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A robust and scalable synthesis for vilazodone was developed to avoid the formation of impurities derived from N-detosylation reactions under alcoholic conditions. During our research, these impurities, potentially genotoxic alkyl tosylate and out-of-specification indole N-alkylated vilazodones, were identified as process impurities that have never been reported. Through adjusting the functionality transformations, this process successfully prevented the tosyl group from encountering any alkoxides, which would inevitably lead to the generation of alkyl tosylate and indole N-alkylated vilazodone byproducts. In addition, this manufacturing process has also been demonstrated on a kilogram scale, delivering 1.05 kg of vilazodone hydrochloride with an overall yield of 71% (calculated from ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate hydrochloride 7·HCl). HPLC purity of the product was detected >99.5%, with any single impurity <0.1% HPLC area percentage. Indole N-alkylated vilazodones were not detected, and the yield was 10% higher than the previous Friedel–Crafts acylation route.

To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism.

The single-photon absorption induced single event transient in the silicon-germanium heterojunction bipolar transistor is investigated. The laser wavelength and bias condition have been proven to have significant impacts on the characterization of the single event transient (SET) response of the device by two-dimensional (2-D) raster scanning. After optical analytical calculation, the laser-induced charge distribution is well-embedded in the 3-D TCAD process simulation conducted to explore the underlying physical mechanism. In addition to the ion shunt effect, the excess electron injection from the emitter to the base could play a vital role in the SET peak amplitude and charge collection. The impact of the metal layer on the SPA experimental results is also determined by establishing a figure of merit that will help researchers estimate the laser-induced transient sensitivity of devices with metal layer blocking.

Radiotherapy is a traditional method for cancer therapy but may become ineffective likely due to the radiation-induced immunosuppression. Instead of simply increasing the radiation dose, reactivation of immunosuppression in the tumor microenvironment is an alternative strategy for successful cancer treatment. In this work, we synthesized bismuth sulfide nanoparticles (BiNP) and conjugated with immunoactive Ganoderma lucidumpolysaccharide (GLP). GLP-BiNP were able to increase the sensitivity of radiotherapy, attributing to the efficient X-ray absorption of bismuth element. BiNP alone can mildly activate dendritic cells (DC) in vitro, while GLP-BiNP further enhanced the level of DC maturation, shown as the increase in phenotypic maturation markers, cytokine release, acid phosphatase activity, and T cell proliferation in DC/T cell co-culture. Compared to BiNP, GLP-BiNP altered the tissue distribution with faster accumulation in the tumor. Meanwhile, mature DC greatly increased in both tumor and spleen by GLP-BiNP within 24 h. GLP-BiNP combination with radiation achieved remarkable inhibition of tumor growth through apoptosis. Alternatively, lung metastasis was largely prohibited by GLP-BiNP, shown as a reduced amount of tumor nodules and cancer cell invasion by pathological findings. Mechanistically, GLP-BiNP altered the tumor immunosuppression microenvironment by preferably increasing the number of intratumor CD8+T cell proliferation, as well as the improved immunobalance shown as the increased serum interferon-γ/interleukin-4 ratio. Specifically, GLP conjugation seemed to protect the kidney from injury occasionally introduced by bare BiNP. As a result, GLP-BiNP play a dual role in tumor treatment through radiosensitization and immunoactivities.

An efficient procedure for enzymatic desymmetrization of the prochiral diphenol compound 2was successfully developed to prepare the pharmaceutical intermediate (1S,4R)-8-hydroxy-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl propionate with 99.0% purity and 97.82% ee in 81.59% overall yield. The enzymatic reaction was scalable and cost-effective and avoided the process of crystallization-induced resolution in the reported synthetic strategy for yimitasvir (1), thus helping to increase utilization of the chiral motif.

An efficient method for the synthesis of (3R)-N-Boc-3-aminoazepane with immobilized ω-transaminase (ω-TA) has been further optimized. In comparison with the crude enzyme powder or wet whole cells, this immobilized enzyme exhibits excellent activity and stability under the optimum process conditions, allowing 20 rounds of enzyme reuse without obvious loss of activity. This procedure simplified the workup and was performed on a multikilogram scale in a reproducible manner to yield (3R)-N-Boc-3-aminoazepane with 99.2% ee and 97.0% purity.

Dispersants are chemical moieties that modify interfacial characteristics by adsorption at the solid–liquid interface, and they have been widely used in modern industrial production. This review focuses on the research and perspectives of anionic dispersants for coal–water slurry (CWS). Various common anionic dispersants are briefly summarized, including natural and synthetic species. The interactions between coal particles in the CWS suspension, including van der Waals attraction and electrostatic repulsion, are described by the DLVO (Derjaguin–Landau–Verwey–Overbeek) theory. Due to the hydrophobic interaction and the steric effect resulting from the adsorption of polymer dispersants, the extended DLVO theory is introduced to elucidate the various interactions in the CWS system. Based on the interactions between the coal particles, the adsorption behaviors at the coal–water interface, and the interactions between coal and water, the dispersion and stabilization mechanisms are systematically and theoretically discussed. According to the variations of interaction energies between the coal particles, the use of anionic polymer dispersants can weaken the hydrophobic attraction and enhance the steric hindrance and electrostatic repulsion. Also, the rheological behaviors of CWSs are outlined, with emphasis on the pipeline transportation of CWS and the three-parameter Herschel–Bulkley model. Additionally, the properties of anionic dispersants for CWS can be improved by adjusting their chemical structures such as molecular weight, side chain length, rigidity and flexibility of the molecular chain, and variety, quantity, position, and proportion of hydrophobic and hydrophilic groups. In view of the relationships between the structure and property, a direction on the selection and preparation of dispersant for CWS is suggested. Finally, the current challenges and future perspectives of dispersants for CWS are put forward.

An efficient and selective biocatalytic process was developed for the reduction of highly bulky and hydrophobic α-bromo ketone 4ausing ketoreductase from Lactobacillus kefiri. A fter the initial identification of this selective reductase, reaction conversion was increased from 25.7 to 94.3% and the substrate concentration increased from 5 to 85 g/L via detailed optimization. Through intramolecular epoxidation, the obtained α-bromohydrin 1awas transformed into epoxide 2as the final product with >99.9% ee, 98.5% HPLC purity, and 90.2% yield over two steps. Eventually, a scale-up demonstration of the telescoped process was successfully performed at a 30 L scale showing excellent reproducibility and consistency, guaranteeing the obtainment of olodaterol with good quality. This biocatalytic process was further demonstrated as environmentally benign by a 50% reduction in process mass intensity (PMI) when compared to the reported (-)-DIP-Cl process.

Reconstruction of large scalp defects after tumor resection is common and challenging. Free skin grafting or free flap transfer is always performed. However, these techniques can result in poor functional and cosmetic outcomes.

A series of novel macrocyclic polyethers, phenylene–diacetylene‐containing macrocycles was synthesized in high yields by employing copper(II)‐mediated Eglinton coupling as the key macrocyclization (80–92 %). As an analogue of the bisphenylene crown ether hosts, the binding behavior of these new macrocycles was investigated by 1H NMR spectroscopy, mass spectrometry (ESI), and X‐ray crystallography. The results obtained indicate that macrocycles with tetraethylene glycol chains (3c–e) bind a paraquat guest to form [2]pseudorotaxane‐like complexes in solution and in the solid state, whereas macrocycles with triethylene glycol chains (i.e., 3f–h) bind a paraquat guest to form [3]pseudorotaxane‐like complexes, which implies that macrocycles 3f–hmay be able to complex to (mono)pyridinium cations in a [2]pseudorotaxane‐like fashion in solution.

A new approach to the synthesis of Emitasvir (DAG181), a small molecule hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, is described. Enantioselective enzymatic desymmetrization with hydrolases in the synthetical approach can significantly avoid the loss of chiral raw materials in the resolution process. The synthesis route is further optimized and scaled-up to establish a new process that is applied to the preparation of kilogram scales of target active pharmaceutical ingredients (APIs). Compared with our initial process, the overall yield of target API was dramatically improved from 17 to 40%.

We developed a direct measurement method for comprehensive analyses of Kerr and plasma effects that cooperated or competed with molecular alignment-induced spatiotemporal modulation for intense aligning and weak probing pulses around zero time delay. The mixed influences were revealed by time-resolving the combined spatial focusing or defocusing dynamics under different molecular alignment directions and degrees. The nonlinear refractive index and plasma density were extracted straightforwardly, facilitating accurate explorations on multiphoton ionization and nonlinear optical Kerr effects of aligned molecular gases.

We experimentally demonstrated that both the electronic Kerr effect and the molecular alignment in gaseous molecules could be applied as transient gates to diagnose 400 nm target pulses. Their birefringence dissimilarity was clearly visualized by the measured spectrogram and retrieved gate function. In the atomic gas argon, a relatively weak and instantaneous cross phase modulation within the pulse duration was observed, while in the molecular gas N_2, the delayed rotational Raman excitation played a dominative role.

Twin photon generation at various emission angles is observed. It is found that different kinds of twin photons using only one crystal under different conditions are obtained. Twin photon generation is more effective at smaller emission angles. Two-photon entanglement is also achieved after compensation.