Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Quantification of dendritic cell subsets in human thymus tissues of various ages.

BACKGROUND: Dendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also have other functions in the thymus, such as pathogen recognition. The density changes of human thymic DCs have been hardly investigated. In this study, human thymus samples of various ages were collected for tissue sectioning and staining. The thymic cortex and medulla area as well as the densities of various subsets of thymic DCs were calculated. RESULTS: All common DC subsets were found in the human thymus of various ages. Most DCs had accumulated in the human thymic epithelial space, especially the medulla. We also found that the human thymic cortex had atrophied relatively faster than the medulla, which led to a gradual increase of the area ratio of the medulla to cortex with the increase of age. The densities of DC subsets in the human thymus showed various changes with increasing age, which contributed to the composition changes of DC subsets. The density of plasmacytoid DCs (pDCs) in the human thymus had increased gradually with aging, which suggested that pDCs plays another essential role in the thymus in addition to central tolerance. CONCLUSIONS: Inconsistent with the shrinking of the epithelial space in the thymus, the densities of DC subsets in the epithelial space of the thymus are maintained at a constant level with aging to preserve highly efficient autoreactive thymocyte screening. An increasing density of the thymic pDCs with aging implies an extra function of DCs in the thymus beyond central tolerance.

Circulating Th1/17 cells serve as a biomarker of disease severity and a target for early intervention in AChR-MG patients.

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered to be critical regulators of thymic inflammation in AChR-MG patients. However, Th17 cells are functionally heterogeneous and circulating Th17 subsets are incompletely understood in AChR-MG patients. Here, we studied characteristics of Th17 subsets in peripheral blood from treatment-naïve AChR-MG patients, patients treated with immunosuppressants, as well as healthy controls. We found increased frequencies of circulating Th1-like Th17 (Th1/17) (IFN-γ + IL-17 + CD4 + CD3+) cells, which declined earlier than conventional Th17 (IFN-γ - IL-17 + CD4 + CD3+) cells in patients who respond well to immunosuppression treatment. Additionally, circulating Th1/17 cell frequencies were found to correlate positively with disease severity. Further, compared to conventional Th17 cells, Th1/17 cells showed an elevated expression of IFNG, TBX21, IL23R, CSF2, and a reduced expression of AHR and IL10. Taken together, our results suggest circulating Th1/17 cells may serve as a biomarker of disease severity and provide a strong rationale for early intervention in AChR-MG patients.

Hospital and healthcare insurance system record-based epidemiological study of myasthenia gravis in southern and northern China.

OBJECTIVE: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations. METHODS: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017. RESULTS: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance. CONCLUSIONS: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.

Nuclear Shp2 directs normal embryo implantation via facilitating the ERα tyrosine phosphorylation by the Src kinase.

Estrogen and progesterone coupled with locally produced signaling molecules are essential for embryo implantation. However, the hierarchical landscape of the molecular pathways that governs this process remains largely unexplored. Here we show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK signaling, is predominately localized in the nuclei in the periimplantation mouse uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor (PR) expression and progesterone resistance, which derails normal uterine receptivity, leading to complete implantation failure in mice. Notably, the PR expression defects are attributed to the limited estrogen receptor α (ERα) activation in uterine stroma. Further analysis reveals that nuclear Shp2, rather than cytosolic Shp2, promotes the ERα transcription activity. This function is achieved by enhancing the Src kinase-mediated ERα tyrosine phosphorylation, which facilitates ERα binding to Pgr promoter in an ERK-independent manner in periimplantation uteri. Besides uncovering a regulatory mechanism, this study could be clinically relevant to dysfunctional ERα-caused endometrial disorders in women.

Imbalance of the two main circulating dendritic cell subsets in patients with myasthenia gravis.

Although it is well documented that circulating dendritic cells (DCs) have specialized features during many kinds of physiological and pathological conditions, there are few reports about the features of DCs in the peripheral blood of myasthenia gravis (MG) patients. We investigated the quantitative and component features of DCs and their implications in MG. Peripheral blood samples from different kinds of MG patients were collected and their clinical characteristics were recorded. Using flow cytometry, we distinguished circulating DC subsets [plasmacytoid DCs (pDCs) and myeloid DCs (mDCs)] and enumerated their densities in peripheral blood. Absolute numbers of circulating pDCs were significantly decreased in naïve MG patients compared with healthy controls, resulting in a markedly lower ratio of the pDC to mDC percentage in total circulating DCs (pDCs/mDCs), suggesting an imbalance in the proportions of the two main circulating DC subsets. The clinical status of MG patients was improved after drug treatment, together with increased pDCs/mDCs. In a longitudinal follow-up, we observed that circulating mDCs were significantly reduced after 1 month of therapy with a corticosteroid and immunosuppressant, resulting in recovery of pDCs/mDCs. Although the exact meaning of the proportion change in circulating DC subsets is unknown, pDCs/mDCs might reflect the balance between the autoimmune response and immune tolerance of a patient. Moreover, changes in pDCs/mDCs during treatment might be a promising marker to predict the efficacy of a specific drug used for MG patients.

The practical self-targeted oncolytic adenoviral nanosphere based on immuno-obstruction method via polyprotein surface precipitation technique enhances transfection efficiency for virotherapy.

Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells also further attack A549. Direct Ad injection was demonstrated to be lethal and prohibited in vivo. In this research a multifunctional principal using polyprotein surface precipitation technique (PSP) whist maintaining biological controls for self-assembly polyprotein Ad nanosphere both biocompatible and reproducible, was demonstrated as a result of the enhanced transfection efficiency and a successful multifunctional drug delivery system for virotherapy.

A novel design for stable self-assembly cubosome precursor-microparticles enhancing dissolution of insoluble drugs.

Cubosomes have been presented to enhance dissolution of insoluble drugs, but their applications are limited by the practical hurdles associated with both preparation and storage instability, resulting in drug delivery failure. In the present study, an innovative cubosome precursor-microparticles (CPMs) spray dried from an aqua-free precursor solution was developed to improve cubosome stability during both preparation and storage as well as to enhance the dissolution of insoluble drugs. These CPMs spontaneously self-assembled in situ forming homogeneous cubosome dispersion by hydration and disintegration after exposure to the aqueous medium. The stable cubosome dispersion was obtained from self-assembly (SA) of CPMs after administration instead of fragmentation of bulk cubic phase gel into cubosomes, which settled the preparation instability due to avoidance of high energy fragmentation (e.g. ultrasonic effect, high speed shear and high pressure homogenization). Also, the subsequent storage instability issue can be excluded as the CPMs were stored in a solid stable form. The CPMs disintegration and cubosome SA were demonstrated by the notable morphology variation and the distinct microparticle size decrease from CPMs (10-20 µm) to SA-cubosomes (150-200 nm). The cumulative release of docetaxel (DTX, model insoluble drug) incorporated in CPMs increased to 96.4% within 120 minutes compared with only 75.2% for blank CPMs and DTX physical mixture, demonstrating that CPMs significantly enhanced the dissolution extent of insoluble drug. The SA-cubosomes possessed quite high drug entrapment efficiency (>95%) and an integrated drug dissolution content, which significantly increased the drug utilization rate.

Systemic morphine treatment derails normal uterine receptivity, leading to embryo implantation failure in mice.

Morphine is the oldest worldwide well-known opioid agonist used for pain treatment in clinic, and its illicit use is often associated with adverse pregnancy outcomes in humans. Because of recent dramatic increases in nonmedicinal morphine abuse, one emerging issue is the further revelation of the dark side of illicit opioid uses, particularly in early pregnancy events. In this respect, we have demonstrated that opioid signaling is functionally operative during preimplantation embryo development in mice. However, the pathophysiological significance of the opioid system on uterine functions at peri-implantation remained elusive. In the present study, we demonstrated that opioid receptors were spatiotemporally expressed in the uterus during the peri-implantation period. Employing a pharmacological approach combined with embryo transfer experiments, we further observed that although systemic morphine treatment exerts no apparent adverse influence on preimplantation ovarian secretion of progesterone and estrogen, this aberrant activation of opioid signaling by morphine induces impaired luminal epithelial differentiation, decreased stromal cell proliferation, and poor angiogenesis, and thus hampers uterine receptivity and embryo implantation. These novel findings add a new line of evidence to better understand the causes for obvious adverse effects of opioid abuse on pregnancy success in women.

Integral proteomic analysis of blastocysts reveals key molecular machinery governing embryonic diapause and reactivation for implantation in mice.

Among nearly 100 mammalian species, implantation can be suspended at blastocyst stage for a certain time and reactivated under favorable conditions, a phenomenon known as embryonic diapause. Until now, the underlying molecular mechanism governing embryonic diapause and reactivation for implantation remained largely unknown. Here we conducted the first integral proteomic analysis of blastocysts from diapause to reactivation by using a physiologically relevant mouse delayed implantation model. More than 6000 dormant and reactivated blastocysts were used for the proteomic analysis. A total of 2255 proteins were detected. Various cellular and molecular processes, including protein translation, aerobic glycolysis, pentose phosphate pathway, purine nucleotide biosynthesis, glutathione metabolism, and chromatin organization were identified as differentially regulated. In particular, we demonstrated a remarkable activation of mitochondria in blastocysts upon reactivation from dormancy, highlighting their essential physiological significance. Moreover, the activities of the endosome-lysosome system were prominently enhanced in the mural trophectoderm of reactivated blastocysts, accompanied by active phagocytosis at the fetal-maternal interface, suggesting a critical role in promoting trophoblast invasion. Collectively, we provided an integral proteomic view upon the regulatory network of blastocyst reactivation from diapause, which will help to better interpret the nature of embryonic diapause and reactivation in wild animals and to identify molecular indicators for selecting blastocysts with high implantation competency.

Targeting HIF-1α alleviates the inflammatory responses and rebuilds the CD4+ T cell subsets balance in the experimental autoimmune myasthenia gravis inflammation model via regulating cellular and humoral immunity.

BACKGROUND: Cells and tissues in an inflammatory state are usually hypoxic. The hypoxic environment can affect the differentiation of immune cells and produce Hypoxia-inducible Factor-1α (HIF-1α). Inflammation is also a major contributor to the development and deterioration of Myasthenia Gravis (MG). There are limited studies on the immunopathological mechanism and targeted therapy associated with MG exacerbated with inflammation. This research aimed to explore whether BAY 87-2243 (HIF-1α inhibitor) ameliorates the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model and study its regulatory mechanism on cellular immunity and humoral immunity. METHODS: We first establish the EAMG inflammation model using Lipopolysaccharide (LPS), BAY 87-2243 was applied to the EAMG inflammation model and its therapeutic effects were evaluated in vivo and in vitro experiments. RESULTS: The proportion of Treg cells was increased whereas Th1, Th17, and Th1/17 cells were decreased in BAY 87-2243-treated EAMG inflammation model. BAY 87-2243 ameliorated the acetylcholine receptors (AChRs) loss and the complement deposited at the neuromuscular junction of the EAMG inflammation model, declined the levels of IFN-γ, IL-17, and IL-6 in serum, and further attenuated responses in the germinal center and reduced the antibody levels by inhibiting the IL-6-dependent STAT3 axis. CONCLUSION: BAY 87-2243 restored the balance of CD4+T cell subsets and reduced the production of the pro-inflammatory cytokines, thus acting as both an immune imbalance regulator and anti-inflammatory. The current study suggests that HIF-1α might be a potential target for the treatment of MG exacerbated with inflammation.

A new ant species of the genus Carebara Westwood, 1840 (Hymenoptera, Formicidae, Myrmicinae) with a key to Chinese species.

A new Chinese ant species Carebaralaevicepssp. nov. is described based on the major and minor workers. This species is most similar to C.lusciosa (Wheeler, 1928) due to a spineless propodeum, the absence of horns, and a smooth head capsule. It is distinguished by the following features: (1) antenna 10-segmented; (2) katepisternum rugose-reticulate; (3) in major workers, lateral sides of head in full-face view parallel; (4) metanotal groove distinct, anterodorsal corner forming an acute tooth behind metanotal groove. Moreover, an updated key to Chinese Carebara species is presented based on major workers, with a checklist comprising a total of 36 Chinese Carebara species and subspecies. Morphological structures and scanning electron micrographs of the newly discovered species' minor and major workers are provided.

Ooceraeahainingensis sp. nov.: A new Chinese Ooceraea (Hymenoptera, Formicidae, Dorylinae) species with a dealate queen, closely allied to the queenless clonal raider ant O.biroi.

The clonal raider ant, Ooceraeabiroi, is a queenless species that reproduces asexually, and these traits make it an attractive model system for laboratory research. However, it is unclear where on the ant phylogeny these traits evolved, partly because few closely related species have been described and studied. Here, we describe a new raider ant species, Ooceraeahainingensis sp. nov., from Zhejiang, China. This species is closely related to O.biroi but can be distinguished by the following features: 1) workers of O.hainingensis sp. nov. have an obvious promesonotal suture and a metanotal groove, whereas these characters are ambiguous in O.biroi; and 2) the subpetiolar process of O.hainingensis is prominent and anteroventrally directed like a thumb with sublinear posteroventral margin, while in O.biroi, it is anteroventrally directed but slightly backward-bent. Molecular phylogenetic analyses confirm that O.hainingensis is genetically distinct from O.biroi. Importantly, unlike O.biroi, O.hainingensis has a queen caste with wings and well-developed eyes. This suggests that the loss of the queen caste and transition to asexual reproduction by workers is specific to O.biroi and occurred after that species diverged from closely related congeneric species.

Long-term efficacy and safety of leflunomide combined with low-dose prednisone in treatment of myasthenia gravis: a retrospective study.

BACKGROUND: Leflunomide and low-dose prednisone (0.25 mg/kg/day) (LEF + Pred) rapidly improved the clinical symptoms of myasthenia gravis (MG) patients. Here, we aimed to analyze the long-term efficacy and safety of LEF + Pred in MG patients. METHODS: This retrospective cohort study enrolled MG patients treated with LEF + Pred in our center between 2012 and 2020. We reviewed all the MG patients continuously treated with LEF + Pred for more than 1 year. MG activities of daily living (MG-ADL) profile score and quantitative MG scale (QMG) score in each clinical follow-up visits were collected for the efficacy analysis. The laboratory testing results of MG patients, the relevant chief complain and physical examination results in each follow-up visits were collected for the safety evaluation. RESULTS: In total, 103 patients were examined. Effective treatment was achieved in 58.3% of patients after 1 month and in 88.4% after 12 months. Overall, 63 patients (61.2%) exhibited only minimal manifestations after 12 months of treatment. The average MG-ADL score decreased from 6.0 to 1.0, while the average QMG score decreased from 10.0 to 4.0. The decrease in MG-ADL and QMG scores of patients with generalized MG was more pronounced than those of the ocular MG patients. Patients with MG who had a thymectomy had a smaller decrease in MG-ADL and QMG scores than those who did not have a thymectomy. Sixteen adverse effects associated with LEF + Pred were observed; none was severe. CONCLUSIONS: Long-term LEF + Pred therapy could considerably improve clinical symptoms in MG patients while being well tolerated with just few side effects.

Clinical evaluation of efficacy of leflunomide combined with low-dose prednisone for treatment of myasthenia gravis.

This study evaluated the clinical efficacy of leflunomide combined with low-dose prednisone (0.25 mg/kg/day) for treatment of myasthenia gravis (MG). We enrolled 32 MG patients treated with leflunomide combined with low-dose prednisone. In the control group, 14 patients were treated with low-dose prednisone. Improvement in MG composite (MGC) score of ≥ 3 points from enrollment to 12-week follow-up indicated that the treatment was effective. In the leflunomide combined low-dose prednisone group, the median of MGC score at the time of enrollment was 8.5 points. After 12 weeks, the MGC score dropped to four points. There was statistically significant difference in MGC score before and after treatment (p < 0.001). In the low-dose prednisone group also followed up for 12 weeks, the median of MGC score of the patients decreased from 7 to 4 points, and the change was not statistically significant (p = 0.05). In the leflunomide combined low-dose prednisone group, the improvement of clinical symptoms occurred mainly in the first 4 weeks and the last 4 weeks. Relatively, the decline of the score was mostly seen during the first 8 weeks in the low-dose prednisone group. In leflunomide combined with low-dose prednisone group, the effective rate of generalized MG(gMG) was significantly higher than ocular MG(oMG) (χ2 test, p = 0.036). However, there is no significant difference in the effective rate between AChR-Ab-positive and -negative groups (Fisher's Exact Test, p = 0.625). No serious side effects were observed in any of the subjects. Leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of patients with MG. It may be a promising treatment for gMG.

JAK2 inhibitor ameliorates the progression of experimental autoimmune myasthenia gravis and balances Th17/Treg cells via regulating the JAK2/STAT3-AKT/mTOR signaling pathway.

BACKGROUND: An imbalance in Th17/regulatory T (Treg) cells is the major pathogenic mechanism underlying myasthenia gravis (MG). JAK2 inhibitors selectively inhibit JAK2 and reduce inflammatory responses. However, there have been no studies examining the therapeutic effects of JAK2 inhibitors in the context of MG. METHODS: Here, an experimental autoimmune MG (EAMG) rat model was established to explore the therapeutic effect of JAK2 inhibitors on EAMG rats immunized with the AChR α-subunit (97-116 peptide). A JAK2 inhibitor was administered to EAMG rats both in vivo and in vitro. The following experimental methods were used to evaluate the effects of JAK2 inhibitors. The behavioral scores and body weights of the rats were assessed on alternate days. Serum anti-AChR (97-116) IgG and cytokine levels were detected using ELISA. CD4+ T cell subsets and related transcription factors in mononuclear cells were detected using flow cytometry and qPCR, respectively. The expression levels of protein molecules in the signaling pathway were detected by western blotting, and the neuromuscular junctions were observed using immunofluorescence. RESULTS: The results revealed that JAK2 inhibitors could regulate Th17/Treg balance in vivo and in vitro. JAK2 inhibitors reduced the immune response in EAMG rats (including reducing pro-inflammatory cytokines and postsynaptic membrane complement deposition), improved clinical symptoms, and increased AChR aggregation in the postsynaptic membrane. Meanwhile, this study demonstrated that JAK2 inhibitor treatment suppressed the phosphorylation of JAK2/STAT3 and AKT/mTOR pathways and decreased the expression level of the IL-23 receptor. CONCLUSIONS: This study reveals that there is crosstalk between the JAK2/STAT3 and AKT/mTOR pathways in EAMG rats. JAK2 inhibitors can ameliorate EAMG by regulating Th17/Treg balance by inhibiting both signaling pathways. Our study provides new potential therapeutic targets for MG immunotherapy.

Interspecific competition predicts the potential impact of little fire ant Wasmannia auropunctata (Roger) (Hymenoptera: Formicidae) invasion on resident ants in southern China.

The little fire ant Wasmannia auropunctata (Roger) is a major invasive species that seriously threatens the biodiversity of invaded areas. W. auropunctata was first reported in Chinese mainland in 2022 and its impact on native species is still unknown. To evaluate the impact of W. auropunctata invasion on the ant communities in southern China, a series of interspecific competition experiments were conducted in this study. The individual aggression index and group aggression experiments showed the advantage of W. auropunctata in competition with 5 resident ants under equal worker numbers. When encountering Anoplolepis gracilipes, Camponotus nicobarensis, Tetramorium bicarinatum, Polyrhachis dives, and Solenopsis invicta, W. auropunctata gradually gained a competitive advantage with an increase in its number of workers. In the group aggression experiments with equal worker numbers, there was a negative correlation between the body length and mortality rate of resident ants. The results of the foraging behavior experiments showed that W. auropunctata was able to dominate food resources under competition with Carebara diversa, which also displayed weak competition in the group aggression bioassay. In addition, the abilities to recruit workers and retrieve food were inhibited under competition with S. invicta and T. bicarinatum. The results of the nesting behavior experiments showed that in the 24-h bout of space resource competition, W. auropunctata was dominant over C. diversa, S. invicta, and T. bicarinatum. The results of this study show that W. auropunctata has certain advantages in competition for food and space resources over resident ants in southern China, and some resident ant species may be replaced in the future.

Corrigendum: Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients.

[This corrects the article DOI: 10.3389/fneur.2022.961628.].

Connotation of urban ecological quality and the construction of its core index system.

Urban ecological quality is a necessary attribute for a healthy urban ecological state. In the period of urban development from large-scale incremental construction to stock improvement and quality transformation and incremental structural adjustment, there are many gaps between urban ecological quality construction and the requirements of the new stage. There is an urgent need to understand and integrate multiple needs, and construct an indicator system to promote the balance between supply and demand of ecological resources and efficient use to enhance urban ecological quality. We used the analysis methods of CiteSpace literature analysis, relevant policy collation and questionnaire survey to systematically sort out the key points of concern and differences in understanding among the three perspectives of science, government, and the public. The results showed that all the three perspectives, i.e., science, government, and public, were more concerned with indicators related to urban green space, gray infrastructure, and policy control. The concerns of science and public addressed indicators related to urban green space the most, while government being most concerned with indicators related to gray infrastructure. Based on those findings, we developed a core urban ecological quality index system with a total of 25 indicators, covering 10 major types of urban green space, environmental quality, gray infrastructure, and so on.

Microstructure Heterogeneity and Mechanical Properties of a High-Strength Ductile Laminated Steel by Electron Beam Welding.

The aim of this study is to fabricate high-strength steel with exceptional yield strength and superior ductility by employing a novel design approach of nanolamellar/equiaxial crystal "sandwich" heterostructures, utilizing rolling and electron-beam-welding techniques. The microstructural heterogeneity of the steel is manifested in the phase content and grain size, ranging from nanolamellae comprising a small quantity of martensite on both sides to the completely coarse austenite in the center, which are interconnected via gradient interfaces. The structural heterogeneity and phase-transformation-induced plasticity (TIRP) offer remarkable strength and ductility for the samples. Furthermore, the synergistic confinement of the heterogeneous structures leads to the formation of Lüders bands, which exhibit stable propagation under the TIRP effect and impede the onset of plastic instability, ultimately resulting in a significant improvement in the ductility of the high-strength steel.