Effectiveness of early high-flow nasal oxygen therapy after extubation of patients in the intensive care unit.

PURPOSE: This study aimed to evaluate the impact of early high-flow nasal oxygen (HFNO) therapy initiation using a pre-determined respiratory rate­oxygenation (ROX) index on reducing reintubation rates and duration of intensive care unit (ICU) stay in post-extubated patients. MATERIALS AND METHODS: We enrolled a total of 145 extubated patients (mean age: 67.1 ± 12.9 years; sex: 96 male and 49 female; acute physiology and chronic health evaluation II score: 18.4 ± 6.8 points) classified into two groups: 71 patients admitted to the ICU before establishing extubation criteria and 74 patients after criteria implementation, over a 6-month period. We compared the HFNO reintubation rates and ROX index at 2 h post-extubation before and after implementing early HFNO criteria. RESULTS: The utilization rate of HFNO pre- and post-establishment of early HFNO criteria did not differ significantly (19.7% vs. 17.6%). However, the reintubation rate significantly decreased (11.3% vs. 4.1%, P < 0.05) with early HFNO use. Additionally, significant differences were observed in the total intubation period (5.2 ± 7.0 vs. 2.5 ± 2.7 days, P < 0.05) and ICU duration (8.6 ± 9.7 vs. 5.8 ± 5.6 days, P < 0.05). CONCLUSIONS: Early initiation of HFNO guided by the ROX index threshold post-extubation in patients admitted to ICU is associated with reduced reintubation rates and shorter ICU stays.

Strobilurin X acts as an anticancer drug by inhibiting protein synthesis and suppressing mitochondrial respiratory chain activity.

PURPOSE: Strobilurins act as antifungal agents by inhibiting the mitochondrial respiratory chain. The cytotoxic activity of strobilurins, focusing on its anticancer activities, has been reported. However, the mechanisms involved in these activities remain unclear. METHODS: The cytotoxic effects of strobilurin X isolated from the mycelium of Mucidula. venosolamellata were examined in human cancer cell lines (A549 and HeLa) and normal fibroblasts (WI-38). RESULTS: Strobilurin X significantly decreased the viability of A549 and HeLa cells compared to that in the WI-38 cells after 48 h of exposure. The EC50 values for cytotoxicity in the A549, HeLa, and WI-38 cells were 3.4, 5.4, and 16.8 µg/mL, respectively. Strobilurin X inhibited the mitochondrial respiratory chain and enhanced the release of lactate in the A549 cells. The IC50 value of strobilurin X against the mitochondrial respiratory chain complex III activity was 139.8 ng/mL. The cytotoxicity induced by strobilurin X was not completely rescued after adding uridine, methyl pyruvate, or N-acetyl cysteine. Furthermore, pharmacological approaches demonstrated that strobilurin X failed to modulate the mitogen-activated protein kinase family and phosphoinositide 3-kinase-Akt pathways; alternatively, it suppressed protein synthesis independent of uridine. CONCLUSION: Strobilurin X induced cytotoxicity by blocking the mitochondrial respiratory chain and suppressing protein synthesis. These findings may aid in the development of novel anticancer drugs using strobilurins.

Suppression of anthracnose disease by orsellinaldehyde isolated from the mushroom Coprinus comatus.

AIMS: Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. METHODS AND RESULTS: The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. CONCLUSIONS: Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.

Inhibition of melanoma cell proliferation by strobilurins isolated from mushrooms and their synthetic analogues.

Strobilurins A and X, isolated from Mucidula venosolamellata culture extracts, demonstrated potent inhibition of human melanoma G-361 cell proliferation. Strobilurin X exhibited milder inhibitory effects on human fibroblast cells (NB1RGB) compared to strobilurin A. Additional strobilurin-related compounds were isolated from the other mushroom species. Oudemansins A and B displayed weaker activities on G-361 cells than strobilurins A and B, respectively, emphasizing the importance of a conjugated double-bond structure. Among isolated compounds, strobilurin G showed the lowest IC50 value for G-361 cells. Additional strobilurins bearing various substituents on the benzene ring were synthesized. Synthetic intermediates lacking the methyl ß-methoxyacrylate group and a strobilurin analogue bearing modified ß-methoxyacrylate moiety showed almost no inhibitory activity against G-361 cells. The introduction of long or bulky substituents at the 4' position of the benzene ring of strobilurins enhanced the activity and selectivity, suggesting differential recognition of the benzene ring by G-361 and NB1RGB cells.

Identification and evolution of a diterpenoid phytoalexin oryzalactone biosynthetic gene in the genus Oryza.

The natural variation of plant-specialized metabolites represents the evolutionary adaptation of plants to their environments. However, the molecular mechanisms that account for the diversification of the metabolic pathways have not been fully clarified. Rice plants resist attacks from pathogens by accumulating diterpenoid phytoalexins. It has been confirmed that the composition of rice phytoalexins exhibits numerous natural variations. Major rice phytoalexins (momilactones and phytocassanes) are accumulated in most cultivars, although oryzalactone is a cultivar-specific compound. Here, we attempted to reveal the evolutionary trajectory of the diversification of phytoalexins by analyzing the oryzalactone biosynthetic gene in Oryza species. The candidate gene, KSLX-OL, which accounts for oryzalactone biosynthesis, was found around the single-nucleotide polymorphisms specific to the oryzalactone-accumulating cultivars in the long arm of chromosome 11. The metabolite analyses in Nicotiana benthamiana and rice plants overexpressing KSLX-OL indicated that KSLX-OL is responsible for the oryzalactone biosynthesis. KSLX-OL is an allele of KSL8 that is involved in the biosynthesis of another diterpenoid phytoalexin, oryzalexin S and is specifically distributed in the AA genome species. KSLX-NOL and KSLX-bar, which encode similar enzymes but are not involved in oryzalactone biosynthesis, were also found in AA genome species. The phylogenetic analyses of KSLXs, KSL8s, and related pseudogenes (KSL9s) indicated that KSLX-OL was generated from a common ancestor with KSL8 and KSL9 via gene duplication, functional differentiation, and gene fusion. The wide distributions of KSLX-OL and KSL8 in AA genome species demonstrate their long-term coexistence beyond species differentiation, suggesting a balancing selection between the genes.

Production of Sustainable Aviation Fuel by Hydrocracking of n-Heptadecane Using Pt-Supported Y-Zeolite-Al2O3 Composite Catalysts.

Hydrocracking of fat or Fischer-Tropsch (FT) wax from biomass to produce the jet fuel of sustainable aviation fuel has been one of the key reactions. n-Heptadecane, which is one of the model diesel fractions produced from fat or FT wax, has hardly been used for hydrocracking of hydrocarbon for jet fuel production, while n-hexadecane has often been used as one of the model compounds for this reaction. In the present study, a HY-zeolite (50 wt %, SiO2/Al2O3 = 100)-Al2O3 (50 wt %) composite-supported Pt (0.5 wt %) catalyst [0.5Pt/Y(100)35A] was tested for hydrocracking of n-heptadecane using a fixed-bed flow reactor at a H2 pressure of 0.5 MPa, H2 flow rate of 300 mL/min, WHSV of 2.3 h-1, and a catalyst weight of 2 g. Fine-tuning of the temperature to 295 °C achieved the highest selectivity of 74% for the jet fuel fraction C8-C15 with the high conversion of 99%. The jet fuel yield reached 73%, which was almost an ideal maximum yield of 75%. Similar hydrocracking of n-hexadecane has just reported the maximum yield of 51% for jet fuel fraction. Further, 0.5Pt/Z(110)35A, which has a composition similar to that of 0.5Pt/Y(100)35A except for the type of zeolite, could not give as high yield of jet fuel as 0.5Pt/Y(100)35A because the rapid conversion to lighter fractions than the jet fuel occurred by the slight increase in the reaction temperature even at a lower temperature range.

Identification of two phthalide derivatives and an oxindole compound isolated from the edible mushroom Pleurotus ostreatus and their inhibitory activities against plant pathogenic microorganisms.

The excessive use of chemical pesticides in agricultural fields for controlling plant pathogenic microorganisms harms human health, the environment, and other beneficial microorganisms in the soil and plants. To address this challenge, it is essential to isolate and discover bioactive compounds from biological resources that could inhibit plant pathogenic microorganisms. In this study, the culture filtrate of the edible mushroom Pleurotus ostreatus was subjected to bioassay-guided isolation, and two phthalide derivatives-4,6-dimethoxyphthalide (1) and 5,7-dimethoxyphthalide (2)-were identified, along with an oxindole compound-3-hydroxy-3-methyloxindole (3). The inhibitory activities of the three compounds were evaluated against four fungal and five bacterial pathogens. Remarkably, 1 and 2 exhibited the lowest IC50 values against the conidial germination and germ tube elongation of the rice blast fungus Pyricularia oryzae. However, their effectiveness against bacterial pathogens was relatively low. The (S) and (R)-enantiomers of 3-hydroxy-3-methyloxindole showed different activities against plant fungal pathogens and bacterial plant pathogens.

Isolation, structure elucidation, and biological activities of sesquiterpenes and phthalides from two edible mushrooms Pleurotus species.

Antimicrobial compounds were purified from culture filtrates from 2 edible Pleurotus species. Using a bioassay-guided fractionation of the culture filtrate extracts, 3 compounds (1-3) were obtained from Pleurotus ostreatus, and another compound (4) was obtained from Pleurotus pulmonarius. Spectroscopic analysis revealed that 1-3 was identified as 5,7-dimethoxyphthalide, 4,6-dimethoxyphthalide, and cheimonophyllon E, respectively, while 4 were identified as pleuroton A. The minimum inhibitory concentration and minimum bactericidal concentration of these compounds were determined against 6 pathogenic bacterial species, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. Compounds 2 and 4 were inhibitory against all tested bacteria, while 1 and 4 were inhibitory against 3 and 2 species, respectively. In addition, 1-4 inhibited tyrosinase, with IC50 values of 0.10-0.30 mg/mL, and α-glucosidase, with IC50 values of 0.12-0.54 mg/mL. However, their antioxidant capacities were marginal.

Identification of Cyclocybe erebia metabolites that affect the circadian rhythm of Eluc expression under control of Bmal1 promoter in mouse fibroblast cells.

Pharmacological intervention of circadian rhythms is a potentially useful approach for ameliorating various health problems caused by disturbed circadian rhythms including sleep disorder and metabolic diseases. To find compounds that affect circadian rhythms, we screened mushroom extracts using mouse cells expressing the luciferase gene under the control of the mouse Bmal1 promoter. The culture filtrate extract from the basidiomycete Cyclocybe erebia enhanced the oscillation of bioluminescence caused by the expression of the luciferase gene and prolonged the period of bioluminescence. Bioassay-guided fractionation of the extract resulted in purification of compounds 1 and 2. Spectroscopic analyses along with single-crystal X-ray diffraction analysis, revealed that these compounds were diterpenoids with a unique skeleton and a fused ring system comprising 3-, 7-, and 5-membered rings. Compounds 1 and 2 were named cyclocircadins A and B, respectively. These findings suggested that natural diterpenoids could be a source of compounds with the activity affecting circadian rhythms.

(E)-7-phenyl-2-heptene-4,6-diyn-1-ol from Bidens pilosa as a repellent against isopods.

The development of repellents as alternatives to insecticides has expanded in recent years. However, their use in isopod pest control is limited. To develop an isopod repellent, a plant extract library from wild plants native to the Kochi Prefecture was screened for repellent activity against pillbugs, and 82 samples (87%) exhibited repellent activity. Among them, (E)-7-phenyl-2-heptene-4,6-diyn-1-ol was isolated and identified as a repellent from the root of Bidens pilosa. It had a half-maximal effective concentration of 0.20 µm, with a strong repellency. A study of the structure-activity relationship to (E)-7-phenyl-2-heptene-4,6-diyn-1-ol revealed that the presence of a hydroxyl group and an aromatic at both ends of the length of the seven-carbon chain is important for the expression of repellency. These results can potentially lead to a new repellent of phenylalkyl alcohol.

Molecular identification of a laccase that catalyzes the oxidative coupling of a hydroxycinnamic acid amide for hordatine biosynthesis in barley.

Plants produce dimerized phenolic compounds as secondary metabolites. Hordatine A (HA), a dehydrodimer of p-coumaroylagmatine (pCA), is an antifungal compound accumulated at high levels in young barley (Hordeum vulgare) seedlings. The enzyme responsible for the oxidative dimerization of pCA, which is the final step of the hordatine biosynthetic pathway, has not been identified. In this study, we first verified the presence of this enzyme activity in the crude extract of barley seedlings. Because the enzyme activity was not dependent on H2 O2 , the responsible enzyme was not peroxidase, which was previously implicated in HA biosynthesis. The analysis of the dissection lines of wheat (Triticum aestivum) carrying aberrant barley 2H chromosomes detected HA in the wheat lines carrying the distal part of the 2H short arm. This chromosomal region contains two laccase genes (HvLAC1 and HvLAC2) that are highly expressed at the seedling stage and may encode enzymes that oxidize pCA during the formation of HA. Changes in the HvLAC transcript levels coincided with the changes in the HA biosynthesis-related enzyme activities in the crude extract and the HA content in barley seedlings. Moreover, HvLAC genes were heterologously expressed in Nicotiana benthamiana leaves and in bamboo (Phyllostachys nigra) suspension cells and HA biosynthetic activities were detected in the crude extract of transformed N. benthamiana leaves and bamboo suspension cells. The HA formed by the enzymatic reaction had the same stereo-configuration as the naturally occurring HA. These results demonstrate that HvLAC enzymes mediate the oxidative coupling of pCA during HA biosynthesis.

Natural variation of diterpenoid phytoalexins in rice: Aromatic diterpenoid phytoalexins in specific cultivars.

Rice (Oryza sativa L.) plants accumulate antimicrobial compounds known as phytoalexins in response to pathogen attack. To date, more than 20 compounds have been isolated as phytoalexins from rice, mostly diterpenoids. However, the quantitative analysis of diterpenoid phytoalexins in various cultivars has revealed that the cultivar 'Jinguoyin' does not accumulate these compounds at detectable concentrations. Therefore, in this study, we attempted to detect a new class of phytoalexins from Bipolaris oryzae infected leaves of 'Jinguoyin'. We detected five compounds in the leaves of the target cultivar, whereas these compounds were not detected in the leaves of 'Nipponbare' or 'Kasalath', which are representative cultivars of the japonica and indica subspecies. Subsequently, we isolated these compounds from ultraviolet (UV)-light-irradiated leaves and determined their structures by spectroscopic analysis and the crystalline sponge method. All the compounds were diterpenoids containing a benzene ring and were detected from the pathogen-infected rice leaves for the first time. Because the compounds showed antifungal activity against B. oryzae and Pyricularia oryzae, we propose that they function as phytoalexins in rice and named them abietoryzins A-E. The abietoryzins tended to accumulate at high concentrations in cultivars that accumulated low levels of known diterpenoid phytoalexins after UV-light irradiation. Of the total of 69 cultivars in the WRC, 30 cultivars accumulated at least one of the abietoryzins, and, in 15 cultivars, the amounts of some abietoryzins were the highest among those of the analyzed phytoalexins. Therefore, abietoryzins are a major phytoalexin group in rice, although their presence has, to date, been overlooked.

Development of pulmonary arterial hypertension following long-term Qing-Dai use for ulcerative colitis.

A 20-year-old woman using Qing-Dai for about 7 years for intractable ulcerative colitis was admitted to the emergency room because of dyspnea and syncope following exertion. The patient was diagnosed with drug-induced pulmonary arterial hypertension (PAH). Discontinuation of Qing-Dai rapidly improved PAH symptoms. The REVEAL 2.0 risk score, which is useful for assessing the severity of PAH and predicting prognosis, improved from high risk (12) to low risk (4) within 10 days. Discontinuing long-term use of Qing-Dai can rapidly improve Qing-Dai-induced PAH. Learning objective: Discontinuing the long-term use of Qing-Dai used for treating ulcerative colitis (UC) can rapidly improve Qing-Dai induced pulmonary arterial hypertension (PAH). REVEAL 2.0 risk score in patients who developed PAH due to Qing-Dai was useful for screening PAH in patients taking Qing-Dai for treatment of UC.

Evaluating the one-time chair stand test for predicting the coronavirus disease severity in patients during hospital admission: a cohort study in Japan.

BACKGROUND: This study aimed to understand whether the one-time chair stand test (CS-1) is useful for predicting the severity of coronavirus disease (COVID-19) in 101 patients admitted to the hospital with acute respiratory failure. METHODS: This single-centered, prospective observational cohort study enrolled 101 critically ill adult patients hospitalized with COVID-19 who underwent the CS-1 as a dynamic evaluation tool in clinical practice between late April 2020 and October 2021. Data on demographic characteristics, symptoms, laboratory values, computed tomography findings, and clinical course after admission were collected. Furthermore, the data was compared, and the association between the intubation and non-intubation groups was determined. We also calculated the cutoff point, area under the curve (AUC), and 95% confidence interval (CI) of the change in oxygen saturation (ΔSpO2) during the CS-1. RESULTS: Thirty-three out of 101 patients (33%) were intubated during hospitalization. There was no significant difference in the resting SpO2 (93.3% versus 95.2%, P = 0.22), but there was a significant difference in ΔSpO2 during the CS-1 between the intubation and non-intubation groups (10.8% versus 5.5%, P < 0.01). In addition, there was a significant correlation between hospitalization and ΔSpO2 during the CS-1 (ρ = 0.60, P < 0.01). The generated cutoff point was calculated as 9.5% (AUC = 0.94, 95% CI = 0.88-1.00). CONCLUSION: For COVID-19 patients with acute respiratory failure, the CS-1 performed on admission was useful for predicting the severity of COVID-19. Furthermore, the CS-1 can be utilized as a remote and simple evaluation parameter. Thus, it could have potential clinical applications in the future.

Integrating Both Parallax and Latency Compensation into Video See-through Head-mounted Display.

This work introduces a perspective-corrected video see-through mixed-reality head-mounted display with edge-preserving occlusion and low-latency capabilities. To realize the consistent spatial and temporal composition of a captured real world containing virtual objects, we perform three essential tasks: 1) to reconstruct captured images so as to match the user's view; 2) to occlude virtual objects with nearer real objects, to provide users with correct depth cues; and 3) to reproject the virtual and captured scenes to be matched and to keep up with users' head motions. Captured image reconstruction and occlusion-mask generation require dense and accurate depth maps. However, estimating these maps is computationally difficult, which results in longer latencies. To obtain an acceptable balance between spatial consistency and low latency, we rapidly generated depth maps by focusing on edge smoothness and disocclusion (instead of fully accurate maps), to shorten the processing time. Our algorithm refines edges via a hybrid method involving infrared masks and color-guided filters, and it fills disocclusions using temporally cached depth maps. Our system combines these algorithms in a two-phase temporal warping architecture based upon synchronized camera pairs and displays. The first phase of warping is to reduce registration errors between the virtual and captured scenes. The second is to present virtual and captured scenes that correspond with the user's head motion. We implemented these methods on our wearable prototype and performed end-to-end measurements of its accuracy and latency. We achieved an acceptable latency due to head motion (less than 4 ms) and spatial accuracy (less than 0.1° in size and less than 0.3° in position) in our test environment. We anticipate that this work will help improve the realism of mixed reality systems.

NAD+ enhances the activity and thermostability of S-adenosyl-L-homocysteine hydrolase from Pyrococcus horikoshii OT3.

S-Adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) are important biochemical intermediates. SAM is the major methyl donor for diverse methylation reactions in vivo. The SAM to SAH ratio serves as a marker of methylation capacity. Stable isotope-labeled SAM and SAH are used to measure this ratio with high sensitivity. SAH hydrolase (EC 3.13.2.1; SAHH), which reversibly catalyzes the conversion of adenosine and L-homocysteine to SAH, is used to produce labeled SAH. To produce labeled SAH with high efficiency, we focused on the SAHH of Pyrococcus horikoshii OT3, a thermophilic archaeon. We prepared recombinant P. horikoshii SAHH using Escherichia coli and investigated its enzymatic properties. Unexpectedly, the optimum temperature and thermostability of P. horikoshii SAHH were much lower than its optimum growth temperature. However, addition of NAD+ to the reaction mixture shifted the optimum temperature of P. horikoshii SAHH to a higher temperature, suggesting that NAD+ stabilizes the structure of the enzyme.

[Surgical Technique for Mesorectal Division in the Robotic Anterior Resection for Rectal Cancer].

Since April 2018, robot-assisted rectal resection has been approved as an insurance medical treatment, and robot- assisted rectal resection is rapidly becoming widespread. Even in robot-assisted laparoscopic surgery, mesorectal division is difficult in a narrow pelvic cavity. At the beginning of the operation, Vessel Sealer ExtendTM(price 89,250 yen)was used, but as the procedure became stable, the mesorectal division was started with bipolar forceps and monopolar scissors. The purpose of this study was to investigate the mesorectal division time and postoperative complications associated with changes in the procedure. 36 patients who underwent robot-assisted anterior resection for rectal cancer by the same surgeon from January 2019 to December 2021. We compared mesorectal division time and postoperative complication. Median operation time were 267 minutes, median console time were 132 minutes. There were no complications such as intestinal obstruction or anastomotic leakage. There was no difference in mesorectal division time time between Vessel Sealer groups and Scissors groups(14 min 55 sec vs 16 min 5 sec). The mesorectal division with bipolar forceps and monopolar scissors could be performed without extending the operation time, and could be performed with cost-benefit and safely.

pH response and mechanical properties of Fe2O3-TeO2-based glass/stainless steel enamel electrodes for pH sensors.

Glass pH sensors are unsuitable for in vivo biomedical, clinical, or food applications because of the brittleness of glass and the difficulty in measuring small volumes. Enamel structures such as glass/stainless steel are candidates for glass-based pH electrodes. In this study, new enamel electrodes for pH sensors using Fe2O3-TeO2-based glass/stainless steel were developed. The effect of NiO addition to Fe2O3-TeO2 glass on the pH sensitivity and the three-point bending strength of enamels were investigated. The effect of NiO addition to Fe2O3-TeO2 glass/stainless steel on the pH sensitivity was negligible. Fe2O3-TeO2-based glass/stainless steel showed pH sensitivity appropriate to a working electrode. Enameling at a lower temperature under an air atmosphere was desirable for narrowing the gap between pH 4-7 and pH 7-9 sensitivities. The NiO addition to Fe2O3-TeO2 glass/stainless steel decreased the three-point bending strength. Therefore, NiO did not serve as an adhesion oxide in the Fe2O3-TeO2 glass. Fe2O3-TeO2 glass/stainless steel possessed the highest three-point bending strength among all samples when prepared at 670 °C under an air atmosphere. Therefore, no NiO addition and enameling at a lower temperature under an air atmosphere are desirable for obtaining more robust Fe2O3-TeO2 glass/stainless steel than Li2O-SiO2-based glass electrodes for pH sensors.

Synthesis and antifungal activity of the proposed structure of a volatile compound isolated from the edible mushroom Hypsizygus marmoreus.

We synthesized the proposed structure of an antifungal compound detected in the culture broth of the edible mushroom Hypsizygus marmoreus. Using the Evans aldol and Abiko-Masamune aldol reactions as the key steps, we synthesized all of the stereoisomers of the compound with high stereoselectivity. The GC retention times and the fragmentation patterns in the mass spectra of the synthesized isomers did not match those of the natural product. Therefore, this result may imply that it is necessary to reisolate the natural product and reconsider its structure. All of the synthesized isomers were found to exhibit antifungal activity against the phytopathogenic fungus Alternaria brassicicola. Due to their simple structures, the obtained isomers could be lead compounds for new pesticides.

Relative bradycardia in patients with moderate-to-severe COVID-19: a retrospective cohort study.

Coronavirus-related disease (COVID-19) can result in relative bradycardia; however, there are no reports on relative bradycardia in patients with moderate-to-severe COVID-19 who require oxygen. We retrospectively investigated 45 patients with moderate-to-severe COVID-19 and examined the relationship between heart rate and body temperature at the time of initiating oxygen or mechanical ventilation. For three consecutive days after initiating oxygen therapy, body temperature (day's highest temperature), heart rate, and other vital signs were measured simultaneously. We checked for relative bradycardia and analyzed the differences between patients with moderate COVID-19 (oxygen requirement ≤ 5 L/min) and those with severe COVID-19 (oxygen requirement ≥ 5 L/min). Of the 45 patients, 28 and 17 had moderate and severe COVID-19, respectively. The heart rate increased with increasing body temperature, and almost all patients satisfied the criteria of relative bradycardia. In Spearman's rank correlation analysis, body temperature was significantly correlated with heart rate (ρ = 0.483, p = 0.012) in moderately ill patients but not in severely ill patients (ρ = 0.261, p = 0.297). Multiple regression analysis revealed that the severity of COVID-19 and body temperature were independent predictors of heart rate. The predicted change in heart rate was 6.0 beats/min for each 1 °C rise in body temperature. Relative bradycardia was suggested to be a characteristic finding in patients with moderate-to-severe COVID-19 who require oxygen. Additionally, severely ill patients were more likely to develop relative bradycardia than moderately ill patients. Focusing on the relationship between heart rate and body temperature might help clinicians diagnose this disease in patients with worsening respiratory failure.