Influence of leaf inclination angle and tillering on population transpiration, soil evaporation, and yield in winter wheat near-isogenic lines.

Leaf inclination angle (LIA) and tillering impact the winter wheat (Triticum aestivum L.) population canopy structure. Understanding their effects on water use (WU) parameters and yield can guide water-saving strategies through population control. In this study, six near-isogenic lines (NILs) and their parents were selected as materials. These special materials were characterized by varying tillering at the current sowing density, a similar genetic background, and, particularly, a gradient in mean flag leaf LIA. The investigation focused on the jointing to early grain-filling stage, the peak water requirement period of wheat crops. Population-scale transpiration (PT) and evaporation from the soil surface (E) were partitioned from total evapotranspiration (ET) by the means of micro-lysimeters. The results showed decreased PT, E, and ET with increased population density (PD) within a narrow density range derived from varying tillering across genotypes. Significant correlations existed between PD and ET, E, and PT, especially in the wettest 2017-2018 growing season. Within such narrow PD range, all the correlations between WU parameters and PD were negative, although some correlations were not statistically significant, thereby suggesting the population structure's predominant impact. No significant correlation existed between LIA and both ET and PT within the LIA range of 35°-65°. However, significant correlations occurred between LIA and E in two growing seasons. Genotypes with similar LIA but different PD produced varied ET; while with similar PD, the four pairs of genotypes with different LIA each consumed similar ET, thus highlighting PD's more crucial role in regulating ET. The yield increased with higher LIA, and showed a significant correlation, emphasizing the LIA's significant effect on yield. However, no correlation was observed with PD, indicating the minor effect of tillering at the current sowing density. Therefore these results might offer valuable insights for breeding water-saving cultivars and optimizing population structures for effective field water conservation.

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Rapid and Amplification-free Nucleic Acid Detection with DNA Substrate-Mediated Autocatalysis of CRISPR/Cas12a.

To enable rapid and accurate point-of-care DNA detection, we have developed a single-step, amplification-free nucleic acid detection platform, a DNA substrate-mediated autocatalysis of CRISPR/Cas12a (DSAC). DSAC makes use of the trans-cleavage activity of Cas12a and target template-activated DNA substrate for dual signal amplifications. DSAC employs two distinct DNA substrate types: one that enhances signal amplification and the other that negatively modulates fluorescent signals. The positive inducer utilizes nicked- or loop-based DNA substrates to activate CRISPR/Cas12a, initiating trans-cleavage activity in a positive feedback loop, ultimately amplifying the fluorescent signals. The negative modulator, which involves competitor-based DNA substrates, competes with the probes for trans-cleaving, resulting in a signal decline in the presence of target DNA. These DNA substrate-based DSAC systems were adapted to fluorescence-based and paper-based lateral flow strip detection platforms. Our DSAC system accurately detected African swine fever virus (ASFV) in swine's blood samples at femtomolar sensitivity within 20 min. In contrast to the existing amplification-free CRISPR/Dx platforms, DSAC offers a cost-effective and straightforward detection method, requiring only the addition of a rationally designed DNA oligonucleotide. Notably, a common ASFV sequence-encoded DNA substrate can be directly applied to detect human nucleic acids through a dual crRNA targeting system. Consequently, our single-step DSAC system presents an alternative point-of-care diagnostic tool for the sensitive, accurate, and timely diagnosis of viral infections with potential applicability to human disease detection.

Semi-liquid metal-based highly permeable and adhesive electronic skin inspired by spider web.

Soft and stretchable electronics have garnered significant attention in various fields, such as wearable electronics, electronic skins, and soft robotics. However, current wearable electronics made from materials like conductive elastomers, hydrogels, and liquid metals face limitations, including low permeability, poor adhesion, inadequate conductivity, and limited stretchability. These issues hinder their effectiveness in long-term healthcare monitoring and exercise monitoring. To address these challenges, we introduce a novel design of web-droplet-like electronics featuring a semi-liquid metal coating for wearable applications. This innovative design offers high permeability, excellent stretchability, strong adhesion, and good conductivity for the electronic skin. The unique structure, inspired by the architecture of a spider web, significantly enhances air permeability compared to commercial breathable patches. Furthermore, the distribution of polyborosiloxane mimics the adhesive properties of spider web mucus, while the use of semi-liquid metals in this design results in remarkable conductivity (9 × 106 S/m) and tensile performance (up to 850% strain). This advanced electronic skin technology enables long-term monitoring of various physiological parameters and supports machine learning recognition functions with unparalleled advantages. This web-droplet structure design strategy holds great promise for commercial applications in medical health monitoring and disease diagnosis.

A causal counterfactual graph neural network for arising-from-chair abnormality detection in parkinsonians.

The arising-from-chair task assessment is a key aspect of the evaluation of movement disorders in Parkinson's disease (PD). However, common scale-based clinical assessment methods are highly subjective and dependent on the neurologist's expertise. Alternate automated methods for arising-from-chair assessment can be established based on quantitative susceptibility mapping (QSM) images with multiple-instance learning. However, performance stability for such methods can be typically undermined by the presence of irrelevant or spuriously-relevant features that mask the intrinsic causal features. Therefore, we propose a QSM-based arising-from-chair assessment method using a causal graph-neural-network framework, where counterfactual and debiasing strategies are developed and integrated into this framework for capturing causal features. Specifically, the counterfactual strategy is proposed to suppress irrelevant features caused by background noise, by producing incorrect predictions when dropping causal parts. The debiasing strategy is proposed to suppress spuriously relevant features caused by the sampling bias and it comprises a resampling guidance scheme for selecting stable instances and a causal invariance constraint for improving stability under various interferences. The results of extensive experiments demonstrated the superiority of the proposed method in detecting arising-from-chair abnormalities. Its clinical feasibility was further confirmed by the coincidence between the selected causal features and those reported in earlier medical studies. Additionally, the proposed method was extensible for another motion task of leg agility. Overall, this study provides a potential tool for automated arising-from-chair assessment in PD patients, and also introduces causal counterfactual thinking in medical image analysis. Our source code is publicly available at https://github.com/SJTUBME-QianLab/CFGNN-PDarising.

ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

A novel OsGST gene encoding 9glutathione reductase negatively regulates cadmium accumulation in rice.

Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice.

Tailoring Highly Branched Poly(ß-amino ester)s for Efficient and Organ-Selective mRNA Delivery.

Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(ß-amino ester)s (HPAEs) for efficacious organ-selective mRNA delivery through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library of 219 HPAEs with varied backbone structures, terminal groups, and branching degrees are synthesized. The branched topological structures of HPAEs provide enhanced serum resistance and significantly higher mRNA expression in vivo. The terminal amine structures of HPAEs determine the organ-selectivity of mRNA delivery following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, while methylpentane enables mRNA delivery to the liver, spleen, and lungs simultaneously. This study represents a comprehensive exploration of the structure-activity relationship governing both the efficiency and organ-selectivity of mRNA delivery by HPAEs, suggesting promising candidates for treating various organ-related diseases.

Rotational inertia-induced glassy transition in chiral particle systems.

The dense active matter exhibits characteristics reminiscent of traditional glassy phenomena, yet the role of rotational inertia in glass dynamics remains elusive. In this study, we investigate the glass dynamics of chiral active particles influenced by rotational inertia. Rotational inertia endows exponential memory to particle orientation, restricting its alteration and amplifying the effective persistence time. At lower spinning frequencies, the diffusion coefficient exhibits a peak function relative to rotational inertia for shorter persistence times, while it steadily increases with rotational inertia for longer persistence times. In the realm of high-frequency spinning, the impact of rotational inertia on diffusion behavior becomes more pronounced, resulting in a nonmonotonic and intricate relationship between the diffusion coefficient and rotational inertia. Consequently, the introduction of rotational inertia significantly alters the glassy dynamics of chiral active particles, allowing for the control over transitions between fluid and glassy states by modulating rotational inertia. Moreover, our findings indicate that at a specific spinning temperature, there exists an optimal spinning frequency at which the diffusion coefficient attains its maximum value.

Photoinduced Electron Donor Acceptor Complex-Enabled α-C(sp3)-H Alkenylation of Amines.

Allylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide-ranging applications in organic synthesis. However, direct α-C(sp3)-H alkenylation of feedstock amines, particularly for the preparation of α-alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition-metal-free α-alkenylation of various readily available amines with alkenylborate esters in excellent E/Z - and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late-stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor-acceptor complex between 2-iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5-hydrogen atom transfer to generate the crucial α-amino radicals, is the key to success of this chemistry.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

A Novel Machine Learning Model for Predicting Stroke-Associated Pneumonia After Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Pneumonia is one of the most common complications after spontaneous intracerebral hemorrhage (sICH), i.e., stroke-associated pneumonia (SAP). Timely identification of targeted patients is beneficial to reduce poor prognosis. So far, there is no consensus on SAP prediction, and application of existing predictors is limited. The aim of this study was to develop a machine learning model to predict SAP after sICH. METHODS: We retrospectively reviewed 748 patients diagnosed with sICH and collected data from 4 dimensions-demographic features, clinical features, medical history, and laboratory tests. Five machine learning algorithms-logistic regression, gradient boosting decision tree, random forest, extreme gradient boosting, and category boosting-were used to build and validate the predictive model. We also applied recursive feature elimination with cross-validation to obtain the best feature combination for each model. Predictive performance was evaluated by area under the receiver operating characteristic curve. RESULTS: SAP was diagnosed in 237 patients. The model developed by category boosting yielded the most satisfactory outcomes overall with area under the receiver operating characteristic curves in the training set and test set of 0.8307 and 0.8178, respectively. CONCLUSIONS: The incidence of SAP after sICH in our center was 31.68%. Machine learning could potentially provide assistance in the prediction of SAP after sICH.

Metabolomics and transcriptomics analysis revealed the response mechanism of alfalfa to combined cold and saline-alkali stress.

Cold and saline-alkali stress are frequently encountered by plants, and they often occur simultaneously in saline-alkali soils at mid to high latitudes, constraining forage crop distribution and production. However, the mechanisms by which forage crops respond to the combination of cold and saline-alkali stress remain unknown. Alfalfa (Medicago sativa L.) is one of the most essential forage grasses in the world. In this study, we analyzed the complex response mechanisms of two alfalfa species (Zhaodong [ZD] and Blue Moon [BM]) to combined cold and saline-alkali stress using multi-omics. The results revealed that ZD had a greater ability to tolerate combined stress than BM. The tricarboxylic acid cycles of the two varieties responded positively to the combined stress, with ZD accumulating more sugars, amino acids, and jasmonic acid. The gene expression and flavonoid content of the flavonoid biosynthesis pathway were significantly different between the two varieties. Weighted gene co-expression network analysis and co-expression network analysis based on RNA-Seq data suggested that the MsMYB12 gene may respond to combined stress by regulating the flavonoid biosynthesis pathway. MsMYB12 can directly bind to the promoter of MsFLS13 and promote its expression. Moreover, MsFLS13 overexpression can enhance flavonol accumulation and antioxidant capacity, which can improve combined stress tolerance. These findings provide new insights into improving alfalfa resistance to combined cold and saline-alkali stress, showing that flavonoids are essential for plant resistance to combined stresses, and provide theoretical guidance for future breeding programs.

Dual drug-loaded metal-phenolic networks for targeted magnetic resonance imaging and synergistic chemo-chemodynamic therapy of breast cancer.

The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)-iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo-chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.5 nm, which could accumulate at tumor sites after circulation and be specifically taken up by metastatic 4T1 cells overexpressing CD44 receptors. In the tumor microenvironment, TFP@ATO-HA could release ATO/cisplatin and Fe3+ in a pH-responsive manner, deplete glutathione, and generate reactive oxygen species with endogenous H2O2 for chemodynamic therapy (CDT). Additionally, ATO could enhance chemotherapeutic efficacy by inhibiting mitochondrial respiration, relieving hypoxia, and amplifying the CDT effect by decreasing intracellular pH and elevating Fenton reaction efficiency. In vivo experiments demonstrated that TFP@ATO-HA could effectively inhibit tumor growth and suppress lung metastases without obvious systemic toxicity. Furthermore, TFP@ATO-HA exhibited a r1 relaxivity of 2.6 mM-1 s-1 and targeted MR imaging of 4T1 tumors. Dual drug-loaded metal-phenolic networks can be easily prepared and act as effective theranostic nanoplatforms for targeted MR imaging and synergistic chemo-chemodynamic therapy.

Causality-Enhanced Multiple Instance Learning With Graph Convolutional Networks for Parkinsonian Freezing-of-Gait Assessment.

Freezing of gait (FoG) is a common disabling symptom of Parkinson's disease (PD). It is clinically characterized by sudden and transient walking interruptions for specific human body parts, and it presents the localization in time and space. Due to the difficulty in extracting global fine-grained features from lengthy videos, developing an automated five-point FoG scoring system is quite challenging. Therefore, we propose a novel video-based automated five-classification FoG assessment method with a causality-enhanced multiple-instance-learning graph convolutional network (GCN). This method involves developing a temporal segmentation GCN to segment each video into three motion stages for stage-level feature modeling, followed by a multiple-instance-learning framework to divide each stage into short clips for instance-level feature extraction. Subsequently, an uncertainty-driven multiple-instance-learning GCN is developed to capture spatial and temporal fine-grained features through GCN scheme and uncertainty learning, respectively, for acquiring global representations. Finally, a causality-enhanced graph generation strategy is proposed to exploit causal inference for mining and enhancing human structures causally related to clinical assessment, thereby extracting spatial causal features. Extensive experimental results demonstrate the excellent performance of the proposed method on five-classification FoG assessment with an accuracy of 62.72% and an acceptable accuracy of 91.32%, which is confirmed by independent testing. Additionally, it enables temporal and spatial localization of FoG events to a certain extent, facilitating reasonable clinical interpretations. In conclusion, our method provides a valuable tool for automated FoG assessment in PD, and the proposed causality-related component exhibits promising potential for extension to other general and medical fine-grained action recognition tasks.

Highly Sensitive Detection of Hydrogen Peroxide in Cancer Tissue Based on 3D Reduced Graphene Oxide-MXene-Multi-Walled Carbon Nanotubes Electrode.

Hydrogen peroxide (H2O2) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more H2O2 during abnormal tumor growth. There has been a considerable amount of interest in utilizing H2O2 as a biomarker for the diagnosis of cancer tissue. In this study, an electrochemical sensor for H2O2 was constructed based on 3D reduced graphene oxide (rGO), MXene (Ti3C2), and multi-walled carbon nanotubes (MWCNTs) composite. Three-dimensional (3D) rGO-Ti3C2-MWCNTs sensor showed good linearity for H2O2 in the ranges of 1-60 µM and 60 µM-9.77 mM at a working potential of -0.25 V, with sensitivities of 235.2 µA mM-1 cm-2 and 103.8 µA mM-1 cm-2, respectively, and a detection limit of 0.3 µM (S/N = 3). The sensor exhibited long-term stability, good repeatability, and outstanding immunity to interference. In addition, the modified electrode was employed to detect real-time H2O2 release from cancer cells and cancer tissue ex vivo.

Maternal Oxidative Balance Score during Pregnancy and Congenital Heart Defects.

The relationship between maternal oxidative balance score (OBS) in pregnancy, representing overall oxidative balance status by integrating dietary and lifestyle factors, and congenital heart defects (CHD) remains unclear; therefore, this study attempted to explore their associations among the Chinese population. We conducted a case-control study including 474 cases and 948 controls in Northwest China. Pregnant women were interviewed to report diets and lifestyles in pregnancy by structured questionnaires. Logistic regression models were used to estimate the adjusted ORs (95%CIs). Maternal OBS ranged from 6 to 34 among cases, and 5 to 37 among controls. Comparing the highest with the lowest tertile group, the adjusted OR for CHD was 0.31 (0.19-0.50). The CHD risk was reduced by 7% (OR = 0.93, 95%CI = 0.90-0.95) in association with per 1 higher score of OBS during pregnancy. The inverse relationship between maternal OBS and CHD risk appeared to be more pronounced among participants in urban areas (OR = 0.89, 95%CI = 0.86-0.93). Maternal OBS during pregnancy showed good predictive values for fetal CHD, with the areas under the receiver operating characteristic curve 0.78 (0.76-0.81). These findings highlighted the importance of reducing oxidative stress through antioxidant-rich diets and healthy lifestyles among pregnant women to prevent fetal CHD.

Global burdens of nasopharyngeal carcinoma in children and young adults and predictions to 2040.

OBJECTIVES: To investigate the epidemiological trend for nasopharyngeal carcinoma among children and young adults and the disease burden they caused. MATERIALS AND METHODS: Data were collected from the Global Burden of Disease (GBD) study 2019. A comprehensive analysis was performed, with age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), disability-adjusted life-years (DALYs) and estimated annual percentage changes (EAPC). And decomposition and frontier analyses were done. Future trends were predicted using Bayesian age-period-cohort model. RESULTS: Globally, there were decreases in the ASIR (EAPC -0.175, 95 % confidence interval [CI]: -0.352 to 0.002), ASMR (EAPC -2.681, 95 % CI: -2.937 to -2.424), and age-standardized DALYs rates (EAPC -2.643, 95 % CI: -2.895 to -2.391). However, the ASIR for males in global (EAPC 0.454, 95 % CI: 0.302 to 0.606), Asia (EAPC 0.782, 95 % CI: 0.610 to 0.954) and America (EAPC 0.448, 95 % CI: 0.379 to 0.517), as well as females in European (EAPC 0.595, 95 % CI: 0.479 to 0.712) and American (EAPC 0.369, 95 % CI: 0.324 to 0.415), showed an increasing trend. The future ASIR per 100,000 will likely show a slight upward trend in 2020 to 2040 (increased from 0.254 to 0.284), particularly among females (increased from 0.177 to 0.206), and a continued decline in ASMR for both sexes (decreased from 0.070 to 0.061). CONCLUSIONS: Globally, NPC in children and young adults remains a major public health issue, with the global distribution and magnitude of the burden varies markedly, highlighting the need to formulate regional and population-based policies for primary prevention.

Construction of a Full-Length Transcriptome of Western Honeybee Midgut Tissue and Improved Genome Annotation.

Honeybees are an indispensable pollinator in nature with pivotal ecological, economic, and scientific value. However, a full-length transcriptome for Apis mellifera, assembled with the advanced third-generation nanopore sequencing technology, has yet to be reported. Here, nanopore sequencing of the midgut tissues of uninoculated and Nosema ceranae-inoculated A. mellifera workers was conducted, and the full-length transcriptome was then constructed and annotated based on high-quality long reads. Next followed improvement of sequences and annotations of the current reference genome of A. mellifera. A total of 5,942,745 and 6,664,923 raw reads were produced from midguts of workers at 7 days post-inoculation (dpi) with N. ceranae and 10 dpi, while 7,100,161 and 6,506,665 raw reads were generated from the midguts of corresponding uninoculated workers. After strict quality control, 6,928,170, 6,353,066, 5,745,048, and 6,416,987 clean reads were obtained, with a length distribution ranging from 1 kb to 10 kb. Additionally, 16,824, 17,708, 15,744, and 18,246 full-length transcripts were respectively detected, including 28,019 nonredundant ones. Among these, 43,666, 30,945, 41,771, 26,442, and 24,532 full-length transcripts could be annotated to the Nr, KOG, eggNOG, GO, and KEGG databases, respectively. Additionally, 501 novel genes (20,326 novel transcripts) were identified for the first time, among which 401 (20,255), 193 (13,365), 414 (19,186), 228 (12,093), and 202 (11,703) were respectively annotated to each of the aforementioned five databases. The expression and sequences of three randomly selected novel transcripts were confirmed by RT-PCR and Sanger sequencing. The 5' UTR of 2082 genes, the 3' UTR of 2029 genes, and both the 5' and 3' UTRs of 730 genes were extended. Moreover, 17,345 SSRs, 14,789 complete ORFs, 1224 long non-coding RNAs (lncRNAs), and 650 transcription factors (TFs) from 37 families were detected. Findings from this work not only refine the annotation of the A. mellifera reference genome, but also provide a valuable resource and basis for relevant molecular and -omics studies.