The clinicopathological significance of angiogenesis in hindgut neuroendocrine tumors obtained via an endoscopic procedure

Background

As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors.

Methods

We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses.

Results

A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm² to 73.9/mm² and LMVD values from 0/mm² to 22.9/mm². MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor.

Conclusions

Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.

     

Cell wall structure and biogenesis in Aspergillus species

Aspergillus species are among the most important filamentous fungi from the viewpoints of industry, pathogenesis, and mycotoxin production. Fungal cells are exposed to a variety of environmental stimuli, including changes in osmolality, temperature, and pH, which create stresses that primarily act on fungal cell walls. In addition, fungal cell walls are the first interactions with host cells in either human or plants. Thus, understanding cell wall structure and the mechanism of their biogenesis is important for the industrial, medical, and agricultural fields. Here, we provide a systematic review of fungal cell wall structure and recent findings regarding the cell wall integrity signaling pathways in aspergilli. This accumulated knowledge will be useful for understanding and improving the use of industrial aspergilli fermentation processes as well as treatments for some fungal infections.     

Room Temperature Processed Highly Efficient Large‐Area Polymer Solar Cells Achieved with Molecular Engineering of Copolymers

The room temperature (RT) processability of the photoactive layers in polymer solar cells (PSCs) from halogen‐free solvent along with their highly reproducible power conversion efficiencies (PCEs) and intrinsic thickness tolerance are extremely desirable for the large‐area roll‐to‐roll (R2R) production. However, most of the photoactive materials in PSCs require elevated processing temperatures due to their strong aggregation, which are unfavorable for the industrial R2R manufacturing of PSCs. These limiting factors for the commercialization of PSCs are alleviated by synthesizing random terpolymers with components of (2‐decyltetradecyl)thiophen‐2‐yl)naphtho[1,2‐c:5,6‐c′]bis[1,2,5]thiadiazole and bithiophene substituted with methyl thiophene‐3‐carboxylate (MTC). In contrast to the temperature‐dependent PNTz4T polymer, the resulting random terpolymers (PNTz4T‐MTC) show better solubility, slightly reduced crystallinity and aggregation, and weaker intermolecular interaction, thus enabling PNTz4T‐MTC to be processed at RT from a halogen‐free solvent. Particularly, the PNTz4T‐5MTC‐based photoactive layer exhibits an excellent PCE of 9.66%, which is among the highest reported PCEs for RT and ecofriendly halogen‐free solvent processed fullerene‐based PSCs, and a thickness tolerance with a PCE exceeding 8% from 100 to 520 nm. Finally, large‐area modules fabricated with the PNTz4T and PNTz4T‐5MTC polymer have shown 4.29% and 6.61% PCE respectively, with an area as high as 54.45 cm² in air.     

The occurrence of the Broad‐toothed Rat Mastacomys fuscus in relation to feral Horse impacts

Feral Horse (Equus caballus) impacts in northern Kosciuszko National Park, New South Wales, Australia are directly occurring in habitat of the nationally threatened Broad‐toothed Rat (Mastacomys fuscus). This species is endemic primarily to the mountain regions of south‐eastern mainland Australia and Tasmania, with a disjunct population at Barrington Tops. The Broad‐toothed Rat's preferred habitat is being increasingly impacted by browsing and trampling associated with the expansion of feral horse populations. This study surveyed 180 sites supporting preferred habitat for this species to determine Broad‐toothed Rat presence and relative abundance in relation to the level of feral horse impacts within the reserve. There was a significant negative relationship between feral horse impacts and both Broad‐toothed Rat presence and abundance. No scats were identified at localities where feral horse impacts were severe, and at moderate horse impact sites, there was a proportion (34%) without scats found. Locations with low horse impacts had little impact on Broad‐toothed Rat occurrence. As feral horse populations increase, Broad‐toothed Rat populations may be further impacted. Such impacts will be due to the loss of vegetation cover from feral horse trampling and grazing, making animals more vulnerable to predation by predators or impacting on their ability to disperse to more suitable habitat. Habitat remnants and vegetation corridors along drainage lines require protection from feral horses to prevent localized extinctions of Broad‐toothed Rat.     

Sequential Ubiquitination of Ribosomal Protein uS3 Triggers the Degradation of Non-functional 18S rRNA

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Modeling Patient-Derived Glioblastoma with Cerebral Organoids

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The pivotal role of hepatocytes in drug discovery

This review promotes the value of isolated hepatocytes in modern Drug Discovery programmes and outlines how increased understanding, particularly in the area of in vitro-in vivo extrapolation (IVIVE), has led to more widespread use. The importance of in vitro metabolic intrinsic clearance data for predicting in vivo clearance has been acknowledged for several years and the greater utility of hepatocytes, compared with hepatic microsomes and liver slices, for this application is discussed. The application of hepatocytes in predicting drug-drug interactions (DDIs) resulting from reversible and irreversible (time-dependent) inhibition is relatively novel but affords the potential to study both phase I and phase II processes together with any impact of drug efflux and/or uptake (cellular accumulation). Progress in this area is reviewed along with current opinions on the comparative use of primary hepatocytes and higher throughput reporter gene-based systems for studying cytochrome P450 (CYP) induction. The appreciation of the role of transporter proteins in drug disposition continues to evolve. The study of hepatic uptake using isolated hepatocytes and the interplay between drug transport and metabolism with respect to both clearance and DDIs and subsequent IVIVE is also considered.