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Abstract Background Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. Materials and methods SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. Results The expressions of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3ʹ-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. Conclusions DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH. Graphical Abstract

Abstract Binder plays a crucial role in constructing high‐performance electrodes for water electrolysis. While most research has been focused on advancing electrocatalysts, the application of binders in electrode design has yet to be fully explored. Herein, the in situ incorporation of polytetrafluoroethylene (PTFE) as a multifunctional binder, which increases electrochemical active sites, enhances mass transfer, and strengthens the mechanical and chemical robustness of oxygen evolution reaction (OER) electrodes, is reported. The NiFe‐LDH@PTFE/NF electrode prepared by co‐deposition of PTFE with NiFe‐layered double hydroxide onto nickel foam demonstrates exceptional long‐term stability with a minimal potential decay rate of 0.034 mV h−1 at 500 mA cm−2 for 1000 h. The alkaline water electrolyzer utilizing NiFe‐LDH@PTFE/NF requires only 1.584 V at 500 mA cm−2 and sustains high energy efficiency over 1000 h under industrial operating conditions. This work opens a new path for stabilizing active sites to obtain durable electrodes for OER as well as other electrocatalytic systems.

Abstract Invertebrates greatly support the growth, development, and reproduction of insectivorous birds. However, the influence of human activity (e.g., pesticide use, deforestation, and urbanization) inevitably leads to a decrease in global arthropods. The diversity and variation in invertebrate diet influence the food composition of birds, especially species living in rapidly changing environments, such as the Tibetan Plateau. However, little is known of the seasonal variation in invertebrate diet in response to environmental changes. Here, we characterized the invertebrate diet composition in pre‐ and post‐breeding black‐necked crane (Grus nigricollis) using fecal metabarcoding. We identified 38 invertebrate genera; the top three were Tipula (82.1% of relative abundance), Ceramica (3.0%), and unclassified_Hymenoptera (2.5%), with Tipula predominated the diet in both seasons. We also observed 20 and 16 unique genera in the pre‐ and post‐breeding periods, and the genera composition was distinct between seasons (R = .036, p = .024). In pre‐breeding, black‐necked cranes tended to consume more diverse foods, and individual cranes exhibited greater heterogeneity at the genus level. At the genera and species level, pre‐breeding black‐necked cranes showed a wider dietary niche than post‐breeding cranes. We observed season‐specific features, with Tipula (common crane fly) and Stethophyma (grasshoppers) being enriched in the post‐breeding period and Ceramica (moth) being more abundant in the pre‐breeding period. Three Tipula species had the greatest importance in discriminating between seasonal diets. This study demonstrated a seasonal pattern of invertebrate diet in the black‐necked crane, suggesting diet composition in response to resource and species availability. These results elaborate on the foraging ecology of highland birds and can inform the management of black‐necked crane conservation.

Abstract We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Abstract Regulated cell death (RCD) plays a pivotal role in various biological processes, including development, tissue homeostasis, and immune response. However, a comprehensive assessment of RCD status and its associated features at the pan-cancer level remains unexplored. Furthermore, despite significant advancements in immune checkpoint inhibitors (ICI), only a fraction of cancer patients currently benefit from treatments. Given the emerging evidence linking RCD and ICI efficacy, we hypothesize that the RCD status could serve as a promising biomarker for predicting the ICI response and overall survival (OS) in patients with malignant tumors. We defined the RCD levels as the RCD score, allowing us to delineate the RCD landscape across 30 cancer types, 29 normal tissues in bulk, and 2,573,921 cells from 82 scRNA-Seq datasets. By leveraging large-scale datasets, we aimed to establish the positive association of RCD with immunity and identify the RCD signature. Utilizing 7 machine-learning algorithms and 18 ICI cohorts, we developed an RCD signature (RCD.Sig) for predicting ICI response. Additionally, we employed 101 combinations of 10 machine-learning algorithms to construct a novel RCD survival-related signature (RCD.Sur.Sig) for predicting OS. Furthermore, we obtained CRISPR data to identify potential therapeutic targets. Our study presents an integrative framework for assessing RCD status and reveals a strong connection between RCD status and ICI effectiveness. Moreover, we establish two clinically applicable signatures and identify promising potential therapeutic targets for patients with tumors.

There has been debate about whether individuals with different color phenotypes should have different taxonomic status. In order to determine whether the different color phenotypes of Nedyopus patrioticus require separate taxonomic status or are simply synonyms, here, the complete mitochondrial genomes (mitogenomes) of two different colored N. patrioticus, i.e., red N. patrioticus and white N. patrioticus, are presented. The two mitogenomes were 15,781 bp and 15,798 bp in length, respectively. Each mitogenome contained 13 PCGs, 19 tRNAs, 2 rRNAs, and 1 CR, with a lack of trnI, trnL2, and trnV compared to other Polydesmida species. All genes were located on a single strand in two mitogenomes. Mitochondrial DNA analyses revealed that red N. patrioticus and white N. patrioticus did not show clear evolutionary differences. Furthermore, no significant divergence was discovered by means of base composition analysis. As a result, we suggest that white N. patrioticus might be regarded as a synonym for red N. patrioticus. The current findings confirmed the existence of color polymorphism in N. patrioticus, which provides exciting possibilities for future research. It is necessary to apply a combination of molecular and morphological methods in the taxonomy of millipedes.

The rice-fish co-culture system (RFS) is a traditional cooperative farming model employed in southern China that can achieve doubling the harvest of rice (Oryza sp.) and fish. Most studies on RFS have focused on ecological mechanisms, benefits, ecosystem services, and agroecosystem functions; however, little is known about the baseline dietary composition in common carp of RFS, particularly across different developmental stages. In this study, we applied DNA metabarcoding of invertebrates (COI) and plants (Rbcl) to investigate the natural diets of common carp (Cyprinus carpio) across three developmental stages: juvenile (May), sub-adult (July), and adult (September). The animal-derived diets of common carp were dominated by prey from the orders Diptera, Lepidoptera, and Hemiptera, and the main plant-derived food items belonged to the families Poaceae, Araceae, and Hydrocharitaceae. We examined variations in the dietary compositions of common carp across three developmental stages to capture adaptations to seasonal changes in food resource availability. Additionally, we detected insect pests (species from the genera Macrosteles and Mythimna) and weeds (Eleusine indica, Alternanthera philoxeroides, Mazus japonicus, and Poa annua) in the diets of common carp, confirming the ecological benefits of common carp in rice fields by reducing insect pests and weeds. Characterizing the dietary composition and variation of common carp over developmental stages contributes to our understanding of its foraging ecology, dietary niche, and dynamics of trophic interactions, and provides critical information for evaluating the ecological benefits of common carp in RFS.

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877–3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877–3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877–3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877–3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Abstract Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.

Abstract In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.

Abstract Background Specific pathogen-free ducks are a valuable laboratory resource for waterfowl disease research and poultry vaccine development. High throughput sequencing allows the systematic identification of structural variants in genomes. Copy number variation (CNV) can explain the variation of important duck genetic traits. Herein, the genome-wide CNVs of the three experimental duck species in China (Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)) were characterized using resequencing to determine their genetic characteristics and selection signatures. Results We obtained 4,810 CNV regions (CNVRs) by merging 73,012 CNVs, covering 4.2% of the duck genome. Functional analysis revealed that the shared CNVR-harbored genes were significantly enriched for 31 gene ontology terms and 16 Kyoto Encyclopedia of Genes and Genomes pathways (e.g., olfactory transduction and immune system). Based on the genome-wide fixation index for each CNVR, growth (SPAG17 and PTH1R), disease resistance (CATHL3 and DMBT1), and thermoregulation (TRPC4 and SLIT3) candidate genes were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Conclusions In conclusion, we investigated the genome-wide distribution of experimental duck CNVs, providing a reference to establish the genetic basis of different phenotypic traits, thus contributing to the management of experimental animal genetic resources.

Quadruped robots, with their superior terrain adaptability and flexible movement capabilities, demonstrate greater application potential in complex environments compared to traditional ground robots. However, their non-negligible body shape and anisotropic motion characteristics complicate the achievement of high-precision motion planning and autonomous navigation. In this paper, we propose a safe and robust motion planning system tailored for autonomous navigation of quadruped robots in cluttered environments. We adopt a hierarchical architecture and decompose the planning process into front-end searching and back-end optimization. In the front-end searching stage, the robot finds a smooth, feasible, and energy-efficient initial trajectory with safety consideration. In the back-end optimization stage, we leverage B-splines to enhance the trajectory smoothness, safety, and motion stability. Finally, the time allocation is fine-tuned through iterative refinement, ensuring the feasibility of the optimized trajectory. Our method is extensively validated in challenging simulations as well as in real-world testing environments, benchmark comparisons also demonstrate the improved performance of our method.

Maize leaf spot, which is caused by Curvularia lunata (Wakkre) Boedijn, was epidemic in the maize-growing regions of northeastern and northern China in the mid-1990s, where it led to large yield losses. Since then, the epidemic has evolved into a kind of common disease. In recent years, however, a tendency of becoming an epidemic disease again has been observed in some areas in China due to significant changes in climate, farming, systems and crop varieties. The significance of methyl-(5hydroxymethyl) furan-2-carboxylate (M5HF2C) as a nonspecific host toxin in causing maize leaf spot disease has been demonstrated in previous research. However, the key enzymes involved in M5HF2C toxin synthesis remain unclear. In our study, we demonstrate that the synthesis of M5HF2C toxin starts from a precursor substrate in the pathogen, furfural, which is then catalytically dehydrogenated into furoic acid via an alcohol dehydrogenase (CLADH6). The furoic acid was further confirmed as one of the raw materials for the biosynthesis of M5HF2C toxin based on deletion mutants of the alcohol dehydrogenase gene (Cladh6) in C. lunata, which had reduced M5HF2C toxin-producing ability; however, this ability could be restored in all deletion mutants through complementation with furoic acid, thereby confirming that furoic acid is an intermediate in the biosynthesis of M5HF2C toxin. In summary, the biosynthesis process of M5HF2C toxin in C. lunata involves three transformation steps: (1) from xylose to furfural; (2) then from furfural to furoic acid; and (3) eventually from furoic acid to M5HF2C toxin. Our research findings provide new clues in elucidating the major steps in the process of M5HF2C toxin biosynthesis in C. lunata.

Swine leukocyte antigen (SLA) class I molecule-restricted T-cell epitopes, which induce cytotoxic T lymphocyte (CTL) responses, play a critical role in the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) and the development of efficient protective vaccines. The SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01 alleles, assigned the Hp-4.0 haplotype, are highly prevalent and usually present in all pig breeds. However, the SLA Hp-4.0 haplotype-restricted CTL epitopes in the structural membrane (M) protein of PRRSV are still unknown. In this study, we predicted 27 possible 9-mer epitope peptides in M protein with high binding scores for SLA-1*04:01:01 using CTL epitope prediction tools. In total, 45 SLA class I complexes, comprising the predicted peptide, extracellular region of the SLA-I molecules, and β2-microglobulin, were constructed in vitro to detect the specific binding of these peptides to SLA-1*04:01:01 (27 complexes), SLA-2*04:01 (9 complexes), and SLA-3*04:01 (9 complexes), respectively. Our results showed that the M27 (T91WKFITSRC), M39 (N130HAFVVRRP), and M49 (G158RKAVKQGV) peptides bind specifically to SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01, respectively. Subsequently, using peripheral blood mononuclear cells (PBMCs) isolated from the homozygous Hp-4.0 and Hp-26.0 haplotype piglets vaccinated with commercial PRRSV HuN4-F112 strain, we determined the capacities of these 27 potential peptides to stimulate their proliferation with a Cell Counting Kit-8 and their secretion and expression of interferon gamma (IFN-γ) with an ELISpot assay and real-time qPCR, respectively. The immunological activities of M27, M39, and M49 were therefore confirmed when they efficiently induced PBMC proliferation and IFN-γ secretion in PBMCs from piglets with the prevalent SLA Hp-4.0 haplotype. The amino acid sequence alignment revealed that M27, M39, and M49 are highly conserved among 248 genotype II PRRSV strains collected between 1998 and 2019. These findings contribute to the understanding of the mechanisms of cell-mediated immune responses to PRRSV. Our study also provides a novel strategy for identifying and confirming potential SLA haplotype-restricted CTL epitopes that could be used to develop novel peptide-based vaccines against swine diseases.

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.

In this study, mitochondrial genomes (mitogenomes) of seven cichlid species (Lamprologus kungweensis, L. meleagris, L. ornatipinnis, Neolamprologus brevis, N. caudopunctatus, N. leleupi, and N. similis) are characterized for the first time. The newly sequenced mitogenomes contained 37 typical genes [13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs) and 22 transfer RNA genes (tRNAs)]. The mitogenomes were 16,562 ~ 16,587 bp in length with an A + T composition of 52.1~58.8%. The cichlid mitogenomes had a comparable nucleotide composition, A + T content was higher than the G + C content. The AT-skews of most mitogenomes were inconspicuously positive and the GC-skews were negative, indicating higher occurrences of C than G. Most PCGs started with the conventional start codon, ATN. There was no essential difference in the codon usage patterns of these seven species. Using Ka/Ks, we found the fastest-evolving gene were atp8. But the results of p-distance indicated that the fastest-evolving gene was nad6. Phylogenetic analysis revealed that L. meleagris did not cluster with Lamprologus species, but with species from the genus Neolamprologus. The novel information obtained about these mitogenomes will contribute to elucidating the complex relationships among cichlid species.

The “321” prefabricated highway steel truss bridge is widely used for highway rescue, disaster relief, and emergency traffic. This paper uses a 33 m double-row monolayer “321” prefabricated highway steel truss bridge to analyze its mechanical properties and component stability. The actual traffic flow capacity of a total weight of 53.32 tons is used in this study. The results show that the maximum internal force in the truss chord (including the stiffening chord) occurs in the middle span section when a centrally distributed load is applied. Meanwhile, the maximum internal force of truss diagonal members and truss vertical bars appears at the fulcrum section. Under the eccentrically distributed load, the maximum internal forces of truss chords (including stiffening chords) appear in the middle span section, which is closest to the vehicle load, while the maximum internal forces of truss diagonal members and truss vertical bars appear in the fulcrum section, which is closest to the vehicle load. While the maximum internal forces under the eccentrically distributed load are greater than the maximum internal forces under the centered-layout load, under the vehicle load, truss chords (including stiffening chords) are prone to buckling instability, and the buckling mode is mainly reverse out-of-plane buckling. The inclined members of the truss are prone to buckling instability, and the buckling mode is mainly the combination of out-of-plane bending and two-way out-of-plane bending. Truss vertical bars have good stability and are not easy to buckle. The main conclusions of this paper can provide references for the optimal design and operation safety of prefabricated highway steel truss bridges.

Channidae (snakehead fish) is a family of medium-to-large freshwater carnivorous fish and contain the genus, Channa. Here, the complete mitogenomes of two Channa fish were determined and comparatively analyzed with the mitogenomes of 16 other Channidae fish species. The two newly sequenced complete mitogenomes were circular DNA molecules with sizes of 16,953 bp (Channa burmanica; OP954106) and 16,897 bp (Channa aurantimaculata; OQ134162). The mitogenomes were composed of 37 genes and one D-loop region. Positive AT skews and negative GC skews were found in the mitogenomes. Most protein-coding genes (PCGs) started with the conventional start codon, ATG; however, the sequence of the stop codon was variable. There was no obvious difference in relative synonymous codon usage among the two mitogenomes, and the two species shared a similar number of codon usage of mitogenomic PCGs, which was also similar to the mean values for the other 15 species of Channa. All Ka/Ks values were cox1 had the lowest value, and atp8 had the highest. All of the tRNAs were typical clover structures, except trnS1. Phylogenetic analysis showed that C. burmanica and C. aurantimaculata shared a close relationship and that they were also closely related to C. gachua. These findings enrich the gene database of Channidae species, clarify the mitochondrial genome structure of the two species, and provide basic data for invasive biological surveillance in the future.

Abstract Sm1 and Chit42 of Trichoderma have been universally confirmed as crucial biocontrol factors against pathogen infection through induced resistance and mycoparasitism, respectively. However, not enough work has been conducted to understand the novel function of fused expression of these two proteins in Trichoderma. The results of this study demonstrated that Sm1-Chit42 protein (SCf) engineered T. afroharzianum strain OE:SCf exerted synergistic inhibition to Botrytis cinerea growth at multiple stages of mycoparasitic interaction of T. afroharzianum and B. cinerea including chemotropism sensing, hyphal coiling, hydrophobicity modulation, cell wall adhesion, virulence reduction and pathogen killing by ROS. These results highlight a novel mycoparasitic system in Trichoderma strains engineered with Sm1-Chit42 chimeric protein to combat B. cinerea growth and reproduction, which would lay a strong foundation for exploring a new engineered Trichoderma biofungicide created with chimeric proteins in the future.

Abstract Identification and quantification of different soil phosphorus (P) fractions level are important for improving agricultural productivity and developing sustainable management practices in these agricultural soils under long-term cultivation. However, few studies have been conducted to investigate P fractions level and their transformation in these soils. This study was conducted to characterize P fractions as affected by different paddy cultivation ages (200, 400-yr and 900-yr) among soils of the Pearl River Delta Plain in China. A sequential chemical fractionation scheme and 31P nuclear magnetic resonance spectroscopy (31P NMR) were employed to quantify various P fractions and speciation. Results showed soil easily-labile P, moderately-labile P and non-labile P had a positive relationship with total P (TP) and available P (AP). Analysis with 31P NMR spectroscopy revealed that inorganic P including orthophosphate (Ortho-P) and pyrophosphate (Pyro-P) increased with cultivation age, while organic species monoester phosphate (Mono-P) and diester phosphate (Diester-P) decreased. Moreover, acid phosphatase (AcP), neutral phosphatase (NeP), exchangeable Ca and sand contents are the main factors that affected the transformation of soil P composition, and non-labile P (Dil.HCl-Pi) and Pyro-P had significant contribution to soil P availability by affecting P activation coefficient. Therefore, long-term paddy cultivation, influenced by these soil parameters including NeP, AcP, exchangeable Ca and sand, accelerated the transformation of soil organic P/non-labile P to inorganic P.

Abstract Background Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated. Methods The link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA. Results According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p

Abstract Background Exploring the association of diet and indoor and outdoor environments on the gut microbiome of red-crowned cranes. We investigated the microbiome profile of the 24 fecal samples collected from nine cranes from day 1 to 35. Differences in the gut microbiome composition were compared across diet and environments. Results A total of 2,883 operational taxonomic units (OTUs) were detected, with 438 species-specific OTUs and 106 OTUs common to the gut microbiomes of four groups. The abundance of Dietzia and Clostridium XI increased significantly when the red-crowned cranes were initially fed live mealworms. Skermanella and Deinococcus increased after the red-crowned cranes were fed fruits and vegetables and placed outdoors. Thirty-three level II pathway categories were predicted. Our study revealed the mechanism by which the gut microbiota of red-crowned cranes responds to dietary and environmental changes, laying a foundation for future breeding, nutritional and physiological studies of this species. Conclusions The gut microbiome of red-crowned cranes could adapt to changes in diet and environment, but the proportion of live mealworms in captive red-crowned cranes can be appropriately reduced at the initial feeding stage, reducing the negative impact of high-protein and high-fat foods on the gut microbiome and growth and development.

ABSTRACTBackground Virtual simulation experiments have been rapidly applied to medical education curricula in recent years. China constructed a national virtual simulation experimental teaching center (iLAB-X), and this platform covered almost all of the virtual simulation experiment curricula of domestic colleges or universities. We aimed to comprehensively assess the characteristics and usages of virtual simulation experiments in medical education based on iLAB-X.Methods A total of 480 virtual simulation experiment courses had been constructed on iLAB-X (https://www.ilab-x.com/) by December 20, 2022, and the curriculum level, type and design were all searched in this platform. We also conducted an evaluation of curriculum usage and online tests, including the page view, frequency of participation, number of participants, duration of experimental learning and passing rate of the experimental test.Results The national and provincial high-quality virtual simulation experiment curricula accounted for 33.5% (161/480) and 35.8% (172/480), respectively. The curricula were mainly set as basic practice experiments (46.5%) and synthetic designing experiments (48.8%). Significantly, forensic medicine (100%), public health and preventive medicine (83%) and basic medical sciences (66%) focused on synthetic design experiments. In terms of usage experiments, the average duration of experimental learning was 25 minutes per course, and the average number of participants was just 1257. The average passing (score ≥60) rate of online tests was 80.6%, but the average rate of score ≥ 85 was only 58.5%. In particular, the average page views, the number of participants, the duration of learning and the test passing rate of clinical medicine were relatively low.Conclusions The curriculum design features, construction level and utilization rate varied in different medical majors. Virtual simulation experiments are particularly underutilized in clinical medicine. There is a long way for virtual simulation experiments to go to become a supplement or alternative for traditional medical education in the future.

Abstract Background Massive open online courses (MOOCs) have become innovative open-learning approach in medical education. This study aimed to evaluate the dynamic changes in the construction and application of medical MOOCs before and after the coronavirus disease 2019 (COVID-19) pandemic in China. Methods The dynamic changes of usages about medical MOOCs before and after 2020 were mainly searched on the Smart Education of China Higher Education platform, and the detailed learning profiles and outcome indicators were further analyzed using 40 national first-class medical MOOCs from ‘zhihuishu’ platform. Results A total of 2,405 medical MOOCs were exported from the Smart Education of China Higher Education platform, of which 1,313 (54.6%) were launched since 2020. The total and average numbers of participants of 141 national first-class medical MOOCs peaked during the initial spread of COVID-19 in 2020. We further analyzed the dynamic usage of MOOCs from 2018 to 2022 based on 40 national first-class medical MOOCs launched on the ‘Zhihuishu’ platform. The findings revealed that the number of registered learners (3,240 versus 2,654), questions and answers (27,005 versus 5,116) and students taking the final examination (2,782 versus 1,995) per semester were significantly higher since 2020 compared to these before 2020. Especially, the number of registered learners, registered schools, questions and answers, and students participating in online discussion, taking the unit quiz, taking final examinations and passing final examinations all peaked in the 2020 spring–summer semester. Pearson's correlation analysis found that the number of questions and answers and the number of learners who participated in online discussion were both positively correlated with the number of students who passed the final examination, and the correlation was especially strong since 2020. Moreover, the number of publications on medical MOOC research has soared since 2020 and has maintained a continuous upward trend. Conclusions High-quality medical MOOCs have been launched rapidly since the COVID-19 pandemic in China. The number of participants and online interactions of medical MOOCs peaked during the initial spread of COVID-19 in 2020. MOOCs are reliable and valid digital sources that facilitate medical higher education and play irreplaceable roles in emergency management.

Although the pencilfish is a globally popular economic fish in the aquarium market, its taxonomic classification could be further refined. In order to understand the taxonomy of species of the genus Nannostomus (Characiformes, Lebiasinidae) and their phylogenetic position within the order Characiformes, in this study, we characterized mitochondrial genomes (mitogenomes) from four Nannostomus species for the first time. The four mitogenomes exhibited the typical circular structure, with overall sizes varying from 16,661 bp to 16,690 bp. They contained 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 1 control region (CR). Nucleotide composition analysis suggested that the mitochondrial sequences were biased toward A and T. Bayesian inference and maximum likelihood analyses based on PCGs support the family Lebiasinidae classification, described using four Nannostomus species, clustering together with Lebiasina multimaculata from the same family. The results of this study support the current taxonomic classification of the family Lebiasinidae. Phylogenetic analysis also suggested that gene rearrangement would not significantly impact the phylogenetic relationships within the order Characiformes. These results might provide new data regarding the phylogeny and classification of the order Characiformes, thus providing a theoretical basis for the economic development of aquarium fish markets.

Summary: T cell activation is a key event in adaptive immunity. However, the dynamics and influencing factors of T cell activation remain unclear. Here, we analyzed CD4 T cells that were stimulated with anti-CD3/CD28 under several conditions to explore the factors affecting T cell activation. We found a stimulated T subset (HSPhi T) highly expressing heat shock proteins, which was derived from stimulated naive T. We identified and characterized inert T, a stimulated T cell subset in transitional state from resting T to activated T. Interestingly, resting CXCR4low T responded to stimulation more efficiently than resting CXCR4hi T. Furthermore, stimulation of CD4 T in the presence of CD8 T resulted in more effector T and more homogeneous expressions of CD25, supporting that presence of CD8 T reduces the extreme response of T cells, which can be explained by regulation of CD4 T activation through CD8 T-initiated cytokine signaling and FAS/FASLG signaling.

Abstract Background Albumin is the most abundant protein in serum and serves as a transporter of free fatty acids (FFA) in blood vessels. In type 2 diabetes mellitus (T2DM) patients, the reduced serum albumin level is a risk factor for T2DM development and progression, although this conclusion is controversial. Moreover, there is no study on the effects and mechanisms of albumin administration to relieve T2DM. We examined whether the administration of young and undamaged recombinant albumin can alleviate T2DM in mice. Methods The serum albumin levels and metabolic phenotypes including fasting blood glucose, glucose tolerance tests, and glucose-stimulated insulin secretion were studied in db/db mice or diet-induced obesity mice treated with saline or young, undamaged, and ultrapure rMSA. Apoptosis assays were performed at tissue and cell levels to determine the function of rMSA on islet β cell protection. Metabolic flux and glucose uptake assays were employed to investigate metabolic changes in saline-treated or rMSA-treated mouse hepatocytes and compared their sensitivity to insulin treatments. Results In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet β-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of rMSA can alleviate T2DM in mice. Conclusion Our study demonstrates that increasing serum albumin levels can promote glucose homeostasis and protect islet β cells, which alleviates T2DM.

Abstract Purpose To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. Methods The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. Results A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. Conclusion The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

The Unmanned Aerial Vehicle (UAV) swarm cooperative networks across diverse domains present significant challenges in management and control to maximize collaborative efficiency, particularly in applications for large-scale and dynamic environments where real-time coordination is essential. This challenge has led to the development of a UAV swarm cooperative network flow prediction model, facilitating the strategic anticipation of network dynamics. A novel algorithm for distributed, finite-time cooperative control is introduced, grounded in this model. This algorithm optimizes the operational efficiency and control precision of UAV systems, while simultaneously augmenting the collaborative efficiency and stability of the UAV swarms. It marks a significant advancement in distributed computing strategies, offering a viable solution for the real-time coordination challenges in extensive UAV swarm cooperative networks. The proposed approach leverages multi-agent technology, integrating spatial-temporal constraints, location limitations, and path selection in cooperative behavior for dynamic and effective network management. This study not only enhances the understanding of UAV swarm dynamics but also contributes to the practical application of UAV swarms in areas requiring precise coordination and robust network stability.

Abstract Background Epilepsy is one of the most common glioma complications, and the two may be connected in more ways than we understand. We aimed to investigate the clinical features of glioma-associated epilepsy and explore the risk factors associated with it. Methods We collected clinical information from 485 glioma patients in the Nanjing Brain Hospital and conducted 4 periodic follow-up visits. Based on the collected data, we analyzed the clinical characteristics of glioma patients with or without epilepsy and their relationship with survival. Results Among glioma patients, younger people were more likely to have epilepsy. However, epilepsy incidence was independent of gender. Patients with grade II gliomas were most likely to develop epilepsy, while those with grade IV gliomas were least likely. There was no difference in Karnofsky Performance Status scores between patients with glioma-associated epilepsy and those without epilepsy. Additionally, epilepsy was independently associated with longer survival in the World Health Organization grade IV glioma patients. For grades II, III, and IV tumors, the 1-year survival rate of the epilepsy group was higher than that of the non-epilepsy group. Conclusions Epilepsy did not lead to worse admission performance and correlated with a better prognosis for patients with grade IV glioma.

Abstract The migratory and omnivorous common crane (Grus grus) uses a nature reserve with crucial ecological value that provides supplementary food resources, although the extent of their use by these cranes is unknown. In this study, we used DNA metabarcoding of plants through the chloroplast rbcL gene to investigate the diets of 25 common crane fecal samples and performed analyses in conjunction with supplementary feeding. The results showed that common cranes preferred plants of the families Poaceae and Cyperaceae, similar to common cranes in other nature reserves. Before supplementary feeding, Poaceae and Cyperaceae accounted for 43.83 ± 20.58% and 53.51 ± 19.24%, respectively, while after that, they accounted for 61.23 ± 35.19% and 24.07 ± 28.20%, respectively. The relative abundance of Hordeum increased significantly in January, accounting for 33.88 ± 31.32%, which was mainly affected by supplementary feeding. Therefore, under supplementary feeding, foraging grounds and feeding preferences of common cranes may change correspondingly. The quantity of corn kernels and wheat grains can be increased appropriately in supplementary feeding measures in the nature reserve, and more supplementary feeding sites should be set up in response to the shortage of wild bird food resources. This study applied an effective method to study the diet preference of common cranes under supplementary feeding and further provided insights to improve management measures in the nature reserve.

ABSTRACT: Specific pathogen-free ducks are important high-grade laboratory animals, with a key role in research related to poultry biosecurity, production, and breeding. However, the genetic characteristics of experimental duck varieties remain poorly explored. Herein we performed whole-genome resequencing to construct a single nucleotide polymorphism genetic map of the genomes of 3 experimental duck varieties [Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)] to determine their genetic characteristics and identify selection signatures. Subsequent analyses of population structure and genetic diversity revealed that each duck variety formed a monophyletic group, with SM showing richer genetic diversity than JD and SX. Further, on exploring shared selection signatures, we found 2 overlapping genomic regions on chromosome Z of all experimental ducks, which comprised immune response-related genes (IL7R and IL6ST). Moreover, growth and skeletal development (IGF1R and GDF5), meat quality (FoxO1), and stress resistance (HSP90B1 and Gpx8-b) candidate gene loci were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Our results identified the population genetic basis of experimental ducks at the whole-genome level, providing a framework for future molecular investigations of genetic variations and phenotypic changes. We believe that such studies will eventually contribute to the management of experimental animal resources.

China has established a government recycling fund system based on the principle of extended producer responsibility (EPR). The principle of EPR is the key to the sustainable development of waste electrical and electronic equipment (WEEE) recycling. The implementation of the recycling fund system has been facing major problems. This article proposes a plan on refining the producer's recycling target to improve the current fund system in China. With the aim to maximize the amount of WEEE recycling, minimize the overall producer's recycling cost, and providing the best supports to the recycling industry, a multi-objective decision-making model is constructed to identify the optimum producer's recycling target for WEEE. Data from the recycling fund system and EPR pilot project of the Ministry of Industry and Information Technology are used to test the model. The results show that, under the condition that the amount of recycling is equal to the current level, the levy of recycling fund can be reduced by 20%, which can effectively drive the producers to take more responsibility in the collection and recycling of their end-of-life products. The multi-objective decision-making model for producer's recycling target provides a basis for the adjustment of China's WEEE recycling fund system policy, which will alleviate the challenge at present, and involve more producers to devote in collection systems. It also shows the alternative solution for EPR in non-fund business models in the recycling industry.

Background: Interferons (IFNs) have been implemented as anti-tumor immunity agents in clinical trials of glioma, but only a subset of glioblastoma (GBM) patients profits from it. The predictive role of IFNs stimulated genes in GBM needs further exploration to investigate the clinical role of IFNs. Methods: This study screened 526 GBM patients from three independent cohorts. The transcriptome data with matching clinical information were analyzed using R. Immunohistochemical staining data from the Human Protein Atlas and DNA methylation data from MethSurv were used for validation in protein and methylation level respectively. Results: We checked the survival effect of all 491 IFNs response genes, and found 54 genes characterized with significant hazard ratio in overall survival (OS). By protein-protein interaction analysis, 10 hub genes were selected out for subsequent study. And based on the expression of these 10 genes, GBM patients could be divided into two subgroups with significant difference in OS. Furthermore, the least absolute shrinkage and selection operator cox regression model was utilized to construct a multigene risk signature, including STAT3, STAT2 and SOCS3, which could serve as an independent prognostic predictor for GBM. The risk model was validated in two independent GBM cohorts. The GBM patients with high risk scores mainly concentrated in the GBM Mesenchymal subtype. The higher risk group was enriched in hypoxia, angiogenesis, EMT, glycolysis and immune pathways, and had increased Macrophage M2 infiltration and high expression of immune checkpoint CD274 (namely PD-L1). Conclusions: Our findings revealed the three-gene risk model could be an independent prognostic predictor for GBM, and they were crucial participants in immunosuppressive microenvironment of GBM.

BackgroundHigh-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG).MethodsA total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs).ResultThe medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements.ConclusionThe observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.

Objective: Hereditary colorectal cancer (CRC) accounts for approximately 5%–10% of all CRC cases. The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population. Methods: We performed the first population study investigating the germline mutation status in more than 1,000 (n = 1,923) Chinese patients with CRC and examined their relationship with the somatic mutational landscape. Germline alterations were examined with a 58-gene next-generation sequencing panel, and somatic alterations were examined with a 605-gene panel. Results: A total of 92 pathogenic (P) mutations were identified in 85 patients, and 81 likely pathogenic (LP) germline mutations were identified in 62 patients, accounting for 7.6% (147/1,923) of all patients. MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups, respectively. Patients with P/LP mutations had a significantly higher ratio of microsatellite instability, highly deficient mismatch repair, family history of CRC, and lower age. The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group. The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the non-Lynch syndrome group. Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Population risk analysis indicated that the overall odds ratio was 11.13 (95% CI: 8.289–15.44) for the P group and 20.68 (95% CI: 12.89–33.18) for the LP group. Conclusions: Distinct features were revealed in Chinese patients with CRC with germline mutations. The Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Patients with P/LP germline mutations exhibited higher CRC risk.

Abstract Background Colon cancer remains one of the most common malignancies across the world. Thus far, a biomarker, which can comprehensively predict the survival outcomes, clinical characteristics, and therapeutic sensitivity, is still lacking. Methods We leveraged transcriptomic data of colon cancer from the existing datasets and constructed immune-related lncRNA (irlncRNA) pairs. After integrating with clinical survival data, we performed differential analysis and identified 11 irlncRNAs signature using Lasso regression analysis. We next plotted the 1-, 5-, and 10-year curve lines of receiver operating characteristics, calculated the areas under the curve, and recognized the optimal cutoff point. Then, we validated the pair-risk model in terms of the survival outcomes of the patients involved. Moreover, we tested the reliability of the model for predicting tumor aggressiveness and therapeutic susceptibility of colon cancer. Additionally, we reemployed the 11 of irlncRNAs involved in the pair-risk model to construct an expression-risk model to predict the prognostic outcomes of the patients involved. Results We recognized a total of 377 differentially expressed irlncRNAs (DEirlcRNAs), including 28 low-expressed and 349 high-expressed irlncRNAs in colon cancer patients. After performing a univariant Cox analysis, we identified 115 risk irlncRNAs that were significantly correlated with survival outcomes of patients involved. By taking the overlap of the DEirlcRNAs and the risk irlncRNAs, we ultimately recognized 55 irlncRNAs as core irlncRNAs. Then, we established a Cox HR model (pair-risk model) as well as an expression HR model (exp-risk model) based on 11 of the 55 core irlncRNAs. We found that both of the two models significantly outperformed the commonly used clinical characteristics, including age, T, N, and M stages when predicting survival outcomes. Moreover, we validated the pair-risk model as a potential tool for studying the tumor microenvironment of colon cancer and drug susceptibility. Additionally, we noticed that combinational use of the pair-risk model and the exp-risk model yielded a more robust approach for predicting the survival outcomes of patients with colon cancer. Conclusions We recognized 11 irlncRNAs and created a pair-risk model and an exp-risk model, which have the potential to predict clinical characteristics of colon cancer, either solely or conjointly.

Trichoderma, a well-known and extensively studied fungal genus, has gained significant attention for its remarkable antagonistic abilities against a wide range of plant pathogens. In this study, a total of 108 Trichoderma isolates were screened through in vitro dual antagonistic assays and culture filtrate inhibition against Fusarium graminearum. Of these, the YNQJ1002 displayed noteworthy inhibitory activities along with thermal stability. To validate the metabolic differences between YNQJ1002 and GZLX3001 (with strong and weak antagonism, respectively), UPLC-TOF-MS/MS mass spectrometry was employed to analyze and compare the metabolite profiles. We identified 12 significantly up-regulated metabolites in YNQJ1002, which include compounds like Trigoneoside, Torvoside, trans,trans-hepta-2,4,6-trienoic acid, and Chamazulene. These metabolites are known for their antimicrobial properties or signaling roles as components of cell membranes. Enriched KEGG analysis revealed a significant enrichment in sphingolipid metabolism and linoleic acid metabolism, as well as autophagy. The results demonstrated that YNQJ1002’s abundance of antimicrobial substances, resulting from specific metabolic pathways, enhanced its superior antagonistic activity against F. graminearum. Finally, YNQJ1002 was identified using the ITS, tef1-1α, and rpb2 regions, with MIST system sequence matching confirming its classification within the species. Overall, we have obtained a novel strain, T. asperellum YNQJ1002, which is rich in metabolites and shows potential antagonistic activity against F. graminearum. This study has opened promising prospects for the development of innovative Trichoderma-derived antifungal compounds, featuring a unique mechanism against pathogens.

Rocking piers using ultra-high-performance concrete (UHPC) have high damage-control capacity and self-centering characteristics that can limit the post-earthquake recovery time of bridges. To study the hysteretic behavior of UHPC rocking piers, a lumped plasticity model is proposed that comprises two parallel rotational springs and which can accurately calculate their force-displacement hysteretic behavior. Three states of the rocking piers, decompression, yield, and large deformation, are considered in this study. The model is verified based on existing experimental results, and the hysteretic characteristics of the UHPC rocking piers, such as strength, stiffness, and energy dissipation, are further analyzed. The research results show that the lumped plasticity analysis model proposed in this study can predict the force-displacement hysteretic behavior of the rocking piers accurately. Moreover, the hysteretic performance of the UHPC rocking piers is better than that of rocking piers using normal-strength concrete. An increase in the energy dissipation reinforcement ratio, pre-stressed tendon ratio, and initial pre-stress improves the lateral stiffness and strength of the UHPC rocking piers. However, the increase in the pre-stressed tendon ratio and initial pre-stress reduces their energy-dissipation capacity.

Surgical resection and postoperative radiotherapy remained the most common therapeutic modalities for malignant tumors. However, tumor recurrence after receiving such combination is difficult to be avoided because of high invasiveness and radiation resistance of cancer cells during long-term therapy. Hydrogels, as novel local drug delivery systems, presented excellent biocompatibility, high drug loading capacity and sustained drug release property. Compared with conventional drug formulations, hydrogels are able to be administered intraoperatively and directly release the entrapped therapeutic agents to the unresectable tumor sites. Therefore, hydrogel-based local drug delivery systems have their unique advantages especially in sensitizing postoperative radiotherapy. In this context, classification and biological properties of hydrogels were firstly introduced. Then, recent progress and application of hydrogels for postoperative radiotherapy were summarized. Finally, the prospects and challenges of hydrogels in postoperative radiotherapy were discussed.

Understanding the diet of threatened wildlife is vital for species-specific conservation and habitat management measures. The Red-crowned Crane (Grus japonensis) is a vulnerable bird distributed in Northeast Asia. Previous dietary studies of this bird focused mainly on its plant food composition based on field observations and microhistological identification. Herein, a total of 45 fecal samples were collected in November, December and January (15 fecal samples each month) from wintering cranes, and then subjected to a high throughput sequencing meta-barcoding approach to determine the primary plant (rbcL) and animal (COI) food items in their diet. A total of 230 operational taxonomic units (OTUs) of plant foods and 371 OTUs of animal foods were obtained. The main plant foods in the wintering period were Miscanthus, Zea, and Hordeum genera, which were similar to those in the breeding and the migration periods. Both agricultural and natural plants were detected, indicating a relatively broad dietary niche for this crane species. However, the main animal foods were representatives of Theridiidae, Megascolecidae, and Agelenidae, in sharp contrast to previous studies. The higher number of small terrestrial arthropods in animal foods might be due to the indirect intake of plants. The composition of both plant and animal foods in the diet showed the highest diversity in December, while it was homogeneous in January. The plant of Zea genus became the main source of nutrition in late winter, as supplementary feeding was performed in the reserve, which could help Red-crowned Cranes to get through the cold season. The results obtained in this work would contribute to the development of effective conservation strategies for the Red-crowned Crane.

Abstract The red-crowned crane (Grus japonensis) is an endangered species distributed across southeast Russia, northeast China, Korea, and Japan. Here, we sequenced for the first time the full-length unreferenced transcriptome of red-crowned crane mixed samples using a PacBio Sequel platform. A total of 359,136 circular consensus sequences (CCS) were obtained via clustering to remove redundancy. A total of 303,544 full-length non-chimeric sequences were identified by judging whether CCS contained 5′ and 3′ adapters, and the poly(A) tail. Eight samples were sequenced using Illumina, and PacBio sequencing data were corrected according to the collected Illumina data to obtain more accurate full-length transcripts. A total of 4,100 long non-coding RNAs, 13,115 simple sequences repeat loci and 29 transcription factor families were identified. The expression of lncRNAs and TFs in pancreas was lowest comparing with other tissues. Many enriched immune-related transmission pathways (MHC and IL receptors) were identified in the spleen. This study will contribute to a better understanding of the gene structure and post-transcriptional regulatory network, and provide references for future studies on red-crowned cranes.

Abstract To date, the taxonomic status and phylogenetic affinities within Hyphessobrycon, even among other genera in Characidae, remain unclear. Here, we determined five new mitochondrial genomes (mitogenomes) of Hyphessobrycon species (H. elachys, H. flammeus, H. pulchripinnis, H. roseus, and H. sweglesi). The mitogenomes were all classical circular structures, with lengths ranging from 16,008 to 17,224 bp. The type of constitutive genes and direction of the coding strand that appeared in the mitogenomes were identical to those of other species in Characidae. The highest value of the Ka/Ks ratio within 13 protein‐coding genes (PCGs) was found in ND2 with 0.83, suggesting that they were subject to purifying selection in the Hyphessobrycon genus. Comparison of the control region sequences among seven Hyphessobrycon fish revealed that repeat units differ in length and copy number across different species, which led to sharp differences in mitogenome sizes. Phylogenetic trees based on the 13 PCGs did not support taxonomic relationships, as the Hyphessobrycon fish mixed with those from other genera. These data were combined to explore higher level relationships within Characidae and could aid in the understanding of the evolution of this group.

ObjectiveThis study aimed to investigate the contralateral structural and functional plasticity induced by frontal gliomas.MethodsPatients with left (n = 49) or right (n = 52) frontal diffuse glioma were enrolled along with 35 age- matched healthy controls (HCs). The gray-matter volumes (GMVs) of the contralesional region were measured using the voxel-based morphometry (VBM) analysis. Additionally, the amplitude of low-frequency fluctuation (ALFF) of the contralesional region was calculated via resting state functional magnetic resonance imaging (MRI) to assess functional alterations.ResultThe GMV of the contralateral orbitofrontal cortex of the right or left frontal gliomas was significantly larger than the corresponding GMV in the controls. In the patients with right frontal glioma, the GMV and ALFF in the left inferior frontal gyrus were significantly increased compared with those in the controls.ConclusionGlioma invasion of the frontal lobe can induce contralateral structural compensation and functional compensation, which show synergy in the left inferior frontal gyrus. Our findings explain why patients with unilateral frontal glioma can have functional balance, and offer the possibility of preserving the brain function while maximizing tumor removal.

In most cases, co-culture of Trichoderma and other microorganism principally takes advantage of biological control of plant diseases, which is superior to axenic culture. However, the approach to establish the optimal co-culture system of multiple Trichoderma strains was less studied, particularly for high production of microbial metabolites synergistically to promote plant growth and antagonistic activity against pathogens. The inoculation technique, fermentation kinetic modeling and response surface methodology were used to obtain the optimal inoculum sequence, fermentation time and co-culture nutrient formula. It was demonstrated that co-culture metabolites of Trichoderma strains obtained by simultaneous inoculation were more effective than those by sequence inoculation in promoting cucumber seedling growth. Furthermore, the optimal fermentation time was determined at 96–120 h by evaluating fermentation kinetic model, the activities of inhibitory potential of pathogenic Fusarium and cucumber seedling hypocotyl growth. Interestingly, the optimized nutrient formula was set to make co-culture metabolites of Trichoderma strains more effective in the plant growth promotion, which was determined through the assessment of cucumber test-tube plantlet. The components and each concentration in the optimized medium were confirmed at corn flour 16.22 g⋅L–1, potassium hydrogen phosphate 1.13 g⋅L–1, tryptophan 0.154 g⋅L–1, seaweed residue 30 g⋅L–1, ferrous sulfate heptahydrate 1 g⋅L–1 and ammonium sulfate 1.5 g⋅L–1. The hypocotyl length increased in the treatment with co-culture metabolites from the optimal medium by 2.3-fold compared with control. Thus, the results provide an optimal co-culture system of Trichoderma multiple strains aiming to produce high activity of metabolites in plant growth promotion.

ObjectiveTo identify whether tumor invasion of the temporal lobe induces functional compensation of the hippocampal-subregion (HIPsub) network connectivity before surgery, and to further validate the stability of this functional compensation within the HIPsub network in patients with temporal glioma tumor (TTumor) after surgical resection of the tumor.MethodsIn the first cohort, analysis of HIPsub functional connectivity (FC) was conducted to identify the functional compensation of the altered HIPsub connectivity pattern in TTumor through a pattern classification approach. Then, the second cohort investigated whether functional compensation in TTumor patients changed after surgical resection of the tumor.ResultsIn the first cohort, this study identified altered HIPsub network connectivity patterns and its functional compensation regions (i.e., left parahippocampal gyrus and bilateral cerebellum anterior lobe) in TTumor patients. Second, the altered HIPsub network connectivity patterns had the power to discriminate TTumor patients from healthy controls (CN) on an individual subject basis, with an AUC of 97.0%, sensitivity of 93.5%, and specificity of 90.3%. Finally, in the second cohort, we found that functional connectivities of functional compensation regions within the HIPsub network in TTumor patients did not change between before and after surgery.ConclusionThis study provides novel evidence regarding functional compensation within the HIPsub network in TTumor patients. It has been suggested that the fine hippocampal subregion was more sensitive, which reveals functional compensation induced by tumor invasion of the temporal lobe. Furthermore, this study verified the stability and persistence of this functional compensation in TTumor patients after surgical resection of the tumor.

Compared to more developed countries, the use of land resources is less efficient in China. China’s vast forest land area gives it a rich and underutilized carbon sink. This is an important way for China to achieve the goals of “carbon peaking” and “carbon neutrality”, which is of great significance to China’s sustainable development. In the past 20 years, China has designed a series of policies to serve the development of forestry carbon sinks, namely the forestry carbon sink mechanism (FCSM). However, the questions of which policy is the most important, and what is the socio-economic value it generates, have not been fully investigated. Accordingly, this paper studied 30 provincial-level regions in China from 2005 to 2020 using the difference-in-differences (DID) model. The conclusions show that: (1) the FCSM does increase the socio-economic value of land resources, thus improving the sustainability of land resources; (2) the FCSM helps to increase forest coverage, forest stock volume and the forest coverage rate, which increases the social value of land resources from the greening path; (3) the FCSM helps to increase the gross forestry product, which increases the economic value of land resources through the path of increasing production value.