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Substrate specificity in non-aqueous esterification catalyzed by commercial lipases activated by hydration-aggregation pretreatment was investigated. Four microbial lipases from Rhizopus japonicus, Burkholderia cepacia, Rhizomucor miehei, and Candida antarctica (fraction B) were used to study the effect of the carbon chain length of saturated fatty acid substrates on the esterification activity with methanol in n-hexane. Hydration-aggregation pretreatment had an activation effect on all lipases used, and different chain length dependencies of esterification activity for lipases from different origins were demonstrated. The effects of various acidic substrates with different degrees of unsaturation, aromatic rings, and alcohol substrates with different carbon chain lengths on esterification activity were examined using R. japonicus lipase, which demonstrated the most remarkable activity enhancement after hydration-aggregation pretreatment. Furthermore, in the esterification of myristic acid with methanol catalyzed by the hydrated-aggregated R. japonicus lipase, maximum reaction rate (5.43 × 10 -5 mmol/(mg-biocat min)) and Michaelis constants for each substrate (48.5 mM for myristic acid, 24.7 mM for methanol) were determined by kinetic analysis based on the two-substrate Michaelis-Menten model., Competing Interests: Declaration of Competing Interest This study did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the effectiveness of a hands-on seminar using a Web conferencing system, based on the post-event questionnaires of the face-to-face and online seminars of the hands-on seminar. For participants to feel realistic training in the online seminars, four educational videos explaining the procedure of the practical skill were created. We compared results of questionnaires acquired from participants after the face-to-face and online seminars. The questions about expectation, comprehension, satisfaction level, and lecture time for the seminars were graded on a 5-point scale. The higher the scores, the higher the rating, except for lecture time. A score of 3 was appropriate for the lecture time, with a higher score indicating that the seminar felt longer and a lower score indicating that the seminar felt shorter. In the evaluation of classroom lectures, such as expectation, comprehension, and satisfaction level for the seminars, there were no significant differences between the face-to-face and online seminars, and both achieved high scores of 4 or more. There was a significant difference in the evaluation of lecture time for classroom lectures, with participants feeling that it was too short in the face-to-face but just right in the online. In all evaluations for hands-on training and discussion, there were no significant differences between the face-to-face and online seminars, and both achieved high scores of 4 or more and time was short. It was concluded that our proposed online seminar approach could achieve a high level of evaluation as face-to-face seminars.

The circadian clock allows plants to anticipate and adapt to periodic environmental changes. Organ- and tissue-specific properties of the circadian clock and shoot-to-root circadian signaling have been reported. While this long-distance signaling is thought to coordinate physiological functions across tissues, little is known about the feedback regulation of the root clock on the shoot clock in the hierarchical circadian network. Here, we show that the plant circadian clock conveys circadian information between shoots and roots through sucrose and K+. We also demonstrate that K+ transport from roots suppresses the variance of period length in shoots and then improves the accuracy of the shoot circadian clock. Sucrose measurements and qPCR showed that root sucrose accumulation was regulated by the circadian clock. Furthermore, root circadian clock genes, including PSEUDO-RESPONSE REGULATOR7 (PRR7), were regulated by sucrose, suggesting the involvement of sucrose from the shoot in the regulation of root clock gene expression. Therefore, we performed time-series measurements of xylem sap and micrografting experiments using prr7 mutants and showed that root PRR7 regulates K+ transport and suppresses variance of period length in the shoot. Our modeling analysis supports the idea that root-to-shoot signaling contributes to the precision of the shoot circadian clock. We performed micrografting experiments that illustrated how root PRR7 plays key roles in maintaining the accuracy of shoot circadian rhythms. We thus present a novel directional signaling pathway for circadian information from roots to shoots and propose that plants modulate physiological events in a timely manner through various timekeeping mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Purpose: We aimed to investigate the usefulness of iViz air ver.4 Convex (FUJIFILM, Tokyo) as a tool to determine the bladder capacity before prostate radiotherapy by comparing it with the existing BladderScan BVI 6100 (Verathon Inc., Bothell, Washington)., Methods: We investigated the usefulness of iViz air as a tool to determine the bladder capacity before prostate radiotherapy by comparing it with the current BladderScan., Results: The absolute value of each error rate was approximately 30.9%±27.2% and 26.4%±18.9% for the BladderScan and iViz air, respectively, with no significant differences between the instruments (p=0.16). Evaluated by urine volume, the mean error rates for bladder volumes >50 ml were 26.9%±19.0% and 26.1%±18.5% for the Bladder Scan and iViz air, respectively, with no significant differences (p=0.56). However, the BladderScan and iViz air had significantly higher error rates of 89.5%±52.5% and 31.5%±25.1%, respectively, if the bladder volume was <50 ml (p=0.005)., Conclusion: The iViz air has limited measurement error to confirm images, especially in limited volumes, suggesting that it is a useful bladder capacity measurement device in performing prostate radiotherapy.

Circadian rhythms and progression of cell differentiation are closely coupled in multicellular organisms. However, whether establishment of circadian rhythms regulates cell differentiation or vice versa has not been elucidated due to technical limitations. Here, we exploit high cell fate plasticity of plant cells to perform single-cell RNA sequencing during the entire process of cell differentiation. By analyzing reconstructed actual time series of the differentiation processes at single-cell resolution using a method we developed (PeakMatch), we find that the expression profile of clock genes is changed prior to cell differentiation, including induction of the clock gene LUX ARRYTHMO (LUX). ChIP sequencing analysis reveals that LUX induction in early differentiating cells directly targets genes involved in cell-cycle progression to regulate cell differentiation. Taken together, these results not only reveal a guiding role of the plant circadian clock in cell differentiation but also provide an approach for time-series analysis at single-cell resolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Circadian rhythms are based on biochemical oscillations generated by clock genes/proteins, which independently evolved in animals, fungi, plants, and cyanobacteria. Temperature compensation of the oscillation speed is a common feature of the circadian clocks, but the evolutionary-conserved mechanism has been unclear. Here, we show that Na + /Ca 2+ exchanger (NCX) mediates cold-responsive Ca 2+ signaling important for the temperature-compensated oscillation in mammalian cells. In response to temperature decrease, NCX elevates intracellular Ca 2+ , which activates Ca 2+ /calmodulin-dependent protein kinase II and accelerates transcriptional oscillations of clock genes. The cold-responsive Ca 2+ signaling is conserved among mice, Drosophila , and Arabidopsis The mammalian cellular rhythms and Drosophila behavioral rhythms were severely attenuated by NCX inhibition, indicating essential roles of NCX in both temperature compensation and autonomous oscillation. NCX also contributes to the temperature-compensated transcriptional rhythms in cyanobacterial clock. Our results suggest that NCX-mediated Ca 2+ signaling is a common mechanism underlying temperature-compensated circadian rhythms both in eukaryotes and prokaryotes., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

We evaluated the diagnostic value of atrial fibrillation (AF) measured by a wrist-type pulse wave monitor in this case-control study. Six serial pulse wave values (three in the left and three in the right wrist) were measured using a wrist-type monitor in 29 AF patients and 30 subjects with sinus rhythm. We defined "monitor AF in irregular pulse peak (IPP) 15/20/25" as follows: (a) IPP: |interval of pulse peak - the average of the interval of the pulse peak| ≥ the average of the interval of the pulse peak × 15/20/25%; (b) irregular heartbeat (IHB): beats of IPP ≥ total pulse × 20%; and (c) monitor AF: ≥4 IHBs of the six pulse wave measurements. In IPP 15, the sensitivity and specificity were 0.97 and 1.00, respectively. Pulse wave analysis by a wrist-type monitor was shown to have high sensitivity and specificity for the diagnosis of AF., (©2019 Wiley Periodicals, Inc.)

Purpose: To analyze the outcomes following re-irradiation for local recurrence of rare head and neck tumors., Material and Methods: We retrospectively analyzed 11 patients who had received intensity-modulated radiation therapy (IMRT) for recurrent tumors in the head and neck except for laryngopharynx., Results: Primary tumor sites included the maxillary sinus, nasal cavity, and external ear canal in six, three, and two patients, respectively. The median follow-up times were 13 (range, 3-54) months. The median survival time was 17 months with 1- and 2-year survival rates of 63.64 and 39.77%, respectively. Among 11 patients, five experienced local failure in the follow-up period. The 1- and 2-year local control rates were 58 and 47%, respectively. Patients who had received a radiation dose of ≥3 Gy per fraction showed significantly better local control than those receiving less (p = .0419). One patient experienced Grade 3 facial pain as acute toxicity. Late toxicities included radiographic findings of partial central nervous system necrosis in three patients and Grade 3 osteonecrosis and Grade 3 facial nerve disorder in one patient., Conclusions: Re-irradiation of rare head and neck tumors using IMRT for loco-regional recurrence may be an acceptable treatment option.

Background: This study aimed to assess the need to consider microscopic invasion in terms of treatment planning in stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma and elucidate the appropriate clinical target volume (CTV) margin., Patients and Methods: A total of 121 patients (with 146 liver tumors) who underwent SBRT between July 2007 and August 2016 were analyzed, regarding overall survival and local control (LC)., Results: The 2- and 5-year LC rates were 91.5% and 89.8%, respectively. Planning target volume (PTV) margin <8 mm was associated with poor LC. Of the 77 patients with PTV margin of <8 mm, age <75 years was associated with poor LC, while alpha-fetoprotein (AFP) ≤20 ng/ml was associated with good LC., Conclusion: In patients with high AFP levels, there is a possibility of microscopic invasion around the tumor, suggesting that LC may be improved by adding an additional clinical target volume margin to the gross tumor volume., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 70's man had been treated with gemcitabine(GEM)and nab-paclitaxel(nabPTX)combination for advanced pancreatic tail cancer with splenic invasion and liver metastases. However, the primary lesion was not controlled, then intensity-modulat- ed radiation therapy(76.5 Gy/17 Fr)was performed for primary lesion. Three grown hypovascular liver metastases were detected by follow-up EOB-MRI and PET-computed tomography(CT)imaging with 18F-FDG. Unfortunately, these lesions were not detected by intravenous injection of contrast media with CT nor ultrasonography. Radiofrequency ablation(RFA) under computed tomography during arterial portography(CTAP)guidance was performed. The patient has been alive for 1 year after RFA with no recurrence. CTAP could be a feasible image guidance for the treatment of hypovascular liver metastases with RFA.

Cell-type-specific transcription factors are key to deducing the distinct functions of specialized cells from gene expression profiles. Mesophyll is a major tissue for photosynthesis, and contributes about 80% of total RNA from leaves. Palisade and spongy mesophyll cells are sub-tissues that have different morphologies and physiologies. Thus, determining the palisade and spongy mesophyll-specific transcription factors from the respective sub-tissue-specific transcriptomes is vital to understanding or verifying functions of major plant tissues. One way in which gene expression profiles can be addressed is through direct isolation. Here, we present rapid and simple methods to isolate palisade and spongy mesophyll cells mechanically and enzymatically. This method provides a good yield of each isolated cell type, and the isolated cells can be used for various downstream applications.

Aim: The purpose of this study was to determine the optimal mean liver biologically effective dose (BED) to prevent radiation-induced liver disease (RILD) in stereotactic body radiation therapy (SBRT)., Background: The actual mean doses appropriate for liver irradiation in modern radiotherapy techniques have not been adequately investigated, although SBRT is sometimes alternatively performed using fractionated regimens., Materials and Methods: SBRT treatment plans for liver tumors in 50 patients were analyzed. All distributions of the physical doses were transformed to BED 2 using the linear-quadratic model. The relationship between physical doses and the BED 2 for the liver were then analyzed, as was the relationship between the mean BED 2 for the liver and the planning target volume (PTV)., Results: A significantly positive correlation was observed between the mean physical dose for the background liver and the mean BED 2 for the whole liver ( P  < 0.0001, r  = 0.9558). Using the LQ model, a mean BED 2 of 73 and 16 Gy for the whole liver corresponded to the hepatic tolerable mean physical dose of 21 and 6 Gy for Child-Pugh A- and B-classified patients, respectively. Additionally, the PTV values were positively correlated with the BEDs for the whole liver ( P  < 0.0001, r  = 0.8600), and the background liver ( P  < 0.0001, r  = 0.7854)., Conclusion: A mean BED 2 of 73 and 16 Gy for the whole liver appeared appropriate to prevent RILD in patients with Child-Pugh classes A and B, respectively. The mean BED 2 for the liver correlated well with the PTV.

Metastatic liver tumors (MLTs) from colorectal cancer (CRC) are often treated with stereotactic body radiation therapy (SBRT). The present study aimed to examine the predictive factors for response of MLTs to SBRT. A total of 39 MLTs from 24 patients with CRC were retrospectively analyzed. Radiotherapy for MLT was typically performed with a prescribed dose equivalent to a biologically effective dose (BED) 10 of 100 Gy. The median follow-up period was 16 months (range, 5-64 months). The median prescribed dose and total BED 10 were 56 Gy (range, 45-72 Gy) and 97.5 Gy (range, 71.7-115.5 Gy), respectively, in a median of 8 fractions (range, 4-33 fractions). The 1- and 2-year local control rates were 67.2 and 35.9%, respectively. For patients with MLT treated with ablative SBRT (BED 10 ≥100 Gy in ≤5 fractions), the 1- and 2-year local control rates were 83.3 and 62.5%, respectively. Univariate analysis showed that primary tumor location (left-sided colon), maximum tumor diameter (≤30 mm) and ablative SBRT (BED 10 ≥100 Gy in ≤5 fractions) were significantly associated with improved local control (P=0.0058, P=0.0059 and P=0.0268, respectively). Multivariate analysis showed that tumor diameter was significantly associated with improved local control (P=0.0314). In addition, patients who received ablative SBRT had significantly prolonged overall survival times compared with those treated with non-ablative SBRT (P=0.0261). To conclude, tumors ≤30 mm that can be treated with ablative SBRT are associated with good local control rates. The primary tumor location may affect the radiosensitivity of MLTs.

We aimed to describe the feasibility and efficacy of a novel non-invasive fixation and monitoring (F-M) device for the eyeballs (which uses a right-angle prism mirror as the optic axis guide) in three consecutive patients with choroidal melanoma who were treated with intensity-modulated radiotherapy (IMRT). The device consists of an immobilization shell, a right-angle prism mirror, a high magnification optical zoom video camera, a guide lamp, a digital voice recorder, a personal computer, and a National Television System Committee standard analog video cable. Using the right-angle prism mirror, the antero-posterior axis was determined coincident with the optic axis connecting the centers of the cornea and pupil. The axis was then connected to the guide light and video camera installed on the couch top on the distal side. Repositioning accuracy improved using this method. Furthermore, the positional error of the lens was markedly reduced from ±1.16, ±1.68 and ±1.11 mm to ±0.23, ±0.58 and ±0.26 mm in the horizontal direction, and from ±1.50, ±1.03 and ±0.48 mm to ±0.29, ±0.30 and ±0.24 mm in the vertical direction (Patient #1, #2 and #3, respectively). Accordingly, the F-M device method decreased the planning target volume size and improved the dose-volume histogram parameters of the organ-at-risk via IMRT inverse planning. Importantly, the treatment method was well tolerated., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Sphingosine 1-phosphate (S1P) receptors are G-protein-coupled receptors. Among the five identified subtypes S1P1-5, the S1P3 receptor expressed on vascular endothelial cells has been shown to play an important role in cell proliferation, migration, and inflammation. A pharmacophore-based database search was used to identify a potent scaffold for an S1P3 receptor antagonist by common feature-based alignment and further validated using the Güner-Henry (GH) scoring method. Assumed excluded volumes were merged into this model to evaluate the steric effect with the S1P3 receptor. Three commercially available compounds were identified as S1P3 receptor antagonists, with IC50 values <5 microM. The synthesis of further derivatives revealed that the 3,4-dialkoxybenzophenone scaffold is a potent component of an S1P3 receptor antagonist. Our results indicate that pharmacophore-based design of S1P3 receptor antagonists can be used to expand the possibility of structural modification through scaffold-hopping based on a database search.

We evaluated the activities of 2-alkynyladenosine derivatives, relatively selective adenosine A2 receptor agonists, in the intraocular pressure regulation in rabbits. An adenosine A2 receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680) decreased intraocular pressure, while another A2 receptor agonist 2-(phenylamino)adenosine transiently increased it. The first group of 2-alkynyladenosine derivatives (1-hexyn-1-yl derivatives) caused a transient increase followed by decrease in intraocular pressure, while the second group (1-octyn-1-yl and 6-cyano-1-hexyn-1-yl derivatives) only decreased it. The second group is also effective in the ocular hypertensive models induced by water-loading and alpha-chymotrypsin. The outflow facility was increased by a 1-octyn-1-yl derivative. Both increase and decrease in intraocular pressure induced by 2-alkynyladenosine derivatives were inhibited by an adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropyl xanthine. These findings suggest that 2-alkynyladenosine derivatives may affect intraocular pressure via adenosine A2 receptor, and 2-alkynyladenosine derivative-induced ocular hypotension is due to the increase of outflow facility.

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (Cmax) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng.h/mL, and the mean Cmax were 42.6 and 86.6 micrograms/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

Chemical control against larvae of Simulium ochraceum, the principal vector of onchocerciasis, was carried out from 1979 to 1984 in a 91.3 km2 area of Guatemala where onchocerciasis is endemic. The control operation was divided chronologically into three phases according to the different tactics employed. Phase 1 (1979-1981), using briquettes of fat and detergent containing 10% temephos, was effective only in perennial streams. Phase 2 (1981-1982), which limited the application target to small streams with discharges of 0.1-1 litre/sec, was not effective. Successful control was achieved by Phase 3 (1982-1984), which consisted of fort-nightly applications of 5% temephos water dispersable powder in fixed doses of 24 g (1.2 g active ingredient) to every 50-100 m stretch of all streams with discharge rates of 0.1-50 l/sec. Vector biting rates were reduced by 97.8% in 1982 to 1983 and 97.6% in 1983-1984. The biting density of S. ochraceum at all five stations was reduced to less than 1.9/man/hour, the proposed critical level for long term transmission of onchocerciasis. The biting density of the S. metallicum/horacioi complex was not apparently affected by this operation. Through analysis of the density of S. ochraceum at various distances from the untreated areas, infiltration of the flies was found to be rare, if the distance was beyond 2 km. Fly-round surveys proved to be practical as a surveillance method for detecting larval breeding in untreated or improperly treated streams. The cost for a nation-wide vector control operation was presented.