ABSTRACT
The global climate change has resulted in huge flood damages, which seriously hinders the sustainable development of rural economy and society and causes famers' livelihood problems. In flood-prone areas, it is imperative to actively study short and long-term strategies and solve farmers' livelihood problems accordingly. Following the sustainable development analysis framework proposed by the Department for International Development (DFID), this study collects empirical data of 360 rural households in six sample villages in the Jialing River Basin of Sichuan Province, China through a village-to-household field questionnaire and applies the Multinominal Logit Model (MNL) to explore the influence of farmer households' capital on livelihood strategy choice. Research results show that: (1) In human capital category, the education level of the household head has a significant positive impact on the livelihood strategies of farmers' families; (2) In physical capital category, farmer households with larger space have more funds to choose among flood adaptation strategies; (3) In natural capital category, house location and the sale of family property for cash have the greatest negative impact on farmers' livelihood strategies; (4) Rural households with more credit opportunities in financial capital are more willing to obtain emergency relief funds; (5) Farmers' families helped by the village for a long time will probably not choose to move to avoid floods, but are more likely to choose buying flood insurance. This study provides an empirical reference for effective short and long term prevention and mitigation strategies design and application in rural in flood-prone areas.
Subject(s)
Farmers , Floods , Agriculture , China , Family Characteristics , Humans , Rural PopulationABSTRACT
We have previously developed a universal chimeric antigen receptor (CAR), which recognizes dinitrophenyl (DNP) and can redirect T and NK cells to target cancer and HIV antigens using DNP-conjugated antibodies as adaptor molecules. However, the DNP-antibody conjugates are generated by random modification, which may not be optimal for this modular system. Here, we report the development of enhanced adaptor molecules by site-specific DNP modification. We use the genetic code expansion technology to generate single-chain fragment variable (scFv) antibodies with site-specific DNP. We compare four anti-CD19 scFv mutants and find that the one with DNP at the flexible peptide linker between VL and VH is the most effective in redirecting anti-DNP CAR-T cells against CD19+ cells. The other three mutants are ineffective in doing so due to reduced DNP exposure or abrogated CD19 binding. We also use the anti-CD22 scFv as another model adaptor molecule and again find that the peptide linker is ideal for DNP derivatization. Our approach can potentially be used to design enhanced adaptor molecules to redirect the DNP-mediated universal CAR against other tumor antigens.
Subject(s)
Dinitrobenzenes , Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , Single-Chain Antibodies , Antigens, CD19/genetics , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Cell Line, Tumor , Dinitrobenzenes/chemistry , Humans , Neoplasms/immunology , Neoplasms/therapy , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Single-Chain Antibodies/genetics , T-Lymphocytes/immunology , T-Lymphocytes/transplantationABSTRACT
Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.
