Spatio-temporal dynamics of phytohormones in the tomato graft healing process

Graft healing involves a series of cytological and molecular events including wound responses, callus formation and vascular bundle remodelling. Hormones are important signalling molecules regulating plant development and responses to environmental stimuli. However,the detailed dynamics of phytohormones in graft healing remain elusive. In this research, internodes above and below the graft site were harvested from 0 to 168 h after grafting(HAG), and liquid chromatography tandem mass spectrometry(LC-MS/MS) was used to determinate jasmonic acid, auxin, cytokinin, ethylene, salicylic acid, abscisic acid and gibberellin levels during the graft healing process. Uniform manifold approximation and projection(UMAP) and k-means analyses were performed to explore hormone spatio-temporal dynamics. We found the stage-specific and asymmetric accumulation of phytohormones in the tomato graft healing process. At the early healing stage(before vascular bundle reconnection), IAA, cZ, ABA, JA and SA mainly accumulated above the graft site, while tZ and ACC mainly accumulated below the graft site. MEIAA, ICAld and IP mainly accumulated at the later stage. Comminated with the healing process, we suggested that JA is mainly involved in wound responses, IAA is beneficial to the formation of callus and vascular cell development, tZ promotes cell division, and IP is linked to vascular bundle remodelling. In addition, expression of JA-related genes SlMYC2 and SlJAZ2, IAA-related gene SlIAA1, tZ-related genes SlHP2 and SlRR8, and IP-related gene SlRR9 correlated with hormone accumulation. The findings provide important information about the hormones and genes involved in the tomato graft healing process.

Transgelin as a potential target in the reversibility of pulmonary arterial hypertension second to congenital heart disease

Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.

Sodium dichloroacetate could inhibit the endothelial-to-mesenchymal transition:a novel treatment target for pulmonary arterial hypertension

Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.

Blockade of neutrophil recruitment to tumor sites based on sialic acid-modified nanoplatforms enhances the efficacy of checkpoint blockade immunotherapy

Checkpoint inhibitors are designed to rejuvenate depleted or suppressed T cells in the tumor microenvironment,relying on the immune system to control and kill tumors.However,accumulating evidence indicates that tumor-infiltrating neutrophils impede the proliferation and activation of T cells and determine the resistance to checkpoint blockade and chemotherapy.In this study,sialic acid ligand-modified colchicine derivative phospholipid complexes specifically targeted tumor-associated neutrophils in the peripheral blood,blocked neutrophil accumulation in tumors,and attenuated the inhibitory effect of infiltrating neutrophils on T cells.Neutrophil blocking therapy enhanced the immunotherapy effect of the PD-L1 antibody in S180 advanced tumors and 4T1 breast cancer.Our study found that PD-L1 antibody monotherapy increased the tumor infiltration of immunosuppressive neutrophils.Combination therapy with neutrophil blocking can greatly reduce tumor-infiltrating neutrophils and increase the proliferation of cytotoxic CD8^(+) T lymphocytes in the tumor.The combination therapy significantly improved the survival rate of mice with advanced S180 tumors and increased the sensitivity of immune checkpoint inhibitors to 4T1 cold tumors.

Forecasting supernova observations with the CSST:I.Photometric samples

The China Space Station Telescope(CSST,also known as Xuntian)is a serviceable two-meter-aperture wide-field telescope operating in the same orbit as the China Space Station.The CSST plans to survey a sky area of 17,500 deg^(2)of the medium-to-high Galactic latitude to a depth of 25-26 AB mag in at least 6 photometric bands over 255-1,000 nm.Within such a large sky area,slitless spectra will also be taken over the same wavelength range as the imaging survey.Even though the CSST survey is not dedicated to time-domain studies,it would still detect a large number of transients,such as supernovae(SNe).In this paper,we simulate photometric SN observations based on a strawman survey plan using the Sncosmo package.During its 10-year survey,the CSST is expected to observe about 5 million SNe of various types.With quality cuts,we obtain a“gold”sample that comprises roughly 7,400 SNe Ia,2,200 SNe Ibc,and 6,500 SNeⅡcandidates with correctly classified percentages reaching 91%,63%,and 93%(formally defined as classification precision),respectively.The same survey can also trigger alerts for the detection of about 15,500 SNe Ia(precision 61%)and 2,100 SNeⅡ(precision 49%)candidates at least two days before the light maxima.Moreover,the near-ultraviolet observations of the CSST will be able to catch hundreds of shock-cooling events serendipitously every year.These results demonstrate that the CSST can make a potentially significant contribution to SN studies.

Biomarkers for predicting efficacy of chimeric antigen receptor T cell therapy and their detection methods

Cancer immunotherapy has emerged as the fourth most prevalent approach to tumor treatment,alongside surgery,radiotherapy,and chemotherapy.After several decades of development,chimeric antigen receptor T(CAR-T)cell therapy,a promising branch of adoptive T-cell therapy,has demonstrated superior efficacy and safety in comparison to other cell therapies in the treatment of cancer.At present,CAR-T cells are predominantly used to treat hematological malignancies,although their application in solid tumors is being readily investigated.Although numerous studies have examined the biomarkers associated with the safety of CAR-T cell therapy,few have evaluated predictors of CAR-T cell therapeutic efficacy.Thus,the primary objective of this review article was to provide a comprehensive overview of the factors predicting the efficacy of CAR-T cell therapy,with a particular focus on biomarkers and their detection methods.

Sialic acid-mediated photochemotherapy enhances infiltration of CD8^(+)T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

Immunoscenescence plays a key role in the initiation and development of tumors.Furthermore,immunoscenescence also impacts drug delivery and cancer therapeutic efficacy.To reduce the impact of immunosenescence on anti-tumor therapy,this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid(SA)-modified liposomes into the tumor,kill tumor cells via SA-mediated photochemotherapy,enhance infiltration of neutrophils into the tumor,induce immunogenic death of tumor cells with chemotherapy,enhance infiltration of CD8^(+)T cells into the tumordraining lymph nodes and tumors of immunosenescent mice,and achieve SA-mediated photochemotherapy.We found that CD8^(+)T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2-and 8-month-old mice;16-month-old mice exhibited immunosenescence.The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice,and tumors recurred after scabbing.SA-mediated photochemotherapy enhanced tumor infiltration by CD8^(+)T cells and neutrophils,induced crusting and regression of tumors in 8-month-old mice,inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.