Tumor Endothelial Marker 8 Amplifies Canonical Wnt Signaling in Blood Vessels

Tumor Endothelial Marker 8/Anthrax Toxin Receptor 1 (TEM8/ANTXR1) expression is induced in the vascular compartment of multiple tumors and therefore, is a candidate molecule to target tumor therapies. This cell surface molecule mediates anthrax toxin internalization, however, its physiological function in blood vessels remains largely unknown. We identified the chicken chorioallantoic membrane (CAM) as a model system to study the endogenous function of TEM8 in blood vessels as we found that TEM8 expression was induced transiently between day 10 and 12 of embryonic development, when the vascular tree is undergoing final development and growth. We used the cell-binding component of anthrax toxin, Protective Antigen (PA), to engage endogenous TEM8 receptors and evaluate the effects of PA-TEM8 complexes on vascular development. PA applied at the time of highest TEM8 expression reduced vascular density and disrupted hierarchical branching as revealed by quantitative morphometric analysis of the vascular tree after 48h. PA-dependent reduced branching phenotype was partially mimicked by Wnt3a application and ameliorated by the Wnt antagonist, Dikkopf-1. These results implicate TEM8 expression in endothelial cells in regulating the canonical Wnt signaling pathway at this day of CAM development. Consistent with this model, PA increased beta catenin levels acutely in CAM blood vessels in vivo and in TEM8 transfected primary human endothelial cells in vitro. TEM8 expression in Hek293 cells, which neither express endogenous PA-binding receptors nor Wnt ligands, stabilized beta catenin levels and amplified beta catenin-dependent transcriptional activity induced by Wnt3a. This agonistic function is supported by findings in the CAM, where the increase in TEM8 expression from day 10 to day 12 and PA application correlated with Axin 2 induction, a universal reporter gene for canonical Wnt signaling. We postulate that the developmentally controlled expression of TEM8 modulates endothelial cell response to canonical Wnt signaling to regulate vessel patterning and density

Controlled Release of Insulin Based on Temperature and Glucose Dual Responsive Biomicrocapsules

The treatment of diabetes lies in developing novel functional carriers, which are expected to have the unique capability of monitoring blood glucose levels continuously and dispensing insulin correctly and timely. Hence, this study is proposing to create a smart self-regulated insulin delivery system according to changes in glucose concentration. Temperature and glucose dual responsive copolymer microcapsules bearing N-isopropylacrylamide and 3-acrylamidophenylboronic acid as main components were developed by bottom-spray coating technology and template method. The insulinoma β-TC6 cells were trapped in the copolymer microcapsules by use of temperature sensitivity, and then growth, proliferation, and glucose-responsive insulin secretion of microencapsulated cells were successively monitored. The copolymer microcapsules showed favorable structural stability and good biocompatibility against β-TC6 cells. Compared with free cells, the biomicrocapsules presented a more effective and safer glucose-dependent insulin release behavior. The bioactivity of secreted and released insulin did not differ between free and encapsulated β-TC6 cells. The results demonstrated that the copolymer microcapsules had a positive effect on real-time sensing of glucose and precise controlled release of insulin. The intelligent drug delivery system is supposed to mimic insulin secretion in a physiological manner, and further provide new perspectives and technical support for the development of artificial pancreas

Superamphiphile Based Cross-Linked Small-Molecule Micelles for pH-Triggered Release of Anticancer Drugs

A new superamphiphile based cross-linked small-molecule micelle (SA-CSM) is developed for pH-triggered release of anticancer drugs. This strategy revolves around the use of a noncovalent superamphiphile formed by the elaborate zwitterion <b>1</b> and anticancer drug doxorubicin (DOX) via their “spontaneous attraction” of carboxylic acid and amino group. The superamphiphiles self-assemble into micelles in water, which were further stabilized by cross-linking the surface via the thiol-acrylate Michael addition to achieve the establishment of the pH-sensitive SA-CSMs. The biological evaluation shows that the new drug delivery system exhibits highly efficient anticancer efficacy both <i>in vitro</i>, on the HeLa cancer cell line, and <i>in vivo</i>, on the HeLa xenograft model, while suppressing the inherent toxicity of the employed chemotherapeutics. Compared with the reported covalent amphiphile based CSMs, the noncovalent superamphiphile based CSMs not only have comparable drug loading content (up to 45.0%), robust stability, and superior predictable biosafety but also feature nonchemical synthesis, low production cost, specific stimulus response, and anticancer activity of the original drugs and thus represent a good example for clinical application

The Phenotypic Variation in Moso Bamboo and the Selection of Key Traits

This research aimed to explore the diverse phenotypic characteristics of moso bamboo in China and pinpoint essential characteristics of moso bamboo. In this study, 63 grids were selected using the grid method to investigate 28 phenotypic traits of moso bamboo across the entire distribution area of China. The results suggest that the phenotypic traits of moso bamboo exhibit rich diversity, with coefficients of variation ranging from 5.87% to 36.57%. The phenotypic traits of moso bamboo showed varying degrees of correlation. A principal component analysis was used to identify seven main phenotypic trait indicators: diameter at breast height (DBH), leaf area (LA), leaf weight (LW), branch-to-leaf ratio (BLr), leaf moisture content (Lmc), wall-to-cavity ratio (WCr), and node length at breast height (LN), which accounted for 81.64% of the total information. A random forest model was used, which gave good results to validate the results. The average combined phenotypic trait value (D-value) of most germplasm was 0.563. The highest D-value was found in Wuyi 1 moso in Fujian (0.803), while the lowest D-value was observed in Pingle 2 moso in Guangxi (0.317). The clustering analysis of phenotypic traits classified China’s moso bamboo germplasm into four groups. Group I had the highest D-value and is an important candidate germplasm for excellent germplasm screening

Construction and practice of infection prevention and control system in large Fangcang shelter hospitals

The management team from Ruijin Hospital had successively participated in the design, construction and operation of many Fangcang shelter hospitals. Combined with the large scale of the hospital, large amount of patients and medical wastes, high infection risk of staff, this paper summarizes the experience of our team in the prevention and control work from design of Fangcang shelter hospital, infection prevention and control system and operation process, staff training, health management, medical waste management, which may provide reference for the safe and stable operation of large shelter hospitals

Practice and Exploration on the construction of medical affairs management system in large Fangcang hospitals

In view of the difficulties, including simple facilities, temporary team formation, high working intensity, medical safety hazards and difficult emergency disposal etc. in medical management when large-scale Fangcang hospitals admitted and treated large quantity of patients during the epidemic period of the COVID-19 Omicron variant. We explored the medical management system of large-scale Fangcang hospital from the aspects of establishing a medical management team, formulating medical management system and disease diagnosis and treatment standards, upgrading the safety precautions and control, refining quality control evaluation and strengthening hospital-wide training and supervision. Aiming at improving the safety and the medical quality as the core goal, strengthening the medical system and optimizing the workflow are optimized via summarized the practical experience, to make large-scale Fangcang hospitals respond well to public health emergencies

Tetraphenylethylene-Induced Cross-Linked Vesicles with Tunable Luminescence and Controllable Stability

Luminescence-tunable vesicles (LTVs) are becoming increasingly attractive for their potential application in optics, electronics, and biomedical technology. However, for real applications, luminous efficiency and durability are two urgent constraints to be overcome. Combining the advantages of aggregation-induced emission in luminous enhancement and cross-linking in stability, we herein fabricated tetraphenylethylene-induced cross-linked vesicles with an entrapped acceptor of RhB (TPE-CVs@RhB), which achieved a high-efficiency multicolor emission of the visible spectrum, including white, by altering the amount of entrapped acceptor. Stability tests show that the luminescence of TPE-CVs@RhB has excellent environmental tolerance toward heating, dilution, doping of organic solvent, and storage in serum. Further outstanding performance in the application of fluorescent inks suggests that the new LTVs hold high potential in industrialization. More attractively, although the TPE-CVs@RhB can tolerate various harsh conditions, their stability can actually be controlled through the cross-linker adopted. For example, the employment of dithiothreitol in the present work produces an acid-labile β-thiopropionate linker. The cellular uptake by HepG2 cells shows that the acid-labile TPE-CVs@RhB can effectively respond to the acidic environment of cancer cells and release the entrapped RhB molecules, indicative of promising applications of this new type of LTVs in bioimaging and drug delivery

Comprehensive Characterization of Organic Light-Emitting Materials in Breast Milk by Target and Suspect Screening

Organic light-emitting materials (OLEMs) are emerging contaminants in the environment and have been detected in various environment samples. However, limited information is available regarding their contamination within the human body. Here, we developed a novel QuEChERS (quick, easy, cheap, effective, rugged, and safe) method coupled with triple quadrupole/high-resolution mass spectrometry to determine OLEMs in breast milk samples, employing both target and suspect screening strategies. Our analysis uncovered the presence of seven out of the 39 targeted OLEMs in breast milk samples, comprising five liquid crystal monomers and two OLEMs commonly used in organic light-emitting diode displays. The cumulative concentrations of the seven OLEMs in each breast milk sample ranged from ND to 1.67 × 103 ng/g lipid weight, with a mean and median concentration of 78.76 and 0.71 ng/g lipid weight, respectively, which were higher compared to that of typical organic pollutants such as polychlorinated biphenyls and polybrominated diphenyl ethers. We calculated the estimated daily intake (EDI) rates of OLEMs for infants aged 0–12 months, and the mean EDI rates during lactation were estimated to range from 30.37 to 54.89 ng/kg bw/day. Employing a suspect screening approach, we additionally identified 66 potential OLEMs, and two of them, cholesteryl hydrogen phthalate and cholesteryl benzoate, were further confirmed using pure reference standards. These two substances belong to cholesteric liquid crystal materials and raise concerns about potential endocrine-disrupting effects, as indicated by in silico predictive models. Overall, our present study established a robust method for the identification of OLEMs in breast milk samples, shedding light on their presence in the human body. These findings indicate human exposure to OLEMs that should be further investigated, including their health risks