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Although p53 inactivation promotes genomic instability1 and presents a route to malignancy for more than half of all human cancers2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases—Trp53 (encoding mouse p53) loss of heterozygosity, accumulation of deletions, genome doubling, and the emergence of gains and amplifications—each associated with specific histological stages across the premalignant and malignant spectrum. Despite rampant heterogeneity, the deletion events that follow p53 inactivation target functionally relevant pathways that can shape genomic evolution and remain fixed as homogenous events in diverse malignant populations. Thus, loss of p53—the ‘guardian of the genome’—is not merely a gateway to genetic chaos but, rather, can enable deterministic patterns of genome evolution that may point to new strategies for the treatment of TP53-mutant tumours.

With the aim of analyzing the post-deformation Recrystallization (PDRX) of 22MnB5 steel and the grain size evolution after hot forming of the sheet and using the BAEHR 805 A/D thermo-mechanical simulator, several isothermal stress relaxation tests were performed in a temperature range of 800 to 950 °C, a predeformation range of 0.4 to 0.8 and a strain rate range of 0.01 to 0.8 s−1. As a result of isothermal stress relaxation after deformation, PDRX kinetics can be described based on an Avrami equation as a function of temperature, degree of predeformation and strain rate. As the temperature increases, the recrystallization kinetics accelerates. The strain rate also has a positive influence on the fast PDRX. Predeformation has the opposite effect, as the consumption of stored energy occurred in predeformation process of relaxation tests. Furthermore, the microstructure evolution is described as a function of the predeformation parameters. The investigation of the microstructure after isothermal stress relaxation tests showed that the PDRX kinetics corresponds to the calculations. Furthermore, EBSD analysis helped to analyze the effects of certain stress relaxation conditions on the martensite morphology. The results indicate that a lower temperature and higher strain rate lead to fine martensite packages. In contrast, the martensite block width increases when applying higher strain rates.

Background Ferroptosis has been linked to tumor progression and resistance to antineoplastic therapy. Long noncoding RNA (lncRNA) exerts a regulatory role in various biological processes of tumor cells, while the function and molecular mechanism of lncRNA in ferroptosis are yet to be clarified in glioma. Methods Both gain-of-function and loss-of-function experiments were employed to investigate the effects of SNAI3-AS1 on the tumorigenesis and ferroptosis susceptibility of glioma in vitro and in vivo. Bioinformatics analysis, Bisulfite sequencing PCR, RNA pull-down, RIP, MeRIP and dual-luciferase reporter assay were performed to explore the low expression mechanism of SNAI3-AS1 and the downstream mechanism of SNAI3-AS1 in ferroptosis susceptibility of glioma. Results We found that ferroptosis inducer erastin downregulates SNAI3-AS1 expression in glioma by increasing the DNA methylation level of SNAI3-AS1 promoter. SNAI3-AS1 functions as a tumor suppressor in glioma. Importantly, SNAI3-AS1 enhances the anti-tumor activity of erastin by promoting ferroptosis both in vitro and in vivo. Mechanistically, SNAI3-AS1 competitively binds to SND1 and perturbs the m6A-dependent recognition of Nrf2 mRNA 3’UTR by SND1, thereby reducing the mRNA stability of Nrf2. Rescue experiments confirmed that SND1 overexpression and silence can rescue the gain- and loss-of-function ferroptotic phenotypes of SNAI3-AS1, respectively. Conclusions Our findings elucidate the effect and detailed mechanism of SNAI3-AS1/SND1/Nrf2 signalling axis in ferroptosis, and provide a theoretical support for inducing ferroptosis to improve glioma treatment.

A natural feed of fresh seaweed and sixteen diets designed by L16 (43) orthogonal array were formulated to contain differentlevels of protein (200, 250 g, 300, 350 g/kg), α- Vitamin E (VE) (0, 0.1, 0.3, 0.5 g/kg) and Vitamin E (VC) (0, 0.5, 1, 1.5 g/kg) to evaluate the effects of dietary protein, VE, VC and their combination on growth and gonadal development of hybrid male abalone (Haliotis fulgens ♂×H. discus hannai ♀). Each diet was randomly assigned to triplicate groups of 18 abalones (34.27±2.93 g) that were stocked in sea cages for eight weeks. Results showed that the maximum weight gain (WG) and specific growth rate (SGR) were obtained in hybrid male abalone fed D10 diets. The highest gonad somatic index (GSI) value was found in the D14 diet. Moreover, the ANOVA results showed that only dietary protein could significantly affect the GSI of hybrid male abalones (P < 0.05). The mRNA expression of vasa in the testis of D14 abalone was the lowest. Abalones fed the D14 diet had higher testosterone level and sperm in testis than those fed other diets. In conclusion, protein of 300 g/kg, VE of 0.1 g/kg and VC of 1.5 g/kg (D10) and protein of 350 g/kg, VE of 0.1 g/kg and VC of 1 g/kg (D14) might be the optimal combinations in the diet for growth and gonadal development of hybrid male abalones respectively.

Background Filamentous fungi with the ability to use complex carbon sources has been developed as platforms for biochemicals production. Myceliophthora thermophila has been developed as the cell factory to produce lignocellulolytic enzymes and plant biomass-based biofuels and biochemicals in biorefinery. However, low fungal growth rate and cellulose utilization efficiency are significant barriers to the satisfactory yield and productivity of target products, which needs our further exploration and improvement. Results In this study, we comprehensively explored the roles of the putative methyltransferase LaeA in regulating mycelium growth, sugar consumption, and cellulases expression. Deletion of laeA in thermophile fungus Myceliophthora thermophila enhanced mycelium growth and glucose consumption significantly. Further exploration of LaeA regulatory network indicated that multiple growth regulatory factors (GRF) Cre-1, Grf-1, Grf-2, and Grf-3, which act as negative repressors of carbon metabolism, were regulated by LaeA in this fungus. We also determined that phosphoenolpyruvate carboxykinase (PCK) is the core node of the metabolic network related to fungal vegetative growth, of which enhancement partially contributed to the elevated sugar consumption and fungal growth of mutant ΔlaeA. Noteworthily, LaeA participated in regulating the expression of cellulase genes and their transcription regulator. ΔlaeA exhibited 30.6% and 5.5% increases in the peak values of extracellular protein and endo-glucanase activity, respectively, as compared to the WT strain. Furthermore, the global histone methylation assays indicated that LaeA is associated with modulating H3K9 methylation levels. The normal function of LaeA on regulating fungal physiology is dependent on methyltransferase activity. Conclusions The research presented in this study clarified the function and elucidated the regulatory network of LaeA in the regulation of fungal growth and cellulase production, which will significantly deepen our understanding about the regulation mechanism of LaeA in filamentous fungi and provides the new strategy for improvement the fermentation properties of industrial fungal strain by metabolic engineering.

Background The present study aimed to investigate the prevalence, predictors, and management of left atrial appendage (LAA) thrombogenic milieu (TM) identified with transesophageal echocardiography (TEE) in non-valvular atrial fibrillation (NVAF) patients with low to moderate thromboembolic (TE) risk. Methods We retrospectively analyzed the baseline clinical data and TEE findings in 391 NVAF patients (54.7 ± 8.9 years, 69.1% male) with low to moderate TE risk according to the CHA2DS2-VASc score. LAA TM was defined as LAA thrombus (LAAT), sludge or spontaneous echo contrast (SEC). Management of LAA TM was at the discretion of the treating physician. Results A total of 43 patients (11.0%) were detected with LAA TM, including 5 with LAAT (11.6%), 4 with LAAT + Sect. (9.3%), 3 with sludge (7.0%), and 31 with Sect. (72.1%). In multivariate model, non-paroxysmal AF (OR 3.121; 95% CI 1.205–8.083, p = 0.019), and a larger left atrial diameter (LAD) (OR 1.134; 95% CI 1.060–1.213, p ± 20.0 days for oral anticoagulant (OAC) medication. TE events occurred in 3 patients (18.8%) among those discontinuing OAC over a mean follow-up of 26.2 ± 8.8 months, while no TE events occurred in patients with continuous OAC. Conclusions LAA TM could be identified in 11.0% in NVAF patients with low to moderate TE risk, especially in those with non-paroxysmal AF and enlarged LAD. Short-term OAC medication could effectively resolve the LAAT or sludge.

Background Filamentous fungi possess an array of secreted enzymes to depolymerize the structural polysaccharide components of plant biomass. Sugar transporters play an essential role in nutrient uptake and sensing of extracellular signal molecules to inhibit or trigger the induction of lignocellulolytic enzymes. However, the identities and functions of transceptors associated with the induction of hemicellulase genes remain elusive. Results In this study, we reveal that the l-arabinose transporter MtLat-1 is associated with repression of hemicellulase gene expression in the filamentous fungus Myceliophthora thermophila. The absence of Mtlat-1 caused a decrease in l-arabinose uptake and consumption rates. However, mycelium growth, protein production, and hemicellulolytic activities were markedly increased in a ΔMtlat-1 mutant compared with the wild-type (WT) when grown on arabinan. Comparative transcriptomic analysis showed a different expression profile in the ΔMtlat-1 strain from that in the WT in response to arabinan, and demonstrated that MtLat-1 was involved in the repression of the main hemicellulase-encoding genes. A point mutation that abolished the l-arabinose transport activity of MtLat-1 did not impact the repression of hemicellulase gene expression when the mutant protein was expressed in the ΔMtlat-1 strain. Thus, the involvement of MtLat-1 in the expression of hemicellulase genes is independent of its transport activity. The data suggested that MtLat-1 is a transceptor that senses and transduces the molecular signal, resulting in downstream repression of hemicellulolytic gene expression. MtAra-1 protein directly regulated the expression of Mtlat-1 by binding to its promoter region. Transcriptomic profiling indicated that the transcription factor MtAra-1 also plays an important role in expression of arabinanolytic enzyme genes and l-arabinose catabolism. Conclusions M. thermophila MtLat-1 functions as a transceptor that is involved in l-arabinose transport and signal transduction associated with suppression of the expression of hemicellulolytic enzyme-encoding genes. The data presented in this study add to the models of the regulation of hemicellulases in filamentous fungi.

Background In the clinic, gluteal muscle contracture (GMC) causes pelvic structural changes, including acetabular retroversion. However, its causes and forms are not well understood. This study aimed to investigate and analyse the clinical significance of pelvic structural differences between GMC patients and healthy individuals. Methods As the GMC group, we identified 100 GMC patients who received treatment and met the inclusion criteria between January 2019 and January 2020. Control subjects were drawn from the hospital’s emergency trauma patients who had no history of pelvic or hip joint disease. All subjects underwent CT scans to measure their pelvic rotation, including the superior iliac angle (SIA), inferior iliac angle (IIA), and ischiopubic angle (IPA), and acetabular coverage, which includes anterior acetabular sector angle (AASA), posterior acetabular sector angle (PASA), horizontal acetabular sector angle (HASA), and superior acetabular sector angle (SASA). Results The SIA, IIA, IPA, and PASA of the GMC group were considerably smaller than those of the control group, while the AASA of the GMC group was higher, indicating a statistically significant difference (P r = 0.750, P r = 0.749, P r = 0.555, P r = 0.273, P r = 0.552, P r = − 0.355, P r = − 0.551, P r = − 0.30, P r = 0.315, P P > 0.05); and the IIA had a positive correlation with both the SIA and IPA (r = 0.664, P r = 0.465, P Conclusion Individuals with GMC have an abnormal pelvic morphology, with acetabular retroversion caused by ilial rotation rather than dysplasia of the acetabular wall.

Background The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status. Objective To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults. Design We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI. Participants Two hundred twenty-nine study participants at a major academic medical center. Main Measures We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI. Key Results In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9–89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46–0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians’ clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result. Conclusions Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07265-8.

In gas drilling operations, the rate of penetration (ROP) parameter has an important influence on drilling costs. Prediction of ROP can optimize the drilling operational parameters and reduce its overall cost. To predict ROP with satisfactory precision, a stacked generalization ensemble model is developed in this paper. Drilling data were collected from a shale gas survey well in Xinjiang, northwestern China. First, Pearson correlation analysis is used for feature selection. Then, a Savitzky-Golay smoothing filter is used to reduce noise in the dataset. In the next stage, we propose a stacked generalization ensemble model that combines six machine learning models: support vector regression (SVR), extremely randomized trees (ET), random forest (RF), gradient boosting machine (GB), light gradient boosting machine (LightGBM) and extreme gradient boosting (XGB). The stacked model generates meta-data from the five models (SVR, ET, RF, GB, LightGBM) to compute ROP predictions using an XGB model. Then, the leave-one-out method is used to verify modeling performance. The performance of the stacked model is better than each single model, with R2 = 0.9568 and root mean square error = 0.4853 m/h achieved on the testing dataset. Hence, the proposed approach will be useful in optimizing gas drilling. Finally, the particle swarm optimization (PSO) algorithm is used to optimize the relevant ROP parameters.

We consider the strategy-proof rules for reallocating individual endowments of an infinitely divisible good when agents’ preferences are single-peaked. In social endowment setting, the seminal work established by Sprumont (Econometrica 59:509–519, 1991) proves that the uniform rule is the unique one which satisfies strategy-proofness, efficiency, and envy-freeness. However, the uniform rule is not so appealing in our model since it disregards the differences in individual endowments. In other words, the uniform rule is not individually rational. In this paper, we propose a new rule named the uniform proportion rule. First, we prove that it is the unique rule which satisfies strategy-proofness, efficiency, and envy-freeness on proportion and we show that it is individually rational. Then, we show that our rule is indeed a member of the class of sequential allotment rules characterized by Barbera et al. (Games Econ Behav 18:1–21, 1997).

Spiral springs have a wide range of applications in various fields. As a result of the complexity of friction, few theoretical analyses of spring belts under static loading have been carried out. Considering the piecewise smooth property of the whole contact area, a simplified static model of spiral springs under loading is established in this paper. Besides, three main stress and friction distribution areas of the spring belt are proposed, namely, internal, transitional, and external regions. Since the outermost side of the spring is not subject to any pressure, a recursive method is adopted from the outside to the inside. The model provides the parameter conditions, i.e., the internal and external forces are independent or dependent. Therefore, the case that the whole contact region of the spring belt has one subregion, two subregions, and three subregions is obtained. The model gives a theoretical basis for the parameter optimization of spiral springs.

In this paper, a local surface nanocrystallization technology is used for thin-walled structures with square cross sections, and an energy absorption device of two-staged combined energy absorption structure is proposed. In virtue of the surface nanocrystallization that enables to change the material on local positions, the structural deformation is induced and controlled to maximize the energy absorption capacity. A numerical model of the two-staged combined energy absorption structure is established, and the local surface nanocrystallization layout is optimized. The results show that the specific energy absorption of two-staged combined structure with local surface nanocrystallization can be increased by 34.36% compared with the untreated counterpart of the same material and structural shape. The ratio between the first and second peak crushing forces and the energy absorption allocation ratio between the two stages can be adjusted in the ranges of 0.26–0.55 and 0.31–0.45, respectively, which can be controlled by the local surface nanocrystallization designs. The numerical simulation and experimental results are in good agreement, which shows that the design for energy absorption device with local surface nanocrystallization is feasible and effective.

The dust on indoor and outdoor surfaces of the window glasses were collected using sterile cotton balls in 11 cities from China. Two sampling campaigns were conducted with the time interval of 7 days to investigate the accumulation especially during the Spring festival holidays. Twenty-nine perfluoroalkyl acids (PFAA) were quantified to investigate concentration, composition, and toddlers' exposure. The concentrations of ∑PFAA ranged from no detection (nd) to 43 ng/m2 (mean 8.9 ± 10 ng/m2). Perfluorobutanoic acid (PFBA) was detected in 78% samples and accounted for 55 ± 21% of ∑PFAA concentrations. 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and hexafluoropropylene oxide dimer acid (HFPO-DA) were detected in more than 50% samples indicating the use of alternatives. Fluorotelomer carboxylic acid (FTCA) and fluorotelomer unsaturated acid (FTUCA) were found in the dust, implying the degradation of fluorotelomer alcohols (FTOH). The highest concentration of ∑PFAA (43 ng/m2) was found in outdoor dust from Xinzhou, Shanxi Province. Higher ∑PFAA concentrations were found in indoor dust than outdoor in 6 paired samples (3 from Feb. 14 and 3 from Feb. 21). In Tianjin and Handan, the concentrations of ∑PFAA from outdoor surfaces were higher in sampling campaign I (SC I, Feb. 21) than in sampling campaign II (SC II, Feb. 14), implying intensive outdoor release. The exposure of 2-year-old toddlers to PFAA via hand-to-mouth ingestion and dermal absorption was estimated; the mean values of intake were 2.1 and 1.5 pg/kg body weight, respectively, assuming an exposure time of 1 h.

The Nonnegative Blind Source Separation (NBSS) algorithm based on Minimum Volume Simplex (MVS) has a high dependence on the convex hull of mixed scatterplot, in addition, the shape of convex hull is variable, which increases the uncertainty of the algorithm, therefore, algorithms based on MVS have some restrictions on the shape of mixed scatterplot. Particularly, in the most extreme case, i.e. when the mixing system is ill conditioned and the scatterplot degenerates from n-dimension to (n−1)-dimension, these algorithms almost lose the ability of unmixing. On the other hand, the shape of the mixed scatterplot of sparse signals such as speech is generally fixed, specifically, it is an inclined cross in the two-dimension case. This paper proposes an algorithm based on the slope distribution of edge feature scatters. After sparsity mixtures by extracting edge features, the edge feature scatterplot with inclined cross shape can be obtained. By statistical the slope distribution of edge feature scatterplot, the optimal estimation of the mixing matrix can be found by finding the interval extremum of the slope distribution. In order to improve the accuracy of the geometric method, this paper proposes a Minimum Jaccard Index (MJI) criterion to judge whether the estimation of the mixed matrix is optimal or not. The proposed method does not need the assumption of source independence, or even the locally dominant assumption or pure pixel assumption often mentioned in algorithms based on MVS, and this method only needs the source boundedness assumption indeed. Our method is robust to ill condition, which enriches the theory and method of bounded component analysis and makes up for the shortcomings of other related algorithms.

The transition-metal kagome lattice materials host frustrated, correlated, and topological quantum states of matter1–9. Recently, a new family of vanadium-based kagome metals AV3Sb5 (A=K, Rb, and Cs) with topological band structures has been discovered10,11. These layered compounds are nonmagnetic and undergo charge density wave transitions before developing superconductivity at low temperatures11–19. Here we report the observation of unconventional superconductivity and pair density wave (PDW) in CsV3Sb5 using scanning tunneling microscope/spectroscopy (STM/STS) and Josephson STS. We find that CsV3Sb5 exhibits a V-shaped pairing gap Δ~0.5 meV and is a strong-coupling superconductor (2∆/kBTc~5) that coexists with 4a0 unidirectional and 2a0×2a0 charge order. Remarkably, we discover a 3Q PDW accompanied by bidirectional 4a0/3 spatial modulations of the superconducting gap, coherence peak and gap-depth in the tunneling conductance. We term this novel quantum state a roton-PDW associated with an underlying vortex-antivortex lattice that can account for the observed conductance modulations. Probing the electronic states in the vortex halo in an applied magnetic field, in strong-field that suppresses superconductivity, and in zero-field above Tc reveals that the PDW is a primary state responsible for an emergent pseudogap and intertwined electronic order. Our findings show striking analogies and distinctions to the phenomenology of high-Tc cuprate superconductors, and provide groundwork for understanding the microscopic origin of correlated electronic states and superconductivity in vanadium-based kagome metals.

To determine the flow behavior of SUS304 stainless steel under different conditions, axisymmetric compression tests were conducted over a wide range of forming temperatures (25 °C to 400 °C) and strain rates (10−3 to 10 s−1). Flow curves were obtained for different forming conditions to study the influence of the forming temperature and strain rate on the flow behavior. Moreover, electron backscatter diffraction analysis, X-ray diffraction analysis, transmission electron microscopy, and Feritscope were used to study the microstructure evolution of SUS304 stainless steel under different conditions for determining the underlying reasons for the variations in flow behavior. The experimental results indicated that the flow stress decreased with increasing the forming temperature. With increasing strain rate at 25 °C to 200 °C, the flow stress first increased and then decreased; however, the strain rate had little effect on the flow stress at 300 °C and 400 °C. By analyzing the variation in the phase transformation inside compressed SUS304 stainless steel samples under different forming conditions, the key factors affecting the flow behavior of stainless steel were identified. Finally, by examining the variation in the martensite content and the dislocation density, the dominant deformation mechanism under different forming conditions was determined.

High electroactivity and good mechanical robustness of electrode materials are essential to deliver excellent electrochemical energy storage performance. Herein, metal–organic frameworks (MOF) derived mixed metal oxides (MMO, ZnO@NiO and Co3O4@NiO) are prepared by a two-step annealing process in air. Zinc-based MOF (ZIF-8) and cobalt-based MOF (ZIF-67) were employed, respectively, as hard templates for the chemical encapsulation of Ni(OH)2 nanostructures by hydrothermal synthesis. The as-prepared ZIF-8@Ni(OH)2 and ZIF-67@Ni(OH)2 were then converted to corresponding MMO through annealing in air. Meanwhile, MOF-derived carbon was preserved in the as-fabricated MMO structure, thus improving the electronic conductivity as well as the mechanical stability of the materials. In virtue of these features, high specific capacitance of 1017 and 744 F·g−1 can be delivered at a current density of 1 A·g−1 for the Co3O4@NiO and ZnO@NiO samples, respectively. In addition, both of the samples have shown excellent cycling performance, which exhibited excellent capacitance retentions of 90.1% and 93.0% after 10,000 cycles for the Co3O4@NiO and ZnO@NiO samples, respectively, demonstrating their very promising use in next-generation pseudocapacitors.

Realization of functional flexible artificial synapse is a significant step toward neuromorphic computing. Herein, a flexible artificial synapse based on ferroelectric tunnel junctions (FTJs) is demonstrated, using BiFeO3 (BFO) thin film as the functional layer. The inorganic single crystalline FTJs grown on rigid perovskite substrates at high temperatures are integrated with the flexible plastic substrates, by using the water-soluble Sr3Al2O6 (SAO) as the sacrificial layer and the following transfer. The transferred freestanding BFO thin film exhibits excellent ferroelectric properties. Moreover, the memristive properties and the brain-like synaptic learning performance of the flexible FTJs are investigated. The results show that multilevel resistance states were maintained well of the flexible artificial synapse, together with their stable synaptic learning properties. Our work indicates the promising opportunity of ferroelectric thin film based flexible synapse used in the future neuromorphic computing system.

As a priority environmental pollutant, toxic trace metals enriched in atmospheric particulate matters (PMs) pose potential threats to both ecological system and human health. To sufficiently clarify the relationships between airborne trace metals and environmental impacts, considering the chemical speciation and bioaccessibility of trace metals in PMs becomes necessary. In this mini-review, such recent research progresses were summarized, including the concepts and developed methods for metal fractionation and bioaccessibility evaluation, especially the human body (lung)–related bioaccessible fractions of inhalable particle metals. Chemical extraction methods for different fractions and a compilation of in vitro bioaccessibility approaches for trace metals in PMs were presented. For future risk assessments and toxicity tests of atmospheric particulate metals, incorporating the bioaccessibility supported by standardized speciation methods are directions.