Enrichment performance and salt tolerance of polyhydroxyalkanoates (PHAs) producing mixed cultures under different saline environments.

The key to the resource recycling of saline wastes in form of polyhydroxyalkanoates (PHA) is to enrich mixed cultures with salt tolerance and PHA synthesis ability. However, the comparison of saline sludge from different sources and the salt tolerance mechanisms of salt-tolerant PHA producers need to be clarified. In this study, three kinds of activated sludge from different salinity environments were selected as the inoculum to enrich salt-tolerant PHA producers under aerobic dynamic feeding (ADF) mode with butyric acid dominated mixed volatile fatty acid as the substrate. The maximum PHA content (PHAm) reached 0.62 ± 0.01, 0.62 ± 0.02, and 0.55 ± 0.03 g PHA/g VSS at salinity of 0.5%, 0.8%, and 1.8%, respectively. Microbial community analysis indicated that Thauera, Paracoccus, and Prosthecobacter were dominant salt-tolerant PHA producers at low salinity, Thauera, NS9_marine, and SM1A02 were dominant salt-tolerant PHA producers at high salinity. High salinity and ADF mode had synergistic effects on selection and enrichment of salt-tolerant PHA producers. Combined correlation network with redundancy analysis indicated that trehalose synthesis genes and betaine related genes had positive correlation with PHAm, while extracellular polymeric substances (EPS) content had negative correlation with PHAm. The compatible solutes accumulation and EPS secretion were the main salt tolerance mechanisms of the PHA producers. Therefore, adding compatible solutes is an effective strategy to improve PHA synthesis in saline environment.

FeS and Fe3O4 Co-modified biochar to build a highly resistant advanced oxidation process system for quinclorac degradation in irrigation water.

Advanced oxidation processes (AOPs), based on sulfate radical (SO4·-) produced by peroxymonosulfate (PMS), can effectively mineralize refractory organic pollutants. However, the coexistence of anions and natural organic matters in actual wastewater prevents the application of AOPs. A simple one-step method was used to prepare FeS/Fe3O4 co-modified biochar materials (FFB) that could activate PMS to degrade quinclorac (QNC) with a removal rate of 100%, even exhibiting optimum degradation of QNC reached 99.31% in irrigation water, demonstrating excellent anti-interference performance for co-existing anions and natural organic matter. Meanwhile, ecotoxicity analysis showed that the toxicity of degradation intermediates was lower than that of QNC. Characterization results demonstrated the even distribution of FeS and Fe3O4 onto biochar, supplying abundant Fe2+ to activate PMS producing reactive oxygen species (ROS), while the generated Fe3+ after reactive continue to be reduced with sulfur species to promote the cycle of Fe2+/Fe3+. The coexistence of ·OH, SO4·-, 1O2, and O2·- in the FFB/PMS-QNC system suggest the possession of two pathway with free radical and non-free radical pathways to degrade QNC. The density functional theory (DFT) was used to analyze the adsorption sites and adsorption energy of PMS, as well as the differential charge density, which further proved the generation of SO4·-, O2·- and 1O2. In addition, the electrochemical test results showed that electron transfer also played an important role in the degradation of QNC. This study provides a feasible approach for the removal of organic pollutants in actual water.

Lipoic acid based core cross-linked micelles for multivalent platforms: design, synthesis and application in bio-imaging and drug delivery.

Natural lipoic acid derived small-molecule amphiphiles self-assemble into micelles in water. The presence of numerous disulfides accumulated in the core makes the micelles readily cross-linked to achieve the establishment of core cross-linked micelles (CCMs). Thanks to the inherent biocompatibility, the resulting lipoic acid based CCMs (LA-CCMs) are good multivalent platforms for biomedical applications.

Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates.

After several notable clinical failures in early generations, antibody-drug conjugates (ADC) have made significant gains with seven new FDA approvals within the last 3 years. These successes have been driven by a shift towards mechanistically informed ADC design, where the payload, linker, drug-to-antibody ratio, and conjugation are increasingly tailored to a specific target and clinical indication. However, fundamental aspects needed for design, such as payload distribution, remain incompletely understood. Payloads are often classified as "bystander" or "nonbystander" depending on their ability to diffuse out of targeted cells into adjacent cells that may be antigen-negative or more distant from tumor vessels, helping to overcome heterogeneous distribution. Seven of the 11 FDA-approved ADCs employ these bystander payloads, but the depth of penetration and cytotoxic effects as a function of physicochemical properties and mechanism of action have not been fully characterized. Here, we utilized tumor spheroids and pharmacodynamic marker staining to quantify tissue penetration of the three major classes of agents: microtubule inhibitors, DNA-damaging agents, and topoisomerase inhibitors. PAMPA data and coculture assays were performed to compare with the 3D tissue culture data. The results demonstrate a spectrum in bystander potential and tissue penetration depending on the physicochemical properties and potency of the payload. Generally, directly targeted cells show a greater response even with bystander payloads, consistent with the benefit of deeper ADC tissue penetration. These results are compared with computational simulations to help scale the data from in vitro and preclinical animal models to the clinic.

Hydrogen-bond super-amphiphile based drug delivery system: design, synthesis, and biological evaluation.

Drug delivery systems (DDSs) show great application prospects in tumor therapy. So far, physical encapsulation and covalent grafting were the two most common strategies for the construction of DDSs. However, physical encapsulation-based DDSs usually suffered from low drug loading capacity and poor stability, and covalent grafting-based DDSs might reduce the activity of original drug, which greatly limited their clinical application. Therefore, it is of great research value to design a new DDS with high drug loading capacity, robust stability, and original drug activity. Herein, we report a super-amphiphile based drug delivery system (HBS-DDS) through self-assembly induced by hydrogen bonds between amino-substituted N-heterocycles of the 1,3,5-triazines and hydrophilic carmofur (HCFU). The resulting HBS-DDS had a high drug loading capacity (38.1%) and robust stability. In addition, the drug delivery system exhibited pH-triggered size change and release of drugs because of the pH responsiveness of hydrogen bonds. In particular, the anticancer ability test showed that the HBS-DDS could be efficiently ingested by tumor cells, and its half-maximal inhibitory concentration (IC50 = 3.53 µg mL-1) for HeLa cells was close to that of free HCFU (IC50 = 5.54 µg mL-1). The hydrogen bond-based DDS represents a potential drug delivery system in tumor therapy.

Antibacterial coordination polymer hydrogels composed of silver(i)-PEGylated bisimidazolylbenzyl alcohol.

Herein, antibacterial coordination polymer hydrogels were conveniently fabricated in water via coordination between silver nitrate and PEGylated bisimidazolylbenzyl alcohol (1a-c). These coordination polymer hydrogels exhibit much better antibacterial activity than silver nitrate against both Gram-negative and Gram-positive pathogens including multidrug-resistant pathogens. The coordination polymer Ag/1c with a long PEG chain (PEG1000) was demonstrated to be the most effective antibacterial material, and its minimum inhibition concentrations (MICs) could be as low as 15.2 times for common Staphylococcus aureus and 4.8 times for methicillin-resistant Staphylococcus aureus over that of silver nitrate. With improved antibacterial performance, easy preparation method, improved stability, sustained releasability, outstanding ductility and low cytotoxicity, the as-prepared coordination polymer hydrogels should find various potential applications such as in clinical burn and wound dressings, biofilms, bioadhesives, and coatings of biomedical materials.

Coiled-coil networking shapes cell molecular machinery.

The highly abundant α-helical coiled-coil motif not only mediates crucial protein-protein interactions in the cell but is also an attractive scaffold in synthetic biology and material science and a potential target for disease intervention. Therefore a systematic understanding of the coiled-coil interactions (CCIs) at the organismal level would help unravel the full spectrum of the biological function of this interaction motif and facilitate its application in therapeutics. We report the first identified genome-wide CCI network in Saccharomyces cerevisiae, which consists of 3495 pair-wise interactions among 598 predicted coiled-coil regions. Computational analysis revealed that the CCI network is specifically and functionally organized and extensively involved in the organization of cell machinery. We further show that CCIs play a critical role in the assembly of the kinetochore, and disruption of the CCI network leads to defects in kinetochore assembly and cell division. The CCI network identified in this study is a valuable resource for systematic characterization of coiled coils in the shaping and regulation of a host of cellular machineries and provides a basis for the utilization of coiled coils as domain-based probes for network perturbation and pharmacological applications.