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The number of DNA double-strand breaks (DSBs) initiating meiotic recombination is elevated in Saccharomyces cerevisiae mutants that are globally defective in forming crossovers and synaptonemal complex (SC), a protein scaffold juxtaposing homologous chromosomes. These mutants thus appear to lack a negative feedback loop that inhibits DSB formation when homologs engage one another. This feedback is predicted to be chromosome autonomous, but this has not been tested. Moreover, what chromosomal process is recognized as "homolog engagement" remains unclear. To address these questions, we evaluated effects of homolog engagement defects restricted to small portions of the genome using karyotypically abnormal yeast strains with a homeologous chromosome V pair, monosomic V, or trisomy XV. We found that homolog engagement-defective chromosomes incurred more DSBs, concomitant with prolonged retention of the DSB-promoting protein Rec114, while the rest of the genome remained unaffected. SC-deficient, crossover-proficient mutants ecm11 and gmc2 experienced increased DSB numbers diagnostic of homolog engagement defects. These findings support the hypothesis that SC formation provokes DSB protein dissociation, leading in turn to loss of a DSB competent state. Our findings show that DSB number is regulated in a chromosome-autonomous fashion and provide insight into how homeostatic DSB controls respond to aneuploidy during meiosis.
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Cromossomos Fúngicos/genética , Quebras de DNA de Cadeia Dupla , Retroalimentação Fisiológica/fisiologia , Meiose/genética , Saccharomyces cerevisiae/genética , Complexo Sinaptonêmico/genética , Aneuploidia , Pareamento Cromossômico/genética , Recombinases/genética , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Triboelectric nanogenerators (TENGs) have manifested a remarkable potential for harvesting environmental energy and have the prospects to be utilized for various uses, for instance, self-powered sensing devices, flexible wearables, and marine corrosion protection. However, the potential for further development of TENGs is restricted on account of their low output power that in turn is determined by their surface charge density. The current review majorly focuses on the selection and optimization of triboelectric materials. Subsequently, various methods capable of enhancing the surface charge density of TENGs, including environmental regulation, charge excitation, charge pumping, electrostatic breakdown, charge trapping, and liquid-solid structure are comprehensively reviewed. Lastly, the review is concluded by highlighting the existing challenges in enhancing the surface charge density of TENGs and exploring potential opportunities for future research endeavors in this area.
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With the rapid development of the Industrial Internet of Things in rotating machinery, the amount of data sampled by mechanical vibration wireless sensor networks (MvWSNs) has increased significantly, straining bandwidth capacity. Concurrently, the safety requirements for rotating machinery have escalated, necessitating enhanced real-time data processing capabilities. Conventional methods, reliant on experiential approaches, have proven inefficient in meeting these evolving challenges. To this end, a fault detection method for rotating machinery based on mobileNet in MvWSNs is proposed to address these intractable issues. The small and light deep learning model is helpful to realize nearly real-time sensing and fault detection, lightening the communication pressure of MvWSNs. The well-trained deep learning is implanted on the MvWSNs sensor node, an edge computing platform developed via embedded STM32 microcontrollers (STMicroelectronics International NV, Geneva, Switzerland). Data acquisition, data processing, and data classification are all executed on the computing- and energy-constrained sensor node. The experimental results demonstrate that the proposed fault detection method can achieve about 0.99 for the DDS dataset and an accuracy of 0.98 in the MvWSNs sensor node. Furthermore, the final transmission data size is only 0.1% compared to the original data size. It is also a time-saving method that can be accomplished within 135 ms while the raw data will take about 1000 ms to transmit to the monitoring center when there are four sensor nodes in the network. Thus, the proposed edge computing method shows good application prospects in fault detection and control of rotating machinery with high time sensitivity.
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Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.
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Neoplasias do Colo , Proteômica , Humanos , Microambiente Tumoral/genética , Carcinogênese/genética , Adesão Celular , Neoplasias do Colo/genéticaRESUMO
Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.
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Antibacterianos , Disenteria Bacilar , Humanos , Antibacterianos/farmacologia , Shigella flexneri/genética , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/tratamento farmacológicoRESUMO
Crossovers generated during the repair of programmed meiotic double-strand breaks must be tightly regulated to promote accurate homolog segregation without deleterious outcomes, such as aneuploidy. The Mlh1-Mlh3 (MutLγ) endonuclease complex is critical for crossover resolution, which involves mechanistically unclear interplay between MutLγ and Exo1 and polo kinase Cdc5. Using budding yeast to gain temporal and genetic traction on crossover regulation, we find that MutLγ constitutively interacts with Exo1. Upon commitment to crossover repair, MutLγ-Exo1 associate with recombination intermediates, followed by direct Cdc5 recruitment that triggers MutLγ crossover activity. We propose that Exo1 serves as a central coordinator in this molecular interplay, providing a defined order of interaction that prevents deleterious, premature activation of crossovers. MutLγ associates at a lower frequency near centromeres, indicating that spatial regulation across chromosomal regions reduces risky crossover events. Our data elucidate the temporal and spatial control surrounding a constitutive, potentially harmful, nuclease. We also reveal a critical, noncatalytic role for Exo1, through noncanonical interaction with polo kinase. These mechanisms regulating meiotic crossovers may be conserved across species.
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Proteínas de Ciclo Celular/metabolismo , Troca Genética , Exodesoxirribonucleases/metabolismo , Meiose/genética , Proteínas MutL/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Sítios de Ligação , Proteínas de Ciclo Celular/genética , Cromossomos Fúngicos , Exodesoxirribonucleases/química , Exodesoxirribonucleases/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Modelos Biológicos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Recombinação GenéticaRESUMO
Two new acridinium esters with a 2-(succinimidyloxycarbonyl)ethyl side arm, namely, 9-(2,6-dibromophenoxycarbonyl)-10-methyl-2-(2-(succinimidyloxycarbonyl)ethyl)acridinium trifluoromethanesulfonate and 9-(4-(2-(succinimidyloxycarbonyl)ethyl)phenoxycarbonyl)-2,7-dimethoxy-10-methylacridinium triflate, have been produced and characterized. The chemiluminescent properties and hydrolytic stabilities of the new acridinium esters have been investigated.
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Ésteres , Medições Luminescentes , Hidrólise , AcridinasRESUMO
Several new acridinium esters 2-9 having their central acridinium ring bearing a 9-(2,5-dimethylphenoxycarbonyl), 9-(2,6-bis(trifluoromethyl)phenoxycarbonyl) or 9-(2,6-dinitrophenoxycarbonyl) group, and a 10-methyl, 10-(3-(succinimidyloxycarbonyl)propyl), 10-(5-(succinimidyloxycarbonyl)pentyl), or 10-(10-(succinimidyloxycarbonyl)decyl) group, have been synthesized and their chemiluminescent properties have been tested. The 2,5-dimethylphenyl acridinium esters emit light slowly (glow) when treated with alkaline hydrogen peroxide, while the 2,6-dinitrophenyl and 2,6-bis(trifluoromethyl)phenyl esters emit light rapidly (flash). The substituent at the 10 position affects the hydrolytic stabilities of the compounds.
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Ésteres , Medições Luminescentes , Ésteres/química , Acridinas/química , Peróxido de HidrogênioRESUMO
Several novel N-substituted acridinium esters 7-16 containing a 10-methyl, 10-dodecyl, or 10-(ω-[succinimidyloxycarbonyl]alkyl) group have been synthesized and their chemiluminescent properties have been tested. Their chemiluminescent efficiencies and hydrolytic stabilities have been found to be affected by the characteristics of the group on the nitrogen atom. Dibromo-substituted leaving groups slightly accelerate the chemiluminescence process.
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Ésteres , Medições Luminescentes , Acridinas , LuminescênciaRESUMO
The novel coronavirus (COVID-19) is spreading globally due to its super contagiousness, and the pandemic caused by it has caused serious damage to the health and social economy of all countries in the world. However, conventional diagnostic methods are not conducive to large-scale screening and early identification of infected persons due to their long detection time. Therefore, there is an urgent need to develop a new COVID-19 test method that can deliver results in real time and on-site. In this work, we develop a fast, ultra-sensitive, and multi-functional plasmonic biosensor based on surface-enhanced infrared absorption for COVID-19 on-site diagnosis. The genetic algorithm intelligent program is utilized to automatically design and quickly optimize the sensing device to enhance the sensing performance. As a result, the quantitative detection of COVID-19 with an ultra-high sensitivity (1.66%/nm), a wide detection range, and a diverse measurement environment (gas/liquid) is achieved. In addition, the unique infrared fingerprint recognition characteristics of the sensor also make it an ideal choice for mutant virus screening. This work can not only provide a powerful diagnostic tool for the ultra-rapid, label-free, and multi-functional detection of COVID-19 but also help gain new insights into the field of label-free and ultrasensitive biosensing.
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Técnicas Biossensoriais , COVID-19 , Algoritmos , Humanos , Pandemias , SARS-CoV-2RESUMO
The programmed formation of DNA double-strand breaks (DSBs) in meiotic prophase I initiates the homologous recombination process that yields crossovers between homologous chromosomes, a prerequisite to accurately segregating chromosomes during meiosis I (MI). In the budding yeast Saccharomyces cerevisiae, proteins required for meiotic DSB formation (DSB proteins) accumulate to higher levels specifically on short chromosomes to ensure that these chromosomes make DSBs. We previously demonstrated that as-yet undefined cis-acting elements preferentially recruit DSB proteins and promote higher levels of DSBs and recombination and that these intrinsic features are subject to selection pressure to maintain the hyperrecombinogenic properties of short chromosomes. Thus, this targeted boosting of DSB protein binding may be an evolutionarily recurrent strategy to mitigate the risk of meiotic mis-segregation caused by karyotypic constraints. However, the underlining mechanisms are still elusive. Here, we discuss possible scenarios in which components of the meiotic chromosome axis (Red1 and Hop1) bind to intrinsic features independent of the meiosis-specific cohesin subunit Rec8 and DNA replication, promoting preferential binding of DSB proteins to short chromosomes. We also propose a model where chromosome position in the nucleus, influenced by centromeres, promotes the short-chromosome boost of DSB proteins.
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Proteínas Cromossômicas não Histona/genética , Cromossomos Fúngicos/genética , Proteínas de Ligação a DNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/genética , Segregação de Cromossomos/genética , Quebras de DNA de Cadeia Dupla , Recombinação Homóloga , Prófase Meiótica I/genética , Saccharomyces cerevisiae/genética , CoesinasRESUMO
Reactive molecular dynamics (ReaxFF) simulations are performed to explore the tribological behavior between fully hydroxylated amorphous silica (a-SiO2) surfaces as a function of surface silanol density. The results show that the interfacial friction and wear are greatly reduced by increasing surface silanol density, which originates from the suppression of the initial formation of interfacial Si-O-Si bridge bonds. Two different tribochemical reactions resulting in the formation of interfacial Si-O-Si bridge bonds are observed: i.e., one occurring between two silanol groups, which is insensitive to changes in silanol density, and the other occurring between a silanol group and a surface Si-O-Si bond, which is strongly suppressed with the increase of silanol density. We decouple the contributions of these two Si-O-Si bond formation mechanisms to the observed tribological behavior and find that the latter formation mechanism plays a dominant role. Furthermore, the changes in the geometry and structure of fully hydroxylated a-SiO2 surface caused by the increased surface silanol groups also play an important role in the tribochemical reactions and the tribological performance of the a-SiO2/a-SiO2 system. This work provides a deeper insight into the effect of surface silanol groups on the tribological behaviors of silicon-based materials.
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Schottky junctions based on one-dimensional semiconductor nanomaterials, such as nanowires (NWs) and nanobelts (NBs), have been widely used in building high-performance nano-electric and nano-optoelectric devices during the past 15 years. Meanwhile, with considerable development in diverse application fields, more and more interests are turning to the investigation of the fundamental physics inside the junctions. The inhomogeneity of the interface between semiconductor NWs/NBs and metal electrodes has significant influence on the electrical transport mechanism of Schottky junctions. However, few researchers are involved in such studies and the physical mechanism here is far from fully understood. In this work, we fabricated Schottky junctions based on single CdSe NWs, in which Au was used as a Schottky contact with CdSe NW. The temperature dependence of the electrical transport characteristics of typical CdSe NW/Au Schottky junctions were characterized. The ideality factor was found to decrease and the zero-bias Schottky barrier height (SBH) increased monotonously as the temperature was increased from 140 to 320 K, and this relationship was ascribed to SBH inhomogeneity. The electrical transport mechanism was analyzed quantitatively with a spatial potential fluctuation model, in which SBHs obey the Gaussian distribution. The standard deviation of the SBH distribution was determined to be as high as 13.54% and 13.94% of the zero-bias mean SBH in the temperature ranges 140-200 K and 200-320 K, respectively. Our work revealed the barrier inhomogeneity at CdSe NW/Au interfaces and its influence on the electrical transport mechanism of NW-based Schottky junctions.
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With the rapid development of mobile communication technology, the POI (piezoelectric on insulator) structure has gained recognition in the field of RF filtering. However, transverse modes remain in the passband of corresponding surface acoustic wave (SAW) devices, which impedes their application in crowded spectra. This article introduces a groove configuration to suppress transverse modes for POI SAW resonators employing a 50°YX-LiTaO3/SiO2/Si multilayered structure. First, the response of conventional POI SAW resonators was calculated by the 3D periodic FEM method, and the results indicate that transverse modes caused by energy leakage to busbar regions are serious in POI SAW resonators. Then, the groove configuration was adopted to confine energy within the aperture region by reducing the velocity at the end of IDT electrodes, and the groove dimension was optimized to achieve a nearly spurious-free response in the passband. Finally, experimental results of fabricated one-port SAW resonators with optimal groove configuration were provided to validate the suppression of transverse modes and the enhancement of the Q factor in the POI SAW resonator.
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Staphylococcus aureus inhabits diverse habitats including food waste and wastewater treatment plants. Cases of S. aureus-induced infection are commonly reported worldwide. The emergence of antimicrobial resistance (AMR) of S. aureus is a growing public health threat worldwide. Here, we longitudinally monitored global trends in antibiotic resistance genes (ARGs) of 586 S. aureus strains, isolated between 1884 and 2022. The ARGs in S. aureus exhibited a significant increase over time (P < 0.0001). Mobile genetic elements play a crucial role in the transfer of ARGs in S. aureus strains. The structural equation model results revealed a significant correlation between the human development index and rising antibiotic consumption, which subsequently leads to an indirect escalation of AMR in S. aureus strains. Lastly, a machine learning algorithm successfully predicted the AMR risk of global terrestrial S. aureus with over 70% accuracy. Overall, these findings provided valuable insights for managing AMR in S. aureus.
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Eliminação de Resíduos , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Alimentos , Farmacorresistência BacterianaRESUMO
Activated sludge (AS) plays a vital role in removing organic pollutants and nutrients from wastewater. However, the risks posed by horizontal gene transfer (HGT) between bacteria in AS are still unclear. Here, a total of 478 high-quality non-redundant metagenome-assembled genomes (MAGs) were obtained. >50 % and 5 % of MAGs were involved in at least one HGT and recent HGT, respectively. Most of the transfers (82.4 %) of antimicrobial resistance genes (ARGs) occurred among the classes of Alphaproteobacteria and Gammaproteobacteria. The bacteria involved in the transfers of virulence factor genes (VFGs) mainly include Alphaproteobacteria (42.3 %), Bacteroidia (19.2 %), and Gammaproteobacteria (11.5 %). Moreover, the number of ARGs and VFGs in the classes of Alphaproteobacteria and Gammaproteobacteria was higher than that in other bacteria (P < 0.001). Mobile genetic elements were important contributors to ARGs and VFGs in AS bacteria. These results have implications for the management of antimicrobial resistance and virulence in activated sludge microorganisms.
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Antibacterianos , Esgotos , Esgotos/microbiologia , Virulência/genética , Antibacterianos/farmacologia , Genes Bacterianos , Transferência Genética Horizontal , Farmacorresistência Bacteriana/genética , Bactérias/genética , Fatores de Virulência/genéticaRESUMO
Human biomechanical energy, with features of fluctuating amplitudes and low frequency, has been considered as a potential sustainable power source for wearable healthcare monitoring devices. Developing an effective energy harvester to ensure robust energy harvesting efficiency remains highly desired. Herein, we propose a wearable pendulum-rotor-separated triboelectric-electromagnetic hybrid generator (PTEHG). The novel pendulum-rotor separation design can make the rotor propelled in one direction by the swinging pendulum, which can further facilitate a wearable hybrid energy harvester with stable energy harvesting, a broad operating bandwidth, and system reliability. By converting the biomechanical energy into electric power, the peak power density of 83.12 W/m3 is delivered by the PTEHG at a frequency of 1.6 Hz. A PTEHG-based healthcare monitoring system was also demonstrated for real-time motion tracking and fall detection. This work paves a new way for enhancing the efficiency of human biomechanical energy harvesting and presents a practical pathway for continuous healthcare monitoring.
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Dispositivos Eletrônicos Vestíveis , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Fontes de Energia Elétrica , Desenho de EquipamentoRESUMO
Surface-enhanced infrared absorption (SEIRA) has proven its ability to improve the detection performance of traditional infrared spectroscopy at unprecedented levels. However, the resonant frequency of the metamaterial absorber (MA) lacks tunability once the structure is fabricated, which poses a challenge for broadband fingerprint retrieval of molecules. Here, we propose a pixelated and electric tunable hybrid graphene MA with a broadband response for molecular fingerprint retrieval. Loss engineering is employed to optimize the sensing sensitivity of MA. The resonant frequency of MA is approximately linearly modulated with a change in the graphene Fermi level. This design allows a meta-pixel to match multiple characteristic absorption spectra, thereby establishing a one-to-many mapping relationship between spatial and spectral information. The one-to-many mapping relationship greatly reduces the number of meta-pixels. As a concept demonstration, we integrate 9 meta-pixels to achieve full spectral coverage from 1000 cm-1 to 2000 cm-1. Based on the broadband spectral properties of the sensor, we demonstrate its potential for multi-fingerprint detection, quantitative detection, chemical identification, and compositional analysis. Our proposed hybrid graphene MA can be easily integrated with other on-chip devices, providing a potential platform for optical sensing, infrared spectroscopy, and photodetection.
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One of the fundamental hurdles in infrared spectroscopy is the failure of molecular identification when their infrared vibrational fingerprints overlap. Refractive index (RI) is another intrinsic property of molecules associated with electronic polarizability, but with limited contribution to molecular identification in mixed environments currently. Here, we investigate the coupling mode of localized surface plasmon and surface phonon polaritons for vibrational de-overlapping. The coupling mode is sensitive to the molecular refractive index, attributed to the RI-induced vibrational variations of surface phonon polaritons (SPhP) within the Reststrahlen band, referred to as RI-dependent SPhP vibrations. The RI-dependent SPhP vibrations are linked to molecular RI features. According to the deep-learning-augmented demonstration of bond-breaking-bond-making dynamic profiling in biological reaction, we substantiate that the RI-dependent SPhP vibrations effectively disentangle overlapping vibrational modes, achieving a 92% identification accuracy even for the strongly overlapping vibrational modes in the reaction. Our findings offer insights into the realm of light-matter interaction and provide a valuable toolkit for biomedicine applications.
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Vibrio parahaemolyticus is a common pathogen, and has emerged with multiple antimicrobial resistance (AMR). However, few studies have conducted large-scale investigations of AMR and virulence trends of V. parahaemolyticus worldwide. This study longitudinally monitored antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) trends of 1540 V. parahaemolyticus isolates isolated from 1951 to 2021. The number of ARGs in V. parahaemolyticus isolates distinctly increased over the years (P = 5.9e-10), while the number of VFGs decreased significantly (P < 2.2e-16). However, the number of VFGs of isolates isolated from humans has not changed significantly over the years (R = 0.013, P = 0.74), suggesting that the pathogenic risk to humans has not been reduced. Besides, mobile genetic elements are important contributors to ARGs in V. parahaemolyticus (R = 0.34, P < 2.2e-16), but have no promoting effect on VFGs (P = 0.50). The structural equation model illustrated that the human development index promoted the consumption of antibiotics, thereby indirectly promoting an increase in the AMR of the V. parahaemolyticus isolates. Finally, the random forest was performed to predict the ARG and VFG risks of global terrestrial V. parahaemolyticus isolates, and successfully map these threats with over 80% accuracy. This study aimed to evaluate the global risks posed by AMR and virulence, which helps to develop methods specifically targeting V. parahaemolyticus to mitigate these threats.