For a number of years, antimicrobial resistance (AMR) has been a critical issue for humanity. Drug discovery efforts have been very limited and the spread of bacterial pathogens has over-run our traditional arsenal of antibiotics. Bacteria can involve to evade compounds that can halt their rapid growth. The authors have discovered a potent macrocycle derivative that when dosed concomitantly with the standard of care (SOC) antibiotic vancomycin, can clear methicillin resistant Staphylococcus aureus (MRSA) infections. In addition, we have probed the lead compounds in Salmonella typhimurium bacterial strains. In vitro, in vivo, and ADME data have been included to stress the virtues of this new antibiotic.

A condition of scarring of lung tissue due to a wide range of causes (such as environmental pollution, cigarette smoking (CS), lung diseases, some medications, etc.) has been reported as pulmonary fibrosis (PF). This has become a serious problem all over the world due to the lack of efficient drugs for treatment or cure. To date, no drug has been designed that could inhibit fibrosis. However, few medications have been reported to reduce the rate of fibrosis. Meanwhile, ongoing research indicates pulmonary fibrosis can be treated in its initial stages when symptoms are mild. Here, an attempt is made to summarize the recent studies on the effects of various chemical drugs that attenuate PF and increase patients' quality of life. The review is classified based on the nature of the drug molecules, e.g., natural/biomolecule-based, synthetic-molecule-based PF inhibitors, etc. Here, the mechanisms through which the drug molecules attenuate PF are discussed. It is shown that inhibitory molecules can significantly decrease the TGF-β1, profibrotic factors, proteins responsible for inflammation, pro-fibrogenic cytokines, etc., thereby ameliorating the progress of PF. This review may be useful in designing better drugs that could reduce the fibrosis process drastically or even cure the disease to some extent.

AbstractThe purpose of this investigation was to develop an initial set of Power number versus Reynolds number results for a family of vertical‐wheel bioreactors. These bioreactors are increasingly being used for the manufacture of cells for cell therapy but have not been characterized according to this approach. A novel gravimetric method to measure power was used, and the validity of this method was assessed by measuring power for a standard stirred tank bioreactor with a Rushton impeller. The results of the gravimetric method were found to closely match those derived from traditional methods. The validated method was then used to measure the power draw and develop an initial set of Power number versus Reynolds number results for a family of vertical‐wheel bioreactors.

A copper iodide-Pyox complex catalyzes the first conjugate addition of diverse sulfur, nitrogen, and carbon nucleophiles to isocyanoalkenes. The anionic addition generates metalated isocyanoalkanes capable of SNi displacements, providing a rapid route to a series of functionalized, cyclic isocyanoalkanes. The Cu(I)I-Pyox complex efficiently catalyzes a first-in-class conjugate addition affording a range of complex, functionalized isocyanoalkanes that are otherwise challenging to synthesize while laying a foundation for catalytic reactions that maintain the isocyanide group.

Membrane chromatography is routinely used to remove host cell proteins, viral particles, and aggregates during antibody downstream processing. The application of membrane chromatography to the field of antibody-drug conjugates (ADCs) has been applied in a limited capacity and in only specialized scenarios. Here, we utilized the characteristics of the membrane adsorbers, Sartobind® S and Phenyl, for aggregate and payload clearance while polishing the ADC in a single chromatographic run. The Sartobind® S membrane was used in the removal of excess payload, while the Sartobind® Phenyl was used to polish the ADC by clearance of unwanted drug-to-antibody ratio (DAR) species and aggregates. The Sartobind® S membrane reproducibly achieved log-fold clearance of free payload with a 10 membrane-volume wash. Application of the Sartobind® Phenyl decreased aggregates and higher DAR species while increasing DAR homogeneity. The Sartobind® S and Phenyl membranes were placed in tandem to simplify the process in a single chromatographic run. With the optimized binding, washing, and elution conditions, the tandem membrane approach was performed in a shorter timescale with minimum solvent consumption and high yield. The application of the tandem membrane chromatography system presents a novel and efficient purification scheme that can be realized during ADC manufacturing.

AbstractA new accurate formula for the extended Woodward UV rules for all possible eight structures of α,β‐unsaturated ketones, λmax = 212.82 + 11.37Nsub + 4.79Nexo, was discovered by solving 56 ordered triples using Microsoft Excel's inverse matrix method, with an overall 99.9% accuracy between the observed and calculated maxima values. This discovered formula and these eight unique data points can be illustrated in the linear‐equation plane or visualized in the three‐dimensional graphics using computer software.

ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.

Major scientific discoveries in the last two decades have been enabled by the development of high-throughput sequencing and mass spectrometry (MS) technologies. Omics analysis, at the genome, transcriptome, proteome, or metabolome levels has paved the way for the elucidation of many molecular mechanisms that underlie disease, biomarker and drug-target discovery, and diagnostics and precision medicine applications. With the realization that the biological interpretation of results generated from biological tissues or cell-derived samples is highly impacted by cell heterogeneity in an apparently homogeneous cell population, many efforts have been redirected toward the omics characterization of single cells. As miniaturized devices represent ideal platforms for the analysis of small sample amounts, omics analysis has found a flourishing ground in the microfluidics instrumentation development arena. This review aims at capturing the latest protein and proteome analysis technologies that have been developed and implemented on microfluidic platforms, with focus on developments that have been documented in the past two years, and emphasis placed on challenging aspects that relate to sensitivity and handling sample complexity, as well as on applications that target the solving of demanding biological and biomedical problems.