Tumor-Targeted Delivery of IL-2 by NKG2D Leads to Accumulation of Antigen-Specific CD8+ T Cells in the Tumor Loci and Enhanced Anti-Tumor Effects

Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci

Research on the Package Feature Selection of Talent Attracting Factors in International Trade in Guangdong-Hong Kong-Macao Greater Bay Area

This paper designs a survey questionnaire based on the Guangdong-Hong Kong-Macao Greater Bay Area’s demand for talents in international trade, adds job types, filters through package features, and performs feature filtering with the error filter criteria set in this paper, and conducts logistic regression analysis on talent types, so as to realize the classification and dynamic analysis of talents. The dynamic needs of various types of talents in international trade in the Guangdong-Hong Kong-Macao Greater Bay Area are drawn, and specific measures such as increasing salaries and benefits, reducing living costs, providing housing subsidies, solving children's employment problems, and ensuring quality of life are proposed for the development of international trade talents. Reducing the cost of talent migration can promote them to make more contributions to the Guangdong-Hong Kong-Macao Greater Bay Area. This will help the Guangdong-Hong Kong-Macao Greater Bay Area government to attract outstanding international trade talents and formulate detailed and feasible strategies, which has certain reference significance

A Supramolecular Hydrogel Enabled by the Synergy of Hydrophobic Interaction and Quadruple Hydrogen Bonding

The increasing preference for minimally invasive surgery requires novel soft materials that are injectable, with rapid self-healing abilities, and biocompatible. Here, by utilizing the synergetic effect of hydrophobic interaction and quadruple hydrogen bonding, an injectable supramolecular hydrogel with excellent self-healing ability was synthesized. A unique ABA triblock copolymer was designed containing a central poly(ethylene oxide) block and terminal poly(methylmethacrylate) (PMMA) block, with ureido pyrimidinone (UPy) moieties randomly incorporated (termed MA-UPy-PEO-UPy-MA). The PMMA block could offer a hydrophobic microenvironment for UPy moieties in water and thus boost the corresponding quadruple hydrogen bonding interaction of Upy–Upy dimers. Owing to the synergetic effect of hydrophobicity and quadruple hydrogen bonding interaction, the obtained MA-UPy-PEO-UPy-MA hydrogel exhibited excellent self-healing properties, and injectable capability, as well as superior mechanical strength, and therefore, it holds great promise in tissue engineering applications, including in cell support and drug release

Research progress in Haim-Munk syndrome

Haim-Munk syndrome is an extremely rare autosomal recessive genetic disease, characterized by palmoplantar hyperkeratosis, severe early-onset periodontitis, arachnodactyly, acro-osteolysis, pes planus foot and nail atrophic deformation. Studies have shown that the disease is often caused by parental consanguinity and is associated with homozygous mutations in the Cathepsin C (CTSC) gene. At present, there are few related articles, most of which are case reports. Few studies have been conducted on the etiology and pathogenesis thereof. Patients are often confronted with the problems of missed diagnosis, misdiagnosis and poor therapeutic efficacy. Based on the current research status at home and abroad, this paper reviews the pathogenesis, clinical manifestations, histopathology and immunohistochemistry, diagnosis and differential diagnosis, treatment and prognosis of HMS, in order to provide reference for the clinical diagnosis and the treatment

Clinical and Pathological Analysis of 4910 Patients Who Received Renal Biopsies at a Single Center in Northeast China

Purpose. To identify the epidemiology and pathological types of kidney diseases and their changes during the past decade, in a population from Northeast China. Methods. We retrospectively analysed clinical and renal pathological data from 4910 patients who received renal biopsies in the Second Hospital of Jilin University from 2008 to 2017. Results. Males received more renal biopsies than females (p < 0.001). The average age (p < 0.001) and percentage of elderly patients (p < 0.001) increased over time. The pathological types were primary glomerulonephritis (PGN, 73.2%), secondary glomerulonephritis (SGN, 23.7%), tubular-interstitial nephropathy (TIN, 2.8%), and hereditary nephropathy (HN, 0.3%). The most common forms of PGN were membranous nephropathy (MN, 37.2%) and IgA nephropathy (IgAN, 29.9%). Over time, the prevalence of IgAN decreased, but the prevalence of MN increased. MN was more common in middle-aged and elderly patients, but IgAN was most common in young adults. Analysis of SGN data indicated that lupus nephritis (LN, 34.0%), Henoch-Schönlein purpura glomerulonephritis (HSPN, 17.9%), and diabetic nephropathy (DN, 11.7%) were the most common forms. Over time, the prevalence of DN (p = 0.003), hypertension-associated renal damage (p = 0.005), and systemic vasculitis-associated nephritis (SVARD, p < 0.001) increased, but the prevalence of HSPN (p < 0.001) and hepatitis B virus-associated glomerulonephritis (HBV-GN, p = 0.001) decreased. Nephrotic syndrome was the main clinical manifestation of PGN. Conclusion. From 2008 to 2017, renal biopsies were increasingly performed in the elderly. There were notable changes in the epidemiology and pathological types of kidney disease among renal biopsy patients at our centre

Geological Storage Conditions and Potential Analysis of Carbon Dioxide in the High-steep Fold Belt in Eastern Sichuan Basin

Carbon sequestration refers to the technology of capturing carbon and storing it safely instead of directly discharging CO2 into the atmosphere. Rock salt is a promising CO2 reservoir, and the underground rock salt structure formed by salt cavern reservoirs in geological history has a natural sealing function. Storing carbon dioxide in salt caves can ensure that carbon dioxide is stably stored underground for a long time. However, at present, there are few studies on carbon sequestration in abandoned salt caves. This study analyses the characteristics of carbonate-evaporite strata in the high fold zone of eastern Sichuan and qualitatively evaluates Triassic carbonate-evaporite layers formed in the depth range of 800-3000 m in various sedimentary basins in Chongqing. A large set of carbonates-evaporites are developed in Chongqing, and the carbonate rocks near evaporites have low porosity and permeability, which can be used as CO2 storage caprock in salt cavities. Thick evaporated strata can also provide a good cover for CO2 storage in abandoned salt caves, which has great potential space resources