Rate-Distortion Optimized Post-Training Quantization for Learned Image Compression

Quantizing floating-point neural network to its fixed-point representation is crucial for Learned Image Compression (LIC) because it ensures the decoding consistency for interoperability and reduces space-time complexity for implementation. Existing solutions often have to retrain the network for model quantization which is time consuming and impractical. This work suggests the use of Post-Training Quantization (PTQ) to directly process pretrained, off-the-shelf LIC models. We theoretically prove that minimizing the mean squared error (MSE) in PTQ is sub-optimal for compression task and thus develop a novel Rate-Distortion (R-D) Optimized PTQ (RDO-PTQ) to best retain the compression performance. Such RDO-PTQ just needs to compress few images (e.g., 10) to optimize the transformation of weight, bias, and activation of underlying LIC model from its native 32-bit floating-point (FP32) format to 8-bit fixed-point (INT8) precision for fixed-point inference onwards. Experiments reveal outstanding efficiency of the proposed method on different LICs, showing the closest coding performance to their floating-point counterparts. And, our method is a lightweight and plug-and-play approach without any need of model retraining which is attractive to practitioners

Blocking interaction between SHP2 and PD‐1 denotes a novel opportunity for developing PD‐1 inhibitors

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis

Life cycle assessment of bio-based levoglucosan production from cotton straw through fast pyrolysis

This study aimed to evaluate the environmental impacts (i.e. global warming potential (GWP) and resource depletion (RD)) of the bio-based levoglucosan production process through fast pyrolysis of cotton straw via life cycle assessment (LCA). An LCA model consisting of feedstock transportation, biomass pretreatment, fast pyrolysis, bio-oil transportation, bio-oil recovery and levoglucosan extraction was developed. Results indicated that GWP and RD of bio-based levoglucosan production were approximately 2 and 32.5 times less than that of the petroleum-based counterpart. Sensitivity analysis showed that the GWP and RD of levoglucosan production were highly sensitive to plant size, hydrochloric acid usage, cooling energy, levoglucosan yield and bio-oil yield. The results of this research could provide a framework for robust decision making at an industrial level, which is useful for the commercial-scale production of levoglucosan

A Leucine Aminopeptidase-Activated Theranostic Prodrug for Cancer Diagnosis and Chemotherapy

Currently, chemotherapy is a widely used and important treatment for cancer. However, almost all of the treatments have shortcomings associated with poor specificity and high toxicity, which results in severe side effects to normal cells and tissue. This is a very important problem, and yet, it currently remains unanswered. Therefore, the development of the method for the more effective delivery of anticancer drugs to their targets and real-time monitoring of the localization of the drugs are very important. Herein, we designed a theranostic prodrug: CPT-p-Leu, which was constructed using fluorescent camptothecin (CPT), a self-immolative linker and leucine (Leu) residue. Upon exposure to LAP (leucine aminopeptidase: LAP), the amide bond in CPT-p-Leu will be cleaved, followed by an intramolecular 1,6-elimination, which triggers the active anticancer drug (CPT) release and recovers the fluorescence of CPT. With our design, the anticancer drug, CPT, can be used as both a drug and a fluorescence reporter, making our system suitable to accurately and effectively track the released CPT distribution. Based on this strategy, CPT-p-Leu could achieve the chemoselective detection of LAP and monitoring of the anticancer drug release. Furthermore, it also provides a very convenient way to accurately determine the location of the released drug in living samples. In addition, CPT-p-Leu shows a good cell membrane permeability and enhanced cytotoxicity toward LAP overexpressing cancer cells. We anticipate that our research will facilitate the development of improved theranostic systems for cancer therapy.</p

A Leucine Aminopeptidase-Activated Theranostic Prodrug for Cancer Diagnosis and Chemotherapy

Currently, chemotherapy is a widely used and important treatment for cancer. However, almost all of the treatments have shortcomings associated with poor specificity and high toxicity, which results in severe side effects to normal cells and tissue. This is a very important problem, and yet, it currently remains unanswered. Therefore, the development of the method for the more effective delivery of anticancer drugs to their targets and real-time monitoring of the localization of the drugs are very important. Herein, we designed a theranostic prodrug: CPT-p-Leu, which was constructed using fluorescent camptothecin (CPT), a self-immolative linker and leucine (Leu) residue. Upon exposure to LAP (leucine aminopeptidase: LAP), the amide bond in CPT-p-Leu will be cleaved, followed by an intramolecular 1,6-elimination, which triggers the active anticancer drug (CPT) release and recovers the fluorescence of CPT. With our design, the anticancer drug, CPT, can be used as both a drug and a fluorescence reporter, making our system suitable to accurately and effectively track the released CPT distribution. Based on this strategy, CPT-p-Leu could achieve the chemoselective detection of LAP and monitoring of the anticancer drug release. Furthermore, it also provides a very convenient way to accurately determine the location of the released drug in living samples. In addition, CPT-p-Leu shows a good cell membrane permeability and enhanced cytotoxicity toward LAP overexpressing cancer cells. We anticipate that our research will facilitate the development of improved theranostic systems for cancer therapy.</p

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions: These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC

Roadmap on data-centric materials science

Science is and always has been based on data, but the terms ‘data-centric’ and the ‘4th paradigm’ of materials research indicate a radical change in how information is retrieved, handled and research is performed. It signifies a transformative shift towards managing vast data collections, digital repositories, and innovative data analytics methods. The integration of artificial intelligence and its subset machine learning, has become pivotal in addressing all these challenges. This Roadmap on Data-Centric Materials Science explores fundamental concepts and methodologies, illustrating diverse applications in electronic-structure theory, soft matter theory, microstructure research, and experimental techniques like photoemission, atom probe tomography, and electron microscopy. While the roadmap delves into specific areas within the broad interdisciplinary field of materials science, the provided examples elucidate key concepts applicable to a wider range of topics. The discussed instances offer insights into addressing the multifaceted challenges encountered in contemporary materials research