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Background: Modern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques. Methods: We enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients. Results: Using predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability. Conclusion: In summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.
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Soil alkalization is an adverse factor limiting plant growth and yield. As a signaling molecule and secondary metabolite, γ-aminobutyric acid (GABA) responds rapidly to alkaline stress and enhances the alkaline resistance of plants. However, the molecular mechanisms by which the GABA pathway adapts to alkaline stress remain unclear. In this study, a transcription factor, MdNAC104 is identified, from the transcriptome of the alkaline-stressed roots of apple, which effectively reduces GABA levels and negatively regulates alkaline resistance. Nevertheless, applying exogenous GABA compensates the negative regulatory mechanism of overexpressed MdNAC104 on alkaline resistance. Further research confirms that MdNAC104 repressed the GABA biosynthetic gene MdGAD1/3 and the GABA transporter gene MdALMT13 by binding to their promoters. Here, MdGAD1/3 actively regulates alkaline resistance by increasing GABA synthesis, while MdALMT13 promotes GABA accumulation and efflux in roots, resulting in an improved resistance to alkaline stress. This subsequent assays reveal that MdSINA2 interacts with MdNAC104 and positively regulates root GABA content and alkaline resistance by ubiquitinating and degrading MdNAC104 via the 26S proteasome pathway. Thus, the study reveals the regulation of alkaline resistance and GABA homeostasis via the MdSINA2-MdNAC104-MdGAD1/3/MdALMT13 module in apple. These findings provide novel insight into the molecular mechanisms of alkaline resistance in plants.
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Pipeline transportation of CO2 is the key link to realize carbon capture, utilization, and storage. CO2 pipeline transportation may face the risk of leakage, which poses a great threat to the production process and personnel safety. It is of great significance to study the leakage and diffusion characteristics of CO2 in pipeline transportation for the safety design and personnel protection of the offshore CO2 storage platform. In order to study the leakage and diffusion characteristics of CO2 in pipeline transportation on offshore platforms, a physical model of a target platform and several numerical models were built, and a series of pipeline CO2 leakage and diffusion simulations were carried out using the method of numerical simulation. Based on the simulation results, the temperature distribution and CO2 concentration distribution on the offshore platforms after leakage were measured and analyzed. The influence of leakage direction (horizontal and oblique 45° upward) was also studied. Dangerous areas on the platform and suggestions for staff evacuation were given according to the simulation results. The research results of this work can provide guidance for the safe operation of offshore CO2 storage platforms.
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Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.
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Herein we describe the discovery of a 2-aminopyridine scaffold as a potent and isoform selective inhibitor of the Nav1.8 sodium channel. Parallel library synthesis, guided by in silico predictions, rapidly transformed initial hits into a novel 2-aminopyridine lead class possessing good ADME and pharmacokinetic profiles that were able to display activity in a clinically translatable nonhuman primate capsaicin-sensitized thermode pharmacodynamic assay. Progress toward the lead identification, optimization, and in vivo efficacy of these compounds will be discussed.
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The global prevalence of ocular surface diseases (OSDs), such as dry eyes, conjunctivitis, and subconjunctival hemorrhage (SCH), is steadily increasing due to factors such as aging populations, environmental influences, and lifestyle changes. These diseases affect millions of individuals worldwide, emphasizing the importance of early diagnosis and continuous monitoring for effective treatment. Therefore, we present a deep learning-enhanced imaging system for the automated, objective, and reliable assessment of these three representative OSDs. Our comprehensive pipeline incorporates processing techniques derived from dual-mode infrared (IR) and visible (RGB) images. It employs a multi-stage deep learning model to enable accurate and consistent measurement of OSDs. This proposed method has achieved a 98.7% accuracy with an F1 score of 0.980 in class classification and a 96.2% accuracy with an F1 score of 0.956 in SCH region identification. Furthermore, our system aims to facilitate early diagnosis of meibomian gland dysfunction (MGD), a primary factor causing dry eyes, by quantitatively analyzing the meibomian gland (MG) area ratio and detecting gland morphological irregularities with an accuracy of 88.1% and an F1 score of 0.781. To enhance convenience and timely OSD management, we are integrating a portable IR camera for obtaining meibography during home inspections. Our system demonstrates notable improvements in expanding dual-mode image-based diagnosis for broader applicability, effectively enhancing patient care efficiency. With its automation, accuracy, and compact design, this system is well-suited for early detection and ongoing assessment of OSDs, contributing to improved eye healthcare in an accessible and comprehensible manner.
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Diagnóstico Precoz , Humanos , Aprendizaje Profundo , Oftalmopatías/diagnóstico , Oftalmopatías/diagnóstico por imagen , Síndromes de Ojo Seco/diagnóstico por imagen , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/fisiopatología , Técnicas de Diagnóstico Oftalmológico/instrumentación , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
This study introduces a novel nonlinear dynamic analysis method, known as beluga whale optimization-slope entropy (BWO-SlEn), to address the challenge of recognizing sea state signals (SSSs) in complex marine environments. A method of underwater acoustic signal recognition based on BWO-SlEn and one-dimensional convolutional neural network (1D-CNN) is proposed. Firstly, particle swarm optimization-slope entropy (PSO-SlEn), BWO-SlEn, and Harris hawk optimization-slope entropy (HHO-SlEn) were used for feature extraction of noise signal and SSS. After 1D-CNN classification, BWO-SlEn were found to have the best recognition effect. Secondly, fuzzy entropy (FE), sample entropy (SE), permutation entropy (PE), and dispersion entropy (DE) were used to extract the signal features. After 1D-CNN classification, BWO-SlEn and 1D-CNN were found to have the highest recognition rate compared with them. Finally, compared with the other six recognition methods, the recognition rates of BWO-SlEn and 1D-CNN for the noise signal and SSS are at least 6% and 4.75% higher, respectively. Therefore, the BWO-SlEn and 1D-CNN recognition methods proposed in this paper are more effective in the application of SSS recognition.
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Pseudobagrus ussuriensis is an unscaled fish that is more susceptible to skin damage than scaled fish. To investigate the impacts of hypoxia and reoxygenation on skin and brain immunity, juvenile P. ussuriensis were subjected to hypoxia conditions (DO: 0.8 ± 0.05 mg/L) for durations of 0, 3, 6, and 12 h, followed by 12 h of reoxygenation (DO > 6 mg/L). Histological analysis showed a significant increase in the number of skin mucosal cells after 12 h of hypoxia and a significant decrease after 12 h of reoxygenation when compared to the control group. As the duration of hypoxia increased, an increase in antioxidant (SOD, CAT, GSH, MDA) and immune (cortisol, LZM) physiological parameters of the skin and brain appeared. The results of transcriptomic studies showed that the number of differential genes was greater in skin than in brain. Most of the immune pathways in both tissues under hypoxia conditions were all nonspecific immunity (TNF, IL-17, chemokines), while both tissues maintained their homeostasis through active energy supply and cell cycle regulation. Meanwhile, both physiological parameters and RNA transcriptome results showed that 12 h of reoxygenation could not completely eliminate the negative effects of 12 h of hypoxia. This study offers new insights into the immune responses of P. ussuriensis skin and brain during acute hypoxia and reoxygenation.
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In plants under drought stress, sugar content in roots increases, which is important for drought resistance. However, the molecular mechanisms for controlling the sugar content in roots during response to drought remain elusive. Here, we found that the MdDOF3-MdHT1.2 module-mediated glucose influx into the root is essential for drought resistance in apple (Malus × domestica). Drought induced glucose uptake from the rhizosphere and up-regulated the transcription of hexose transporter MdHT1.2. Compared with the wild-type plants, overexpression of MdHT1.2 promoted glucose uptake from the rhizosphere, thereby facilitating sugar accumulation in root and enhancing drought resistance, whereas silenced plants showed the opposite phenotype. Furthermore, ATAC-seq, RNA-seq and biochemical analysis demonstrated that MdDOF3 directly bound to the promoter of MdHT1.2 and was strongly up-regulated under drought. Overexpression of MdDOF3 in roots improved MdHT1.2-mediated glucose transport capacity and enhanced plant resistance to drought, but MdDOF3-RNAihr apple plants showed the opposite phenotype. Moreover, overexpression of MdDOF3 in roots did not attenuate drought sensitivity in MdHT1.2-RNAi plants, which was correlated with a lower glucose uptake capacity and glucose content in root. Collectively, our findings deciphered the molecular mechanism through which glucose uptake from the rhizosphere is mediated by MdDOF3-MdHT1.2, which acts to modulate sugar content in root and promote drought resistance.
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Sequías , Regulación de la Expresión Génica de las Plantas , Glucosa , Malus , Proteínas de Plantas , Plantas Modificadas Genéticamente , Rizosfera , Malus/genética , Malus/metabolismo , Glucosa/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Resistencia a la SequíaRESUMEN
Microplastic (MP) pollution has emerged as a global environmental concern due to its ubiquity and harmful impacts on ecosystems and human health. MP assessment has therefore become increasingly necessary and common in environmental and experimental samples. Microscopy and spectroscopy are widely employed for the physical and chemical characterization of MPs. However, these analytical methods often require time-consuming pretreatments of samples or expensive instrumentation. In this work, we develop a portable and cost-effective polarization holographic imaging system that prominently incorporates deep learning techniques, enabling efficient, high-throughput detection and dynamic analysis of MPs in aqueous environments. The integration enhances the identification and classification of MPs, eliminating the need for extensive sample preparation. The system simultaneously captures holographic interference patterns and polarization states, allowing for multimodal information acquisition to facilitate rapid MP detection. The characteristics of light waves are registered, and birefringence features are leveraged to classify the material composition and structures of MPs. Furthermore, the system automates real-time counting and morphological measurements of various materials, including MP sheets and additional natural substances. This innovative approach significantly improves the dynamic monitoring of MPs and provides valuable information for their effective filtration and management.
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The spliceosome, a multi-megadalton ribonucleoprotein complex, is essential for pre-mRNA splicing in the nucleus and ensuring genomic stability. Its precise and dynamic assembly is pivotal for its function. Spliceosome malfunctions can lead to developmental abnormalities and potentially contribute to tumorigenesis. The specific role of the spliceosome in B cell development is poorly understood. Here, we reveal that the spliceosomal U2 snRNP component PHD finger protein 5A (Phf5a) is vital for early B cell development. Loss of Phf5a results in pronounced defects in B cell development, causing an arrest at the transition from pre-pro-B to early pro-B cell stage in the bone marrow of mutant mice. Phf5a-deficient B cells exhibit impaired immunoglobulin heavy (IgH) chain expression due to defective V-to-DJ gene rearrangement. Mechanistically, our findings suggest that Phf5a facilitates IgH gene rearrangement by regulating the activity of recombination-activating gene endonuclease and influencing chromatin interactions at the Igh locus.
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Empalmosomas , Transactivadores , Animales , Ratones , Empalmosomas/metabolismo , Transactivadores/genética , Proteínas de Unión al ARN/metabolismo , Dedos de Zinc PHD , Linfopoyesis/genéticaRESUMEN
Soil salinization had become a global ecological problem, which restricts the plant growth, and the quantity and quality of fruits. As a signaling molecule, γ-Aminobutyric acid (GABA) mediates a series of physiological processes and stress responses. Our previous research showed that GABA could alleviate drought, low phosphorus, cadmium stresses in apples, but the further research about its physiological mechanisms under salt stress was even more needed. The present study showed that the inhibition of salt stress on plant growth might be effectively alleviated by the treatment of 0.5 mM GABA, and the osmotic balance and photosynthetic capacity of plants could be maintained. Exogenous GABA could effectively inhibit the enrichment of reactive oxygen species and the uptake of Na+, while maintaining ion homeostasis. The experiment results indicated GABA could markedly promote the expression amount of Na+ and K+ transport-related genes (e.g., HKT1, AKT1, NHX1, SOS1, SOS2, and SOS3) in apples under salt stress. Overexpression and interference (RNAi) of MdGAD1 in apple roots, which is a crucial enzyme in the GABA biosynthesis, affected the salt tolerance of plants. Transgenic apple plants with roots of overexpression MdGAD1 showed less relative electrolyte leakage and more expression level of related ion transport genes than CK group, but RNAi MdGAD1 led to the opposite results. These results indicated that GABA accumulation could effectively strengthen the resistance of apple plants to salt stress and alleviate the injury of apple seedlings resulted from salinity.
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Malus , Malus/genética , Malus/metabolismo , Tolerancia a la Sal/genética , Plantones/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Homeostasis , Iones/metabolismo , Ácido gamma-Aminobutírico/farmacología , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
At present, potato seeders in China generally have poor uniformity of seed rows and high coefficients of variation in plant spacing during seed rows, causing difficulties for subsequent mechanized plant protection and harvesting. Based on the effect of seed discharge to analyze the sowing process, a potato seed discharger with a double-layer seed picking spoon structure was designed. By analyzing the seed discharging mechanism and its operation process, the shape and size structural parameters of the seed picking spoon were determined. Finite element simulation of the seed pickup process and seed carrying process of the seed discharging mechanism was carried out by EDEM software to determine the double-layer seed scoop scheme and the range of factors for subsequent tests. A two-factor test was conducted with seeding line speed and seed drop height as test factors, and plant spacing coefficient of variation and seed potato lateral offset dispersion as test indexes. The test results showed that the double-layer seeding spoon chain seeder reduced the coefficient of variation in plant spacing by 5.8%, and the dispersion in lateral offset by 5.5 mm, compared with the single seeding spoon seeder, when the seeding speed was 0.184 m/s and the height of falling seed was 9 cm.
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Taking the heat-sensitive wheat variety 'Fanmai 5' (FM5) and the heat-tolerant variety 'Huaimai 33' (HM33), which were screened out in the previous experiments, as experimental materials, we conducted a field experiment with passive heat-enhancing shelters to simulate post-flowering high-temperature environment (average temperature increase of 5.13 â) during 2021-2022. During the filling period, we analyzed the effects of exogenous trehalose (10, 15 and 20 mmol·L-1) on the filling characteristics and sugar fraction under high temperature, with no spraying at ordinary temperature as control (CK). The results showed that treating without spraying exogenous trehalose at high temperature (H) significantly reduced wheat grain yield and grain weight during the filling period, and spraying exogenous trehalose alleviated the reduction of grain yield and grain weight at the filling stage under high temperature stress. Compared with the H treatment, grain yield and grain weight of HM33 and FM5 wheat varie-ties increased by 3.5%, 6.7% and 4.2%, 5.4%, respectively. High temperature stress significantly increased the trehalose content and trehalase (THL) activity in flag leaves of both wheat varieties, and decreased the fructose and glucose contents. Spraying exogenous trehalose increased the contents of trehalose, fructose, and glucose in flag leaves, and decreased the trehalase activity in flag leaves compared with H treatment, which could improve the glucose metabolism capacity of wheat at filling stage. The increasing effect of FM5 was higher than that of HM33. High temperature stress significantly reduced starch content of flag leaves and grains, while spraying exogenous trehalose alleviated the decrease of starch content of flag leaves and grains under high temperature stress, which was profit able for the substance accumulation of wheat grains under high temperature stress. Under the conditions of this experiment, spraying 15 mmol·L-1 trehalose at flowering stage was the best treatment for the two wheat varieties.
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Azúcares , Triticum , Azúcares/metabolismo , Triticum/metabolismo , Temperatura , Trehalosa/farmacología , Trehalosa/metabolismo , Trehalasa/metabolismo , Carbohidratos , Glucosa , Fructosa/metabolismo , Almidón/metabolismo , Grano Comestible/metabolismoRESUMEN
Carotenoids play an important role in the coloring and nutritional value of apple (Malus spp.) fruits. Here, six carotenoids, including lutein, zeaxanthin, ß-carotene, ß-cryptoxanthin, violaxanthin, and neoxanthin, were detected in 105 fruits of apple germplasm resources, which showed a skewed distribution in both the peel and pulp. There were more carotenoids in the peel than in the pulp, and lutein and ß-carotene were the primary carotenoids that were present. The expression levels of most carotenoid pathway genes in germplasm fruits during fruit development were higher in the fruits that had an abundance of carotenoids. A linear relationship analysis showed that the expression levels of MdCRTISO and MdLCYE were highly correlated with the content of carotenoids. The leaves accumulated the greatest number of carotenoids, while the roots had the lowest amount. MdCRTISO and MdLCYE were highly expressed in the fruits compared to other tissues. Transgenic calli and transiently transformed fruits confirmed that MdCRTISO and MdLCYE affected the biosynthesis of carotenoids owing to their effects on the expression of other genes for enzymes in the carotenoid pathway. Our findings will extend the understanding of carotenoid biosynthesis in apple and excavate apple germplasm resources with rich carotenoids to breed high-quality apples.
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Carotenoides , Malus , Carotenoides/metabolismo , Malus/genética , beta Caroteno/metabolismo , Luteína/metabolismo , Fitomejoramiento , Frutas/metabolismo , Expresión GénicaRESUMEN
Our advances in detection and feature extraction in the processing of acoustic signals allow us to capture more information about a target and extract features with separability [...].
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Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TNT , are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TNT structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TNT , the bispecific trimerbody TNT DNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TNT DNGR-1, but not TNT , protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8+ T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections.
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Anticuerpos Neutralizantes , COVID-19 , Ratones , Animales , Anticuerpos Neutralizantes/uso terapéutico , Linfocitos T Citotóxicos , SARS-CoV-2 , Reactividad Cruzada , Células DendríticasRESUMEN
Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K+) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders.
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Neuronas , Canales de Potasio con Entrada de Voltaje , Humanos , Neuronas/metabolismo , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio/metabolismo , Potenciales de Acción/fisiología , Proteínas de la Membrana/metabolismoRESUMEN
Human coronavirus 229E (HCoV-229E) represents one of the known coronaviruses capable of infecting humans and causes mild respiratory symptoms. It is also considered to have a zoonotic source, originating from animals and being transmitted the humans. In this study, a comprehensive phylogenetic and codon usage analysis of the spike (S) gene of HCoV-229E was conducted. Utilizing phylogenetic analysis and principal component analysis, HCoV-229E was categorized into four distinct clusters, each demonstrating unique host affiliations. Furthermore, it was observed that the codon usage bias within the S gene of HCoV-229E is relatively low, primarily influenced by natural selection patterns, with contributions from mutation pressure and dinucleotide abundance. Comparative analysis involving Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) revealed that the codon usage pattern of HCoV-229E mirrors more closely that of camels, as opposed to alpacas and humans. The elucidation of the codon usage pattern within HCoV-229E, which we have meticulously examined, offers valuable insights for a more comprehensive comprehension of viral features, history, and evolutionary trajectory.
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Coronavirus Humano 229E , Coronavirus , Animales , Humanos , Coronavirus Humano 229E/genética , Filogenia , Uso de Codones , Glicoproteína de la Espiga del Coronavirus/genética , Coronavirus/genéticaRESUMEN
Geographical discrimination of mulberry leaves is very important for their efficacy and quality as a traditional Chinese medicine. Stable hydrogen, oxygen, and carbon isotope ratios were measured in 292 mulberry leaves collected at 2 growth stages in 2 seasons from 8 regions of China. A stepwise linear discriminant analysis (LDA) approach were proposed to combine with stable isotope technology to tracing the origin of mulberry leaves. The results showed that leaves sampled in autumn were extremely depleted in 2H and 18O and slightly enriched in 13C compared with leaves sampled in summer, correlated with the effect of season, transpiration and photorespiration on stable isotopes. δ2H and δ18O of the leaves were enriched during the growth process. The overall discrimination accuracy of the autumn tender model was 81%, demonstrating that analysis of δ2H, δ18O, and δ13C is a promising technique for tracing the geographical origin of mulberry leaves, although season, growth stage and number of samples affect the accuracy of discrimination.