Real-Time Monitoring of Multistep Batch and Flow Synthesis Processes of a Key Intermediate of Lifitegrast by a Combined Spectrometer System with Both Near-Infrared and Raman Spectroscopies Coupled to Partial Least-Squares.

Process analytical technology (PAT) has been successfully applied in numerous chemical synthesis cases and is an important tool in pharmaceutical process research and development. PAT brings new methods and opportunities for the real-time monitoring of chemical processes. In multistep synthesis, real-time monitoring of the complex reaction mixtures is a significant challenge but provides an opportunity to enhance reaction understanding and control. In this study, a combined multichannel spectrometer system with both near-infrared and Raman spectroscopy was built, and calibration models were developed to quantify the desired products, intermediates, and impurities in real-time at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating dynamic experiments in both batch and continuous-flow processes. It represents a significant step forward in data-driven, multistep pharmaceutical ingredient synthesis.

High-k Solution-Processed Barium Titanate/Polysiloxane Nanocomposite for Low-Temperature Ferroelectric Thin-Film Transistors.

Ferroelectric nanoparticles have attracted much attention for numerous electronic applications owing to their nanoscale structure and size-dependent behavior. Barium titanate (BTO) nanoparticles with two different sizes (20 and 100 nm) were synthesized and mixed with a polysiloxane (PSX) polymer forming a nanocomposite solution for high-k nanodielectric films. Transition from the ferroelectric to paraelectric phase of BTO with different nanoparticle dimensions was evaluated through variable-temperature X-ray diffraction measurement accompanied by electrical analysis using capacitor structures. A symmetric single 200 peak was constantly detected at different measurement temperatures for the 20 nm BTO sample, marking a stable cubic crystal structure. 100 nm BTO on the other hand shows splitting of 200/002 peaks correlating to a tetragonal crystal form which further merged, thus forming a single 200 peak at higher temperatures. Smaller BTO dimension exhibits clockwise hysteresis in capacitance-voltage measurement and correlates to a cubic crystal structure which possesses paraelectric properties. Bigger BTO dimension in contrast, demonstrates counterclockwise hysteresis owing to their tetragonal crystal form. Through further Rietveld refinement analysis, we found that the tetragonality (c/a) of 100 nm BTO decreases at a higher temperature which narrows the hysteresis window. A wider hysteresis window was observed when utilizing 100 nm BTO compared to 20 nm BTO even at a lower loading ratio. The present findings imply different hysteresis mechanisms for BTO nanoparticles with varying dimensions which is crucial in understanding the role of how the BTO size tunes the crystal structures for integration in thin-film transistor devices.

Practical Synthesis of 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid-Key Intermediate of Lifitegrast (Xiidra).

In the present study, a practical method for synthesizing the key intermediate 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid (1) of Lifitegrast was proposed. First, an investigation was conducted into the utilization of the impurity and recrystallization method in the synthesis of 5,7-dichlorotetrahydroisoquinoline (5·HCl) via Friedel-Crafts cyclization. Through the screening of different protection groups, a previously unreported quaternary ammonium salt (13) was isolated with a 95.9% yield and 99.6% purity by simply adjusting the pH during the carboxylation reaction. Subsequently, free state 1 was obtained by controlling the pH to 4-5 with HCl(aq), thereby avoiding the need for a free operation in the synthesis of the API of Lifitegrast. Further, the triphenylmethanol (TrOH) was recycled to triphenylmethyl chloride (TrCl) using CaCl2/HCl(aq) with 93.0% yield and 98.0% purity.

Luteolin supports osteogenic differentiation of human periodontal ligament cells.

BACKGROUND: Previous research revealed that luteolin could improve the activation of alkaline phosphatase (ALP) and osteocalcin in mouse osteoblasts. We aimed to determine the effect of luteolin on osteogenic differentiation of periodontal ligament cells (PDLCs). METHODS: Cultured human PDLCs (HPDLCs) were treated by luteolin at 0.01, 0.1, 1, 10, 100 µmol/L, Wnt/ß-catenin pathway inhibitor (XAV939, 5 µmol/L) alone or in combination with 1 µmol/L luteolin. Immunohistochemical staining was performed to ensure cells source. Cell activity and the ability of osteogenic differentiation in HPDLCs were determined by MTT, ALP and Alizarin Red S staining. Real-time Quantitative PCR Detecting System (qPCR) and Western blot were performed to measure the expressions of osteogenic differentiation-related genes such as bone morphogenetic protein 2 (BMP2), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), Osterix (OSX) and Wnt/ß-catenin pathway proteins members cyclin D1 and ß-catenin. RESULTS: Luteolin at concentrations of 0.01, 0.1, 1, 10, 100 µmol/L promoted cell viability, ALP activity and increased calcified nodules content in HPDLCs. The expressions of BMP2, OCN, OSX, RUNX2, ß-catenin and cyclin D1 were increased by luteolin at concentrations of 0.01, 0.1, 1 µmol/L, noticeably, 1 µmol/L luteolin produced the strongest effects. In addition, XAV939 inhibited the expressions of calcification and osteogenic differentiation-related genes in HPDLCs, and 1 µmol/L luteolin availably decreased the inhibitory effect. CONCLUSION: 1 µmol/L luteolin accelerated osteogenic differentiation of HPDLCs via activating the Wnt/ß-catenin pathway, which could be clinically applied to treat periodontal disease.

Effect of edentulous arch restored with implant supported telescopic overdenture / 口腔疾病防治

Objective@#To study the effect of the edentulous arch with implant supported telescopic overdenture. @*Methods@#Fifteen patients with edentulous jaws underwent telescopic overdenture restoration. A total of 26 prostheses were fabricated (11 in the upper jaws, 15 in the lower jaws) with 104 placed implants. The secondary crown was fabricated by wax-lost cast method. Clinical examination and radiographs were conducted. Changes in the marginal bone level around the implants were evaluated by radiograph. The satisfaction level of complete denture and implant-supported overdenture were compared. The mean follow-up time was 32 months (range 6-60 months).@*Results@#Twenty-six prostheses showed better stability, maintenance and occlusion. There were statistical differences between complete denture and implant-supported overdenture in comfort level and chewing function. 1 mm bone lost was found in two patients after 4 years. No implant was lost during the loading time. @*Conclusion @#The preliminary clinical results of this research showed that implant supported telescopic overdentures were reliable for edentulous patients.

The differential roles of mTOR, ERK, and JNK pathways in invariant natural killer T-cell function and survival.

Invariant natural killer T (iNKT) cell is a critical element for both innate and adaptive immunity. The quick responses of mature iNKT cells to TCR stimulation require activation of several different signaling pathways. However, the roles of these signaling pathways in mature iNKT cell biology remain incompletely understood. To address this issue, single signaling pathway was blocked with inhibitor in iNKT cells, and the roles of these signaling pathways were estimated. Results showed that mammalian target of rapamycin (mTOR) plays an essential role for cytokine production and survival in iNKT cells. In contrast, ERK and JNK are more important for iNKT cell effector function, but not survival. Our findings delineate the distinct roles of different signaling pathways in mature iNKT cells and therefore shed new light for modulating iNKT cell function in disease conditions.

[Influence of slot size on torque control].

OBJECTIVE: To study the influence of two slot size brackets on torque control when teeth interacted in the same arch. METHODS: After the upper arch was aligned and leveled in Typodont study, the inclinations of upper teeth 5 +/- 5 were measured when 0.457 2 mm x 0.635 0 mm OPA-K brackets and 0.558 8 mmx0.711 2 mm OPA-K brackets were filled with 0.431 8 mm x 0.635 0 mm stainless steel wire. This experiment was duplicated 10 times. The inclin of each tooth were transformed to the absolute values of the torque play angle psi by computing program, and paired-t test was used. RESULTS: The two kinds of slot size brackets were different with statistical significance on torque control. When the brackets were filled with 0.431 8 mm x 0.635 0 mm stainless steel wire, the absolute values of the angle psi in 0.558 8 mm x 0.711 2 mm and 0.457 2 mm x 0.635 0 mm slot size brackets were 6.140 degrees +/- 3.758 degrees and 2.608 degrees +/- 1.479 degrees respectively, and the average difference of that between the two slot size brackets was 3.532 degrees. The absolute values of the angle psi in the upper left and right canine brackets were 2.560 degrees +/- 2.605 degrees, 4.230 degrees +/- 2.817 degrees, 1.260 degrees +/- 0.747 degrees and 2.070 degrees +/- 0.663 degrees respectively, and average differences between them were smaller than that in the other teeth. CONCLUSION: There was difference between the two kinds of slot size brackets on torque control, and 0.457 2 mm x 0.635 0 mm slot size bracket controls torque better when filled with the same size wire. In this study, the teeth interaction in the same arch probably caused the result that the difference of two slot size brackets on torque control was less than the study results of the theory calculations and material studys before.