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Melanoma is a primary malignant tumor with high lethality, which occurs in the skin and eye tissues, while the molecular mechanisms of melanomagenesis remain largely unknown. Here, we show that death-associated protein-like 1 (DAPL1) expression is lower in melanoma tissues than in paracancerous tissues or nevus tissues, and Uveal melanoma patients with lower DAPL1 expression have a poorer survival rate than those with higher expression of DAPL1. Overexpression of DAPL1 inhibits proliferation of cultured melanoma cells, whereas knockdown of DAPL1 increases cell proliferation. Tumor transplantation experiment results also demonstrate that DAPL1 inhibits tumorigenesis of melanoma cells both in subretinal and subcutaneous tissues of nude mice in vivo. Finally, DAPL1 inhibits proliferation of melanoma cells by increasing the protein level of P21 via decreasing the ubiquitin mediated degradation of P21 and promoting its stability. Conversely, knockdown of P21 neutralizes the effects of inhibition of DAPL1 on melanoma cell proliferation and enhances the severity of melanoma tumorigenesis. These results suggest that DAPL1 is a novel melanoma tumor suppressor gene and thus a potential therapeutic target for melanoma.
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This study investigated the spatiotemporal dynamics, bioaccumulation, and critical influencing factors of antibiotics in tilapia aquaculture, focusing on source identification and environmental fate within typical farming systems. The results revealed a progressive increase in antibiotic concentrations in pond water and sediments over the cultivation period, with suspended solids and chemical oxygen demand identified as significant environmental factors influencing the distribution and dissemination of antibiotics. The aquaculture water source was the primary contributor of antibiotics in the farming system. Furthermore, the bioaccumulation factor (BAF) calculations indicated varying degrees of antibiotic enrichment in tilapia tissues, with sulfadimethoxine exhibiting the highest BAFs. Correlation analyses, redundancy analysis, and multivariate linear regression analysis provided insights into the relationship between environmental factors and antibiotics, identifying key antibiotics and influencing factors. The study highlighted the importance of managing and treating water sources to reduce the inflow of antibiotics into aquaculture systems and emphasized the need for non-antibiotic aquaculture practices to minimize the impact on the environment and public health. In conclusion, this research contributes valuable information for the development of effective management strategies and policies aimed at curbing antibiotic pollution in aquaculture environments, ensuring the sustainability of the aquaculture industry, and protecting ecosystem and consumer health.
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The complex and harsh tumor microenvironment imped the efficacy of single-modality tumor therapy. With the advantages of biosafety, organic/inorganic nanohybrids have attracted more and more interest of researchers, and it is critical to investigate the development of highly efficient nanohybrids for multimodality combination therapy of cancers. Herein, a naphthalene diimide-based polycyclic conjugated molecule (NDI-S) is designed and synthesized, which has broader light absorption in the near infrared (NIR) region, outstanding photothermal conversion ability, and excellent photostability. Inorganic CoFe2O4 is synthesized via a solvothermal technique, which can produce much more reactive oxygen species (ROS) as a sonosensitizer when activated by ultrasonic (US). NDI-S and CoFe2O4 are then nanoprecipitated to create the organic/inorganic nanohybrids, NDI-S@CoFe2O4. According to the results of in vitro and in vivo experiments, NDI-S@CoFe2O4 can serve as a multifunctional nanoplatform for multimodal treatment of tumors in combination with photothermal/photodynamic/sonodynamic- therapy under the guidance of photoacoustic imaging, which provides a new vision of the development of organic/inorganic nanohybrids for cancer theranostics.
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Aiming to automatically monitor and improve stereoscopic image and video processing systems, stereoscopic image quality assessment approaches are becoming more and more important as 3D technology gains popularity. We propose a full-reference stereoscopic image quality assessment method that incorporate monocular and binocular features based on binocular competition and binocular integration. To start, we create a three-channel RGB fused view by fusing Gabor filter bank responses and disparity maps. Then, using the monocular view and the RGB fusion view, respectively, we extract monocular and binocular features. To alter the local features in the binocular features, we simultaneously estimate the saliency of the RGB fusion image. Finally, the monocular and binocular quality scores are calculated based on the monocular and binocular features, and the quality scores of the stereo image prediction are obtained by fusion. Performance testing in the LIVE 3D IQA database Phase I and Phase II. The results of the proposed method are compared with newer methods. The experimental results show good consistency and robustness.
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A method integrating machine learning with first-principles calculations is employed to forecast the formation energy of delafossite crystals, facilitating the rapid identification of stable crystals. This approach identifies several stable candidates and highlights the importance of atomic ionization energy and electron affinity in the formation of delafossite crystals.
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BACKGROUND: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM. METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing. RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044). CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
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Ceria has been extensively utilized in different fields, with surface oxygen vacancies playing a central role. However, versatile oxygen vacancy regulation is still in its infancy. In this work, we propose an effective strategy to manipulate the oxygen vacancy formation energy via transition metal doping by combining first-principles calculations and analytical learning. We elucidate the underlying mechanism driving the formation of oxygen vacancies using combined symbolic regression and data analytics techniques. The results show that the Fermi level of the system and the electronegativity of the dopants are the paramount parameters (features) influencing the formation of oxygen vacancies. These insights not only enhance our understanding of the oxygen vacancy formation mechanism in ceria-based materials to improve their functionality but also potentially lay the groundwork for future strategies in the rational design of other transition metal oxide-based catalysts.
ABSTRACT
Understanding the structures of oxygen vacancies in bulk ceria is crucial as they significantly impact the material's catalytic and electronic properties. The complex interaction between oxygen vacancies and Ce3+ ions presents challenges in characterizing ceria's defect chemistry. We introduced a machine learning-assisted cluster-expansion model to predict the energetics of defective configurations accurately within bulk ceria. This model effectively samples configurational spaces, detailing oxygen vacancy structures across different temperatures and concentrations. At lower temperatures, vacancies tend to cluster, mediated by Ce3+ ions and electrostatic repulsion, while at higher temperatures, they distribute uniformly due to configurational entropy. Our analysis also reveals a correlation between thermodynamic stability and the band gap between occupied O 2p and unoccupied Ce 4f orbitals, with wider band gaps indicating higher stability. This work enhances our understanding of defect chemistry in oxide materials and lays the groundwork for further research into how these structural properties affect ceria's performance.
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Background: Metabolic associated fatty liver disease (MAFLD) is a widespread liver disease that can lead to liver fibrosis and cirrhosis. Therefore, it is essential to develop early diagnosic and screening methods. Methods: We performed a cross-sectional observational study. In this study, based on data from 92 patients with MAFLD and 74 healthy individuals, we observed the characteristics of tongue images, tongue coating and intestinal flora. A generative adversarial network was used to extract tongue image features, and 16S rRNA sequencing was performed using the tongue coating and intestinal flora. We then applied tongue image analysis technology combined with microbiome technology to obtain an MAFLD early screening model with higher accuracy. In addition, we compared different modelling methods, including Extreme Gradient Boosting (XGBoost), random forest, neural networks(MLP), stochastic gradient descent(SGD), and support vector machine(SVM). Results: The results show that tongue-coating Streptococcus and Rothia, intestinal Blautia, and Streptococcus are potential biomarkers for MAFLD. The diagnostic model jointly incorporating tongue image features, basic information (gender, age, BMI), and tongue coating marker flora (Streptococcus, Rothia), can have an accuracy of 96.39%, higher than the accuracy value except for bacteria. Conclusion: Combining computer-intelligent tongue diagnosis with microbiome technology enhances MAFLD diagnostic accuracy and provides a convenient early screening reference.
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Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.
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In this study, we developed a rapid and effective method for enriching the culture of nitrifying bioflocs (NBF) from aquacultural brackish water. The self-designed mixotrophic mediums with a single or mixed addition of sodium acetate, sodium citrate, and sucrose were used to investigate the enrichment process and nitrification efficiency of NBF in small-scale reactors. The results showed that NBF with an MLVSSs from 1170.4 mg L-1 to 2588.0 mg L-1 were successfully enriched in a period of less than 16 days. The citrate group performed the fastest enrichment time of 10 days, while the sucrose group had the highest biomass of 2588.0 ± 384.7 mg L-1. In situ testing showed that the highest nitrification efficiency was achieved in the citrate group, with an ammonia oxidation rate of 1.45 ± 0.34 mg N L-1 h-1, a net nitrification rate of 2.02 ± 0.20 mg N L-1 h-1, and a specific nitrification rate of 0.72 ± 0.14 mg N g-1 h-1. Metagenomic sequencing revealed that Nitrosomonas (0.0~1.0%) and Nitrobacter (10.1~26.5%) were dominant genera for AOB and NOB, respectively, both of which had the highest relative abundances in the citrate group. Linear regression analysis further demonstrated significantly positive linear relations between nitrification efficiencies and nitrifying bacterial genera and gene abundance in NBF. The results of this study provide an efficient enrichment culture method of NBF for the operation of biofloc technology aquaculture systems, which will further promote its wide application in modern intensive aquaculture.
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INTRODUCTION: At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD. METHODS: Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library, and Web of Science from inception to 10 May 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0. RESULTS: Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD -1.57; 95% CI: -2.64 to -0.51), Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD -0.28; 95% CI: -0.41 to -0.15), the Neuropsychiatric Inventory (NPI) (both SMD -1.67; 95% CI: -2.88 to -0.47 for 10-tiem total score and SMD -1.83; 95% CI: -3.25 to -0.42 for 12-tiem total score), and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI: 1.29-3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death. CONCLUSIONS: Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.
Subject(s)
Alzheimer Disease , Cholinesterase Inhibitors , Randomized Controlled Trials as Topic , Humans , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/therapeutic use , Neuropsychological Tests , Treatment OutcomeABSTRACT
BACKGROUND: Pulse width, which can reflect qi, blood excess, and deficiency, has been used for diagnosing diseases and determining the prognosis in traditional Chinese medicine (TCM). This study aimed to devise an objective method to measure the pulse width based on an array pulse diagram for objective diagnosis. METHODS: The channel 6, the region wherein the pulse wave signal is the strongest, is located in the middle of the pulse sensor array and at the guan position of cunkou during data collection. Therefore, the main wave (h1) time of the pulse wave was collected from the channel 6 through calculation. The left h1 time was collected from the remaining 11 channels. The amplitudes at these time points were extracted as the h1 amplitudes for each channel. However, the pulse width could not be calculated accurately at 12 points. Consequently, a bioharmonic spline interpolation algorithm was used to interpolate the h1 amplitude data obtained from the horizontal and vertical points, yielding 651 (31 × 21) h1 amplitude data. The 651 data points were converted into a heat map to intuitively calculate the pulse width. The pulse width was calculated by multiplying the number of grids on the vertical axis with the unit length of the grid. The pulse width was determined by TCM doctors to verify the pulse width measurement accuracy. Meanwhile, a color Doppler ultrasound examination of the volunteers' radial arteries was performed and the intravascular meridian widths of the radial artery compared with the calculated pulse widths to determine the reliability. RESULTS: The pulse width determined using the maximal h1 amplitude method was comparable with the radial artery intravascular meridian widths measured using color Doppler ultrasound. The h1 amplitude was higher in the high blood pressure group and the pulse width was greater. CONCLUSIONS: The pulse width determined using the maximal h1 amplitude was objective and accurate. Comparison between the pulse widths of the normal and high blood pressure groups verified the reliability of the method.
Subject(s)
Hypertension , Humans , Reproducibility of Results , Heart Rate , Blood Pressure/physiology , Medicine, Chinese Traditional/methodsABSTRACT
An integrated and projected-based laboratory course was described, integrating interconnected knowledge points and biochemistry and molecular biology techniques on a research project-based system. The program, which served as an essential extension of theoretical courses to practice, was conducted with a sophomore of basic medical science who had completed the course in medical biochemistry and molecular biology. This course engaged students in learning "genetic manipulation" and "recombinant DNA technology" to understand the target gene's role in disease mechanics, thus altering evaluation and treatment for clinical disease. Students could master applied and advanced techniques, such as cell culture, transfection, inducing exogenous fusion protein expression, purifying protein and its concentration assay, quantitative polymerase chain reaction, and western bot analysis. This laboratory exercise links laboratory practices with the methods of current basic research. Students need to complete the experimental design report and laboratory report, which could be advantageous for improving their ability to write lab summaries and scientific papers in the future. The reliability and validity analyses were conducted on the questionnaire, and we examined students' satisfaction with the course and their gains from the course. The student feedback was generally positive, indicating that the exercise helped consolidate theoretical knowledge, increase scientific research enthusiasm, and provide a powerful tool to be a better person and make informed decisions.
Subject(s)
Biochemistry , Laboratories , Molecular Biology , Molecular Biology/education , Biochemistry/education , Humans , Curriculum , Students , Surveys and Questionnaires , Educational MeasurementABSTRACT
The accuracy of classical force fields (FFs) has been shown to be limited for the simulation of cation-protein systems despite their importance in understanding the processes of life. Improvements can result from optimizing the parameters of classical FFs or by extending the FF formulation by terms describing charge transfer (CT) and polarization (POL) effects. In this work, we introduce our implementation of the CTPOL model in OpenMM, which extends the classical additive FF formula by adding CT and POL. Furthermore, we present an open-source parametrization tool, called FFAFFURR, that enables the (system-specific) parametrization of OPLS-AA and CTPOL models. The performance of our workflow was evaluated by its ability to reproduce quantum chemistry energies and by molecular dynamics simulations of a zinc-finger protein.
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Acute kidney injury (AKI) is a prevalent condition in critically ill patients that is often associated with significant morbidity and mortality. As the lack of effective early diagnosis methods often delays AKI treatment, there is currently no definitive clinical intervention available. In this study, we aimed to address these challenges by developing a nano-system called Platelet membranes-ICG-SS31-PLGA (PISP), which was designed to selectively target to the kidney site, taking advantage of the natural tendency of platelets to accumulate at sites of vascular injury. This approach allowed for the accumulation of PISP within the kidney as the disease progresses. By incorporating ICG, the in vivo distribution of PISP can be observed for NIR diagnosis of AKI. This non-invasive imaging technique holds great promise for early detection and monitoring of AKI. Furthermore, Elamipretide (SS31) acts as a mitochondria-targeted antioxidant that protects against mitochondrial damage and reduces oxidative stress, inflammation, and apoptosis. The combination of diagnostic and therapeutic capabilities within a single nano-system makes the PISP approach a valuable tool for addressing AKI. This intervention helps to prevent the deterioration of AKI and promotes the recovery. STATEMENT OF SIGNIFICANCE.
Subject(s)
Acute Kidney Injury , Nanoparticles , Humans , Antioxidants/pharmacology , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Acute Kidney Injury/diagnosis , Acute Kidney Injury/drug therapy , Kidney , Nanoparticles/therapeutic useABSTRACT
Although previous studies have investigated the occurrence of antibiotic resistance genes (ARGs) in aquaculture, few have monitored the concentrations and propagation of ARGs in biological tissues or investigated the key factors influencing their spread in aquaculture. This study investigated the concentration, propagation, and distribution of ARGs and bacterial communities in water sources, pond water, and tilapia tissues, and their key influencing factors, in a typical tilapia farm. ErmF, sul1, and sul2 were the dominant ARGs with high concentrations. The total concentrations of ARGs (TCAs) in tilapia tissues decreased in the following order: stomach > scales > intestine > gills (P < 0.05). Redundancy analysis and multiple linear regression revealed that suspended solids (SS) and chemical oxygen demand (COD) were positively correlated with the dominant ARGs ermF sul2, and the TCAs (P < 0.05); additionally, Chloroflexi and Bacteroidetes in tilapia aquaculture water were positively correlated with the dominant ARGs ermF and sul2, as well as the TCAs (P < 0.05). This study suggests that SS and COD were the key factors driving the distribution and spread of ARGs in tilapia aquaculture water. Additionally, Chloroflexi and Bacteroidetes were the key bacterial flora affecting the propagation of ARGs in tilapia aquaculture systems.
Subject(s)
Genes, Bacterial , Tilapia , Animals , Tilapia/genetics , Water , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Drug Resistance, Microbial/genetics , China , AquacultureABSTRACT
Saliency-driven mesh simplification methods have shown promising results in maintaining visual detail, but effective simplification requires accurate 3D saliency maps. The conventional mesh saliency detection method may not capture salient regions in 3D models with texture. To address this issue, we propose a novel saliency detection method that fuses saliency maps from multi-view projections of textured models. Specifically, we introduce a texel descriptor that combines local convexity and chromatic aberration to capture texel saliency at multiple scales. Furthermore, we created a novel dataset that reflects human eye fixation patterns on textured models, which serves as an objective evaluation metric. Our experimental results demonstrate that our saliency-driven method outperforms existing approaches on several evaluation metrics. Our method source code can be accessed at https://github.com/bkballoon/mvsm-fusion and the dataset can be accessed at 10.5281/zenodo.8131602.
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Theoretically pulse wave velocity (PWV) is obtained by calculating the distance between two waveform probes divided by the time difference, and PWV ratio is used to assess the arterial stiffness gradient (SG) from proximal to distal. The aim was to investigate segmental upper-limb PWV (ulPWV) differences and the effects of hypertension and or aging on each ulPWV and SG. The study collected multi-waveform signals and conduction distances from 167 healthy individuals and 92 hypertensive patients. The results showed significant differences between ulPWVs (P < 0.001), with increased and then decreased vascular stiffness along the proximal transmission to the distal peripheral artery and then to the finger. Adjusted for age and sex, ulPWVs in hypertension exceeded that of healthy individuals, with significant differences between groups aged ≥ 50 years (P < 0.05). The hrPWV/rfPWV (heart-radial/radial-finger) was reduced in hypertension and differed significantly between the aged ≥ 50 years (P = 0.015); the ratio of baPWV (brachial-ankle) to ulPWV differed significantly between groups (P < 0.05). Hypertension affected the consistency of rfPWV with hfPWV (heart-finger). The findings suggest that segmented ulPWV is instrumental in providing stiffness corresponding to the physiological structure of the vessel. The superimposition of hypertension and or aging exacerbates peripheral arterial stiffness, as well as alteration in stiffness gradient.
Subject(s)
Hypertension , Vascular Stiffness , Humans , Vascular Stiffness/physiology , Pulse Wave Analysis/methods , Arteries , Upper ExtremityABSTRACT
For orbital angular momentum (OAM) recognition in atmosphere turbulence, how to design a self-adapted model is a challenging problem. To address this issue, an efficient deep learning framework that uses a derived extreme learning machine (ELM) has been put forward. Different from typical neural network methods, the provided analytical machine learning model can match the different OAM modes automatically. In the model selection phase, a multilayer ELM is adopted to quantify the laser spot characteristics. In the parameter optimization phase, a fast iterative shrinkage-thresholding algorithm makes the model present the analytic expression. After the feature extraction of the received intensity distributions, the proposed method develops a relationship between laser spot and OAM mode, thus building the steady neural network architecture for the new received vortex beam. The whole recognition process avoids the trial and error caused by user intervention, which makes the model suitable for a time-varying atmospheric environment. Numerical simulations are conducted on different experimental datasets. The results demonstrate that the proposed method has a better capacity for OAM recognition.