Quantitative 3D Temperature Rendering of Deep Tumors by a NIR-II Reversibly Responsive W-VO2@PEG Photoacoustic Nanothermometer to Promote Precise Cancer Photothermal Therapy.

Accurately monitoring the three-dimensional (3D) temperature distribution of the tumor area in situ is a critical task that remains challenging in precision cancer photothermal (PT) therapy. Here, by ingeniously constructing a polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO2@PEG) photoacoustic (PA) nanothermometer (NThem) that linearly and reversibly responds to the thermal field near the human-body-temperature range, the authors propose a method to realize quantitative 3D temperature rendering of deep tumors to promote precise cancer PT therapy. The prepared NThems exhibit a mild phase transition from the monoclinic phase to the rutile phase when their temperature grows from 35 to 45 °C, with the optical absorption sharply increased ∼2-fold at 1064 nm in an approximately linear manner in the near-infrared-II (NIR-II) region, enabling W-VO2@PEG to be used as NThems for quantitative temperature monitoring of deep tumors with basepoint calibration, as well as diagnostic agents for PT therapy. Experimental results showed that the temperature measurement accuracy of the proposed method can reach 0.3 °C, with imaging depths up to 2 and 0.65 cm in tissue-mimicking phantoms and mouse tumor tissue, respectively. In addition, it was verified through PT therapy experiments in mice that the proposed method can achieve extremely high PT therapy efficiency by monitoring the temperature of the target area during PT therapy. This work provides a potential demonstration promoting precise cancer PT therapy through quantitative 3D temperature rendering of deep tumors by PA NThems with higher security and higher efficacy.

Ling-Gui-Qi-Hua formula alleviates left ventricular myocardial fibrosis in rats with heart failure with preserved ejection fraction by blocking the transforming growth factor-ß1 /Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown. AIM OF THE STUDY: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway from the perspective of animal experiments. MATERIALS AND METHODS: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-ß1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-ß1/Smads pathways. RESULTS: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-ß1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-ß1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-ß1/Smads pathway. CONCLUSION: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-ß1/Smads pathways in HFpEF rats.

Linggui Qihua Decoction Inhibits Atrial Fibrosis by Regulating TGF-ß1/Smad2/3 Signal Pathway.

Myocardial fibrosis is a critical factor in the development of heart failure with preserved ejection fraction (HFpEF). Linggui Qihua decoction (LGQHD) is an experienced formula, which has been proven to be effective on HFpEF in clinical and in experiments. Objective. This study aimed to observe the effect of LGQHD on HFpEF and its underlying mechanism. Methods. Spontaneously hypertensive rats (SHR) were induced with high-glucose and high-fat to establish HFpEF models and were treated with LGQHD for 8 weeks. The heart structure was detected by echocardiography, and the histopathological changes of the myocardium were observed by hematoxylin-eosin (HE) and Masson staining. Reverse transcription PCR (RT-PCR) and western blot were used to detect mRNA and protein expression of the target gene in rat myocardium. Results. In this study, LGQHD improved cardiac morphology and atrial fibrosis in HfpEF rats, decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression, up-regulated matrix metalloproteinase-9 (MMP-9) mRNA expression, and inhibited the expression of angiotensin II (Ang II), angiotensin II type 1 receptor (AT1), transforming growth factor ß1 (TGF-ß1), Smad2/3 mRNA, and protein in myocardial tissue of HFpEF rats. Conclusion. LGQHD can suppress atrial fibrosis in HFpEF by modulating the TGF-ß1/Smad2/3 pathway.

Geometry-Guided Street-View Panorama Synthesis From Satellite Imagery.

This paper presents a new approach for synthesizing a novel street-view panorama given a satellite image, as if captured from the geographical location at the center of the satellite image. Existing works approach this as an image generation problem, adopting generative adversarial networks to implicitly learn the cross-view transformations, but ignore the geometric constraints. In this paper, we make the geometric correspondences between the satellite and street-view images explicit so as to facilitate the transfer of information between domains. Specifically, we observe that when a 3D point is visible in both views, and the height of the point relative to the camera is known, there is a deterministic mapping between the projected points in the images. Motivated by this, we develop a novel satellite to street-view projection (S2SP) module which learns the height map and projects the satellite image to the ground-level viewpoint, explicitly connecting corresponding pixels. With these projected satellite images as input, we next employ a generator to synthesize realistic street-view panoramas that are geometrically consistent with the satellite images. Our S2SP module is differentiable and the whole framework is trained in an end-to-end manner. Extensive experimental results on two cross-view benchmark datasets demonstrate that our method generates more accurate and consistent images than existing approaches.

Subdiffraction-limited second harmonic photoacoustic microscopy based on nonlinear thermal diffusion.

We have developed a second harmonic photoacoustic microscopy (SH-PAM) for subdiffraction-limited imaging based on nonlinear thermal diffusion. When a sine-modulated Gaussian temperature field is introduced by a laser beam, the temperature dependence of the thermal diffusivity induces a nonlinear photoacoustic (PA) effect and thus results in the production of second harmonic PA signals. We demonstrate through both simulation and experiment that the second harmonic PA images can be reconstructed with a lateral resolution exceeding that of conventional optical resolution PA microscopy. The feasibility of SH-PAM was verified on phantom samples. Amphioxus zygotes and germinated pollens have been studied by SH-PAM to demonstrate its biomedical imaging capability. This method expands the scope of conventional PA imaging and opens up new possibilities for super-resolution imaging, prefiguring great potential for biological imaging and material inspection.

Chemo/Photoacoustic Dual Therapy with mRNA-Triggered DOX Release and Photoinduced Shockwave Based on a DNA-Gold Nanoplatform.

A multifunctional nanoparticle based on gold nanorod (GNR), utilizing mRNA triggered chemo-drug release and near-infrared photoacoustic effect, is developed for a combined chemo-photoacoustic therapy. The constructed nanoparticle (GNR-DNA/FA:DOX) comprises three functional components: (i) GNR as the drug delivery platform and photoacoustic effect enhancer; (ii) toehold-possessed DNA dressed on the GNR to load doxorubicin (DOX) to implement a tumor cell specific chemotherapy; and (iii) folate acid (FA) modified on GNR to guide the nanoparticle to target tumor cells. The results show that, upon an effective and specific delivery of the nanoparticles to the tumor cells with overexpressed folate receptors, the cytotoxic DOX loaded on the GNR-DNA nanoplatform can be released through DNA displacement reaction in melanoma-associated antigen gene mRNA expressed cells. With 808 nm pulse laser irradiation, the photoacoustic effect of the GNR leads to a direct physical damage to the cells. The combined treatment of the two modalities can effectively destroy tumor cells and eradicate the tumors with two distinctively different and supplementing mechanisms. With the nanoparticle, photoacoustic imaging is successfully performed in situ to monitor the drug distribution and tumor morphology for therapeutical guidance. With further in-depth investigation, the proposed nanoparticle may provide an effective and safe alternative cancer treatment modality.