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We propose a high-security hyperchaotic orthogonal frequency division multiplexing (OFDM) encryption scheme based on the orbital angular momentum system, and our research focuses on the security and high-order modulation of the orbital angular momentum (OAM)system. In order to effectively prevent violent decryption by eavesdroppers, we adopt a high security Zhan's hyperchaotic model. In the experiments, the high security performance of the proposed encryption scheme is verified by the OAM optical transmission platform, the proposed encryption scheme has a large key space of 10191, and it is demonstrated that the high-order spatial optical modulation has a small impact on the bit error rate (BER) of the OAM system within the forward error correction (FEC) threshold. The experimental results show that the proposed encryption scheme significantly improves the security performance of OAM spatial optical transmission, and is a promising candidate for the next-generation high-security OAM high-order multiplexed transmission system.

An optical fiber sensor based on the parallel Vernier effect for temperature and transverse load measurement is reported in this paper. The sensor is composed of a novel compact fiber Michelson interferometer (MI) and a closed-cavity Fabry–Perot interferometer (FPI) connected in parallel. The fiber MI consists of a bent single-mode fiber (SMF) structure and a short length of hollow core silicon tube (HCST). A section of HCST is fused between two segments of SMF to form the fiber FPI. Two sensors in parallel can easily measure different physical parameters independently, thus realizing multi-parameter sensing. The fiber MI and FPI are used for temperature and transverse load measurement, respectively. Fiber optic MI and FPI are Vernier effect mutual reference interferometers. When MI is used for temperature sensing, FPI is the reference interferometer. When FPI is used for transverse load sensing, MI is the reference interferometer. It can improve the sensitivity of temperature and transverse load. Two samples were made and the sensing experiment was carried out. Through the sensing experiment, we get the maximum temperature sensitivity of 85.1 pm/°C in the temperature range of 30–80 °C and a transverse load sensitivity of −3.15 nm/N in the temperature range of 0–1.96 N. In addition, the sensor has the advantages of tiny size, low cost, and easy manufacture, which is suitable for temperature and transverse load sensing applications.

In this paper, transmission of orthogonal chirp division multiplexing (OCDM) based on asymmetric pair mapping over a seven core fiber is proposed. High-order 32 quadrature amplitude modulation (QAM) is reduced to quadrature phase-shift keying (QPSK) and 8 QAM signal employing asymmetric pair mapping, which will not affect the rate of the system. Combined with geometric shaping (GS), the average transmission power is successfully lowered, realizing signal damage suppression. In order to verify the performance of the proposed asymmetric pair mapping scheme, a 140 Gb/s asymmetric pair mapping OCDM signal transmission over 2 km seven core fiber is experimentally demonstrated. The experimental results show that the proposed transmission scheme has the best performance when the power distribution ratio (PDR) is 4 dB. Meanwhile, compared with GS 32 QAM with QPSK+rectangle 8 QAM, GS 32 QAM with QPSK+star 8 QAM and GS 32 QAM, the proposed asymmetric pair mapping OCDM signal has improved by 1.55 dB, 1.45 dB, and 0.7 dB, respectively. It has a wide range of applications in the future optical transmission system due to its outstanding performance in the suppression of high-order modulation signal degradation.

Abstract Background AsCas12a and LbCas12a nucleases are reported to be promising tools for genome engineering with protospacer adjacent motif (PAM) TTTV as the optimal. However, the C-containing PAM (CTTV, TCTV, TTCV, etc.) recognition by Cas12a might induce extra off-target edits at these non-canonical PAM sites. Results Here, we identify a novel Cas12a nuclease CeCas12a from Coprococcus eutactus, which is a programmable nuclease with genome-editing efficiencies comparable to AsCas12a and LbCas12a in human cells. Moreover, CeCas12a is revealed to be more stringent for PAM recognition in vitro and in vivo followed by very low off-target editing rates in cells. Notably, CeCas12a renders less off-target edits located at C-containing PAM at multiple sites compared to LbCas12a and AsCas12a, as assessed by targeted sequencing methods. Conclusions Our study shows that CeCas12a nuclease is active in human cells and the stringency of PAM recognition could be an important factor shaping off-target editing in gene editing. Thus, CeCas12a provides a promising candidate with distinctive characteristics for research and therapeutic applications.

Abstract Presently, multi-label classification algorithms are mainly based on positive and negative logical labels, which have achieved good results. However, logical labeling inevitably leads to the label misclassification problem. In addition, missing labels are common in multi-label datasets. Recovering missing labels and constructing soft labels that reflect the mapping relationship between instances and labels is a difficult task. Most existing algorithms can only solve one of these problems. Based on this, this paper proposes a soft-label recover based label-specific features learning (SLR-LSF) to solve the above problems simultaneously. Firstly, the information entropy is used to calculate the confidence matrix between labels, and the membership degree of soft labels is obtained by combining the label density information. Secondly, the membership degree and confidence matrix are combined to construct soft labels, and this process not only solves the problem of missing labels but also obtains soft labels with richer semantic information. Finally, in the process of learning specific label features for soft labels. The local smoothness of the labels learned through stream regularization is complemented by the global label correlation, thus improving the classification performance of the algorithm. To demonstrate the effectiveness of the proposed algorithm, we conduct comprehensive experiments on several datasets.

Abstract Objective To review the evidence for clinical adoption of clear cell likelihood score (ccLS) for identifying clear cell renal cell carcinoma (ccRCC) from small renal masses (SRMs). Methods We distinguished the literature on ccLS for identifying ccRCC via systematic search using PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data until 31 March, 2024. The risk of bias and concern on application was assessed using the modified quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The level of evidence supporting the clinical adoption of ccLS for identifying ccRCC was determined based on meta-analyses. Results Eight MRI studies and three CT studies were included. The risk of bias and application were mainly related to the index test and flow and timing, due to incomplete imaging protocol, unclear rating process, and inappropriate interval between imaging and surgery. The diagnostic odds ratios (95% confidence intervals) of MRI and CT ccLS were 14.69 (9.71–22.22; 6 studies, 1429 SRM, 869 ccRCC), and 5.64 (3.34–9.54; 3 studies, 296 SRM, 147 ccRCC), respectively, for identifying ccRCC from SRM. The evidence level for clinical adoption of MRI and CT ccLS were both rated as weak. MRI ccLS version 2.0 potentially has better diagnostic performance than version 1.0 (1 study, 700 SRM, 509 ccRCC). Both T2-weighted-imaging with or without fat suppression might be suitable for MRI ccLS version 2.0 (1 study, 111 SRM, 82 ccRCC). Conclusion ccLS shows promising diagnostic performance for identifying ccRCC from SRM, but the evidence for its adoption in clinical routine remains weak. Critical relevance statement Although clear cell likelihood score (ccLS) demonstrates promising performance for detecting clear cell renal cell carcinoma, additional evidence is crucial to support its routine use as a tool for both initial diagnosis and active surveillance of small renal masses. Key Points Clear cell likelihood score is designed for the evaluation of small renal masses. Both CT and MRI clear cell likelihood scores are accurate and efficient. More evidence is necessary for the clinical adoption of a clear cell likelihood score. Graphical Abstract

Abstract Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

Abstract Background Studies evaluating the effectiveness of immune checkpoint inhibitors (ICI) for endometrial cancer (EC) are limited. This study aimed to assess the efficacy of PD-1/PD-L1 inhibitors as monotherapy for EC by conducting a meta-analysis. The predictive significance of MMR status, a biomarker for ICI response, also required further investigation. Methods A systematic literature search was conducted in English databases until September 2023. The analysis included objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and odds ratios (OR), along with their corresponding 95% confidence intervals (CI). Results There were twelve trials totaling 685 individuals. PD-1/PD-L1 inhibitor monotherapy resulted in an ORR for 34% (95% CI = 24–44%) of the pooled EC patients. Subgroup analysis revealed a significantly higher ORR in dMMR EC (45%) compared to pMMR EC (8%), with an OR of 6.36 (95% CI = 3.64–11.13). The overall DCR was 42%, with dMMR EC at 51% and pMMR EC at 30% (OR = 2.61, 95% CI = 1.69–4.05). Grade three or higher adverse events (AEs) occurred in 15% of cases (95% CI = 9–24%) of the pooled incidence of AEs, which was 68% (95% CI = 65–72%). Conclusions This meta-analysis provides significant evidence for the effectiveness of PD-1/PD-L1 inhibitors as monotherapy for EC. Notably, dMMR EC patients demonstrated superior treatment efficacy with PD-1/PD-L1 inhibitor immunotherapy. Further research is required to explore subclassifications of EC based on dMMR molecular subtypes, enabling improved treatment strategies and outcomes for EC patients.

Unsaturated fatty acids (UFA) in lipids are the key to nutraceutical oil applications, with various potential applications in nutraceutical functional foods and pharmaceutical industries. In Idesia polycarpa (Salicaceae), more than 80 % of UFA have been found in the fruits; yet, the underlying genetic mechanism remains poorly understood. Due to the lack of theoretical research on the genes related to lipid biosynthesis and the complete genetic transformation system of I. polycarpa fruit, the selection and breeding of I. polycarpa, an excellent oil tree, has been severely restricted. In-depth understanding of the molecular mechanism and gene function of lipid biosynthesis of I. polycarpa fruit is therefore of great significance for the development of I. polycarpa resources. This is not only conducive to the genetic improvement of I. polycarpa by molecular breeding technologies but can also provide a reference for the study of the gene functions of other oil plants. In this study, the FA accumulation patterns of I. polycarpa fruits during 8 growth periods were analysed. Fruit from two developmental periods with different UFA levels were analysed for RNA sequencing by an Illumina NovaSeq 6000 HiSeq platform. De novo transcriptome assembly presented 115,350 unigenes and 4382 differentially expressed genes (DEGs). Functional annotation in the KEGG pathway and combined with DEG data revealed candidate genes potentially involved in UFA biosynthesis. Expression analysis of q-PCR of IpDGAT2, IpGPAT, IpKASII, IpSAD, IpFAD2, IpFAD3 and IpFAD8 suggested that these genes are highly involved in UFA biosynthesis. Full-length candidate genes were cloned and analysed by bioinformatic tools, and function analysis of IpSAD and IpFAD3 showed that these genes regulated the products of linoleic acid metabolism. This study provides a foundation for UFA biosynthesis in Idesia polycarpa, facilitating its genetic breeding in the future.

Abstract Untethered magnetic soft robots capable of performing adaptive locomotion and shape reconfiguration open up possibilities for various applications owing to their flexibility. However, magnetic soft robots are typically composed of soft materials with fixed modulus, making them unable to exert or withstand substantial forces, which limits the exploration of their new functionalities. Here, water‐induced, shape‐locking magnetic robots with magnetically controlled shape change and water‐induced shape‐locking are introduced. The water‐induced phase separation enables these robots to undergo a modulus transition from 1.78 MPa in the dry state to 410 MPa after hydration. Moreover, the body material's inherent self‐healing property enables the direct assembly of morphing structures and magnetic soft robots with complicated structures and magnetization profiles. These robots can be delivered through magnetic actuation and perform programmed tasks including supporting, blocking, and grasping by on‐demand deformation and subsequent water‐induced stiffening. Moreover, a water‐stiffening magnetic stent is developed, and its precise delivery and water‐induced shape‐locking are demonstrated in a vascular phantom. The combination of untethered delivery, on‐demand shape change, and water‐induced stiffening properties makes the proposed magnetic robots promising for biomedical applications.

Abstract Gene‐editing technology shows great potential in glioblastoma (GBM) therapy. Due to the complexity of GBM pathogenesis, a single gene‐editing‐based therapy is unlikely to be successful; therefore, a multi‐gene knockout strategy is preferred for effective GBM inhibition. Here, a non‐invasive, biodegradable brain‐targeted CRISPR/Cas12a nanocapsule is used that simultaneously targeted dual oncogenes, EGFR and PLK1, for effective GBM therapy. This cargo nanoencapsulation technology enables the CRISPR/Cas12a system to achieve extended blood half‐life, efficient blood‐brain barrier (BBB) penetration, active tumor targeting, and selective release. In U87MG cells, the combinatorial gene editing system resulted in 61% and 33% knockout of EGFR and PLK1, respectively. Following systemic administration, the CRISPR/Cas12a system demonstrated promising brain tumor accumulation that led to extensive EGFR and PLK1 gene editing in both U87MG and patient‐derived GSC xenograft mouse models with negligible off‐target gene editing detected through NGS. Additionally, CRISPR/Cas12a nanocapsules that concurrently targeted the EGFR and PLK1 oncogenes showed superior tumor growth suppression and significantly improved the median survival time relative to nanocapsules containing single oncogene knockouts, signifying the potency of the multi‐oncogene targeting strategy. The findings indicate that utilization of the CRISPR/Cas12a combinatorial gene editing technique presents a practical option for gene therapy in GBM.

Abstract The life cycle of genome builds spans interlocking pillars of assembly, annotation, and comparative genomics to drive biological insights. While tools exist to address each pillar separately, there is a growing need for tools to integrate different pillars of a genome project holistically. For example, comparative approaches can provide quality control of assembly or annotation; genome assembly, in turn, can help to identify artifacts that may complicate the interpretation of genome comparisons. The JCVI library is a versatile Python‐based library that offers a suite of tools that excel across these pillars. Featuring a modular design, the JCVI library provides high‐level utilities for tasks such as format parsing, graphics generation, and manipulation of genome assemblies and annotations. Supporting genomics algorithms like MCscan and ALLMAPS are widely employed in building genome releases, producing publication‐ready figures for quality assessment and evolutionary inference. Developed and maintained collaboratively, the JCVI library emphasizes quality and reusability.

Abstract Background Mimosa bimucronata originates from tropical America and exhibits distinctive leaf movement characterized by a relative slow speed. Additionally, this species possesses the ability to fix nitrogen. Despite these intriguing traits, comprehensive studies have been hindered by the lack of genomic resources for M. bimucronata. Results To unravel the intricacies of leaf movement and nitrogen fixation, we successfully assembled a high-quality, haplotype-resolved, reference genome at the chromosome level, spanning 648 Mb and anchored in 13 pseudochromosomes. A total of 32,146 protein-coding genes were annotated. In particular, haplotype A was annotated with 31,035 protein-coding genes, and haplotype B with 31,440 protein-coding genes. Structural variations (SVs) and allele specific expression (ASE) analyses uncovered the potential role of structural variants in leaf movement and nitrogen fixation in M. bimucronata. Two whole-genome duplication (WGD) events were detected, that occurred ~ 2.9 and ~ 73.5 million years ago. Transcriptome and co-expression network analyses revealed the involvement of aquaporins (AQPs) and Ca2+-related ion channel genes in leaf movement. Moreover, we also identified nodulation-related genes and analyzed the structure and evolution of the key gene NIN in the process of symbiotic nitrogen fixation (SNF). Conclusion The detailed comparative genomic and transcriptomic analyses provided insights into the mechanisms governing leaf movement and nitrogen fixation in M. bimucronata. This research yielded genomic resources and provided an important reference for functional genomic studies of M. bimucronata and other legume species.

Abstract Sugarcane is a vital crop with significant economic and industrial value. However, the cultivated sugarcane’s ultra-complex genome still needs to be resolved due to its high ploidy and extensive recombination between the two subgenomes. Here, we generate a chromosomal-scale, haplotype-resolved genome assembly for a hybrid sugarcane cultivar ZZ1. This assembly contains 10.4 Gb genomic sequences and 68,509 annotated genes with defined alleles in two sub-genomes distributed in 99 original and 15 recombined chromosomes. RNA-seq data analysis shows that sugar accumulation-associated gene families have been primarily expanded from the ZZSO subgenome. However, genes responding to pokkah boeng disease susceptibility have been derived dominantly from the ZZSS subgenome. The region harboring the possible smut resistance genes has expanded significantly. Among them, the expansion of WAK and FLS2 families is proposed to have occurred during the breeding of ZZ1. Our findings provide insights into the complex genome of hybrid sugarcane cultivars and pave the way for future genomics and molecular breeding studies in sugarcane.

Abstract Objective To appraise the quality of guidelines on intravenous iodinated contrast media (ICM) use in patients with kidney disease, and to compare the recommendations among them. Methods We searched four literature databases, eight guideline libraries, and ten homepages of radiological societies to identify English and Chinese guidelines on intravenous ICM use in patients with kidney disease published between January 2018 and June 2023. The quality of the guidelines was assessed with the Scientific, Transparent, and Applicable Rankings (STAR) tool. Results Ten guidelines were included, with a median STAR score of 46.0 (range 28.5–61.5). The guidelines performed well in “Recommendations” domain (31/40, 78%), while poor in “Registry” (0/20, 0%) and “Protocol” domains (0/20, 0%). Nine guidelines recommended estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as the cutoff for referring patients to discuss the risk-benefit balance of ICM administration. Three guidelines further suggested that patients with an eGFR < 45 mL/min/1.73 m2 and high-risk factors also need referring. Variable recommendations were seen in the acceptable time interval between renal function test and ICM administration, and that between scan and repeated scan. Nine guidelines recommended to use iso-osmolar or low-osmolar ICM, while no consensus has been reached for the dosing of ICM. Nine guidelines supported hydration after ICM use, but their protocols varied. Drugs or blood purification therapy were not recommended as preventative means. Conclusion Guidelines on intravenous ICM use in patients with kidney disease have heterogeneous quality. The scientific societies may consider joint statements on controversial recommendations for variable timing and protocols. Critical relevance statement The heterogeneous quality of guidelines, and their controversial recommendations, leave gaps in workflow timing, dosing, and post-administration hydration protocols of contrast-enhanced CT scans for patients with kidney diseases, calling for more evidence to establish a safer and more practicable workflow. Key points • Guidelines concerning iodinated contrast media use in kidney disease patients vary. • Controversy remains in workflow timing, contrast dosing, and post-administration hydration protocols. • Investigations are encouraged to establish a safer iodinated contrast media use workflow. Graphical Abstract

Abstract Magnetic soft robots have shown great potential for biomedical applications due to their high shape reconfigurability, motion agility, and multi-functionality in physiological environments. Magnetic soft robots with multi-layer structures can enhance the loading capacity and function complexity for targeted delivery. However, the interactions between soft entities have yet to be fully investigated, and thus the assembly of magnetic soft robots with on-demand motion modes from multiple film-like layers is still challenging. Herein, we model and tailor the magnetic interaction between soft film-like layers with distinct in-plane structures, and then realize multi-layer soft robots that are capable of performing agile motions and targeted adhesion. Each layer of the robot consists of a soft magnetic substrate and an adhesive film. The mechanical properties and adhesion performance of the adhesive films are systematically characterized. The robot is capable of performing two locomotion modes, i.e., translational motion and tumbling motion, and also the on-demand separation with one side layer adhered to tissues. Simulation results are presented, which have a good qualitative agreement with the experimental results. The feasibility of using the robot to perform multi-target adhesion in a stomach is validated in both ex-vivo and in-vivo experiments.

Abstract Prediction and identification of tumor recurrence are critical for brain cancer treatment design and planning. Stereotactic radiation therapy delivered with Gamma Knife has been developed as one of the common treatment approaches combined with others by delivering radiation that targets accurately on the tumor while not affecting nearby healthy tissues. In this paper, we release a fully publicly available brain cancer MRI dataset and the companion Gamma Knife treatment planning and follow-up data for the purpose of tumor recurrence prediction. The dataset contains original patient MRI images, radiation therapy data, and clinical information. Lesion annotations are provided, and inclusive preprocessing steps have been specified to simplify the usage of this dataset. A baseline framework based on a convolutional neural network is proposed companionably with basic evaluations. The release of this dataset will contribute to the future development of automated brain tumor recurrence prediction algorithms and promote the clinical implementations associated with the computer vision field. The dataset is made publicly available on The Cancer Imaging Archive (TCIA) ( https://doi.org/10.7937/xb6d-py67 ).

Pulverized coal preheating combustion technology has been proven to be a clean and efficient combustion technology. In view of the limited space and load-bearing capacity around the large coal-fired boiler, a novel technology and system with a compact entrained-flow gasifier to preheat pulverized coal is proposed for the first time. The preheating characteristics in the gasifier and the combustion characteristics of the preheated fuel in the down-fire combustor (DFC) are studied on the novel self-built preheating combustion test rig. The migration and transformation of coal nitrogen during the preheating combustion are investigated. The results show that the experiment system can operate continuously and steadily with small fluctuations in pressure and temperature. The temperature gradient in the gasifier is large, and the high temperature zone is located near the burner plane. The maximum temperature can reach 1 115 ℃, while the outlet temperature of the gasifier decreases to 850 ℃. The high temperature coal gas and char produced by the entrained-flow gasifier are provided to the DFC continuously and steadily. The volume fractions (dry basis) of CO, H2 and CH4 in high temperature coal gas are 13.15%, 8.72% and 0.78%, respectively. Compared to the raw coal, the size of the preheated char decreases. The 50% cut particle size of raw coal is 43 μm, while the preheated semi-coke is 24 μm. The specific surface area increases from 4.05 m2/g to 216.44 m2/g after preheating. At the same time, the pore volume of the char particles increases, and the combustion characteristics are improved. During the preheating process, 96.33% of volatile matter and 40.23% of fixed carbon are released into high temperature coal gas. Also, 69.74% of coal nitrogen is transformed in the gas phase, and 47.67% is converted into N2, the rest into NH3 and HCN. Stable combustion could be achieved with preheated fuels in the DFC with no ignition delay and a uniform temperature distribution. Most of the NH3 and HCN and the nitrogen released from char are converted into N2 in the main combustion zone. There is no NO generation in the main combustion zone. The CO and NOx emissions at the outlet of the DFC are 8.17 mg/Nm3 (6% O2) and 143.02 mg/Nm3 (6% O2), respectively. The combustion efficiency is 99.75%. After the pulverized coal is preheated by the new entrained-flow gasifier and burn in the DFC, only 4.69% of coal N is converted into NO.

Topology identification is important to ensure a safe and stable distribution network operation, especially in the case of high proportion of new energy access to the distribution network. It could provide structural information for distribution network management and the foundation of distribution network system analysis. In consideration of the influence of different power flow parameters on topology identification results, this paper proposes a topology identification method based on gradient boosting decision tree (GBDT) and attribute weighted naive Bayes (AWNB). Firstly, a gradient boosting decision tree was used to calculate the importance of different power flow parameters to reduce the data dimension and computational complexity. Then each attribute is given a weight based on the result of the importance calculation. Secondly, the weighted set was used as input to train the AWNB classifier to make the model more realistic. Finally, the IEEE 30-node model was used to verify the performance of the proposed method. The results indicate that the proposed method has high accuracy and good robustness, which could maintain a high success rate of topology identification under different noise environments.

Abstract Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.

Abstract Background Abscisic acid (ABA) receptor pyrabactin resistance 1/PYR1-like/regulatory components of ABA receptor proteins (PYR/PYL/RCARs) have been demonstrated to play pivotal roles in ABA signaling and in response to diverse environmental stimuli including drought, salinity and osmotic stress in Arabidopsis. However, whether and how GhPYL9-5D and GhPYR1-3A, the homologues of Arabidopsis PYL9 and PYR1 in cotton, function in responding to ABA and abiotic stresses are still unclear. Results GhPYL9-5D and GhPYR1-3A were targeted to the cytoplasm and nucleus. Overexpression of GhPYL9-5D and GhPYR1-3A in Arabidopsis wild type and sextuple mutant pyr1pyl1pyl2pyl4pyl5pyl8 plants resulted in ABA hypersensitivity in terms of seed germination, root growth and stomatal closure, as well as seedling tolerance to water deficit, salt and osmotic stress. Moreover, the VIGS (Virus-induced gene silencing) cotton plants, in which GhPYL9-5D or GhPYR1-3A were knocked down, showed clearly reduced tolerance to polyethylene glycol 6000 (PEG)-induced drought, salinity and osmotic stresses compared with the controls. Additionally, transcriptomic data revealed that GhPYL9-5D was highly expressed in the root, and GhPYR1-3A was strongly expressed in the fiber and stem. GhPYL9-5D, GhPYR1-3A and their homologs in cotton were highly expressed after treatment with PEG or NaCl, and the two genes were co-expressed with redox signaling components, transcription factors and auxin signal components. These results suggest that GhPYL9-5D and GhPYR1-3A may serve important roles through interplaying with hormone and other signaling components in cotton adaptation to salt or osmotic stress. Conclusions GhPYL9-5D and GhPYR1-3A positively regulate ABA-mediated seed germination, primary root growth and stomatal closure, as well as tolerance to drought, salt and osmotic stresses likely through affecting the expression of multiple downstream stress-associated genes in Arabidopsis and cotton.

Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently. Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B. Here, we presented three C. paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly. Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids. Resequencing analysis of 45 C. paliurus individuals uncovered two bottlenecks, consistent with the known events of environmental changes, and many selectively swept genes involved in critical biological functions, including plant defense and secondary metabolite biosynthesis. We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes, in particular gibberellin-related genes, associated with the heterodichogamy in C. paliurus species. Our study sheds light on evolutionary history of C. paliurus and provides genomic resources to study the medicinal herbs.

Over the past 20 years, tremendous advances in sequencing technologies and computational algorithms have spurred plant genomic research into a thriving era with hundreds of genomes decoded already, ranging from those of nonvascular plants to those of flowering plants. However, complex plant genome assembly is still challenging and remains difficult to fully resolve with conventional sequencing and assembly methods due to high heterozygosity, highly repetitive sequences, or high ploidy characteristics of complex genomes. Herein, we summarize the challenges of and advances in complex plant genome assembly, including feasible experimental strategies, upgrades to sequencing technology, existing assembly methods, and different phasing algorithms. Moreover, we list actual cases of complex genome projects for readers to refer to and draw upon to solve future problems related to complex genomes. Finally, we expect that the accurate, gapless, telomere-to-telomere, and fully phased assembly of complex plant genomes could soon become routine.

Objectives. To compare four DNA extraction methods for recovering bacterial DNA from mammalian faecal samples. Methods and Results. Three commercial kits from QIAamp, TIANamp, and MAGEN, together with the classic cetyltrimethylammonium bromide (CTAB) method, were evaluated for their performance in extracting bacterial DNA from the gut microbiota of five mammals, including humans (Homo sapiens), macaques (Macaca mulatta), dogs (Canis lupus familiaris), golden hamsters (Mesocricetus auratus), and mice (Mus musculus). First, we assessed the efficiency of the four methods based on DNA yield, purity, and integrity. Then, we investigated the impact of these methods on microbial composition and diversity and examined the relative abundance of dominant phyla bacteria based on 16S rRNA gene sequencing and real-time quantitative PCR. Our results showed that the CTAB method yielded relatively larger amounts of DNA, while the MAGEN kit yielded more Firmicutes DNA and reflected the true status of the microbiota more accurately. Conclusions. Of the four methods tested, the traditional CTAB method and commercial MAGEN kit accomplished the best performance in terms of DNA concentration and Firmicutes abundance across most of the tested species. As the CTAB method and MAGEN kit exhibited different advantages, we further tested and compared their DNA extraction performance on a defined microbiota comprising six strains from four dominant phyla to see which one better reflected the true status of the microbiota. In conclusion, the MAGEN kit was found to be superior to the CTAB method, as the testing results were closer to that of the defined microbiota.

Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabetes. Previous studies have identified Tumor Protein p53-inducible Nuclear Protein 2 (Trp53inp2) as a molecular link between hyperglycemia and cardiac hypertrophy. However, its role in cardiac pathology has never been determined in vivo. In this study, we generated a cardiac specific knockout model of Trp53inp2 (Trp53inp2-cKO) and investigated the impact of Trp53inp2 inactivation on the pathogenesis of heart failure under mechanic or/and metabolic stresses. Based on echocardiography assessment, inactivation of Trp53inp2 in heart led to accelerated onset of HFrEF in response to pressure-overload, with significantly reduced ejection fraction and elevated heart failure marker genes comparing to the control mice. In contrast, inactivation of Trp53inp2 ameliorated cardiac dysfunction induced by combined stresses of high fat diet and moderate pressure overload (Cardiometabolic Disorder Model). Moreover, Trp53inp2 inactivation led to reduced expression of glucose metabolism genes in lean, pressure-overloaded hearts. However, the same set of genes were significantly induced in the Trp53inp2-cKO hearts under both mechanical and metabolic stresses. In summary, we have demonstrated for the first time that cardiomyocyte Trp53inp2 has diametrically differential roles in the pathogenesis of heart failure and glucose regulation under mechanical vs. mechanical plus metabolic stresses. This insight suggests that Trp53inp2 may exacerbate the cardiac dysfunction during pressure overload injury but have a protective effect in cardiac diastolic function in cardiometabolic disease.

Ovarian cancer is a highly malignant gynecological cancer influenced by the immune microenvironment, metabolic reprogramming, and cellular senescence. This review provides a comprehensive overview of these characteristics. Metabolic reprogramming affects immune cell function and tumor growth signals. Cellular senescence in immune and tumor cells impacts anti-tumor responses and therapy resistance. Targeting immune cell metabolism and inducing tumor cell senescence offer potential therapeutic strategies. However, challenges remain in identifying specific targets and biomarkers. Understanding the interplay of these characteristics can lead to innovative therapeutic approaches. Further research is needed to elucidate mechanisms, validate strategies, and improve patient outcomes in ovarian cancer.