A New Orthonairovirus Associated with Human Febrile Illness.

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant tumors.

Loss of terminal differentiation is a hallmark of cancer and offers a potential mechanism for differentiation therapy. Polycomb repressive complex 2 (PRC2) serves as the methyltransferase for K27 of histone H3 that is crucial in development. While PRC2 inhibitors show promise in treating various cancers, the underlying mechanisms remain incompletely understood. Here, we demonstrated that the inhibition or depletion of PRC2 enhanced adipocyte differentiation in malignant rhabdoid tumors and mesenchymal stem cells, through upregulation of peroxisome proliferator-activated receptor gamma (PPARG) and CEBPA. Mechanistically, PRC2 directly represses their transcription through H3K27 methylation, as both genes exhibit a bivalent state in mesenchymal stem cells. KO of PPARG compromised C/EBPα expression and impeded the PRC2 inhibitor-induced differentiation into adipocytes. Furthermore, the combination of the PPARγ agonist rosiglitazone and the PRC2 inhibitor MAK683 exhibited a higher inhibition on Ki67 positivity in tumor xenograft compared to MAK683 alone. High CEBPA, PLIN1, and FABP4 levels positively correlated with favorable prognosis in sarcoma patients in The Cancer Genome Atlas cohort. Together, these findings unveil an epigenetic regulatory mechanism for PPARG and highlight the essential role of PPARγ and C/EBPα in the adipocyte differentiation of malignant rhabdoid tumors and sarcomas with a potential clinical implication.

Inhibition of CIRBP represses the proliferation and migration of vascular smooth muscle cells via inhibiting Rheb/mTORC1 axis.

The excessive migration and proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in vascular intimal hyperplasia. CIRBP is involved in the proliferation of various cancer cells. This study was aimed to explore the role of CIRBP in the proliferation and migration of VSMCs. Adenovirus was used to interfere with cold-inducible RNA-binding protein (CIRBP) expression, while lentivirus was used to overexpress Ras homolog enriched in brain (Rheb). Western blotting and qRT-PCR were used to evaluate the expression of CIRBP, Rheb, and mechanistic target of rapamycin complex 1 (mTORC1) activity. The cell proliferation was determined by Ki67 immunofluorescence staining and CCK-8 assay. The wound healing assay was performed to assess cell migration. Additionally, immunohistochemistry was conducted to explore the role of CIRBP in intimal hyperplasia after vascular injury. We found that silencing CIRBP inhibited the proliferation and migration of VSMCs, decreased the expression of Rheb and mTORC1 activity. Restoration of mTORC1 activity via insulin or overexpression of Rheb via lentiviral transfection both attenuated the inhibitory effects of silencing CIRBP on the proliferation and migration of VSMCs. Moreover, Rheb overexpression abolished the inhibitory effect of silencing CIRBP on mTORC1 activity in VSMCs. CIRBP was upregulated in the injured carotid artery. Silencing CIRBP ameliorated intimal hyperplasia after vascular injury. In the summary, silencing CIRBP attenuates mTORC1 activity via reducing Rheb expression, thereby supressing the proliferation and migration of VSMCs and intimal hyperplasia after vascular injury.

Emergence of a novel ISS1N-optrA-carrying transposon within an integrative and conjugative element from Streptococcus parasuis.

OBJECTIVES: To investigate the genetic context and transferability of the oxazolidinone resistance gene optrA in a Streptococcus parasuis isolate. METHODS: The optrA-carrying S. parasuis isolate SFJ45 was characterized by PCR, antimicrobial susceptibility testing, complete genome sequencing and bioinformatic analysis. The transferability of optrA was verified by conjugation, followed by SmaI-PFGE and Southern blotting. RESULTS: The S. parasuis isolate SFJ45 was positive for optrA, mef(A), msr(D), erm(B), tetAB(P)', tet(M), aadE, aphA3, catQ, dfrG and mdt(A), conferring an MDR phenotype. The optrA gene was flanked by ISS1N at both termini in the same orientation, representing a novel 8750 bp pseudo-compound transposon, organized as the ISS1N-hth-clb-4hp-optrA-2hp-ISS1N structure. The ISS1N-optrA-carrying transposon was further inserted within an integrative and conjugative element, ICESpsuSFJ45, at 3' end of the fda gene. Conjugative transfer of the ISS1N-optrA-carrying transposon with ICESpsuSFJ45 was observed from S. parasuis to Streptococcus suis at a frequency of (1.01 ± 3.12) × 10-7. CONCLUSIONS: ISS1N was found to be associated with optrA spreading for the first time. Integration of the ISS1N-optrA transposon within ICESpsuSFJ45 may lead to the co-selection of optrA with other antimicrobial resistance genes, contributing to its horizontal transfer from S. parasuis to clinically more important bacterial pathogens.

Higher-order exceptional points in parity-time symmetry and the optical gyroscope.

The practical application of integrated gyroscopes in engineering has not yet been fully realized due to the linear correlation between the Sagnac effect and dimensions. In recent demonstrations, gyroscopes operating near exceptional points (EPs) under parity-time (PT) symmetry have shown significant potential in enhancing their response to rotational rates. However, constructing higher-order EPs with refined physical properties poses a considerable challenge. Additionally, current methods for constructing higher-order EPs with robustness primarily rely on passive cavities, with almost no reports on constructing robust EPs using PT-symmetric systems that encompass both gain and loss. Here, we propose a robust design for a scalable fabrication of higher-order EP gyroscopes with PT-symmetric structure. We investigate the influence of perturbations on the frequency splitting of the higher-order EP gyroscope and demonstrate that it is possible to achieve a resonance splitting eight orders of magnitude higher than that obtained through the classical Sagnac effect. In comparison to the previously proposed PT-symmetric gyroscope, our solution allows a tunable frequency splitting by adjusting the phase shift, making it more measurable at the output power spectrum.

Long non-coding RNA Linc00657 up-regulates Skp2 to promote the progression of cervical cancer through lipid reprogramming and regulation of immune microenvironment.

More and more evidence shows that long non-coding RNA (lncRNA) plays an important role in the biological behavior of many kinds of malignant tumors, but the specific function of lncRNA Linc00657 in cervical cancer is still unknown. The purpose of this study is to explore the effect of Linc00657 on the malignant progression of cervical cancer and its potential mechanism. In two kinds of cervical cancer cell lines and normal cervical epithelial cells, qRT-PCR showed increased expression of Linc00657 in cervical cancer cells. Through MTT, clone formation test, flow cytometry, wound healing test and Transwell test, it has been found that overexpression of Linc00657 could promote the proliferation,migration and invasion of cervical cancer cells，and inhibit apoptosis. Through the StarBase database, it was found that there may be a mutual regulatory relationship between Linc00657 and Skp2, and Skp2 may be the downstream target of Linc00657. QRT-PCR detection confirmed that the expression of Skp2 was increased in cervical cancer cells with overexpression of Linc00657. TIMER2 database found that Skp2 was associated with lipid metabolic enzymes and immune cell infiltration. It was found that Linc00657 knockdown inhibited tumor growth and metastasis and inhibited the expression of Skp2 in vivo. In short, our research shows that Linc00657 has carcinogenic properties in cervical cancer, and LINC00657 promotes the occurrence of cervical cancer by up-regulating the expression of Skp2. We predict that Linc00657/mir30s/Skp2 axis plays a role in the malignant progression of cervical cancer. In addition, Skp2 may participate in cancer immune response and promote lymph node metastasis of cervical cancer through lipid reprogramming. These findings also provide promising targets for the diagnosis and treatment of cervical cancer.

Breast cancer therapy: from the perspective of glucose metabolism and glycosylation.

Breast cancer is a leading cause of mortality and the most prevalent form of malignant tumor among women worldwide. Breast cancer cells exhibit an elevated glycolysis and altered glucose metabolism. Moreover, these cells display abnormal glycosylation patterns, influencing invasion, proliferation, metastasis, and drug resistance. Consequently, targeting glycolysis and mitigating abnormal glycosylation represent key therapeutic strategies for breast cancer. This review underscores the importance of protein glycosylation and glucose metabolism alterations in breast cancer. The current research efforts in developing effective interventions targeting glycolysis and glycosylation are further discussed.

Peptide-guided delivery improves the therapeutic efficacy and safety of glucocorticoid drugs for treating acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with excessive inflammation in the lung. Glucocorticoids had been widely used for ALI/ARDS, but their clinical benefit remains unclear. Here, we tackled the problem by conjugating prednisolone (PSL) with a targeting peptide termed CRV. Systemically administered CRV selectively homes to the inflamed lung of a murine ALI model, but not healthy organs or the lung of healthy mice. The expression of the CRV receptor, retinoid X receptor ß, was elevated in the lung of ALI mice and patients with interstitial lung diseases, which may be the basis of CRV targeting. We then covalently conjugated PSL and CRV with a reactive oxygen species (ROS)-responsive linker in the middle. While being intact in blood, the ROS linker was cleaved intracellularly to release PSL for action. In vitro, CRV-PSL showed an anti-inflammatory effect similar to that of PSL. In vivo, CRV conjugation increased the amount of PSL in the inflamed lung but reduced its accumulation in healthy organs. Accordingly, CRV-PSL significantly reduced lung injury and immune-related side effects elsewhere. Taken together, our peptide-based strategy for targeted delivery of glucocorticoids for ALI may have great potential for clinical translation.

Advancements in employing two-dimensional nanomaterials for enhancing skin wound healing: a review of current practice.

The two-dimensional nanomaterials are characterized by their ultra-thin structure, diverse chemical functional groups, and remarkable anisotropic properties. Since its discovery in 2004, graphene has attracted significant scientific interest due to its potential applications in various fields, including electronics, energy systems, and biomedicine. In medicine, graphene is used for designing smart drug delivery systems, especially for antibiotics, and biosensing. Skin trauma is a prevalent dermatological condition that increasingly contributes to morbidities and mortalities, thus representing a significant health burden. During tissue damage, rapid skin repair is crucial to prevent blood loss and infection. Therefore, drugs used for skin trauma must possess antimicrobial and anti-inflammatory properties. Two-dimensional (2D) nanomaterials possess remarkable physical, chemical, optical, and biological characteristics due to their uniform shape, increased surface area, and surface charge. Graphene and its derivatives, transition-metal dichalcogenides (TMDs), black phosphorous (BP), hexagonal boron nitride (h-BN), MXene, and metal-organic frameworks (MOFs) are among the commonly used 2D nanomaterials. Moreover, they exhibit antibacterial and anti-inflammatory properties. This review presents a comprehensive discussion of the clinical approaches employed for wound healing treatment and explores the applications of commonly used 2D nanomaterials to enhance wound healing outcomes.

Multi-wavelength confocal displacement sensing using a highly dispersive flat-field concave grating.

A multi-wavelength confocal displacement sensor based on a flat-field concave grating (FFCG) was proposed and designed; the large dispersion and small volume of the FFCG make it an ideal candidate for replacing the complex dispersive lens group. The designed displacement sensor was calibrated by displacement meter, and the characteristics were measured. Consequently, for the proposed displacement sensor, the displacement range of 6.8 mm was measured with the R-square linearity evaluation coefficient of 0.998, and the sensitivity preceded 17.1 nm/mm. The resolution of the displacement sensor was characterized by 70 µm, as well as a full width at half maximum (FWHM) fluctuating around 1.63 nm, indicating high precision and accuracy in displacement measurement. Moreover, the stability and reliability of the sensor were verified within 20 min, with no significant wavelength shifts, and gentle power fluctuations of 557.73 counts at 520 nm and 563.67 counts at 545.05 nm, respectively.

Prevalence, incidence density and standardized morbidity rate of melanoma among patients with congenital melanocytic naevi: a systematic review.

BACKGROUND: Congenital melanocytic naevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway. The risk of melanoma is the most important concern among patients with CMN because of its poor prognosis. However, as a result of the great variability between studies, the reported risk of melanoma varies considerably, making it difficult to provide reliable information. OBJECTIVES: To evaluate the prevalence, incidence density and standardized morbidity ratio (SMR) of melanoma among patients with CMN. METHODS: We conducted a systematic literature search of studies providing data on the risk of melanoma in patients with CMN following our registered and published protocol (PROSPERO: CRD42022383009). RESULTS: Overall, 27 studies with a total of 11 480 patients with CMN and 82 patients developing melanoma were included for analysis. The prevalence of melanoma was 1.84% [95% confidence interval (CI) 1.13-2.99] in patients with CMN and 2.73% (95% CI 1.67-4.43) in the subgroup of patients with large CMN (LCMN). The incidence of melanoma was 237.56 (95% CI 97.79-575.96) per 100 000 person-years in patients with CMN and 585.73 (95% CI 315.39-1085.29) per 100 000 person-years in the LCMN subgroup. The SMR of melanoma was 122.27 (95% CI 11.84-1262.88) among all patients with CMN and 285.97 (95% CI 50.65-1614.59) in the subgroup of patients with LCMN. CONCLUSIONS: Our research suggests that the risk of melanoma in the CMN population seems to have been overestimated in previous studies, but it is still significantly higher than that in the general population. In addition to the risk of melanoma, aesthetic improvement and mental health should also be taken into account when making management decisions.

The severity assessment and nucleic acid turning-negative-time prediction in COVID-19 patients with COPD using a fused deep learning model.

BACKGROUND: Previous studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD. PURPOSE: The aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients. METHODS: A total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time. RESULTS: COVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P < 0.05). Importantly, our results demonstrated that model 2 achieved an accuracy of 80.9% in predicting nucleic acid turning-negative time. CONCLUSION: The pre-existing emphysema phenotype of COPD severely aggravated the pulmonary involvement of COVID-19 patients. Deep learning and radiomics features may provide more information to accurately predict the nucleic acid turning-negative time, which is expected to play an important role in clinical practice.

Ferroelectric and Relaxor-Ferroelectric Phases Coexisting Boosts Energy Storage Performance in (Bi0.5Na0.5)TiO3-Based Ceramics.

With the intensification of the energy crisis, it is urgent to vigorously develop new environment-friendly energy storage materials. In this work, coexisting ferroelectric and relaxor-ferroelectric phases at a nanoscale were constructed in Sr(Zn1/3Nb2/3)O3 (SZN)-modified (Bi0.5Na0.5)0.94Ba0.06TiO3 (BNBT) ceramics, simultaneously contributing to large polarization and breakdown electric field and giving rise to a superior energy storage performance. Herein, a high recoverable energy density (Wrec) of 5.0 J/cm3 with a conversion efficiency of 82% at 370 kV/cm, a practical discharged energy density (Wd) of 1.74 J/cm3 at 230 kV/cm, a large power density (PD) of 157.84 MW/cm3, and an ultrafast discharge speed (t0.9) of 40 ns were achieved in the 0.85BNBT-0.15SZN ceramics characterized by the coexistence of a rhombohedral-tetragonal phase (ferroelectric state) and a pseudo-cubic phase (relaxor-ferroelectric state). Furthermore, the 0.85BNBT-0.15SZN ceramics also exhibited excellent temperature stability (25-120 °C) and cycling stability (104 cycles) of their energy storage properties. These results demonstrate the great application potential of 0.85BNBT-0.15SZN ceramics in capacitive pulse energy storage devices.

High Piezoelectric Performance of KNN-Based Ceramics over a Broad Temperature Range through Crystal Orientation and Multilayer Engineering.

Uninterrupted breakthroughs in the room temperature piezoelectric properties of KNN-based piezoceramics have been witnessed over the past two decades; however, poor temperature stability presents a major challenge for KNN-based piezoelectric ceramics in their effort to replace their lead-based counterparts. Herein, to enhance temperature stability in KNN-based ceramics while preserving the high piezoelectric response, multilayer composite ceramics were fabricated using textured thick films with distinct polymorphic phase transition temperatures. The results demonstrated that the composite ceramics exhibited both outstanding piezoelectric performance (d33~467 ± 16 pC/N; S~0.17% at 40 kV/cm) and excellent temperature stability with d33 and strain variations of 9.1% and 2.9%, respectively, over a broad temperature range of 25-180 °C. This superior piezoelectric temperature stability is attributed to the inter-inhibitive piezoelectric fluctuations between the component layers, the diffused phase transition, and the stable phase structure with a rising temperature, as well as the permanent contribution of crystal orientation to piezoelectric performance over the studied temperature range. This novel strategy, which addresses the piezoelectric and strain temperature sensitivity while maintaining high performance, is well-positioned to advance the commercial application of KNN-based lead-free piezoelectric ceramics.

Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism.

Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1ß/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin.

F-Deepwalk: A Community Detection Model for Transport Networks.

The design of transportation networks is generally performed on the basis of the division of a metropolitan region into communities. With the combination of the scale, population density, and travel characteristics of each community, the transportation routes and stations can be more precisely determined to meet the travel demand of residents within each of the communities as well as the transportation links among communities. To accurately divide urban communities, the original word vector sampling method is improved on the classic Deepwalk model, proposing a Random Walk (RW) algorithm in which the sampling is modified with the generalized travel cost and improved logit model. Urban spatial community detection is realized with the K-means algorithm, building the F-Deepwalk model. Using the basic road network as an example, the experimental results show that the Deepwalk model, which considers the generalized travel cost of residents, has a higher profile coefficient, and the performance of the model improves with the reduction of random walk length. At the same time, taking the Shijiazhuang urban rail transit network as an example, the accuracy of the model is further verified.

Dynamic Phosphoproteomics of BRS3 Activation Reveals the Hippo Signaling Pathway for Cell Migration.

Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that is involved in a variety of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. In this study, a quantitative phosphoproteomics approach was employed to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. The lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of BRS3, for different durations. Harvested cellular proteins were digested and phosphopeptides were enriched by immobilized titanium (IV) ion affinity chromatography (Ti4+-IMAC) for label-free quantification (LFQ) analysis. A total of 11,938 phosphopeptides were identified, corresponding to 3,430 phosphoproteins and 10,820 phosphosites. Data analysis revealed that 27 phosphopeptides corresponding to six proteins were involved in the Hippo signaling pathway, which was significantly regulated by BRS3 activation. Verification experiments demonstrated that downregulation of the Hippo signaling pathway caused by BRS3 activation could induce the dephosphorylation and nucleus localization of the Yes-associated protein (YAP), and its association with cell migration was further confirmed by kinase inhibition. Our data collectively demonstrate that BRS3 activation contributes to cell migration through downregulation of the Hippo signaling pathway.

Spermine deficiency shifts the balance between jasmonic acid and salicylic acid-mediated defence responses in Arabidopsis.

Polyamines are small aliphatic polycations present in all living organisms. In plants, the most abundant polyamines are putrescine (Put), spermidine (Spd) and spermine (Spm). Polyamine levels change in response to different pathogens, including Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). However, the regulation of polyamine metabolism and their specific contributions to defence are not fully understood. Here we report that stimulation of Put biosynthesis by Pst DC3000 is dependent on coronatine (COR) perception and jasmonic acid (JA) signalling, independently of salicylic acid (SA). Conversely, lack of Spm in spermine synthase (spms) mutant stimulated galactolipids and JA biosynthesis, and JA signalling under basal conditions and during Pst DC3000 infection, whereas compromised SA-pathway activation and defence outputs through SA-JA antagonism. The dampening of SA responses correlated with COR and Pst DC3000-inducible deregulation of ANAC019 expression and its key SA-metabolism gene targets. Spm deficiency also led to enhanced disease resistance to the necrotrophic fungal pathogen Botrytis cinerea and stimulated endoplasmic reticulum (ER) stress signalling in response to Pst DC3000. Overall, our findings provide evidence for the integration of polyamine metabolism in JA- and SA-mediated defence responses, as well as the participation of Spm in buffering ER stress during defence.

Polarization-multiplexed metasurface enabled tri-functional imaging.

Diffraction-limited focusing imaging, edge-enhanced imaging, and long depth of focus imaging offer crucial technical capabilities for applications such as biological microscopy and surface topography detection. To conveniently and quickly realize the microscopy imaging of different functions, the multifunctional integrated system of microscopy imaging has become an increasingly important research direction. However, conventional microscopes necessitate bulky optical components to switch between these functionalities, suffering from the system's complexity and unstability. Hence, solving the problem of integrating multiple functions within an optical system is a pressing need. In this work, we present an approach using a polarization-multiplexed tri-functional metasurface, capable of realizing the aforementioned imaging functions simply by changing the polarization state of the input and output light, enhancing the system structure's compactness and flexibility. This work offers a new avenue for multifunctional imaging, with potential applications in biomedicine and microscopy imaging.