A proof of concept model to calculate white and grey matter AIS injuries in pedestrian collisions.

In the real world, the severity of traumatic injuries is measured using the Abbreviated Injury Scale (AIS) and is often estimated, in finite element human computer models, with the maximum principal strains (MPS) tensor. MPS can predict when a serious injury is reached, but cannot provide any AIS measures lower and higher from this. To overcome these limitations, a new organ trauma model (OTM2), capable of calculating the threat to life of any organ injured, is proposed. The OTM2 model uses a power method, namely peak virtual power, and defines brain white and grey matters trauma responses. It includes human age effect (volume and stiffness), localised impact contact stiffness and provides injury severity adjustments for haemorrhaging. The focus, in this case, is on real-world pedestrian brain injuries. OTM2 model was tested against three real-life pedestrian accidents and has proven to reasonably predict the post mortem (PM) outcome. Its AIS predictions are closer to the real-world injury severity than the standard maximum principal strain (MPS) methods currently used. This proof of concept suggests that OTM2 has the potential to improve forensic predictions as well as contribute to the improvement in vehicle safety design through the ability to measure injury severity. This study concludes that future advances in trauma computing would require the development of a brain model that could predict haemorrhaging.

On-chip silicon photonic micro-ring processor lights up optical image encryption.

Optical image encryption has long been an important concept in the fields of photonic network processing and communication. Here, we propose a convolution-like operation-based optical image encryption algorithm exploiting a silicon photonic multiplexing architecture to achieve content security. Particularly, the encryption process is completed in a 3 × 3 cross-shaped photonic micro-ring resonator (MRR) array on chip. For the first time, to the best of our knowledge, this algorithm encodes information in an integrated intensity modulation, effectively reducing the encoding difficulty. Moreover, the high reliability and scalability of optical encryption are ensured using both linear and nonlinear operations on photonic chips according to characteristics of MRRs. As the encryption and decryption experiments show, the image restoration accuracy of our optical encryption algorithm exceeds 99% under real system noise at the pixel level, indicating its noise-robust property. Meanwhile, the peak signal-to-noise ratios of the restored and encrypted images are >60 and <15 dB, respectively, revealing both the high accuracy of the restored image and the small correlation between the encrypted and original images. This work adds to the rapidly expanding field of optical image encryption on photonic chips.

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence.

The dual catalysis strategy is an efficient and powerful tool to fulfill the stereodivergent synthesis of stereoisomeric products from the same set of starting materials. Great attention has been given to the construction of chiral compounds with two contiguous stereocenters. However, the synthesis of two remote noncontiguous stereocenters is more challenging and is less developed, despite the high demand for synthetic tactics. We herein developed an unprecedented example of the stereodivergent preparation of synthetically useful and biologically important chiral ζ-hydroxy amino ester derivatives containing remote 1,6-noncontiguous stereocenters and a unique ß,γ-unsaturation moiety. This cascade dehydrogenation/1,6-Michael addition/hydrogenation protocol between readily-available ketoimine esters and racemic branched dienyl carbinols was rationally realized with bimetallic copper/ruthenium relay catalysis. The key features of the process were atom economy, step economy, and redox-neutrality. All four stereoisomers of chiral ζ-hydroxy amino ester derivatives were easily achieved by the orthogonal permutations of a chiral copper catalyst and chiral ruthenium catalyst. Importantly, a much more challenging stereodivergent synthesis of all eight stereoisomers of chiral peptide products containing three remote stereocenters was accomplished with excellent results through the cooperation of two chiral catalyst pairs and substrate enantiomers.

Lipidomics and Mass Spectrometry Imaging unveil Alterations in Mice Hippocampus Lipid Composition exposed to Hypoxia.

Lipids are components of cytomembranes that are involved in various biochemical processes. High-altitude hypoxic environments not only affect the body's energy metabolism, but these environments can also cause abnormal lipid metabolism involved in the hypoxia-induced cognitive impairment. Thus, comprehensive lipidomic profiling of the brain tissue is an essential step toward understanding the mechanism of cognitive impairment induced by hypoxic exposure. In the present study, mice showed reduced new-object recognition and spatial memory when exposed to hypobaric hypoxia for 1 day. Histomorphological staining revealed significant morphological and structural damage to the hippocampal tissue, along with prolonged exposure to hypobaric hypoxia. Dynamic lipidomics of the mouse hippocampus showed a significant shift in both the type and distribution of phospholipids, as verified by spatial lipid mapping. Collectively, these results have provided new insights into the cognitive decline induced by high altitude, in which alterations in lipid metabolism may be an important contributing factor.

p53 lysine-lactylated modification contributes to lipopolysaccharide-induced proinflammatory activation in BV2 cell under hypoxic conditions.

p53 has diversity functions in regulation of transcription, cell proliferation, cancer metastasis, etc. Recent studies have shown that p53 and nuclear factor-κB (NF-κB) co-regulate proinflammatory responses in macrophages. However, the role of p53 lysine lactylation (p53Kla) in mediating proinflammatory phenotypes in microglia under hypoxic conditions remains unclear. In the current study, we investigated the proinflammatory activation exacerbated by hypoxia and the levels of p53Kla in microglial cells. BV2 cells, an immortalized mouse microglia cell line, were divided into control, lipopolysaccharide (LPS)-induced, hypoxia (Hy), and LPS-Hy groups. The protein expression levels of p53 and p53Kla and the activation of microglia were compared among the four groups. Sodium oxamate and mutant p53 plasmids were transfected into BV2 cells to detect the effect of p53Kla on microglial proinflammatory activation. LPS-Hy stimulation significantly upregulated p53Kla levels in both the nucleus and the cytoplasm of BV2 cells. In contrast, the p53 protein levels were downregulated. LPS-Hy stimulation upregulated phosphorylated p65 protein levels in nuclear and activated the NF-κB pathway in BV2 cells, resulting in increased expression of pro-inflammatory cytokines (iNOS, IL6, IL1ß, TNFα), enhanced cell viability, and concomitantly, increased cytotoxicity. In conclusion, p53 lysine-lactylated modification contributes to LPS-induced proinflammatory activation in BV2 cells under hypoxia through NF-κB pathway and inhibition of lactate production may alleviate neuroinflammatory injury.

Color coded metadevices toward programmed terahertz switching.

Terahertz modulators play a critical role in high-speed wireless communication, non-destructive imaging, and so on, which have attracted a large amount of research interest. Nevertheless, all-optical terahertz modulation, an ultrafast dynamical control approach, remains to be limited in terms of encoding and multifunction. Here we experimentally demonstrated an optical-programmed terahertz switching realized by combining optical metasurfaces with the terahertz metasurface, resulting in 2-bit dual-channel terahertz encoding. The terahertz metasurface, made up of semiconductor islands and artificial microstructures, enables effective all-optical programming by providing multiple frequency channels with ultrafast modulation at the nanosecond level. Meanwhile, optical metasurfaces covered in terahertz metasurface alter the spatial light field distribution to obtain color code. According to the time-domain coupled mode theory analysis, the energy dissipation modes in terahertz metasurface can be independently controlled by color excitation, which explains the principle of 2-bit encoding well. This work establishes a platform for all-optical programmed terahertz metadevices and may further advance the application of composite metasurface in terahertz manipulation.

Comparative analysis of short-term efficacy between robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus.

Objective: To investigate the short-term clinical efficacy of robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus (OCLT). Methods: This study was divided into two groups: experimental group: robot-assisted retrograde drilling group; control group: arthroscopic microfracture group. A total of 6 OCLT patients who were treated with robot navigation-assisted retrograde drilling and 10 OCLT patients who were treated with arthroscopic microfracture between October 2020 and October 2021 were retrospectively analyzed. There were 11 males and five females, with a mean age of 36 years. The patients were followed up for 6-12 months to compare the changes in the OCLT lesion area by magnetic resonance imaging (MRI), visual analogue scale/score (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) before and after surgery. Results: All 16 patients were followed up for an average of 8 months, and no complications such as joint infection, nerve injury, or active bleeding occurred during the follow-up period. Only one patient suffered discomfort involving transient postoperative pain in the operative area, but did not experience long-term numbness or chronic pain. Postoperative MRI revealed that none of the patients had severe signs of osteonecrosis, osteolysis or cystic changes of the talus, with lesion areas smaller than those before surgery. The difference was statistically significant (P < 0.01). The patients in the experimental group showed a more significant improvement in the last 3 months than in the first 3 months of the follow-up period. At the last follow-up, the VAS score was 3 points in the experimental group and 2.2 points in the control group, and the AOFAS score was 88.6 points in the experimental group and 88 points in the control group, all of which were significantly higher than those before operation, and the differences were statistically significant, but there was no statistically significant difference between the groups. Conclusion: Both robot navigation-assisted retrograde drilling and arthroscopic microfracture for bone marrow stimulation (BMS) to treat OCLT in all patients obtained satisfactory effects in the short term. In addition, the follow-up revealed that with excellent efficacy and few complications, robot navigation-assisted retrograde drilling was safe and minimally invasive, and greatly reduced operative time. Consequently, robot navigation-assisted retrograde drilling for BMS was a safe and effective procedure for the treatment of OCLT.

Genome-Wide Identification and Expression Analysis of the YTH Domain-Containing RNA-Binding Protein Family in Cinnamomum camphora.

N6-methyladenosine (m6A) is one of the most abundant chemical modifications on mRNA in eukaryotes. RNA-binding proteins containing the YT521-B (YTH) domain play crucial roles in post-transcriptional regulation of plant growth, development, and stress response by reading the m6A mark. However, the YTH domain-containing RNA-binding protein family has not been studied in a valuable and medicinal tree such as Cinnamomum camphora (C. camphora) yet. In this study, we identified 10 YTH genes in C. camphora, located on eight out of 12 chromosomes. Phylogenetic analysis revealed that these genes can be classified into two major classes, YTHDF (CcDF) and YTHDC (CcDC). Closely related CcYTHs within the same class exhibited a similar distribution of conserved motifs and domain organization, suggesting functional similarities among these closely related CcYTHs. All CcYTH proteins possessed a highly conserved YTH domain, with CcDC1A containing an additional CCCH domain. The liquid-liquid phase separation (LLPS) predictions indicate that CcDC1A, CcDF1A, CcDF1C, CcDF3C, CcDF4C, and CcDF5C may undergo phase transitions. Quantitative expression analysis revealed that tissue-specific expression was observed fo CcYTHs. Notably, there were two genes, CcDF1A and CcDF5C; both exhibited significantly higher expression levels in various tissues than other genes, indicating that the m6A-YTH regulatory network in C. camphora might be quite distinct from that in most plants such as Arabidopsis thaliana (A. thaliana) with only one abundant YTH protein. According to the analysis of the up-stream cis-regulatory elements of these YTH genes, these genes could be closely related to stress, hormones, and development. The following stress response experiments further verified that their expression levels indeed changed under both PEG and NaCl treatments. These findings not only provide a foundation for future functional analysis of CcYTHs in C. camphora, but also provide insights into the functions of epigenetic mark m6A in forest trees.

Sleep patterns, genetic susceptibility, and risk of cirrhosis among individuals with nonalcoholic fatty liver disease.

BACKGROUND: The associations between sleep patterns or behaviors and the risk of cirrhosis and the influence of genetic susceptibility on these associations among NAFLD participants remain inadequately elucidated. METHODS: This study conducted a prospective follow-up of 112,196 NAFLD participants diagnosed at baseline from the UK Biobank cohort study. Five sleep behaviors were collected to measure a healthy sleep score. Five genetic variants were used to construct a polygenic risk score. We used Cox proportional hazard model to assess hazard ratios (HR) and 95% confidence intervals (CIs) for incidence of cirrhosis. RESULTS: During the follow-up, 592 incident cirrhosis cases were documented. Healthy sleep pattern was associated with reduced risk of cirrhosis in a dose-response manner (ptrend < 0.001). Participants with favourable sleep score (versus unfavourable sleep score) had an HR of 0.55 for cirrhosis risk (95% CI 0.39-0.78). Multivariable-adjusted HRs (95% CIs) of cirrhosis incidence for NAFLDs with no frequent insomnia, sleeping for 7-8 h per day, and no excessive daytime dozing behaviors were 0.73 (0.61-0.87), 0.79 (0.66-0.93), and 0.69 (0.50-0.95), respectively. Compared with participants with favourable sleep pattern and low genetic risk, those with unfavourable sleep pattern and high genetic risk had higher risks of cirrhosis incidence (HR 3.16, 95% CI 1.88-5.33). In addition, a significant interaction between chronotype and genetic risk was detected for the incidence of cirrhosis (p for multiplicative interaction = 0.004). CONCLUSION: An association was observed between healthy sleep pattern and decreased risk of cirrhosis among NAFLD participants, regardless of low or high genetic risk.

Ultralong Cycling and Interfacial Regulation of Bilayer Heterogeneous Composite Solid-State Electrolytes in Lithium Metal Batteries.

Under the background of "carbon neutral", lithium-ion batteries (LIB) have been widely used in portable electronic devices and large-scale energy storage systems, but the current commercial electrolyte is mainly liquid organic compounds, which have serious safety risks. In this paper, a bilayer heterogeneous composite solid-state electrolyte (PLPE) was constructed with the 3D LiX zeolite nanofiber (LiX-NF) layer and in-situ interfacial layer, which greatly extends the life span of lithium metal batteries (LMB). LiX-NF not only offers a continuous fast path for Li+, but also zeolite's Lewis acid-base interaction can immobilize large anions, which significantly improves the electrochemical performance of the electrolyte. In addition, the in-situ interfacial layer at the electrode-electrolyte interface can effectively facilitate the uniform deposition of Li+ and inhibit the growth of lithium dendrites. As a result, the Li/Li battery assembled with PLPE can be stably cycled for more than 2500 h at 0.1 mA cm-2. Meanwhile, the initial discharge capacity of the LiFePO4/PLPE/Li battery can be 162.43 mAh g-1 at 0.5 C, and the capacity retention rate is 82.74% after 500 cycles. These results emphasize that this bilayer heterogeneous composite solid-state electrolyte has distinct properties and shows excellent potential for application in LMB.

Bipolar Photoelectrochemistry for Phase-Modulated Optoelectronic Hybrid Nanomotor.

Complex micro/nanorobots may be constructed by integrating several independent, controlled nanomotors for high degrees of freedom of maneuvering and manipulation. However, designing nanomotors with distinctive responses to the same global stimuli is challenging due to the nanomotors' simple structure and limited material composition. In this work, we demonstrate that a nanomotor can be designed with the same principles of electronic circuits, where the motion of semiconductor particles can be controlled with synchronized electric and optical signals. This technique relies on transient bipolar photoelectrochemistry in semiconductor microparticles, where the reaction site selectivity is realized by modulating the light pulse in the time domain. Due to the microparticles' intrinsic resistance and surface capacitance, the nanomotors can be designed as an electronic circuit, enabling distinctive responses to the global electric/optical field and achieving the desired movement or deflection/rotation. This work gives new insight into the manipulation technique for independent and untethered nanomotor control. Ultimately, it exploits the potential for particle sorting based on geometry in time and frequency domain modulation.

Necroptosis-Mediated Synergistic Photodynamic and Glutamine-Metabolic Therapy Enabled by a Biomimetic Targeting Nanosystem for Cholangiocarcinoma.

Targeted delivery of glutamine metabolism inhibitors holds promise for cholangiocarcinoma therapy, yet effective delivery vehicles remain a challenge. This study reports the development of a biomimetic nanosystem, termed R-CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species-responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg-Gly-Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R-CM@MSN@BC executed both photodynamic and glutamine-metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time-of-flight mass cytometry analysis revealed that R-CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1-type macrophages, reducing infiltration of M2-type and CX3CR1+ macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti-programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.

Creating Anti-Chiral Exceptional Points in Non-Hermitian Metasurfaces for Efficient Terahertz Switching.

Non-Hermitian degeneracies, also known as exceptional points (EPs), have presented remarkable singular characteristics such as the degeneracy of eigenvalues and eigenstates and enable limitless opportunities for achieving fascinating phenomena in EP photonic systems. Here, the general theoretical framework and experimental verification of a non-Hermitian metasurface that holds a pair of anti-chiral EPs are proposed as a novel approach for efficient terahertz (THz) switching. First, based on the Pancharatnam-Berry (PB) phase and unitary transformation, it is discovered that the coupling variation of ±1 spin eigenstates will lead to asymmetric modulation in two orthogonal linear polarizations (LP). Through loss-induced merging of a pair of anti-chiral EPs, the decoupling of ±1 spin eigenstates are then successfully realized in a non-Hermitian metasurface. Final, the efficient THz modulation is experimentally demonstrated, which exhibits modulation depth exceeding 70% and Off-On-Off switching cycle less than 9 ps in one LP while remains unaffected in another one. Compared with conventional THz modulation devices, the metadevice shows several figures of merits, such as a single frequency operation, high modulation depth, and ultrafast switching speed. The proposed theory and loss-induced non-Hermitian device are general and can be extended to numerous photonic systems varying from microwave, THz, infrared, to visible light.

A case-matched study of imatinib mesylate between different formulations on plasma trough concentration, adverse events, quality of life and outcomes in gastrointestinal stromal tumor patients.

Genike, the imatinib (IM)-alpha form is widely used in the treatment of gastrointestinal stromal tumor (GIST) patients in China. We wanted to investigate whether there are differences in IM plasma concentrations, adverse events, health-related quality of life (QOL) and outcomes between patients treated with Genike and Glivec. Thirty included GIST patients receiving IM treatment were matched to either Genike or Glivec according to gastrectomy, body weight, body surface area and sex. There was no statistically significant difference in IM trough plasma levels between the two groups. There were no significant differences in very common adverse events of IM between the Genike and Glivec groups. IM was well tolerated, although it was associated with a significant change in cognitive function (P < 0.001), fatigue (P = 0.015), pain (P = 0.015), nausea/vomiting (P = 0.029), insomnia (P = 0.019), diarrhea (P = 0.003) and financial difficulties (P < 0.001). Physical functioning, financial burden and insomnia were significantly different between the two groups (P = 0.026). Until Aug. 2022, there was no significant difference in time to imatinib treatment failure (TTF) between the two groups. In conclusion, there was no difference in IM plasma concentration and adverse events between Genike and Glivec. Both Genike and Glivec could partially decrease the QOL of GIST patients. Physical functioning was worse in Genike group than in Glivec group, while the economic burden and symptoms of insomnia in Glivec patients were worse. There was no significant difference in TTF between the two groups.

Thermally Stable and Chemically Recyclable Poly(ketal-ester)s Regulated by Floor Temperature.

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

Effectiveness and Safety of a Novel Intravascular Lithotripsy System for Severe Coronary Calcification: The CALCI-CRACK Trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (ChiCTR2100052058) was a prospective, single-arm, multicentre study. The primary end point was the procedural success rate. Major safety end points included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centres were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50%-97.41%), exceeding the prespecified performance goal of 83.4% (P < 0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at those time points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n = 93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100052058.

Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing.

Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.