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Additional file 1: Characteristics of five excluded Ipomoea batatas proteins obtained by BLASTP search using the GRAS sequence information in Arabidopsis and rice.

Additional file 3: Accession numbers of GRAS genes in sweetpotato and Arabidopsis.

Additional file 8: Differentially expressed IbGRAS genes in sweetpotato transcriptome analysis under salt stress. CR, Control roots; SR, Salt-treated roots.

Additional file 2: Schematic representations of the chromosomal distribution of the 72 IbGRAS genes on 15 sweetpotato chromosomes.

Additional file 4: Chromosomal locations and segmental duplications of IbGRAS genes in sweetpotato.

Additional file 9: Cis-elements associated with hormone and abiotic stress within the IbGRAS gene promoters.

Recently, fluorescent dyes with a structure-inherent mitochondria-targeting capability have obtained great attention as single-molecule self-reporting theranostic agents to distinguish cancer cells from normal cells. However, there was little attempt using these dyes as a self-reporting ligand for cancer-targeted delivery of nanomaterials or drugs for personalized therapy. Herein, we developed a mitochondria-localized multifunctional nanodelivery system for cancer-targeted drug delivery and dual-modal imaging. First, a series of cyanine-structural small molecules with different-charged substituent groups have been screened based on their mitochondria targeting capability. Furthermore, the cyanine-structural molecule with the best mitochondria-targeting ability was decorated on iron oxide nanoparticles (IONP) for dual-modal imaging. The nanoprobes entered into the cancer cell via the organic anion transporting polypeptide (OATP) pathway and anchored on mitochondria due to the strong interaction between the negative mitochondria membrane and the lipophilic cationic cyanine dye. This work opened an avenue using small molecules with structure-inherent-targeting and self-reporting characteristics as a chemical ligand to develop cancer-targeting and subcellular-localized delivery system.

The East Asian summer precipitation exhibits significant spatial differences from inter-annual to sub-orbital timescales, which has been associated with El Niño-Southern Oscillation (ENSO). However, studies on spatial patterns of climate and their mechanisms on orbital and tectonic timescales are still scarce, impeding a better understanding of Asian monsoon dynamics on long timescales. Here, we present a loess section spanning the past 430 ka in the Menyuan (MY) basin from the Northeastern Tibetan Plateau (NETP), and compare it with records from other sites in East Asia in order to explore the spatial patterns of climate changes and their mechanisms. Our results reveal a distinct climate transition at ∼260 ka in various records, which is characterized a transition from a “wet–dry–wet” to a “dry–wet–dry” pattern in the north-south direction and a transition from a “dry–wet” to “wet–dry” pattern in the west-east direction. This climate transition coincides with a significant weakening of the equatorial Pacific zonal (east–west) thermal gradient which indicates a shift to a more El Niño-like state, suggesting that the climate transition in East Asia at ∼260 ka could be related to paleo-ENSO variation. A more El Niño-like state could force an intensification and southwestward extension of the Western Pacific Subtropical High (WPSH) which could in turn move the rainfall front westward with the maximum rainfall belt over central China, resulting in the persistence of the observed climate patterns in East Asia. Our model results suggest that the change of the paleo-ENSO condition at ∼260 ka could be related to the eccentricity-modulated insolation and the ice shelve changes in northern high latitudes. Our study highlights the important role of paleo-ENSO in regulating the long-term climate changes in different sub-regions in East Asia.

Hypoxia is a common characteristic of solid tumors. This important feature is associated with resistance to radio-chemotherapy, which results in poor prognosis and probability of tumor recurrence. Taking advantage of background-free NIR II fluorescence imaging and deeper-penetrating photoacoustic (PA) imaging, we developed a hypoxia-triggered and nitroreductase (NTR) enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy (PTT), which will overcome cellular resistance during hypoxia. Methods: The single molecule probe IR1048-MZ was synthesized by conjugating a nitro imidazole group as a specific hypoxia trigger with an IR-1048 dye as a NIR II/PA signal reporter. We investigated the NIR II fluorescence, NIR absorbance and photothermal effect in different hypoxia conditions in vitro, and performed NIR II/PA tumor imaging and hypoxia-activated photothermal therapy in mice. Results: This versatile molecular probe IR1048-MZ not only realized high-contrast tumor visualization with a clear boundary by NIR II fluorescence imaging, but also afforded deep-tissue penetration at the centimeter level by 3D PA imaging. Moreover, after being activated by NTR that is overexpressed in hypoxic tumors, the probe exhibited a significant photothermal effect for curative tumor ablation with no recurrence. Conclusions: We have developed the first hypoxia-triggered and NTR enzyme-responsive single molecule probe for high-contrast NIR II/PA tumor imaging and hypoxia-activated photothermal therapy. By tracing the activity of NTR, IR1048-MZ may be a promising contrast agent and theranostic formulation for other hypoxia-related diseases (such as cancer, inflammation, stroke, and cardiac ischemia).

One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to antitumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(l-lysine)- b-poly(ethylene glycol) polypeptide micelles (ZnPP PM) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to antitumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs. Poly I:C (PIC, a TLR3 agonist)-loaded ZnPP PM (ZnPP PM/PIC) efficiently repolarized TAMs to M1 macrophages, which were reliant on ROS generation. Further, ZnPP PM/PIC substantially elevated the activated NK cells and T lymphocytes in B16-F10 melanoma tumors, which caused vigorous tumor regression. Therefore, the TAM-targeted transport of an immunologic adjuvant with ZnPP-grafted nanovectors may be a potential strategy to repolarize TAMs to M1 macrophages in situ for effective cancer immunotherapy.

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5′-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy.

Near-infrared (NIR) organic dyes have received increasing attention in recent years as diagnostic and therapeutic agents in the field of tumor research. In this study, IR-822, a near-infrared fluorescence (NIRF) heptamethine cyanine dye, was chosen as a fluorophore due to its high extinction coefficients, and native preferential tumor accumulation property. To enhance its specificity in tumor imaging, N1-(pyridin-4-ylmethyl)ethane-1,2-diamine (PY) was conjugated to IR-822 as a pH-sensing receptor, forming a fluorophore–spacer–receptor molecular probe (IR-PY) that can modulate the fluorescence emission intensity through a fast photoinduced electron-transfer process, which allowed the probe to “switch on” significantly in an acidic tumor microenvironment and which realized enhanced NIRF imaging in vivo. Having a strong NIR absorption at 600–850 nm, this small-molecule IR-PY showed not only high spatial resolution photoacoustic (PA) imaging in mice, but also effective tumor photothermal ablation in vivo. After photothermal therapy (PTT) with IR-PY under NIR 808 nm laser irradiation, the mice exhibited remarkable ablation with no tumor recurrence after treatment. Therefore, a single smart small-molecule probe IR-PY has been designed, synthesized and verified as an “all in one” multifunctional agent, including pH sensitivity, tumor targeting, “switch-on” near-infrared fluorescence imaging, high-spatial-resolution PA imaging and efficient near-infrared photothermal therapy, which is promising for clinical application in NIRF/PA dual-modal imaging-guided cancer diagnosis and treatment.

T cells can kill tumor cells by cell surface immunological recognition, but low affinity for tumor-associated antigens could lead to T cell off-target effects. Herein, a universal T cell targeting strategy based on bio-orthogonal chemistry and glycol-metabolic engineering is introduced to enhance recognition and cytotoxicity of T cells in tumor immunotherapy. Three kinds of bicycle [6.1.0] nonyne (BCN)-modified sugars are designed and synthesized, in which Ac4 ManN-BCN shows efficient incorporation into wide tumor cells with a BCN motif on surface glycans. Meanwhile, activated T cells are treated with Ac4 GalNAz to introduce azide (N3 ) on the cell surface, initiating specific tumor targeting through a bio-orthogonal click reaction between N3 and BCN. This artificial targeting strategy remarkably enhances recognition and migration of T cells to tumor cells, and increases the cytotoxicity 2 to 4 times for T cells against different kinds of tumor cells. Surprisingly, based on this strategy, the T cells even exhibit similar cytotoxicity with the chimeric antigen receptor T-cell against Raji cells in vitro at the effector: target cell ratios (E:T) of 1:1. Such a universal bio-orthogonal T cell-targeting strategy might further broaden applications of T cell therapy against tumors and provide a new strategy for T cell modification.

Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye-anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O2 ) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H2 O2 ) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H2 O2 and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen (1 O2 ) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer.

Targeted phototherapy and multi-modal imaging can effectively improve the therapeutic efficacy and reduce the side effects of theranostics. Herein, we constructed novel biocompatible cyanine dye IR808-conjugated hyaluronic acid nanoparticles (HAIR NPs) for photothermal therapy (PTT) with near-infrared fluorescence (FL) and photoacoustic (PA) dual-modal imaging. The nanoparticles formed stable nanostructures under aqueous conditions with uniform size distribution. The HAIR NPs were rapidly taken up by the human lung cancer cells A549 via CD44 (the hyaluronic acid receptor on the surface of tumor cells) receptor-mediated endocytosis. Upon laser irradiation, the HAIR NPs enabled good near-infrared fluorescence imaging and photoacoustic imaging in tumor-bearing mice. In addition, the tight nanostructure arising from the covalent link between HA and IR808 could significantly improve the light-thermal conversion efficiency of IR808. Under a low dose of laser power, the HAIR NPs presented more effective photothermal therapy for the suppression of tumor growth than free IR808 in vitro and in vivo. Overall, these results indicate that the HAIR NPs may be an extremely promising nanoplatform in cancer theranostics for targeted PTT under FL and PA dual-modal imaging.

The catalytic activity of palladium (Pd) nanostructures highly relies on their size and morphology, especially enclosed with high-index facets, which provide more active sites so as to enhance their catalytic performance comparing with their low-index facet counterparts. Herein, Pd concave nanocubes enclosed with {730} facets by a one-pot scalable liquid method, with various high-index facets are synthesized via tuning reduction kinetics. Due to their high-index facets, the Pd concave nanocubes exhibit much higher electrocatalytic activity and stability for methanol oxidation than the Pd nanocubes enclosed by {100} facets and commercial Pd/C. Furthermore, we scale up synthesis of Pd concave nanocubes by expanding the volume of all species to fifty times with high-yield production.

Intracellular or extracellular pH is influenced by diverse physiological and pathological processes, so quantitativelymeasuring pHis useful for cellular analysis or diagnosis. In this work, a new near-infrared (NIR) fluorescence turn-on probe CP utilizing a fluorophorespacer- receptor molecular framework that can modulate the fluorescence emission intensity through a fast photoinduced electron-transfer process was developed. Our strategy was to choose tricarbocyanine (Cy), an NIR fluorescent dye with high extinction coefficients, as a fluorophore, and N-(4-pyridylmethyl)ethylenediamine (Py) as a receptor. The pH titration indicated that CP can monitor the minor physiological pH fluctuations with a pKa of ∼6.40, which is valuable for intracellular pH researches and tumor diagnosis. The probe responds linearly and rapidly to minor pH fluctuations within the range of 5.00-7.50 and exhibits strong dependence on pH changes. As expected, the realtime imaging of cellular pH and the detection of pH in situ was achieved successfully in living A549 and HeLa cells by this probe. It is shown that the probe effectively avoids the influence of autofluorescence and native cellular species in biological systems and meanwhile exhibits high sensitivity, good photostability, low cytotoxicity and excellent cell membrane permeability. This fluorescence probe is further examined as tumor microenvironment-activatable probes for intravenous in vivo tumor imaging, which is expected to be of crucial importance for clinical tumor diagnostics.