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Tumor angiogenesis is a complex process that is unamenable to intravital whole‐process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging‐optical coherence tomography angiography (OCTA)‐laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo‐chemotherapy of tumor by monitoring blood oxygen saturation (SaO2) and hemoglobin content (HbT), but also capable of long‐term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo‐chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5‐fluorouracil silicon nanosheets (5‐Fu‐Si NSs) therapeutic agent is designed. Furthermore, 2D high‐resolution tumor microvascular images in different stage display that tendency of the thermo‐chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis is a complex process that is unamenable to intravital whole‐process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging‐optical coherence tomography angiography (OCTA)‐laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo‐chemotherapy of tumor by monitoring blood oxygen saturation (SaO2) and hemoglobin content (HbT), but also capable of long‐term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo‐chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5‐fluorouracil silicon nanosheets (5‐Fu‐Si NSs) therapeutic agent is designed. Furthermore, 2D high‐resolution tumor microvascular images in different stage display that tendency of the thermo‐chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale. [ABSTRACT FROM AUTHOR]

B Thermo-Chemotherapy b A promising biocompatible nanotheranostics agent based on chemotherapeutic drug 5-fluorouracil and 2D silicon nanosheets is developed for synergistic thermo-chemotherapy strategy. The tumor tissue functional parameters, including SaO SB 2 sb , HbT, micro microvascular morphology, and hemodynamics, are dynamically monitored by multimodal PA/OCTA/LS imaging strategy to accurately evaluate overall therapeutic effects. Intravital Whole-Process Monitoring Thermo-Chemotherapy Via 2D Silicon Nanoplatform: A Macro Guidance and Long-Term Microscopic Precise Imaging Strategy (Adv. Sci. 16/2021). [Extracted from the article]

Intravital Whole-Process Monitoring Thermo-Chemotherapy Via 2D Silicon Nanoplatform: A Macro Guidance and Long-Term Microscopic Precise Imaging Strategy (Adv. Sci. 16/2021) B Thermo-Chemotherapy b A promising biocompatible nanotheranostics agent based on chemotherapeutic drug 5-fluorouracil and 2D silicon nanosheets is developed for synergistic thermo-chemotherapy strategy. The tumor tissue functional parameters, including SaO SB 2 sb , HbT, micro microvascular morphology, and hemodynamics, are dynamically monitored by multimodal PA/OCTA/LS imaging strategy to accurately evaluate overall therapeutic effects. [Extracted from the article]

Summary: Background: Liver fibrosis is the strongest histological risk factor for liver‐related complications and mortality in metabolic dysfunction‐associated fatty liver disease (MAFLD). Second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) is a powerful tool for label‐free two‐dimensional and three‐dimensional tissue visualisation that shows promise in liver fibrosis assessment. Aim: To investigate combining multi‐photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD. Methods: AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy‐confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre‐processed images and test data sets. Multi‐layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts. Results: AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3‐4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3‐4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts. Conclusion: AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD. [ABSTRACT FROM AUTHOR]

Background: Rowell syndrome (RS) is an uncommon condition characterized by erythema multiforme (EM)‐like lesions and lupus erythematosus. It is more common in females, and EM may be the first manifestation of the disease with positive autoantibodies, such as antinuclear antibody (ANA), SSA, SSB and rheumatoid factor. The pathogenesis of RS is unknown and is likely caused by drug induction, ultraviolet exposure and infection. Method: We describe a case of RS from China which presented as characteristic targetoid‐like lesions and chilblain‐like erythema on hands and feet. This is a case of RS in a female patient from the inpatient department of dermatology. Results: A 41‐year‐old female with systemic lupus erythematosus exhibited chilblain‐like erythema and characteristic EM lesions on her extremities. She tested positive for serum ANA (1:320) and anti‐double‐stranded DNA, as well as other autoantibodies. Systemic glucocorticoids and hydroxychloroquine worked effectively for her. Conclusion: The present case met diagnostic criteria of RS. Notably, there was a co‑occurrence of facial butterfly erythema, chilblain‐like erythema and EM lesions distributed on the limbs in this case. [ABSTRACT FROM AUTHOR]

The meiotic entry of undifferentiated germ cells is sexually specific and strictly regulated by the testicular or ovarian environment. Germline stem cells with a set of abnormal sex chromosomes and associated autosomes undergo defective meiotic processes and are eventually eliminated by yet to be defined post‐transcriptional modifications. Herein, we report the role of gsdf, a member of BMP/TGFβ family uniquely found in teleost, in the regulation of meiotic entry in medaka (Oryzias latipes) via analyses of gametogenesis in gsdf‐deficient XX and XY gonads in comparison with their wild‐type siblings. Several differentially expressed genes, including the FKB506‐binding protein 7 (fkbp7), were significantly upregulated in pubertal gsdf‐deficient gonads. The increase in alternative pre‐mRNA isoforms of meiotic synaptonemal complex gene sycp3 was visualized using Integrative Genomics Viewer and confirmed by real‐time qPCR. Nevertheless, immunofluorescence analysis showed that Sycp3 protein products reduced significantly in gsdf‐deficient XY oocytes. Transmission electron microscope observations showed that normal synchronous cysts were replaced by asynchronous cysts in gsdf‐deficient testis. Breeding experiments showed that the sex ratio deviation of gsdf−/− XY gametes in a non‐Mendelian manner might be due to the non‐segregation of XY chromosomes. Taken together, our results suggest that gsdf plays a role in the proper execution of cytoplasmic and nuclear events through receptor Smad phosphorylation and Sycp3 dephosphorylation to coordinate medaka gametogenesis, including sex‐specific mitotic divisions and meiotic recombination. [ABSTRACT FROM AUTHOR]

Background: Delta‐like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1‐directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1‐positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. Methods: We first characterized a homemade anti‐human DLK1 monoclonal antibody, sequenced the single‐chain Fragment variable (scFv) and integrated it into the second‐generation CAR lentiviral vector, and then developed the DLK1‐directed CAR‐T cells. The cytotoxic activities of DLK1‐directed CAR‐T cells against different HCC cells were evaluated in vitro and in vivo. Results: The genetically modified human T cells with the DLK1‐directed CARs produced cytotoxic activity against DLK1‐positive HCC cells. Additionally, the DLK1‐directed CARs enhanced T cell proliferation and activation in a DLK1‐dependent manner. Interestingly, the DLK1‐targeted CAR‐T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh‐7. Conclusion: DLK1‐directed CAR‐T cells specifically suppresses DLK1‐positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR‐T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Delineating accurate flowlines using digital elevation models is a critical step for overland flow modeling. However, extracting surface flowlines from high‐resolution digital elevation models (HRDEMs) can be biased, partly due to the absence of information on the locations of anthropogenic drainage structures (ADS) such as bridges and culverts. Without the ADS, the roads may act as "digital dams" that prevent accurate delineation of flowlines. However, it is unclear what variables for terrain‐based hydrologic modeling can be used to mitigate the effect of "digital dams." This study assessed the impacts of ADS locations, spatial resolution, depression processing methods, and flow direction algorithms on hydrologic connectivity in an agrarian landscape of Nebraska. The assessment was conducted based on the offset distances between modeled drainage crossings and actual ADS on the road. Results suggested that: (a) stream burning in combination with the D8 or D‐Infinity flow direction algorithm is the best option for modeling surface flowlines from HRDEMs in an agrarian landscape; (b) increasing the HRDEM resolution was found significant for facilitating accurate drainage crossing near ADS locations; and (c) D8 and D‐Infinity flow direction algorithms resulted in similar patterns of drainage crossing at ADS locations. This research is expected to result in improved parameter settings for HRDEMs‐based hydrologic modeling. [ABSTRACT FROM AUTHOR]