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Shaoqi Mou,1,* Shiyu Yan,1,* Shanhong Shen,2 Yibin Shuai,2 Gang Li,3 Zhongxia Shen,2 Ping Shen2 1Department of Psychiatry, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Sleep Medical Center, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, People’s Republic of China; 3College of Engineering, Zhejiang Normal University, Jinhua, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongxia Shen; Ping Shen, Email snowszx@sina.com; 372063474@qq.comObjective: Anxiety disorder (AD) is a common disabling disease. The prolonged disease course may lead to impaired cognitive performance, brain function, and a bad prognosis. Few studies have examined the effect of disease course on brain function by electroencephalogram (EEG).Methods: Resting-state EEG analysis was performed in 34 AD patients. The 34 patients with AD were divided into two groups according to the duration of their illness: anxious state (AS) and generalized anxiety disorder (GAD). Then, EEG features, including univariate power spectral density (PSD), fuzzy entropy (FE), and multivariable functional connectivity (FC), were extracted and compared between AS and GAD. These features were evaluated by three previously validated machine learning methods to test the accuracy of classification in AS and GAD.Results: Significant decreased PSD and FE in GAD were detected compared with AS, especially in the Alpha 2 band. In addition, FC analysis indicated that GAD patients’ connection between the left and right hemispheres decreased. Based on machine learning, AS and GAD are classified on a six-month criterion with the highest classification accuracy of up to 0.99 ± 0.0015.Conclusion: The brain function of patients is more severely impaired in AD patients with longer illness duration. Resting-state EEG demonstrated to be a promising examination in the classification in GAD and AS using machine learning methods with better classification accuracy.Keywords: electroencephalogram, EEG, disease course, anxiety disorder, brain function, machine learning

Abstract We systematically analyze the effects of the derivatives of the hydrodynamic fields on axial Wigner function that describes the spin polarization vector in phase space. We have included all possible first-order derivative contributions that are allowed by symmetry and compute the associated transport functions at one-loop using the linear response theory. In addition to reproducing known effects due to the temperature gradient and vorticity, we have identified a number of potentially significant contributions that are overlooked previously. In particular, we find that the shear strength, the symmetric and traceless part of the flow gradient, will induce a quadrupole for spin polarization in the phase space. Our results, together with hydrodynamic gradients obtained from hydrodynamic simulations, can be employed as a basis for the interpretation of the Λ (anti-Λ) spin polarization measurement in heavy-ion collisions.

The field of energy forecasting has attracted many researchers from different fields (e.g., meteorology, data sciences, mechanical or electrical engineering) over the last decade. Solar forecasting is a fast-growing subdomain of energy forecasting. Despite several previous attempts, the methods and measures used for verification of deterministic (also known as single-valued or point) solar forecasts are still far from being standardized, making forecast analysis and comparison difficult. To analyze and compare solar forecasts, the well-established Murphy–Winkler framework for distribution-oriented forecast verification is recommended as a standard practice. This framework examines aspects of forecast quality, such as reliability, resolution, association, or discrimination, and analyzes the joint distribution of forecasts and observations, which contains all time-independent information relevant to verification. To verify forecasts, one can use any graphical display or mathematical/statistical measure to provide insights and summarize the aspects of forecast quality. The majority of graphical methods and accuracy measures known to solar forecasters are specific methods under this general framework. Additionally, measuring the overall skillfulness of forecasters is also of general interest. The use of the root mean square error (RMSE) skill score based on the optimal convex combination of climatology and persistence methods is highly recommended. By standardizing the accuracy measure and reference forecasting method, the RMSE skill score allows—with appropriate caveats—comparison of forecasts made using different models, across different locations and time periods.

Multiply isotopically substituted molecules (‘clumped’ isotopologues) can be used as geothermometers because their proportions at isotopic equilibrium relative to a random distribution of isotopes amongst all isotopologues are functions of temperature. This has allowed measurements of clumped-isotope abundances to be used to constrain formation temperatures of several natural materials. However, kinetic processes during generation, modification, or transport of natural materials can also affect their clumped-isotope compositions. Herein, we show that methane generated experimentally by closed-system hydrous pyrolysis of shale or nonhydrous pyrolysis of coal yields clumped-isotope compositions consistent with an equilibrium distribution of isotopologues under some experimental conditions (temperature–time conditions corresponding to ‘low,’ ‘mature,’ and ‘over-mature’ stages of catagenesis), but can have non-equilibrium (i.e., kinetically controlled) distributions under other experimental conditions (‘high’ to ‘over-mature’ stages), particularly for pyrolysis of coal. Non-equilibrium compositions, when present, lead the measured proportions of clumped species to be lower than expected for equilibrium at the experimental temperature, and in some cases to be lower than a random distribution of isotopes (i.e., negative Δ18 values). We propose that the consistency with equilibrium for methane formed by relatively low temperature pyrolysis reflects local reversibility of isotope exchange reactions involving a reactant or transition state species during demethylation of one or more components of kerogen. Non-equilibrium clumped-isotope compositions occur under conditions where 'secondary’ cracking of retained oil in shale or wet gas hydrocarbons (C2-5, especially ethane) in coal is prominent. We suggest these non-equilibrium isotopic compositions are the result of the expression of kinetic isotope effects during the irreversible generation of methane from an alkyl precursor. Other interpretations are also explored. These findings provide new insights into the chemistry of thermogenic methane generation, and may provide an explanation of the elevated apparent temperatures recorded by the methane clumped-isotope thermometer in some natural gases. However, it remains unknown if the laboratory experiments capture the processes that occur at the longer time and lower temperatures of natural gas formation.

The isotopic composition of methane is of longstanding geochemical interest, with important implications for understanding petroleum systems, atmospheric greenhouse gas concentrations, the global carbon cycle, and life in extreme environments. Recent analytical developments focusing on multiply substituted isotopologues (‘clumped isotopes’) are opening a valuable new window into methane geochemistry. When methane forms in internal isotopic equilibrium, clumped isotopes can provide a direct record of formation temperature, making this property particularly valuable for identifying different methane origins. However, it has also become clear that in certain settings methane clumped isotope measurements record kinetic rather than equilibrium isotope effects. Here we present a substantially expanded dataset of methane clumped isotope analyses, and provide a synthesis of the current interpretive framework for this parameter. In general, clumped isotope measurements indicate plausible formation temperatures for abiotic, thermogenic, and microbial methane in many geological environments, which is encouraging for the further development of this measurement as a geothermometer, and as a tracer for the source of natural gas reservoirs and emissions. We also highlight, however, instances where clumped isotope derived temperatures are higher than expected, and discuss possible factors that could distort equilibrium formation temperature signals. In microbial methane from freshwater ecosystems, in particular, clumped isotope values appear to be controlled by kinetic effects, and may ultimately be useful to study methanogen metabolism.

Nonlinear dynamics at mid-infrared wavelength is of interest for various applications but has been mainly limited to quantum cascade lasers so far. In this article, we show that interband cascade lasers can generate complex optical chaos with bandwidth in the GHz range and this outperforms the performances of quantum cascade laser chaos. The chaos nature of our signal is confirmed by a thorough time-series analysis. Modeling of the semiconductor laser under short-cavity external optical feedback allows confirming the high bias chaos operation that we observe experimentally. These results pave the way for applications at mid-infrared wavelength, such as private free-space communication. [ABSTRACT FROM AUTHOR]

Two new species of the genus Torodora Meyrick, 1894 are described from China: T. lichi sp. nov. and T. mici sp. nov. Additionally, T. silvatica Park, 2007 is newly recorded for China. Images of the adults and their genitalia are provided.

Abstract Quantifying the features of mitochondrial genome structural variation is crucial for understanding its contribution to complexity. Accurate quantification and interpretation of organizational diversity can help uncover biological evolutionary laws and patterns. The current qMGR approach accumulates the changes in two adjacent genes to calculate the rearrangement frequency RF of each single gene and the rearrangement score RS for specific taxa in the mitogenomes of a given taxonomic group. However, it may introduce bias, as it assigns scores to adjacent genes rather than to rearranged genes. To overcome this limitation, we propose a novel statistical method called qGO to quantify the diversity of gene organization. The qGO method, which is based on the homology of gene order, provides a more accurate representation of genome organizational diversity by partitioning gene strings and individually assigning weights to genes spanning different regions. Additionally, a comprehensive approach is employed for distance computation, generating an extensive matrix of rearrangement distances. Through experiments on more than 5500 vertebrate mitochondrial genomes, we demonstrated that the qGO method outperforms existing methods in terms of accuracy and interpretability. This method improves the comparability of genomes and allows a more accurate comparison of the diversity of mitochondrial genome organization across taxa. These findings have significant implications for unraveling genome evolution, exploring genome function, and investigating the process of molecular evolution.

Abstract Water flooding is an important way to improve recovery in low‐permeability sandstone oil reservoirs. How to decouple the water flooding process using dynamic and static information is a hot topic. In this paper, taking the Paleocene low‐permeability oil sandstone, BY area, eastern Nanxiang Basin as an example, the microscopic water flooding process in the low‐permeability sandstone matrix was systematically investigated, and the characteristics of water channeling under the conditions of fracture existence were analyzed using the dynamic and static monitoring data. The results show that the target layer mainly develops frequently thin stacked composite sand bodies. Under the combined influence of matrix and fracture seepage, the low‐permeability sandstone developed by water flooding shows that there is a single direction of efficiency. The direction of advantageous water advancement is 45° north–east, and the speed of water flooding advancement is 2.57 m/day. Microscopic water‐drive oil experiments show that bound water is mainly distributed in the original low‐permeability sandstone as a membrane in the pore wall and as short rods in the throat. Differences in pore structure and petrophysical properties affect the residual oil content and degree of oil recovery. For sandstones with good petrophysical properties, mild water flooding can improve crude oil recovery. The increase in oil production is mainly concentrated in the early stage of water flooding development, and the increase in oil recovery degree is not significant with the increase in injection multiples in the middle and late stages. However, for sandstones with relatively poor petrophysical properties, water flooding is more effective in the early and late stages than in the middle stages. Therefore, it is necessary to adjust the water flooding measures according to the differences in the petrophysical properties of the sand body. Local tectonics and natural fracture strikes are important factors affecting the direction of the expansion of water flooding fractures. Overall, the prevention of water channeling in low‐permeability sandstones has to take into account the complex coupling between water flooding fractures, natural fractures, and hydraulic fractures.

Purpose: This study aimed to investigate the relationship between magnetic resonance image (MRI) features and the immunohistochemical subtypes of pituitary microadenomas (PMAs) characterized by location and growth pattern. Materials and methods: A double-center, retrospective review of MRI characteristics was conducted in 57 PMA cases recorded from February 2014 to September 2023, identified based on the 2017 World Health Organization classification of pituitary gland tumors. The geometric center of the tumor was defined, and the possibility of PMA vertical or lateral growth patterns was evaluated according to the ratio of maximum diameter between the X and Y axes. Results: Among the PMAs, somatotroph adenomas (STAs) significantly frequented the lateral-anteroinferior portion of the pituitary gland (P = 0.036). Lactotroph adenomas (LTAs) showed a significant locational preference for the lateral-posteroinferior portion (P = 0.037), and gonadotroph adenomas (GTAs) were predominantly located in the central-anteroinferior portion (P = 0.022). Furthermore, PMAs in the suprasellar portion exhibited vertical extension with statistical significance (P = 0.0). Conclusion: In our cohort, micro-STAs were predominantly located in the lateral-anteroinferior portion of the pituitary gland, micro-LTAs in the lateral-posteroinferior portion, and micro-GTAs in the central-anteroinferior portion. The growth pattern of PMAs was highly correlated with their vertical position instead of their immunohistochemical subtypes. Therefore, MRI shows potential in differentiating partial PMA subgroups, especially cases within the silent groups.

Abstract With the widespread use of high-strength concrete structures (HC), the impact of pore structure on their performance has become a current research focus. The mechanism by which different curing conditions and freeze-thaw cycles influence the evolution of pore structure remains unclear. Therefore, this study systematically investigated the frost resistance of high-strength concrete under different curing conditions, measured the mass loss rate, compressive strength, and relative dynamic elastic modulus of concrete under freeze-thaw cycles. Utilizing low-field nuclear magnetic resonance (NMR) technology, this study analyzed the evolution of pore structure in HC under freeze-thaw cycles. Additionally, the fractal dimension was used to evaluate the change of concrete internal pore structure, so as to reflect the influence of pore structure on the mechanical properties of concrete subjected to freeze-thaw cycles, and then evaluated the freeze-thaw damage of HC. The experimental results indicated that the steam curing regimes led to an increase in the porosity of HC, thereby influencing its frost resistance. Steam-cured high-strength concrete (SMHC) exhibited a higher degradation rate under freeze-thaw cycles, resulting in a greater level of deterioration compared to standard curing high-strength concrete (SDHC), even under the same number of freeze-thaw cycles.

Abstract Endophytes play a pivotal role in protecting host plants from both biotic and abiotic stresses, promoting the production of active components (AC) and plant growth. However, the succession of the endophyte community in Eucommia ulmoides (E. ulmoides), particularly the community assembly and function, has not been extensively investigated. In this study, we employed high-throughput sequencing and bioinformatics tools to analyze endophyte diversity across different tree ages, parts, and periods. We examined the population differences, correlations, community assembly mechanisms, and functional roles of these endophytes. Functional predictions via PICRUSt2 revealed that most endophytic fungal functions were linked to biosynthesis, with significant differences in biosynthetic functional abundance across parts and periods. In contrast, the metabolic activity of endophytic bacteria remained stable across different periods and parts. Correlation analysis further confirmed a strong positive relationship between ACs and certain endophytic fungi. Among them, the fungal phyla Ascomycota and Basidiomycota were identified as key contributors to the metabolism of chlorogenic acid (CA), while Aucubin was significantly positively correlated with several endophytic bacteria. These findings provide valuable insights into the functional roles and community assembly mechanism of E. ulmoides endophytes, as well as their symbiotic relationships.

Abstract Metabolism reprogramming (MR) is one of the top ten hallmarks of malignant tumors. The aberrant activation of MR has been recognized as a critical contributory factor to the malignant progression of solid tumors. Moreover, various long non-coding RNAs (lncRNAs) are implicated in the aberrant activation of MR in solid tumor cells. Therefore, in this review, we mainly focus on summarizing the functional relevance and molecular mechanistic underpinnings of lncRNAs in modulating MR of solid tumors by targeting glucose metabolism, lipid metabolism, affecting mitochondrial function, and regulating interactions between tumor and non-tumor cells in tumor microenvironment. Besides, we also underscore the potential for constructing lncRNAs-centered tumor metabolic regulation networks and developing novel anti-tumor strategies by targeting lncRNAs and abnormal MR. Ultimately, this review seeks to offer new targets and avenues for the clinical treatment of solid tumors in the future.

Abstract The authors propose a multi‐agent, multi‐dimensional joint optimisation decision‐making strategy to tackle the challenges jammers encounter when interfering with multi‐functional radars, which possess advanced anti‐interference capabilities. The strategy is divided into optimising the interference style and three parameters: timing, power, and duration, to enhance interference effectiveness. Furthermore, state value reuse is combined with the duelling double deep Q‐learning and multi‐agent deep deterministic policy gradient algorithms to effectively manage the multi‐dimensional optimisation of the interference strategy. Simulation results demonstrate that the proposed algorithm outperforms Ant‐QL, heuristic accelerated Q‐learning, and asynchronous advantage actor‐critic algorithms in terms of convergence speed and stability. It identifies a more efficient strategy for transitioning the radar from its initial state to the state with the lowest threat level to the jammer, achieving a 24% improvement in convergence speed. Additionally, the performance curve exhibits better stability.

Abstract Stress grading systems using non‐linear resistive coatings are a key component to suppress surface corona in the end‐windings of rotating machine. Compared to a sinusoidal‐fed motor, the high slew rate of the voltage at the flanks of the repetitive square voltages from the inverter cause large capacitive currents to flow in the main wall insulation. These large currents, if not properly considered in the design phase, lead to severe electrothermal stress of the grading system. Experiments and simulations were conducted on a stress grading system whose structure arises from limitation posed by the motor structure. Measurements performed with different rise times show that the maximum potential along the conductive armour tape (CAT) increases non‐linearly with increasing axial distance, and the potential at the edge of the CAT reached nearly twice the peak‐to‐peak voltage at 500 ns rise time, leading to corona inception. As metal plates are used in the machine to dampen vibrations in the end‐winding, similar plates were also fastened to the stress grading system, worsening the already inadequate corona suppression performance. The stress grading system was therefore modified, avoiding the surface corona while, at the same time, reducing the temperature in the grading system to acceptable levels.

Abstract Nonlinear charge transport, such as nonreciprocal longitudinal resistance and nonlinear Hall effect, has attracted considerable interest in probing the symmetries and topological properties of new materials. Recent research has revealed significant nonreciprocal longitudinal resistance and nonlinear Hall effect in MnBi2Te4, an intrinsic magnetic topological insulator, induced by the quantum metric dipole. However, the inconsistent response with charge density and conflicting C3z symmetry requirement necessitate a thorough understanding of factors affecting the nonlinear transport measurement. This study uncovers an experimental factor leading to significant nonlinear transport signals in MnBi2Te4, attributed to gate voltage oscillation from the application of large alternating current. Additionally, a methodology is proposed to suppress this effect by individually grounding the voltage electrodes during second-harmonic measurements. The investigation underscores the critical importance of assessing gate voltage oscillation’s impact before determining the intrinsic nature of nonlinear transport in 2D material devices with an electrically connected operative gate electrode.

Abstract Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients, and recent studies have shown that immune regulatory mechanisms are closely associated with retinal damage in DR. Therefore, this study focused on exploring immune cells and immune-related genes (IRGs) in DR and gaining insight into the ceRNA mechanisms by which IRGs regulate DR progression. Four datasets from human DR model retinal tissues were obtained from the Gene Expression Omnibus (GEO) database. R software was first used to identify differentially expressed mRNAs (DE-mRNAs) in the dataset GSE160306-mRNAs, then the distribution of immune cells in the gene matrix was analyzed by xCell and ImmuCellAI, ImmPort and InnateDB database were used to obtain immune-related hub genes (IRHGs) in the DR, and finally the STRING online tool and Cytoscape to construct the immune-related ceRNA network. The datasets GSE102485, GSE160308 and GSE160306-lncRNAs were used to validate the results of the ceRNA network further. The results of immune cell infiltration analysis showed that macrophages are important immune cells in DR; immune-related gene screening showed that FCGR2B is an IRHG in DR, and 2 immune-related ceRNA networks of IRHG were obtained: DDN-AS1/miR-10a-5p/FCGR2B and LINC01515/miR-10a-5p/FCGR2B. Our study suggests that infiltration of immune cells, especially the immune role of macrophages, is an important component of DR progression; the immune-related hub gene FCGR2B and its ceRNA network may be a key regulatory network for DR progression. The discovery of key immune cells, IRHG and ceRNA networks in this study may provide new prospects for early intervention and targeted treatment of DR.

Abstract Vertical natural fractures (NFs) are prevalent in low-permeability sandstone reservoirs. Presently, the impact of NFs on the extension of hydraulic fractures (HFs) remains partially unveiled, which restricts the scientific development of strategies for low-permeability, fractured oil sandstones. In this study, taking the oil sandstone of the He-3 Member, Hetaoyuan Formation, southeastern Biyang Depression as an example, we conducted a comprehensive investigation into the factors influencing vertical fracture development and the interaction between natural and hydraulic fractures. The cohesive unit simulations indicate that geostress is the principal factor influencing HF expansion, more so than NFs, with this influence intensifying as natural fracture density increases. As natural fracture density grows, the potential for two sets of conjugate natural fractures to form short HFs arises, which are limited in expansion scope, suggesting a need to reduce well spacing accordingly. Conversely, areas with a single set of NFs are more prone to developing longer HFs, warranting an increase in well spacing to avoid water channeling. High natural fracture densities may constrain the effectiveness of HFs. In fractured reservoirs with a 10 MPa horizontal stress difference, the length of HFs is 1.52 times that of HFs with 0 MPa and 5 MPa differences. However, the hydraulic fracture effectiveness index (F E) of the latter is 1.74 times higher than the former. For fractured reservoirs, the expansion capacity of HF length within a 5 MPa horizontal stress difference remains relatively stable; beyond this threshold, the expansion capacity increases with the growing horizontal stress difference, and the fracturing effect eventually deteriorates. Furthermore, as the strength of NFs escalates, the length and modified area of HFs initially decrease significantly before stabilizing. The complexity and FE value of HFs formed under strong natural fracture conditions are heightened, indicating a more effective fracturing outcome.

ABSTRACT: High-yield dairy cows typically undergo intense cellular metabolism, leading to oxidative stress in their mammary tissues. Our study found that compared with ordinary cows, these high-yield cows had significantly elevated levels of H2O2, lipoperoxidase, and total antioxidant capacity in their blood. This increased oxidative stress is associated with heightened expression of genes such as GCLC, GCLM, and SIRT1 and proteins such as SIRT1 in the mammary tissue of high-yield cows. We stimulated MAC-T cells with H2O2 at a concentration equal to the average H2O2 level in the serum of ethically high-yielding cows, as detected by an assay kit. Our observations revealed that short-term exposure (12 h) to H2O2 upregulated the expression of the SIRT1 gene and SIRT1 protein. It also increased gene expression for SOD2, CAT, GCLC, GCLM, PGC-1α, and NQO1, elevated the phosphorylation of AMPK, and enhanced protein expression of PGC-1α, NQO1, Nrf2, and HO-1, as well as reduced the phosphorylation of NF-κB. Additionally, short-term H2O2 stimulation resulted in increased total antioxidant capacity and levels of superoxide dismutase, glutathione, and catalase in the mammary epithelial cells of dairy cows. In contrast, prolonged exposure to H2O2 (24 h) yielded opposite results, indicating reduced antioxidant capacity. Further investigation showed that the SIRT1 inhibitor EX 527 could reverse the enhanced cellular antioxidant capacity triggered by short-term oxidative stress. However, it is crucial to note that although 12 h of H2O2 stimulation improved antioxidant capacity, reactive oxygen species (ROS) and malondialdehyde (MDA) levels inside the cell gradually increased over time, suggesting greater damage under long-term stimulation. Conversely, the SIRT1 activator SRT 2104 could reverse the reduced cellular antioxidant capacity caused by long-term oxidative stress and significantly inhibit the accumulation of ROS and MDA. Notably, SRT 2104 demonstrated similar effects in MAC-T cells during lactation. In summary, SIRT1 plays a crucial role in regulating the antioxidant capacity of mammary epithelial cells in dairy cows. This discovery provides valuable insights into the antioxidant mechanisms of mammary cells, which can serve as a theoretical foundation for future mammary health strategies.

Abstract Background This study aims to investigate the morphological characteristics of the distal humerus in healthy adults from northern China using computed tomography and three-dimensional reconstruction techniques and compared whether there were diferences in morphology among populations from diferent geographical regions. Methods The CT data of 80 patients were imported into Mimics software for three-dimensional reconstruction and measurement. The differences in distal humeral morphological parameters between different genders and sides were compared, and the correlation between the parameters was explored. The distal humeral morphological parameters between Western and Chinese populations based on current and previous pooled results were compared. Results Thirty-one morphological parameters were measured and analyzed in this study. The average (and standard deviation) of capitellum depth, capitellum width, capitellum height, distal humerus width, epitrochlea width, and humeral metaphyseal width was 10.83 ± 1.18 mm, 17.60 ± 2.06 mm, 21.10 ± 2.03 mm, 44.38 ± 4.07 mm, 12.02 ± 1.90 mm and 58.95 ± 4.86 mm, these parameters were significantly higher (P

Abstract Germline de novo mutations (DNMs) provide the raw material for evolution. The DNM rate varies considerably between species, sexes and chromosomes. Here, we identify DNMs in the zebra finch (Taeniopygia guttata) across 16 parent-offspring trios using two genome assemblies of different quality. Using an independent genotyping assay, we validate 82% of the 150 candidate DNMs. DNM rates are consistent between both assemblies, with estimates of 6.14 × 10–9 and 6.36 × 10–9 per site per generation. We observe a strong paternal bias in DNM rates (male-to-female ratio ɑ ≈ 4), but this bias is in transition mutations only, leading to a transition-to-transversion ratio of 3.18 and 3.57. Finally, we find that DNMs tend to be randomly distributed across chromosomes, not associated with recombination hotspots or genic regions. However, the sex chromosome chrZ shows a roughly fourfold increased DNM rate compared to autosomes, which is more than the expected increase due to chrZ spending two-thirds of its time in males. Overall, our results further enhance our understanding of DNMs in passerine songbirds.

Abstract Background N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional mechanism, plays a pivotal role in RNA modification and tumor progression. However, the molecular mechanism by which ac4C modification mediates tumor immunosuppression remains elusive in triple-negative breast cancer (TNBC). Methods NAT10 expression was analyzed in TNBC samples in the level of mRNA and protein, and compared with the corresponding normal tissues. ac4C modification levels also measured in the TNBC samples. The effects of NAT10 on immune microenvironment and tumor metabolism were investigated. NAT10-mediated ac4C and its downstream regulatory mechanisms were determined in vitro and in vivo. The combination therapy of targeting NAT10 in TNBC was further explored. Results The results revealed that the loss of NAT10 inhibited TNBC development and promoted T cell activation. Mechanistically, NAT10 upregulated JunB expression by increasing ac4C modification levels on its mRNA. Moreover, JunB further up-regulated LDHA expression and facilitated glycolysis. By deeply digging, remodelin, a NAT10 inhibitor, elevated the surface expression of CTLA-4 on T cells. The combination of remodelin and CTLA-4 mAb can further activate T cells and inhibite tumor progression. Conclusion Taken together, our study demonstrated that the NAT10-ac4C-JunB-LDHA pathway increases glycolysis levels and creates an immunosuppressive tumor microenvironment (TME). Consequently, targeting this pathway may assist in the identification of novel therapeutic strategies to improve the efficacy of cancer immunotherapy.