The interaction of oxytocin and nicotine addiction on psychosocial stress: an fMRI study.

The anxiolytic effect of oxytocin (OXT) on psychosocial stress has been well documented, but the effectiveness under the interference of other factors still requires in-depth research. Previous studies have shown that nicotine addiction interacts with OXT on psychosocial stress on the behavioral level. However, the underlying neural mechanism of interaction between OXT and nicotine addiction on psychosocial stress has not been examined, and we conducted two experiments to reveal it. Firstly, after intranasal administration of randomized OXT or placebo (saline), a group of healthy participants (n = 27) and a group of smokers (n = 26) completed the Montreal Imaging Stress Task (MIST) in an MRI scanner. Secondly, a group of smokers (n = 22) was recruited to complete a transcranial direct current stimulation (tDCS) experiment, in which anodal tDCS was applied on subjects' anterior right superior temporal gyrus (rSTG). In both experiment, subjective stress ratings, salivary cortisol samples and the amount of daily cigarette consumption were obtained from each participant. Analysis of variance were applied on both behavioral and neural data to examine the effects of OXT and nicotine addiction, and correlation analysis were used to examine relationships between neural and behavioral data. In first fMRI experiment, analysis of variance (ANOVA) revealed an interaction of OXT and nicotine addiction on subjective stress. In smokers, OXT failed to suppress the elevation of subjective stress and craving ratings after psychosocial stress. A voxel-wise ANOVA of fMRI data identified an interaction between OXT and nicotine addiction in anterior rSTG, and its functional connectivity with right middle frontal gyrus. Correlations between this functional connectivity and subjective psychosocial stress were also found abnormal in smokers. In second tDCS experiment, we found that under tDCS, OXT successfully suppressed the elevation of subjective stress and craving ratings after stress. In summary, we found that nicotine addiction blocked OXT's anxiolytic on psychosocial stress, which was related to abnormalities in anterior rSTG. By applying anodal tDCS on anterior rSTG, OXT's anxiolytic effect was restored in smokers. These findings will support further development on oxytocin's intervention of psychosocial stress in nicotine addiction, and provides essential information for indicating OXT's effectiveness.

Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

Live Imaging of 3D Hanging Drop Arrays through Manipulation of Light-Responsive Pyroelectric Slippery Surface and Chip Adhesion.

Three-dimensional (3D) hanging drop cell culture is widely used in organoid culture because of its lack of selection pressure and rapid cell aggregation. However, current hanging drop technology has limitations, such as a dependence on complex microfluidic transport channels or specific capillary force templates for drop formation, which leads to unchangeable drop features. These methods also hinder live imaging because of space and complexity constraints. Here, we have developed a hanging drop construction method and created a flexible 3D hanging drop construction platform composed of a manipulation module and an adhesion module. Their harmonious operation allows for the easy construction of hanging drops of varying sizes, types, and patterns. Our platform produces a cell hanging drop chip with small sizes and clear fields of view, thereby making it compatible with live imaging. This platform has great potential for personalized medicine, cancer and drug discovery, tissue engineering, and stem cell research.

Breast intervention device for low-field MRI with a customized unilateral coil.

With the incidence of breast cancer rising to the top among female malignant tumors, magnetic resonance images guided breast biopsy intervention and minimally invasive treatment have developed as a clinically practical research issue. High field studies have shown the diagnostic value of breast MRI, but the examination costs greatly exceed those of competing conventional mammography. In this case, low-field MRI cannot merely provide typical MRI contrast, but also significantly reduce the cost of diagnosis and treatment for breast cancer patients. This work describes a unilateral breast coil and prototype intervention device, which provides a customized solution for low-field MRI-guided breast intervention. Results demonstrate that the low-field MRI breast intervention device facilitates medical intervention procedures. And the designed positioning device can locate the target lesion within 2-3 mm accuracy. Phantom tests with the customized unilateral coil indicate that the open loops perform as well as the 4-channel commercial closed breast coil, presenting a relatively good SNR (signal-to-noise ratio) and uniformity characteristics. MR scanning images of the volunteer breast using the breast intervention coil also show high SNR, which lays a foundation for further implementation of image-guided breast interventional minimally invasive surgery with the low-field MRI system.

Modeling Colorectal Cancer-Induced Liver Portal Vein Microthrombus on a Hepatic Lobule Chip.

Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.

On-chip modeling of tumor evolution: Advances, challenges and opportunities.

Tumor evolution is the accumulation of various tumor cell behaviors from tumorigenesis to tumor metastasis and is regulated by the tumor microenvironment (TME). However, the mechanism of solid tumor progression has not been completely elucidated, and thus, the development of tumor therapy is still limited. Recently, Tumor chips constructed by culturing tumor cells and stromal cells on microfluidic chips have demonstrated great potential in modeling solid tumors and visualizing tumor cell behaviors to exploit tumor progression. Herein, we review the methods of developing engineered solid tumors on microfluidic chips in terms of tumor types, cell resources and patterns, the extracellular matrix and the components of the TME, and summarize the recent advances of microfluidic chips in demonstrating tumor cell behaviors, including proliferation, epithelial-to-mesenchymal transition, migration, intravasation, extravasation and immune escape of tumor cells. We also outline the combination of tumor organoids and microfluidic chips to elaborate tumor organoid-on-a-chip platforms, as well as the practical limitations that must be overcome.

Parthenolide targets NLRP3 to treat inflammasome-related diseases.

Natural products have attracted extensive attention from researchers in medical fields due to their abundant biological activities. Parthenolide (PTL) is a sesquiterpene lactone originally purified from herb Feverfew (Tanacetum parthenium), recent studies have showed its potential activities of anti-cancer and anti-inflammatory. Acting as the most studied inflammasome, NLRP3 inflammasome played an important role in human diseases including type-2 diabetes (T2D), Alzheimer's disease (AD) and cryopyrin-associated periodic syndromes (CAPS). In this article, we show that PTL specially inhibits the activation of NLRP3 inflammation by block the upstream signal and prevent the assembly of NLRP3 inflammasome complex. Furthermore, we showed the treatment of PTL significantly attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis in mice models. Thus, our results demonstrate that PTL alleviates inflammation by targeting NLRP3 inflammasome, which indicate that PTL acting as a promising natural product for the treatment of NLRP3 inflammasome-related diseases.

White matter BOLD signals at 7 Tesla reveal visual field maps in optic radiation and vertical occipital fasciculus.

There is growing evidence that blood-oxygen-level-dependent (BOLD) activity in the white matter (WM) can be detected by functional magnetic resonance imaging (fMRI). However, the functional relevance and significance of WM BOLD signals remain controversial. Here we investigated whether 7T BOLD fMRI can reveal fine-scale functional organizations of a WM bundle. Population receptive field (pRF) analyses of the 7T retinotopy dataset from the Human Connectome Project revealed clear contralateral retinotopic organizations of two visual WM bundles: the optic radiation (OR) and the vertical occipital fasciculus (VOF). The retinotopic maps of OR are highly consistent with post-mortem dissections and diffusion tractographies, while the VOF maps are compatible with the dorsal and ventral visual areas connected by the WM. Similar to the grey matter (GM) visual areas, both WM bundles show over-representations of the central visual field and increasing pRF size with eccentricity. Hemodynamic response functions of visual WM were slower and wider compared with those of GM areas. These findings clearly demonstrate that WM BOLD at 7 Tesla is closely coupled with neural activity related to axons, encoding highly specific information that can be used to characterize fine-scale functional organizations of a WM bundle.

Abnormal resting-state function within language network and its improvement among post-stroke aphasia.

Several studies with resting-state magnetic resonance imaging (rs-fMRI) have examined functional impairments and plasticity within language network in patients with post-stroke aphasia (PSA). However, there is still ubiquitous inconsistency across these studies, partly due to restricted to very small sample size and the absence of validation with follow-up data. In the current study, we aimed at providing relatively strong evidence to support functional impairments and its reorganization in PSA. Here, the amplitude of low frequency fluctuations (ALFF) and functional connectivity were used to assess functional alterations of PSA with moderate sample size at baseline (thirty-five PSA patients and thirty-five healthy controls). Functional abnormalities at baseline were observed whether improved among sixteen follow-up patients. Compared with controls, PSA at baseline presented decreased ALFF in the left inferior frontal gyrus (IFG) and decreased functional connectivity of the left IFG with the bilateral supplementary motor area (SMA) and right superior temporal gyrus (STG). The decreased ALFF in IFG, decreased IFG-SMA and IFG-STG connectivity were enhanced among follow-up patients and was synchronized with language-performance improvement. Our results revealed reduced intrinsic neural activity and inter-connections within language network in PSA, which would be normalized synchronously as the improvement of language performance.

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study.

INTRODUCTION: Predicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs. MATERIALS AND METHODS: We retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs. RESULTS: The WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80). CONCLUSION: Our study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.

Boosting medical image segmentation via conditional-synergistic convolution and lesion decoupling.

Medical image segmentation is a critical step in pathology assessment and monitoring. Extensive methods tend to utilize a deep convolutional neural network for various medical segmentation tasks, such as polyp segmentation, skin lesion segmentation, etc. However, due to the inherent difficulty of medical images and tremendous data variations, they usually perform poorly in some intractable cases. In this paper, we propose an input-specific network called conditional-synergistic convolution and lesion decoupling network (CCLDNet) to solve these issues. First, in contrast to existing CNN-based methods with stationary convolutions, we propose the conditional synergistic convolution (CSConv) that aims to generate a specialist convolution kernel for each lesion. CSConv has the ability of dynamic modeling and could be leveraged as a basic block to construct other networks in a broad range of vision tasks. Second, we devise a lesion decoupling strategy (LDS) to decouple the original lesion segmentation map into two soft labels, i.e., lesion center label and lesion boundary label, for reducing the segmentation difficulty. Besides, we use a transformer network as the backbone, further erasing the fixed structure of the standard CNN and empowering dynamic modeling capability of the whole framework. Our CCLDNet outperforms state-of-the-art approaches by a large margin on a variety of benchmarks, including polyp segmentation (89.22% dice score on EndoScene) and skin lesion segmentation (91.15% dice score on ISIC2018). Our code is available at https://github.com/QianChen98/CCLD-Net.

LMA-Net: A lesion morphology aware network for medical image segmentation towards breast tumors.

Breast tumor segmentation plays a critical role in the diagnosis and treatment of breast diseases. Current breast tumor segmentation methods are mainly deep learning (DL) based methods, which exacted the contrast information between tumors and backgrounds, and produced tumor candidates. However, all these methods were developed based on traditional standard convolutions, which may not be able to model various tumor shapes and extract pure information of tumors (the extracted information usually contain non-tumor information). Besides, the loss functions used in these methods mainly aimed to minimize the intra-class distances, while ignoring the influence of inter-class distances upon segmentation. In this paper, we propose a novel lesion morphology aware network to segment breast tumors in 2D magnetic resonance images (MRI). The proposed network employs a hierarchical structure that contains two stages: breast segmentation stage and tumor segmentation stage. In the tumor segmentation stage, we devise a tumor morphology aware network to incorporate pure tumor characteristics, which facilitates contrastive information extraction. Further, we propose a hybrid intra- and inter-class distance optimization loss to supervise the network, which can minimize intra-class distances meanwhile maximizing inter-class distances, hence reducing the potential false positive/negative pixels in segmentation results. Verified on a clinical 2D MRI breast tumor dataset, our proposed method achieves eminent segmentation results and outperforms state-of-the-art methods, implying that the proposed method has a good prospect for clinical use.

Development of a novel MR-conditional microwave needle for MR-guided interventional microwave ablation at 1.5T.

PURPOSE: To develop an MR-conditional microwave needle that generates a spherical ablation zone and clear MRI visibility for MR-guided microwave ablation. METHODS: An MR-conditional microwave needle consisting of zirconia tip and TA18 titanium alloy tube was investigated. The numerical model was created to optimize the needle's geometry and analyze its performance. A geometrically optimized needle was produced using non-magnetic materials based on the electromagnetics simulation results. The needle's mechanical properties were tested per the Chinese pharmaceutical industry standard YY0899-2013. The MRI visibility performance and ablation characteristics of the needle was tested both in vitro (phantom) and in vivo (rabbit) at 1.5T. The RF-induced heating was evaluated in ex vivo porcine liver. RESULTS: The needle's mechanical properties met the specified requirements. The needle susceptibility artifact was clearly visible both in vitro and in vivo. The needle artifact diameter (A) was small in in vivo (Ashaft: 4.96 ± 0.18 mm for T1W-FLASH, 3.13 ± 0.05 mm for T2-weighted fast spin-echo (T2W-FSE); Atip: 2.31 ± 0.09 mm for T1W-FLASH, 2.29 ± 0.08 mm for T2W-FSE; tip location error [TLE]: -0.94 ± 0.07 mm for T1W-FLASH, -1.10 ± 0.09 mm for T2W-FSE). Ablation zones generated by the needle were nearly spherical with an elliptical aspect ratio ranging from 0.79 to 0.90 at 30 W, 50 W for 3, 5, 10 min duration ex vivo ablations and 0.86 at 30 W for 10 min duration in vivo ablations. CONCLUSION: The designed MR-conditional microwave needle offers excellent mechanical properties, reliable MRI visibility, insignificant RF-induced heating, and a sufficiently spherical ablation zone. Further clinical development of MR-guided microwave ablation appears warranted.

Microstructural properties of major white matter tracts in constant exotropia before and after strabismus surgery.

AIMS: The purpose of this study was to explore the microstructural properties of the major white matter (WM) tracts in constant exotropia (XT) before and after strabismus surgery, and further investigate the association between microstructural alterations and the ocular dominance (OD). METHODS: We collected diffusion tensor imaging data of patients with XT before (n=19) and after (n=15) strabismus surgery and 20 healthy controls and evaluated OD and stereopsis. The probabilistic streamline tractography of the 24 major WM tracts was reconstructed by using the automated fibre quantification package. Fractional anisotropy and mean diffusivity (MD) along each tract were estimated, and their differences between the groups were examined. Furthermore, we evaluated the relationship between OD and the absolute value of altered microstructural parameters. RESULTS: While all postoperative XT patients restored normal stereopsis, most of their OD remained aberrant (9 out of 11). Compared with that of preoperation, the MD of postoperative patients decreased significantly along left anterior thalamic radiation (ATR), left arcuate fasciculus (AF), left corticospinal tract (CST), left cingulum cingulate (CGC) and left inferior fronto-occipital fasciculus. Moreover, OD was negatively correlated with the absolute value of MD changes in left ATR, left AF, left CST and left CGC. CONCLUSION: Microstructural alterations after surgery in the visuospatial network tracts may contribute to the stereopsis restoration. Additionally, the results of the correlation analysis may signify that the balanced binocular input may be more conducive for the restoration and improvement of binocular visual function, including stereopsis. Thus, restoring normal ocular balance after surgical correction may be necessary to achieve more substantial improvements.

IMIIN: An inter-modality information interaction network for 3D multi-modal breast tumor segmentation.

Breast tumor segmentation is critical to the diagnosis and treatment of breast cancer. In clinical breast cancer analysis, experts often examine multi-modal images since such images provide abundant complementary information on tumor morphology. Known multi-modal breast tumor segmentation methods extracted 2D tumor features and used information from one modal to assist another. However, these methods were not conducive to fusing multi-modal information efficiently, or may even fuse interference information, due to the lack of effective information interaction management between different modalities. Besides, these methods did not consider the effect of small tumor characteristics on the segmentation results. In this paper, We propose a new inter-modality information interaction network to segment breast tumors in 3D multi-modal MRI. Our network employs a hierarchical structure to extract local information of small tumors, which facilitates precise segmentation of tumor boundaries. Under this structure, we present a 3D tiny object segmentation network based on DenseVoxNet to preserve the boundary details of the segmented tumors (especially for small tumors). Further, we introduce a bi-directional request-supply information interaction module between different modalities so that each modal can request helpful auxiliary information according to its own needs. Experiments on a clinical 3D multi-modal MRI breast tumor dataset show that our new 3D IMIIN is superior to state-of-the-art methods and attains better segmentation results, suggesting that our new method has a good clinical application prospect.

The Advance of Magnetic Resonance Elastography in Tumor Diagnosis.

The change in tissue stiffness caused by pathological changes in the tissue's structure could be detected earlier, prior to the manifestation of their clinical features. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that uses low-frequency vibrations to quantitatively measure the elasticity or stiffness of tissues. In tumor tissue, stiffness is directly related to tumor development, invasion, metastasis, and chemoradiotherapy resistance. It also dictates the choice of surgical method. At present, MRE is widely used in assessing different human organs, such as the liver, brain, breast, prostate, uterus, gallbladder, and colon stiffness. In the field of oncology, MRE's value lies in tumor diagnosis (especially early diagnosis), selection of treatment method, and prognosis evaluation. This article summarizes the principle of MRE and its research and application progress in tumor diagnosis and treatment.

On-Chip Construction of Liver Lobules with Self-Assembled Perfusable Hepatic Sinusoid Networks.

Although various liver chips have been developed using emerging organ-on-a-chip techniques, it remains an enormous challenge to replicate the liver lobules with self-assembled perfusable hepatic sinusoid networks. Herein we develop a lifelike bionic liver lobule chip (LLC), on which the perfusable hepatic sinusoid networks are achieved using a microflow-guided angiogenesis methodology; additionally, during and after self-assembly, oxygen concentration is regulated to mimic physiologically dissolved levels supplied by actual hepatic arterioles and venules. This liver lobule design thereby produces more bionic liver microstructures, higher metabolic abilities, and longer lasting hepatocyte function than other liver-on-a-chip techniques that are able to deliver. We found that the flow through the unique micropillar design in the cell coculture zone guides the radiating assembly of the hepatic sinusoid, the oxygen concentration affects the morphology of the sinusoid by proliferation, and the oxygen gradient plays a key role in prolonging hepatocyte function. The expected breadth of applications our LLC is suited to is demonstrated by means of preliminarily testing chronic and acute hepatotoxicity of drugs and replicating growth of tumors in situ. This work provides new insights into designing more extensive bionic vascularized liver chips, while achieving longer lasting ex-vivo hepatocyte function.

An iron oxide nanoparticle-based transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors.

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption. STATEMENT OF SIGNIFICANCE: Transdermal delivery is an attractive strategy for treating superficial tumors. However, a highly efficient transdermal nanoplatform remains to be developed. Herein, we designed a multifunctional transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, comprised of a super-paramagnetic iron oxide (SPIO) nanoparticle, which can act as an MRI contrast agent and photothermal agent; a transdermal enhanced peptide (TD) and cationic lipids, which can accelerate skin penetration; and a NIR dye (DiR) and doxorubicin (DOX), which can achieve a synergistic enhanced chemo-photothermal therapy with NIR imaging ability. The transdermal nanoplatform achieved efficient tumor eradication and low systemic toxicity, thus offering strong potential for clinical adoption.

Enhanced transdermal efficiency of curcumin-loaded peptide-modified liposomes for highly effective antipsoriatic therapy.

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.

On-Chip Replication of Extremely Early-Stage Tumor Behavior.

Cancer is a multistep progressive disease that generally involves tumor growth, invasion, and metastasis. It is crucial to understand tumor progression for tumor diagnosis and therapy. However, tumor progression at an extremely early stage (EES) is barely demonstrated because EES tumors are too small to be detected by imaging. Herein, we, for the first time, replicated tumor progression at the EES on a microfluidic chip and uncovered the tumor behaviors affected by the tumor microenvironment. To mimic the progression of a single solid tumor at the EES, a HeLa cell spheroid was seeded and cultured on the chip, and a microvascular network was developed to integrate the microphysiological contexts around the tumor. We revealed not only the growth patterns and cell behaviors of tumor spheroids of different sizes under angiogenesis and fibroblast conditions but also the effect of tumor progression on peritumoral angiogenesis. We found that smaller tumors were more aggressive and that endotheliocytes and fibroblasts significantly accelerated both the proliferation and migration of tumor cells. In addition, we also first present the dynamic epithelial-mesenchymal transition process of tumor cells and the formation of vasculogenic mimicry at the EES. This work can provide insights for understanding tumor progression at the EES and offer new ideas for tumor therapy.