primary focus on the hippocampus and a neglect of the neighboring amygdala. Employing advanced single-neuron recordings and analytical techniques, this study unveils a nuanced functional specialization within the amygdala-hippocampal circuit during various learning repetition. The results highlight the hippocampus's role in sustaining engagement for improved memory with repetition, contrasting with the amygdala's superior ability in representing novel items. This exploration not only deepens our comprehension of memory enhancement intricacies but also sheds light on potential interventions to optimize learning and memory processes.

Poly (ADP-ribose) polymerase 1 promotes HuR/ELAVL1 cytoplasmic localization and inflammatory gene expression by regulating p38 MAPK activity.

Post-transcriptional regulation of cytokine/chemokine mRNA turnover is critical for immune processes and contributes to the mammalian cellular response to diverse inflammatory stimuli. The ubiquitous RNA-binding protein human antigen R (HuR) is an integral regulator of inflammation-associated mRNA fate. HuR function is regulated by various post-translational modifications that alter its subcellular localization and ability to stabilize target mRNAs. Both poly (ADP-ribose) polymerase 1 (PARP1) and p38 mitogen-activated protein kinases (MAPKs) have been reported to regulate the biological function of HuR, but their specific regulatory and crosstalk mechanisms remain unclear. In this study, we show that PARP1 acts via p38 to synergistically promote cytoplasmic accumulation of HuR and stabilization of inflammation-associated mRNAs in cells under inflammatory conditions. Specifically, p38 binds to auto-poly ADP-ribosylated (PARylated) PARP1 resulting in the covalent PARylation of p38 by PARP1, thereby promoting the retention and activity of p38 in the nucleus. In addition, PARylation of HuR facilitates the phosphorylation of HuR at the serine 197 site mediated by p38, which then increases the translocation of HuR to the cytoplasm, ultimately stabilizing the inflammation-associated mRNA expression at the post-transcriptional level.

Entropy-Driven Strongly Confined Low-Toxicity Pure-Red Perovskite Quantum Dots for Spectrally Stable Light-Emitting Diodes.

Spectrally stable pure-red perovskite quantum dots (QDs) with low lead content are essential for high-definition displays but are difficult to synthesize due to QD self-purification. Here, we make use of entropy-driven quantum-confined pure-red perovskite QDs to fabricate light-emitting diodes (LEDs) that have low toxicity and are efficient and spectrum-stable. Based on experimental data and first-principles calculations, multiple element alloying results in a 60% reduction in lead content while improving QD entropy to promote crystal stability. Entropy-driven QDs exhibit photoluminescence with 100% quantum yields and single-exponential decay lifetimes without alteration of their morphology or crystal structure. The pure-red LEDs utilizing entropy-driven QDs have spectrally stable electroluminescence, achieving a brightness of 4932 cd/m2, a maximum external quantum efficiency of over 20%, and a 15-fold longer operational lifetime than the CsPbI3 QD-based LEDs. These achievements demonstrate that entropy-driven QDs can mitigate local compositional heterogeneity and ion migration.

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes.

Atherosclerosis (AS) is the root cause of cardiovascular diseases. Ferroptosis is characterized by highly iron-dependent lipid peroxidation and has been reported to play an important role in the pathogenesis of AS. Visualization of the ferroptosis process in atherosclerotic plaques is of great importance for diagnosing and treating AS. In this work, the rationally designed fluorescent probe FAS1 exhibited excellent advantages including large Stokes shift, sensitivity to environmental viscosity, good photostability, and improved water solubility. It also could co-locate with commercial lipid droplets (LDs) probes (BODIPY 493/503) well in RAW264.7 cells treated by the ferroptosis inducer. After self-assembly into nanoparticles and then encapsulation with macrophage membranes, the engineered FAS1@MM NPs could successfully target the atherosclerotic plaques in Western diet-induced apolipoprotein E knockout (ApoE-/-) mice and reveal the association of ferroptosis with AS through fluorescence imaging in vivo. This study may provide additional insights into the roles of ferroptosis in the diagnosis and treatment of AS.

PCK2 induces gefitinib resistance by suppresses ferroptosis in non-small cell lung cancer.

OBJECTIVES: This study aimed to explore the involvement of phosphoenolpyruvate carboxykinase 2 (PCK2) in gefitinib-resistant non-small cell lung cancer (NSCLC) cells and assess its feasibility as a therapeutic target against gefitinib resistance. METHODS: Gefitinib-resistant cell lines, PC9GR and HCC827GR, were generated through progressive exposure of parental cells to escalating concentrations of gefitinib. Transcriptomic analysis encompassed the treatment of PC9 and PC9GR cells with gefitinib or vehicle, followed by RNA extraction, sequencing, and subsequent bioinformatic analysis. Cell viability was determined via CCK-8 assay, while clonogenic assays assessed colony formation. Apoptosis was detected utilizing the Annexin V-FITC/7AAD kit. Iron ion concentrations were quantified using FerroOrange. mRNA analysis was conducted through quantitative RT-PCR. Western blotting was employed for protein analysis. H&E and immunohistochemical staining were performed on tumor tissue sections. RESULTS: The results revealed that depletion or inhibition of PCK2 significantly enhanced gefitinib's efficacy in inducing cell growth arrest, apoptosis, and ferroptosis in resistant NSCLC. Moreover, PCK2 knockdown led to the downregulation of key ferroptosis-related proteins, GPX4 and SLC7A11, while upregulating ASCL4. Conversely, overexpression of PCK2 in gefitinib-sensitive cells rendered resistance to gefitinib. In vivo experiments using a gefitinib-resistant xenograft model demonstrated that PCK2 silencing not only reduced tumor growth but also considerably increased the anti-tumor effect of gefitinib. CONCLUSIONS: In conclusion, our study presents compelling evidence indicating that PCK2 plays a pivotal role in gefitinib resistance in NSCLC. The modulation of ferroptosis-related proteins and the involvement of Akt activation further elucidate the mechanisms underlying this resistance. Consequently, PCK2 emerges as a promising therapeutic target for overcoming gefitinib resistance in NSCLC, offering a new avenue for the development of more effective treatment strategies.

Fiber Actuators Based on Reversible Thermal Responsive Liquid Crystal Elastomer.

Soft actuators inspired by the movement of organisms have attracted extensive attention in the fields of soft robotics, electronic skin, artificial intelligence, and healthcare due to their excellent adaptability and operational safety. Liquid crystal elastomer fiber actuators (LCEFAs) are considered as one of the most promising soft actuators since they can provide reversible linear motion and are easily integrated or woven into complex structures to perform pre-programmed movements such as stretching, rotating, bending, and expanding. The research on LCEFAs mainly focuses on controllable preparation, structural design, and functional applications. This review, for the first time, provides a comprehensive and systematic review of recent advances in this important field by focusing on reversible thermal response LCEFAs. First, the thermal driving mechanism, and direct and indirect heating strategies of LCEFAs are systematically summarized and analyzed. Then, the fabrication methods and functional applications of LCEFAs are summarized and discussed. Finally, the challenges and technical difficulties that may hinder the performance improvement and large-scale production of LCEFAs are proposed, and the development opportunities of LCEFAs are prospected.

Near-Infrared Light-Driven Nanoparticles for Cancer Photoimmunotherapy by Synergizing Immune Cell Death and Epigenetic Regulation.

Histone deacetylases (HDACs) are a class of epigenetic enzymes that are closely related to tumorigenesis and suppress the expression of tumor suppressor genes. Whereas the HDACs inhibitors can release DNA into the cytoplasm and trigger innate immunity. However, the high density of chromatin limits DNA damage and release. In this study, suitable nanosized CycNHOH NPs (150 nm) and CypNHOH NPs (85 nm) efficiently accumulate at the tumor site due to the enhanced permeability and retention (EPR) effect. In addition, robust single-linear oxygen generation and good photothermal conversion efficiency under NIR laser irradiation accelerated the DNA damage process. By effectively initiating immune cell death, CypNHOH NPs activated both innate and adaptive immunity by maturing dendritic cells, infiltrating tumors with natural killer cells, and activating cytotoxic T lymphocytes, which offer a fresh perspective for the development of photo-immunotherapy.

Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma.

BACKGROUND: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. METHODS: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. RESULTS: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.

Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense.

The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection.

Robotic Versus Thoracoscopic Sub-lobar Resection for Octogenarians with Clinical Stage IA Non-small Cell Lung Cancer: A Propensity Score-Matched Real-World Study.

BACKGROUND: Minimally invasive sub-lobectomy is sufficient in treating small early-stage non-small cell lung cancer (NSCLC). However, comparison of the feasibility and oncologic efficacy between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in performing sub-lobectomy for early-stage NSCLC patients age 80 years or older is scarce. METHODS: Octogenarians with clinical stage IA NSCLC (tumor size, ≤ 2 cm) undergoing minimally invasive wedge resection or segmentectomy at Shanghai Chest Hospital from 2011 to 2020 were retrospectively reviewed from a prospectively maintained database. Propensity score-matching (PSM) with a RATS versus VATS ratio of 1:4 was performed. Perioperative and long-term outcomes were analyzed. RESULTS: The study identified 594 patients (48 RATS and 546 VATS patients), and PSM resulted in 45 cases in the RATS group and 180 cases in the VATS group. The RATS patients experienced less intraoperative bleeding (60 mL [interquartile range (IQR), 50-100 mL] vs. 80 mL [IQR, 50-100 mL]; P = 0.027) and a shorter postoperative hospital stay (4 days [IQR, 3-5 days] vs. 5 days [IQR, 4-6 days]; P = 0.041) than the VATS patients. The two surgical approaches were comparable concerning other perioperative outcomes and postoperative complications (20.00% vs. 26.11%; P = 0.396). Additionally, during a median follow-up period of 66 months, RATS and VATS achieved comparable 5-year overall survival (90.48% vs. 87.93%; P = 0.891), recurrence-free survival (83.37% vs. 83.18%; P = 0.782), and cumulative incidence of death. Further subgroup comparison also demonstrated comparable long-term outcomes between the two approaches. Finally, multivariate Cox analysis indicated that the surgical approach was not independently correlated with long-term outcomes. CONCLUSIONS: The RATS approach shortened the postoperative hospital stay, reduced intraoperative bleeding by a statistically notable but clinically insignificant amount, and achieved long-term outcomes comparable with VATS in performing sub-lobectomy for octogenarians with early-stage small NSCLC.

Critical role of water conditions in the responses of autumn phenology of marsh wetlands to climate change on the Tibetan Plateau.

The Tibetan Plateau, housing 20% of China's wetlands, plays a vital role in the regional carbon cycle. Examining the phenological dynamics of wetland vegetation in response to climate change is crucial for understanding its impact on the ecosystem. Despite this importance, the specific effects of climate change on wetland vegetation phenology in this region remain uncertain. In this study, we investigated the influence of climate change on the end of the growing season (EOS) of marsh wetland vegetation across the Tibetan Plateau, utilizing satellite-derived Normalized Difference Vegetation Index (NDVI) data and observational climate data. We observed that the regionally averaged EOS of marsh vegetation across the Tibetan Plateau was significantly (p < .05) delayed by 4.10 days/decade from 2001 to 2020. Warming preseason temperatures were found to be the primary driver behind the delay in the EOS of marsh vegetation, whereas preseason cumulative precipitation showed no significant impact. Interestingly, the responses of EOS to climate change varied spatially across the plateau, indicating a regulatory role for hydrological conditions in marsh phenology. In the humid and cold central regions, preseason daytime warming significantly delayed the EOS. However, areas with lower soil moisture exhibited a weaker or reversed delay effect, suggesting complex interplays between temperature, soil moisture, and EOS. Notably, in the arid southwestern regions of the plateau, increased preseason rainfall directly delayed the EOS, while higher daytime temperatures advanced it. Our results emphasize the critical role of hydrological conditions, specifically soil moisture, in shaping marsh EOS responses in different regions. Our findings underscore the need to incorporate hydrological factors into terrestrial ecosystem models, particularly in cold and dry regions, for accurate predictions of marsh vegetation phenological responses to climate change. This understanding is vital for informed conservation and management strategies in the face of current and future climate challenges.

Accelerated Wound Healing by Electrospun Multifunctional Fibers with Self-Powered Performance.

Wound healing has been a persistent clinical challenge for a long time. Electrical stimulation is an effective therapy with the potential to accelerate wound healing. In this work, the self-powered electrospun nanofiber membranes (triples) were constructed as multifunctional wound dressings with electrical stimulation and biochemical capabilities. Triple was composed of a hydrolyzable inner layer with antiseptic and hemostatic chitosan, a hydrophilic core layer loaded with conductive AgNWs, and a hydrophobic outer layer fabricated by self-powered PVDF. Triple exhibited presentable wettability and acceptable moisture permeability. Electrical performance tests indicated that triple can transmit electrical signals formed by the piezoelectric effect to the wound. High antibacterial activities were observed for triple against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with inhibition rates of 96.52, 98.63, and 97.26%, respectively. In vitro cell assays demonstrated that triple cells showed satisfactory proliferation and mobility. A whole blood clotting test showed that triple can enhance hemostasis. The innovative self-powered multifunctional fibers presented in this work offer a promising approach to addressing complications and expediting the promotion of chronic wound healing.

Assessing the necessity of screening ≤5 Mb segmental aneuploidy in routine PGT for aneuploidies.

RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.