NavGPT: Explicit Reasoning in Vision-and-Language Navigation with Large Language Models

Trained with an unprecedented scale of data, large language models (LLMs) like ChatGPT and GPT-4 exhibit the emergence of significant reasoning abilities from model scaling. Such a trend underscored the potential of training LLMs with unlimited language data, advancing the development of a universal embodied agent. In this work, we introduce the NavGPT, a purely LLM-based instruction-following navigation agent, to reveal the reasoning capability of GPT models in complex embodied scenes by performing zero-shot sequential action prediction for vision-and-language navigation (VLN). At each step, NavGPT takes the textual descriptions of visual observations, navigation history, and future explorable directions as inputs to reason the agent's current status, and makes the decision to approach the target. Through comprehensive experiments, we demonstrate NavGPT can explicitly perform high-level planning for navigation, including decomposing instruction into sub-goal, integrating commonsense knowledge relevant to navigation task resolution, identifying landmarks from observed scenes, tracking navigation progress, and adapting to exceptions with plan adjustment. Furthermore, we show that LLMs is capable of generating high-quality navigational instructions from observations and actions along a path, as well as drawing accurate top-down metric trajectory given the agent's navigation history. Despite the performance of using NavGPT to zero-shot R2R tasks still falling short of trained models, we suggest adapting multi-modality inputs for LLMs to use as visual navigation agents and applying the explicit reasoning of LLMs to benefit learning-based models

Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice.

Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs). The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML), could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD) rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis

Development and Validation of Prediction Models for Hypertensive Nephropathy, the PANDORA Study

Importance: Hypertension is a leading cause of end-stage renal disease (ESRD), but currently, those at risk are poorly identified. Objective: To develop and validate a prediction model for the development of hypertensive nephropathy (HN). Design Setting and Participants: Individual data of cohorts of hypertensive patients from Kailuan, China served to derive and validate a multivariable prediction model of HN from 12, 656 individuals enrolled from January 2006 to August 2007, with a median follow-up of 6.5 years. The developed model was subsequently tested in both derivation and external validation cohorts. Variables: Demographics, physical examination, laboratory, and comorbidity variables. Main Outcomes and Measures: Hypertensive nephropathy was defined as hypertension with an estimated glomerular filtration rate (eGFR) \u3c 60 ml/min/1.73 m and/or proteinuria. Results: About 8.5% of patients in the derivation cohort developed HN after a median follow-up of 6.5 years that was similar in the validation cohort. Eight variables in the derivation cohort were found to contribute to the risk of HN: salt intake, diabetes mellitus, stroke, serum low-density lipoprotein, pulse pressure, age, hypertension duration, and serum uric acid. The discrimination by concordance statistics (C-statistics) was 0.785 (IQR, 0.770-0.800); the calibration slope was 1.129, the intercept was -0.117; and the overall accuracy by adjusted was 0.998 with similar results in the validation cohort. A simple points scale developed from these data (0, low to 40, high) detected a low morbidity of 7% in the low-risk group (0-10 points) compared with \u3e40% in the high-risk group (\u3e20 points). Conclusions and Relevance: A prediction model of HN over 8 years had high discrimination and calibration, but this model requires prospective evaluation in other cohorts, to confirm its potential to improve patient care

Pathophysiological parameters in NOD/SCID mice injected with K562 EVs.

<p>NOD/SCID mice were injected with K562 EVs or K562 cells and/or actinomycin D via tail-vein, every three days for 2 months. Rectal temperature (<b>A</b>), body weight (<b>B</b>), and spleen weight (<b>C-a</b>) were measured and histologies (<b>C-b</b>) were examined (* <i>P</i><0.05 vs. control, n = 3). In <b>Figure C-b</b>, sections of spleen of NOD/SCID mouse stained with hematoxylin-eosin (HE) were examined under a microscope using 10×40 lens. Spleens of NOD/SCID mice treated with vehicle (PBS) (<b>1</b>), actinomycin D (7 µg/kg) (<b>2</b>), K562 EVs (2×10⁶) and actinomycin D (7 µg/kg) (<b>3</b>), K562 EVs (2×10⁶) (<b>4</b>), and K562 cells (2×10⁶) (<b>5</b>).</p

BCR/ABL expression in neutrophils from NOD/SCID mice.

<p>(<b>A</b>): BCR/ABL DNA expression in neutrophils from NOD/SCID mice. NOD/SCID mice were injected with K562 EVs or K562 cells and/or actinomycin D, via tail-vein every three days for 2 months. (<b>a</b>) The upper figure shows the BCR/ABL DNA detected by PCR that was resolved on precasted 2% agarose gel with ethidium bromide. (<b>b</b>): The lower figure shows the sequence of the PCR product of BCR/ABL DNA in the neutrophils from the NOD/SCID mice; the percentage sequence identity was more than 99.5%. The black arrow indicates the merge point of the BCR DNA and ABL DNA. (<b>B</b>): BCR/ABL mRNA expression in neutrophils from NOD/SCID mice. NOD/SCID mice were injected with K562 EVs or K562 cells and/or actinomycin D, via tail-vein every three days for 2 months. (<b>a</b>): The upper figures show the expression of BCR/ABL mRNA in neutrophils detected by RT-PCR on precasted 2% agarose gel with ethidium bromide. (<b>b</b>): The lower figures show the sequence of the RT-PCR product of BCR/ABL mRNA and β-actin mRNA in the neutrophils from the NOD/SCID mice; the percentage sequence identity is more than 99.5%. The black arrow indicates the merge point of the BCR mRNA and ABL mRNA. (<b>C</b>): BCR/ABL protein expression in neutrophils from NOD/SCID mice. NOD/SCID mice were injected with K562 EVs or K562 cells and/or actinomycin D, via tail-vein every three days for 2 months. The neutrophils were collected and the expression of BCR/ABL protein was detected by immunoblotting. <b>Lane M</b>, DNA marker; neutrophils from NOD/SCID mice treated with vehicle (PBS) (<b>lane 1</b>), actinomycin D (7 µg/kg) (<b>lane 2</b>), K562 EVs (2×10⁶) and actinomycin D (7 µg/kg) (<b>lane 3</b>), K562 EVs (2×10⁶) (<b>lane 4</b>), and K562 cells (2×10⁶) (<b>lane 5</b>); K562 cells and ddH₂O were taken as positive and negative controls, respectively (<b>lane 6 and 7</b>).</p

Inhibition of imatinib on the <i>de novo</i> BCR/ABL protein.

<p>(<b>A</b>): The activity of tyrosine kinases in the neutrophils. Neutrophils were incubated with K562 EVs (10⁵/mL) and/or imatinib (0.5 µmol/L) for 24 h. The activity of tyrosine kinases in neutrophils were determined by ELISA (* <i>P</i><0.01 vs. control, n = 6). (<b>B</b>): Phospho-Crkl protein expression in the neutrophils. Neutrophils were incubated with K562 EVs (10⁵/mL) and/or imatinib (0.5 µmol/L) for 24 h. The representive images (a) and protein expression (b) of phospho-Crkl in the neutrophils were detected by immunofluorescence (* <i>P</i><0.01 vs. other group, n = 4). Green and blue fluorescences indicate phospho-Crkl protein and Nuclei, respectively. Normal neutrophils (<b>1</b>), K562 EVs (2×10⁶) (<b>2</b>), imatinib (0.5 µmol/L) (<b>3</b>), K562 EVs (2×10⁶) and imatinib (0.5 µmol/L) (<b>4</b>).</p