DataSheet_1_Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer.pdf

Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC.</p

Toward “CO in a Pill”: Silica-Immobilized Organic CO Prodrugs for Studying the Feasibility of Systemic Delivery of CO via <i>In Situ</i> Gastrointestinal CO Release

Carbon monoxide (CO), an endogenous signaling molecule, is known to exert a range of pharmacological effects, including anti-inflammation, organ protection, and antimetastasis in various animal models. We have previously shown the ability of organic prodrugs to deliver CO systemically through oral administration. As part of our efforts for the further development of these prodrugs, we are interested in minimizing the potential negative impact of the “carrier” portion of the prodrug. Along this line, we have previously published our work on using benign “carriers” and physically trapping the “carrier” portion in the gastrointestinal (GI) tract. We herein report our feasibility studies on using immobilized organic CO prodrugs for oral CO delivery while minimizing systemic exposure to the prodrug and the “carrier portion.” In doing so, we immobilize a CO prodrug to silica microparticles, which are generally recognized as safe by the US FDA and known to provide large surface areas for loading and water accessibility. The latter point is essential for the hydrophobicity-driven activation of the CO prodrug. Amidation-based conjugation with silica is shown to provide 0.2 mmol/g loading degree, effective prodrug activation in buffer with comparable kinetics as the parent prodrug, and stable tethering to prevent detachment. One representative silica conjugate, SICO-101, is shown to exhibit anti-inflammation activity in LPS-challenged RAW264.7 cells and to deliver CO systemically in mice through oral administration and GI CO release. We envision this strategy as a general approach for oral CO delivery to treat systemic and GI-specific inflammatory conditions

Table_1_Retrospect and Risk Analysis of Foot-and-Mouth Disease in China Based on Integrated Surveillance and Spatial Analysis Tools.XLSX

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock and seriously affects the development of animal husbandry. It is necessary to defend the spread of FMD. To explore the distribution characteristics and transmission of FMD between 2010 and 2017 in China, Global Moran's I test and Getis-Ord Gi index were used to analyze the spatial cluster. A space-time permutation scan statistic was applied to analyze the spatio-temporal pattern. GIS-based method was employed to create a map representing the distribution pattern, directional trend, and hotspots for each outbreak. The number of cases was defined as the number of animals with FMD for the above analysis. We also constructed a phylogenetic tree to compare the homology and variation of FMD virus (FMDV) to provide a clue for the potential development of an effective vaccine. The results indicated that the FMD outbreaks in China had obvious time patterns and clusters in space and space-time, with the outbreaks concentrated in the first half of each year. The outbreaks of FMD decreased each year from 2010 with an obvious downward trend of hotspots. Spatial analysis revealed that the distribution of FMD outbreaks in 2010, 2015, and 2017 exhibited a clustered pattern. Space-time scanning revealed that the spatio-temporal clusters were centered in Guangdong, Tibet and the junction of Wuhan, Jiangxi, Anhui. Comparison of the spatial analysis and space-time analysis of FMD outbreaks revealed that Guangdong was the same cluster of the two in 2010. In addition, the directional trend analysis indicated that the FMD transmission was oriented northwest-southeast. The findings demonstrated that FMDV in China can be divided into three pedigrees and the homology of these strains is very high while comparing the first FMDV strain with the others. The data provide a basis for the effective monitoring and prevention of FMD, and for the development of an FMD vaccine in China.</p

Additional file 5 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 5: S5 Table. FMD outbreaks in Russia from 2006 to 2017

Additional file 1 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 1: S1 Table. Summary of Russian beef market supply and demand from 2011 to 2022

Additional file 3 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 3: S3 Table. Results of Cattle Monitoring for Antibodies to FMD Structural Polyprotein in Russia without FMD

Additional file 1 of Diaphragmatic ultrasonography-based rapid shallow breathing index for predicting weaning outcome during a pressure support ventilation spontaneous breathing trial

Additional file 1. Description of the diaphragmatic ultrasonography measurements

Additional file 4 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 4: S4 Table. Results of cattle monitoring for antibodies to FMDV non-structural polyproteins in the RF

Additional file 2 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 2: S2 Table. FMD outbreaks in Russia from 2005 to 2017 from OIE

Additional file 6 of Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation

Additional file 6: S6 Table. Rating scale of Foot-and-mouth disease prevention and control in Russia