Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side‐effects. Herein, a tumor microenvironment (TME)‐activated NIR‐II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self‐assembling the peptide Fmoc‐His, mercaptopropionic‐functionalized Ag2S quantum dots (MPA‐Ag2S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR‐II fluorescence “off” state, because of Ag2S QDs‐A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc‐His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag2S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME‐activated theranostic strategy holds great promise for future clinical applications.

Accurate intraoperative tissue identification is critical to tumor surgery. However, conventional methods are labor‐ and time‐intensive, which greatly delay the intraoperative decision‐making. Herein, a matrix metalloproteinase (MMP)14‐activated NIR‐II nanoprobe (A&MMP@Ag2S‐AF7P) is presented for rapid unperturbed‐tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag2S‐AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag2S QDs and A1094 mediated by MMP14 overexpressed in neuroblastoma; meanwhile, the exposure of the membrane penetrating peptide R9 (TAT‐peptide) results in efficient internalization of nanoprobes in the cancer cells, providing superior tumor‐to‐normal (T/N) tissue ratio. Instant illumination of the lesion and well‐defined tumor margins make the nanoprobes a suitable rapid diagnostic reagent for cancer surgical or tissue biopsy procedures.

Fluorescence-guided cytoreductive surgery is one of the most promising approaches for facile elimination of tumors in situ, therebyi mproving prognosis.R eported herein is as imple strategy to construct an ovel chainlike NIR-II nanoprobe (APP-Ag 2 S-RGD) by self-assembly of an amphiphilic peptide (APP) into an anochain with subsequent chemical crosslinking of NIR-II Ag 2 SQ Ds and the tumortargeting RGD peptide.T his probe exhibits higher capability for cancer cell detection compared with that of RGD-functionalizedA g 2 SQ Ds (Ag 2 S-RGD) at the same concentration. Upon intraperitoneal injection, superior tumor-tonormal tissue signal ratio is achieved and non-vascularized tiny tumor metastatic foci as small as about 0.2 mm in diameter could be facilely eliminated under NIR-II fluorescent imaging guidance.T hese results clearly indicate the potential of this probe for fluorescence-guided tumor staging,p reoperative diagnosis,and intraoperative navigation.

Ischemic stroke is a devastating disease resulting in high morbidity and mortality. To date, its early diagnosis still faces challenges. Herein, an efficient detection strategy is proposed, in which a targeted activatable NIR‐IIb nanoprobe (V&C/PbS@Ag2Se) is constructed for in vivo highly sensitive detection of early ischemic stroke in a photothrombotic stroke model. At first, the fluorescence of V&C/PbS@Ag2Se displays an “off” state due to the competitive absorption of excitation irradiation between Cy7.5 fluorophores and PbS@Ag2Se quantum dots (QDs). Upon intravenous injection, the V&C/PbS@Ag2Se quickly accumulates in the lesion regions based on VCAM1 binding peptide target to the inflamed vascular endothelium of ischemic stroke. Later, the nanoprobes can be rapidly activated via Cy7.5 oxidation by peroxynitrite (ONOO−), the prodromal biomarker of ischemic stroke, instantly illuminating the lesion regions. Such a targeted activatable strategy offers a favorable approach for in vivo early real‐time assessment of ischemic stroke, which can be expanded to other diseases as a general mothed for in vivo precise diagnosis.

Fluorescence-guided cytoreductive surgery is one of the most promising approaches for facile elimination of tumors in situ, therebyi mproving prognosis.R eported herein is as imple strategy to construct an ovel chainlike NIR-II nanoprobe (APP-Ag 2 S-RGD) by self-assembly of an amphiphilic peptide (APP) into an anochain with subsequent chemical crosslinking of NIR-II Ag 2 SQ Ds and the tumortargeting RGD peptide.T his probe exhibits higher capability for cancer cell detection compared with that of RGD-functionalizedA g 2 SQ Ds (Ag 2 S-RGD) at the same concentration. Upon intraperitoneal injection, superior tumor-tonormal tissue signal ratio is achieved and non-vascularized tiny tumor metastatic foci as small as about 0.2 mm in diameter could be facilely eliminated under NIR-II fluorescent imaging guidance.T hese results clearly indicate the potential of this probe for fluorescence-guided tumor staging,p reoperative diagnosis,and intraoperative navigation.

The heart regeneration after apical resection and myocardial infarction in neonatal mice has been studied for years. However, the response of neonatal mouse heart under pressure overload is seldom explored. This study aimed to induce pressure overload in neonatal mice through a transverse aortic constriction (TAC) with different-gauge needles so as to investigate the effect of pressure overload on cardiomyocyte proliferation and hypertrophy in these mice. Myocardial hypertrophy was evaluated by echocardiographic, pathological, and molecular analyses. Cardiomyocyte proliferation was detected by immune-staining of phospho-histone H3, Ki67, and 5-bromo-2-deoxyuridine. Mild pressure overload induced with a 30-gauge needle stimulated cardiomyocyte proliferation, adaptive hypertrophy, and angiogenesis. The heart function was not hampered even 21 days after the surgery. Moderate pressure overload induced with a 32-gauge needle led to pathological myocardial hypertrophy, fibrosis, and heart failure 7 days after the surgery. The gene and protein expression levels of markers of hypertrophy and fibrosis increased in 32-gauge TAC group compared with that in sham and 30-gauge TAC groups. The mice barely survived after severe pressure overload induced with a 34-gauge needle. The findings of this study might provide new insights into cardiomyocyte proliferation and hypertrophy in neonatal mice under pressure overload.

No abstract

Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated that saponin exhibited an effect on the TRAF2-mediated ubiquitination degradation, which contributed to the inhibition of the CD40 pathway and its downstream members. The findings determine that A. macrostemon saponin inhibits activation of platelets via activation of downstream proteins of the CD40 pathway. This in turn affected TRAF2-associated ubiquitination degradation and caused an anti-thrombotic effect.