A sequence of monsoon surges struck Pakistan and Northwestern India during late July‐early August 2010. The unusually heavy monsoon rainfall resulted in record‐breaking floods, which affected 20 million people with a death toll of near 3000. Simultaneously, a long‐lived blocking high appeared over Europe and Russia in middle June and persisted for nearly two months. Extreme flooding occurred when the southward penetration of extratropical potential vorticity in the deep trough east of the European blocking and the tropical monsoon surges arrived concurrently in Pakistan. This study demonstrates that the interaction between the tropical monsoon surges and the extratropical disturbances downstream of the European blocking was the key factor leading to the severe flooding in Pakistan. The 2010 La Niña condition contributed indirectly to the flooding by inducing a low‐level easterly anomaly in South and Southeast Asia, which weakened eastward moisture transport and helped enhance moisture transport (convergence) to (in) the Northern Arabian Sea and Pakistan.

Multivesicle assemblies with pH‐responsive transmembrane channels in the vesicle walls (see picture) were made by two‐step double emulsion of copolymers comprising acrylic acid and acrylate of 1,2‐distearoyl‐rac‐glycerol. These assemblies mimic eukaryotic cells, which contain functional organelles within the cell walls.

The purpose of this research was to improve probiotic microencapsulation using prebiotics and : The purpose of this research was to improve probiotic microencapsulation using prebiotics and : The purpose of this research was to improve probiotic microencapsulation using prebiotics and : The purpose of this research was to improve probiotic microencapsulation using prebiotics and : The purpose of this research was to improve probiotic microencapsulation using prebiotics and modern optimization techniques to determine optimal processing conditions, performance, and survival rates. modern optimization techniques to determine optimal processing conditions, performance, and survival rates. modern optimization techniques to determine optimal processing conditions, performance, and survival rates. modern optimization techniques to determine optimal processing conditions, performance, and survival rates. modern optimization techniques to determine optimal processing conditions, performance, and survival rates. Prebiotics (fructooligosaccharides or isomaltooligosaccharides), growth promoter (peptide), and sodium algi-Prebiotics (fructooligosaccharides or isomaltooligosaccharides), growth promoter (peptide), and sodium algi-Prebiotics (fructooligosaccharides or isomaltooligosaccharides), growth promoter (peptide), and sodium algi-Prebiotics (fructooligosaccharides or isomaltooligosaccharides), growth promoter (peptide), and sodium algi-Prebiotics (fructooligosaccharides or isomaltooligosaccharides), growth promoter (peptide), and sodium alginate were incorporated as coating materials to microencapsulate 4 probiotics ( nate were incorporated as coating materials to microencapsulate 4 probiotics ( nate were incorporated as coating materials to microencapsulate 4 probiotics ( nate were incorporated as coating materials to microencapsulate 4 probiotics ( nate were incorporated as coating materials to microencapsulate 4 probiotics (Lactobacillus acidophilus Lactobacillus acidophilus Lactobacillus acidophilus Lactobacillus acidophilus Lactobacillus acidophilus, , , , , Lacto-Lacto-Lacto-Lacto-Lactobacillus casei bacillus casei bacillus casei bacillus casei Bifidobacterium longum). The proportion of the prebiotics, pep-). The proportion of the prebiotics, pep-). The proportion of the prebiotics, pep-). The proportion of the prebiotics, pep-). The proportion of the prebiotics, peptide, and sodium alginate was optimized using response surface methodology (RSM) to 1st construct a surface tide, and sodium alginate was optimized using response surface methodology (RSM) to 1st construct a surface tide, and sodium alginate was optimized using response surface methodology (RSM) to 1st construct a surface tide, and sodium alginate was optimized using response surface methodology (RSM) to 1st construct a surface tide, and sodium alginate was optimized using response surface methodology (RSM) to 1st construct a surface model, with sequential quadratic programming (SQP) subsequently adopted to optimize the model and evaluate model, with sequ...

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Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work.Methods: The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers. The hybrid nanoparticles (ANG-IMNPs) were characterized by DLS, TEM, UV/vis and fluorescence spectrophotometer. Cellular uptake was examined by laser scanning confocal microscopy and flow cytometry. The PDT/PTT effect of ANG-IMNPs was evaluated using MTT assay. Tumor accumulation of NPs was determined by a non-invasive in vivo imaging system (IVIS). The in vivo anti-glioma effect of ANG-IMNPs was evaluated by immunohistochemical (IHC) examination of tumor tissues and Kaplan-Meier survival analysis.Results: In vitro data demonstrated enhanced uptake of ANG-IMNPs by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered PDT and PTT. In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro, the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC tissue examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days).Conclusion: In vitro and in vivo data strongly indicate that the ANG-IMNPs were capable of selectively delivering dual photosensitizers to brain astrocytoma tumors for effective PDT/PTT in conjugation with a substantially improved median survival. The therapeutic efficacy of ANG-IMNPs demonstrated in this study suggests their potential in overcoming BBB and establishing an effective treatment against GBM.

To significantly promote tumor uptake and penetration of therapeutics, a nanovehicle system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic cores coated with pH-responsive N-acetyl histidine modified D-α-tocopheryl polyethylene glycol succinate (NAcHis-TPGS) is developed in this work. The nanocarriers with switchable surface charges in response to tumor extracellular acidity (pHe) were capable of selectively co-delivering indocyanine green (ICG), a photothermal agent, and doxorubicin (DOX), a chemotherapy drug, to tumor sites. The in vitro cellular uptake of ICG/DOX-loaded nanoparticles by cancer cells and macrophages was significantly promoted in weak acidic environments due to the increased protonation of the NAcHis moieties. The results of in vivo and ex vivo biodistribution studies demonstrated that upon intravenous injection the theranostic nanoparticles were substantially accumulated in TRAMP-C1 solid tumor of tumor-bearing mice. Immunohistochemical examination of tumor sections confirmed the active permeation of the nanoparticles into deep tumor hypoxia due to their small size, pHe-induced near neutral surface, and the additional hitchhiking transport via tumor-associated macrophages. The prominent imaging-guided photothermal therapy of ICG/DOX-loaded nanoparticles after tumor accumulation induced extensive tumor tissue/vessel ablation, which further promoted their extravasation and DOX tumor permeation, thus effectively suppressing tumor growth.

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In this study, pH-responsive dextran hydrogels were prepared by radical copolymerization of methacrylated dextran (MA-dextran) with acrylic acid (AAc) in aqueous solution, using ammonium peroxydisulfate and N,N,N′,N′-tetramethylethylenediamine as an initiation system. The AAc content in hydrogels was determined quantitatively by FTIR. The swelling response of hydrogels to changes in pH/ salt concentration was characterized by quantitative evaluation of ionic osmotic performance according to the Donnan equilibrium theory, taking account of the Debye-Hu ¨ckel effect on the apparent acidity constant of AAc groups and the ionic binding of acrylate anions with counterions within hydrogel. A close-to-linear relation between the equilibrium swelling of hydrogels and the pH-induced ionic osmotic pressure is observed. The accompanied change of the polymer-solvent interaction parameter (χ) is obtained from free energy balance between ionic osmotic pressure, the elastic retractile force, and the interaction of polymer network with water molecules (the mixing contribution) and is governed by the concentration of fixed ionized AAc units within hydrogels. For hydrogels having varying AAc contents, the difference in swelling under identical osmotic pressure results from the variation in the effective network density of hydrogels. The neutral salt effect on the pH-induced swelling of the same hydrogel follows changes in the ionic osmotic pressure and the degree of dissociation of AAc units associated with the Debye-Hu ¨ckel theory. The change of the degree of dissociation of AAc units in response to the ionic strength effect dominates and describes well the sensitivity of the swelling behavior of hydrogels to the ionic osmotic pressure.