Benchmarking PathCLIP for Pathology Image Analysis.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pre-training (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, pathology-dedicated CLIP (PathCLIP) has been developed, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of osteosarcoma and WSSS4LUAD. In our experiments, we introduce eleven corruption types including brightness, contrast, defocus, resolution, saturation, hue, markup, deformation, incompleteness, rotation, and flipping at various settings. Through experiments, we find that PathCLIP surpasses OpenAI-CLIP and the pathology language-image pre-training (PLIP) model in zero-shot classification. It is relatively robust to image corruptions including contrast, saturation, incompleteness, and orientation factors. Among the eleven corruptions, hue, markup, deformation, defocus, and resolution can cause relatively severe performance fluctuation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-to-image retrieval, revealing that PathCLIP performs less effectively than PLIP on osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it.

Newcastle Disease Virus Manipulates Mitochondrial MTHFD2-Mediated Nucleotide Metabolism for Virus Replication.

Viruses require host cell metabolic reprogramming to satisfy their replication demands; however, the mechanism by which the Newcastle disease virus (NDV) remodels nucleotide metabolism to support self-replication remains unknown. In this study, we demonstrate that NDV relies on the oxidative pentose phosphate pathway (oxPPP) and the folate-mediated one-carbon metabolic pathway to support replication. In concert with [1,2-13C2] glucose metabolic flow, NDV used oxPPP to promote pentose phosphate synthesis and to increase antioxidant NADPH production. Metabolic flux experiments using [2,3,3-2H] serine revealed that NDV increased one-carbon (1C) unit synthesis flux through the mitochondrial 1C pathway. Interestingly, methylenetetrahydrofolate dehydrogenase (MTHFD2) was upregulated as a compensatory mechanism for insufficient serine availability. Unexpectedly, direct knockdown of enzymes in the one-carbon metabolic pathway, except for cytosolic MTHFD1, significantly inhibited NDV replication. Specific complementation rescue experiments on small interfering RNA (siRNA)-mediated knockdown further revealed that only a knockdown of MTHFD2 strongly restrained NDV replication and was rescued by formate and extracellular nucleotides. These findings indicated that NDV replication relies on MTHFD2 to maintain nucleotide availability. Notably, nuclear MTHFD2 expression was increased during NDV infection and could represent a pathway by which NDV steals nucleotides from the nucleus. Collectively, these data reveal that NDV replication is regulated by the c-Myc-mediated 1C metabolic pathway and that the mechanism of nucleotide synthesis for viral replication is regulated by MTHFD2. IMPORTANCE Newcastle disease virus (NDV) is a dominant vector for vaccine and gene therapy that accommodates foreign genes well but can only infect mammalian cells that have undergone cancerous transformation. Understanding the remodeling of nucleotide metabolic pathways in host cells by NDV proliferation provides a new perspective for the precise use of NDV as a vector or in antiviral research. In this study, we demonstrated that NDV replication is strictly dependent on pathways involved in redox homeostasis in the nucleotide synthesis pathway, including the oxPPP and the mitochondrial one-carbon pathway. Further investigation revealed the potential involvement of NDV replication-dependent nucleotide availability in promoting MTHFD2 nuclear localization. Our findings highlight the differential dependence of NDV on enzymes for one-carbon metabolism, and the unique mechanism of action of MTHFD2 in viral replication, thereby providing a novel target for antiviral or oncolytic virus therapy.

Cost-Effective Design of a Miniaturized Zoom Lens for a Capsule Endoscope.

This paper presents a miniaturized design of a 2× zoom lens for application to a one-megapixel image sensor in a capsule endoscope. The zoom lens is composed of four lenses, including three plastic aspheric lenses and one glass spherical lens, and adopts a three-lens group design. This capsule endoscope is mainly for observation of the small intestine, which has a radius of about 12.5 mm. The height of the object is thus set to 12.5 mm. The object surface is designed to be curved surface with a radius of curvature of 15 mm. The focal length of the zoom lens ranges from 1.064 mm to 2.039 mm, and the full angle of view ranges from 60° to 143°, the f-number is F/2.8-F/3.5, the zoom lens is 11.6 mm in length, and the maximum effective diameter of the zoom lens is 6 mm. The zoom lens design is divided into six segments, corresponding to the different magnifications from Zoom 1 to Zoom 6. The magnification ratios are -0.0845, -0.0984, -0.1150, -0.1317, -0.1482, and -0.1690, respectively. Comparing the positions from Zoom 1 to Zoom 6, the maximum optical distortion is -14.89% for the Zoom 1 and 1.45% for the Zoom 6. The maximum vertical video distortion is 8.19% for Zoom 1 and 1.00% for Zoom 6. At a 1.0 field of view, the minimum relative illuminance is 71.8% at a magnification of M = -0.1317. Finally, we perform the tolerance analysis and lens resolution analysis at different zooming positions. Our design can obtain high-quality images for capsule endoscope.

Artemisinin suppresses hepatocellular carcinoma cell growth, migration and invasion by targeting cellular bioenergetics and Hippo-YAP signaling.

The primary liver cancer (PLC) is one of the leading causes of cancer-related death worldwide. The predominant form of PLC is hepatocellular carcinoma (HCC), which accounts for about 85% of all PLC. Artemisinin (ART) was clinically used as anti-malarial agents. Recently, it was demonstrated to inhibit cell growth and migration in multiple cancer types. However, the molecular mechanism underlying these anti-cancer activity remains largely unknown. Herein, it is discovered that ART dramatically suppresses HCC cell growth in vitro through arresting cell cycle progression, and represses cell migration and invasion via regulating N-cadherin-Snail-E-cadherin axis. In addition, the disruption of cellular bioenergetics contributed to ART-caused cell growth, migration and invasion inhibition. Moreover, ART (100 mg/kg, intraperitoneally) substantially inhibits HCC xenograft growth in vivo. Importantly, Hippo-YAP signal transduction is remarkably inactivated in HCC cells upon ART administration. Collectively, these data reveal a novel mechanism of ART in regulating HCC cell growth, migration, and invasion, which indicates that ART could be considered as a potential drug for the treatment of HCC.

Analysis of the biosynthesis genes and chemical components of the capsule of Avibacterium paragallinarum.

The aim of this study was to investigate biosynthesis genes and chemical components of the capsule of Avibacterium paragallinarum. The sequence of a 10-kb region containing the capsule biosynthetic locus of Av. paragallinarum was determined. Two reference strains, i.e., 221 (serovar A) and H18 (serovar C), together with four Taiwanese field strains (all serovar C) were sequenced. The results showed that there are two genotypes (I and II) of the capsule biosynthetic locus in Av. paragallinarum, and the capsule genotype is independent of the serovar. The capsule biosynthetic loci of genotypes I and II consisted of six and five genes, respectively. The genotype I genes encoded proteins that are most similar to proteins from Pasteurella multocida capsule types A and F while the genotype II genes encoded proteins most similar to proteins from P. multocida capsule type D and Escherichia coli K5. The results suggested that genotype I strains contain hyaluronan or chondroitin in the capsule wall while genotype II contain heparosan. Enzymatic digestion of the capsule materials extracted from Av. paragallinarum showed that genotype I strains contained chondroitin while genotype II strains contained heparosan in the capsule. This is the first report on the existence of different genotypes of capsule biosynthesis genes in Av. paragallinarum and the presence of chondroitin and heparosan as chemical components of the capsule of Av. paragallinarum.