Analysis of resistance risk and resistance-related point mutations in Cyt b of QioI fungicide ametoctradin in Phytophthora litchii.

BACKGROUND: Litchi downy blight, caused by Phytophthora litchii, is one of the most important diseases of litchi. Ametoctradin, as the only QioI (quinone inside and outside inhibitor) fungicide, has been registered in China in 2019. However, the ametoctradin-resistance risk and molecular basis in Phytophthora litchii have not been reported. RESULTS: In this study, the sensitivity profile of 144 Phytophthora litchii strains to ametoctradin was determined, with a mean median effective concentration (EC50 ) value of 0.1706 ± 0.091 µg mL-1 . Nine stable resistant Phytophthora litchii mutants [resistance factor (RF) > 400] were derived from sensitive isolates using fungicide adaption. The compound fitness index of three resistant-mutants (HN10-1-1, HN10-1-2 and HN10-2-1) was similar or higher than that of their parental isolates in vitro. All these ametoctradin-resistant mutants were sensitive to metalaxyl, dimethomorph, oxathiapiprolin and cyazofamid. Two point mutations, leading to the S33L and D228N changes in PlCyt b (cytochrome b) were found in ametoctradin-resistant mutants. Eight ametoctradin-resistant mutants containing S33L showed increased sensitivity to azoxystrobin and amisulbrom, and one mutant containing D228N exhibited increased sensitivity to cyazofamid. In vitro enzyme activity test showed that ametoctradin could not inhibit the activity of cytochrome bc1 complex with S33L and D228N point mutation. AS-PCR primers were designed based on the S33L change to detect the ametoctradin-resistant strains in the future. CONCLUSION: These results suggest that Phytophthora litchii has a medium to high resistance risk to ametoctradin in the laboratory. Two changes, S33L and D228N, in PlCyt b are likely to be associated with the observed ametoctradin resistance. © 2022 Society of Chemical Industry.

Near-infrared photocontrolled therapeutic release via upconversion nanocomposites.

Photocontrolled therapeutic release holds great promise due to its versatile manipulability, superb spatiotemporal precision and minimal tissue invasiveness in biomedical purposes. However, most of light-responsive platforms thus far have relied on UV or visible light which substantially limit the potential applicability in living animals. In recent decades, near-infrared (NIR) light-mediated theranostic upconversion nanocomposites (UCNCs) that integrate conventional UV/Vis-sensitive materials and classic lanthanide-doped upconversion nanoparticles (UCNPs) have significantly promoted the development of deep-tissue photoreleasable therapeutics in vivo. Herein, we seek to review current NIR upconversion triggered photorelease techniques and their diverse applications in the biological regulation, as well as diseases therapy. In addition, the future perspectives and challenges for advancing UCNCs based NIR photoreleasable nanotherapeutics into clinical translations are proposed.

Metabolic profile of Fructus Gardeniae in human plasma and urine using ultra high-performance liquid chromatography coupled with high-resolution LTQ-orbitrap mass spectrometry.

1. In China, Fructus Gardeniae was used as a traditional Chinese medicine (TCM) with a wide array of biological activities. The bioactive components identified in Fructus Gardeniae mainly included iridoids, flavonids, pigments, and so on. Among them, iridoids were regarded as important compounds in Fructus Gardeniae. Though analyses of the constituents in biological samples after oral administration of Fructus Gardeniae effective fraction or its active compounds have been reported, few efforts have been made to investigate the metabolic profile of Fructus Gardeniae in humans. In this study, the constituents and metabolites of Fructus Gardeniae in human blood and urine after oral administration of Fructus Gardeniae were investigated using ultra high-performance liquid chromatography (UHPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometery. 2. Totally, 14 constituents (two parent compounds and 12 metabolites) of Fructus Gardeniae were identified in human plasma and urine either by comparing the retention time and mass spectrometry data with that of reference compounds or by the accurate high-resolution MS/MS data of the chemicals. The compounds identified were mainly iridoid glycosides such as geniposide and the derivatives of genipin-O-glucuronide. Among them, 11 metabolites were detected in human plasma and urine while the other three metabolites including geniposidic acid (M1), demethylation derivative of genipin-O-glucuronide (M2), and dehydration product of mono-hydroxylated genipin-O-glucuronide (M9) were only discovered in human urine. Further, the possible metabolic pathways of Fructus Gardeniae in vivo were proposed and the peak area-time curve of the most abundant metabolite genipin-O-glucuronide (M13) in human plasma after oral administration of Fructus Gardeniae was depicted. The results suggested that a metabolic difference existed between rats and humans. 3. The results obtained in the present research would provide basic information to understand the metabolic profile of Fructus Gardeniae in humans and explore the chemicals responsible for the hepatotoxicity of Fructus Gardeniae in vivo. Moreover, it would be beneficial for us to further study the pharmacokinetic behavior of Fructus Gardeniae in humans systematically.

Cerebral autoregulation in response to posture change in elderly subjects-assessment by wavelet phase coherence analysis of cerebral tissue oxyhemoglobin concentrations and arterial blood pressure signals.

This study aims to assess the dynamic cerebral autoregulation (dCA) in response to posture change using wavelet phase coherence (WPCO) of cerebral tissue oxyhemoglobin concentrations (Delta [HbO2]) and arterial blood pressure (ABP) signals in healthy elderly subjects. Continuous recordings of near-infrared spectroscopy (NIRS) and ABP signals were obtained from simultaneous measurements in 16 healthy elderly subjects (age: 68.9±7.1 years) and 19 young subjects (age: 24.9±3.2 years). The phase coherence between Delta [HbO2] and ABP oscillations in six frequency intervals (I, 0.6-2 Hz; II, 0.15-0.6 Hz; III, 0.05-0.15 Hz; IV, 0.02-0.05 Hz, V, 0.0095-0.02 Hz and VI, 0.005-0.0095 Hz) was analyzed using WPCO. The sit-to-stand posture change induces significantly lower WPCO in interval III (F=5.50 p=0.025) in the elderly subjects than in the young subjects. However, the stand-to-sit posture change induces higher WPCO in intervals II (F=5.25 p=0.028) and V (F=6.22 p=0.018) in the elderly subjects than in the young subjects. The difference of WPCO in response to posture change between the elderly and the young subjects indicates an altered CA due to aging. This study provides new insight into the dynamics of CA and may be useful in identifying the risk for dCA processes.

Phase synchronization analysis of prefrontal tissue oxyhemoglobin oscillations in elderly subjects with cerebral infarction.

PURPOSE: This study aims to assess the phase relationship of prefrontal tissue oxyhemoglobin oscillations using wavelet phase coherence analysis of cerebral Delta [HbO2] signals in cerebral infarction (CI) patients during the resting state. METHODS: Continuous recordings of near-infrared spectroscopy signals were obtained from the left and right prefrontal lobes in 21 subjects with CI (Group CI, age: 76.6 ± 8.5 yr) and 21 healthy elderly subjects (Group Healthy, age: 69.0 ± 7.4 yr) during the resting state. The Group CI was further divide into two groups: CI with hypertension and CI without hypertension. The phase synchronization between left and right prefrontal Delta [HbO2] oscillations in four frequency intervals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; and IV, 0.021-0.052 Hz) was analyzed using wavelet phase coherence method. RESULTS: The phase coherences in intervals III and IV were significantly lower in CI with hypertension than in healthy elderly subjects (F = 12.974, p = 0.001 for III and F = 10.073, p = 0.004 for interval IV). The phase coherence of CI without hypertension in interval III was significantly lower than in healthy elderly subjects (F = 9.909, p = 0.004). Also, the phase coherence in interval IV was significantly lower in CI with hypertension than in CI without hypertension (F = 5.665, p = 0.028). Also, the phase agreement in interval IV showed evident difference between Group CI with hypertension and without hypertension. CONCLUSIONS: The difference in phase characteristics of prefrontal tissue oxyhemoglobin oscillations between the CI patients and healthy elderly indicates altered phase synchronization. Moreover, the CI combined with hypertension would aggravate this process. This study provides new insight into the phase dynamics of cerebral oxygenation and may be useful in assessing the risk for stroke.

Wavelet coherence analysis of prefrontal tissue oxyhaemoglobin signals as measured using near-infrared spectroscopy in elderly subjects with cerebral infarction.

This study aims to assess the prefrontal functional connectivity using wavelet coherence analysis of cerebral tissue oxyhaemoglobin concentration (Delta [HbO2]) signals in elderly subjects with cerebral infarction (CI) during the resting state. Continuous recordings of near-infrared spectroscopy (NIRS) signals were obtained from the left and right prefrontal lobes in 10 subjects with CI (age: 74.4±9.0years) and 18 healthy elderly subjects (age: 69.9±7.3years) during the resting state. The coherence between left and right prefrontal Delta [HbO2] oscillations in four frequency intervals (I, 0.6-2Hz; II, 0.145-0.6Hz; III, 0.052-0.145Hz and IV, 0.021-0.052Hz) was analyzed using wavelet coherence analysis. In healthy elderly subjects, the Delta [HbO2] oscillations were significantly wavelet coherent in intervals I and III (p<0.05), wavelet phase coherent in intervals from I to IV. In elderly subjects with CI, the left and right Delta [HbO2] oscillations were significantly wavelet coherent and phase coherent in interval I (p<0.05). In elderly subjects with CI, the power and phase coherences were significantly lower in interval III (p<0.01) than in healthy subjects. The difference in wavelet coherence between the healthy elderly and elderly with CI indicates an altered brain functional connectivity in CI patients. This may be useful for assessing the effectiveness of functional recovery following a CI.

Wavelet coherence analysis of spontaneous oscillations in cerebral tissue oxyhemoglobin concentrations and arterial blood pressure in elderly subjects.

This study aims to assess the relationship between spontaneous oscillations in changes in cerebral tissue oxyhemoglobin concentrations (Delta [HbO2]) and arterial blood pressure (ABP) signals in healthy elderly subjects during the resting state using wavelet coherence analysis. Continuous recordings of near-infrared spectroscopy (NIRS) and ABP signals were obtained from simultaneous measurements in 33 healthy elderly subjects (age: 70.7±7.9 years) and 27 young subjects (age: 25.2±3.7 years) during the resting state. The coherence between Delta [HbO2] and ABP oscillations in six frequency intervals (I, 0.4-2 Hz; II, 0.15-0.4 Hz; III, 0.05-0.15 Hz; IV, 0.02-0.05 Hz, V, 0.005-0.0095 Hz and VI, 0.005-0.0095 Hz) was analyzed using wavelet coherence analysis. In elderly subjects, the Delta [HbO2] and ABP oscillations were significantly wavelet coherent in interval I, and wavelet phase coherent in intervals I, II and IV. The wavelet coherence in interval I was significantly higher (p=0.040), in elderly subjects than in young subjects whereas that in interval V significantly lower (p=0.015). In addition, the wavelet phase coherence in interval IV was significantly higher in elderly subjects than in young subjects (p=0.028). The difference in the wavelet coherence of the elderly subjects and the young subjects indicates an altered cerebral autoregulation caused by aging. This study provides new insight into the dynamics of Delta [HbO2] and ABP oscillations and may be useful in identifying the risk for dynamic cerebral autoregulation processes.

Wavelet coherence analysis of prefrontal oxygenation signals in elderly subjects with hypertension.

This study aims to assess the prefrontal functional connectivity in elderly subjects with hypertension during the resting state using wavelet coherence analysis of changes in prefrontal tissue oxyhaemoglobin concentrations (Δ[HbO2]) signals measured by near-infrared spectroscopy (NIRS). Continuous recordings of NIRS signals were obtained from the left and right prefrontal lobes in 24 elderly subjects with hypertension (age: 70.7 ± 8.4 years) and 26 elderly normotensive subjects (age: 70.6 ± 7.9 years) during the resting state. The coherence between the left and right prefrontal oscillations in four frequency intervals (I, 0.4 Hz to 2 Hz; II, 0.15 Hz to 0.4 Hz; III, 0.05 Hz to 0.15 Hz; and IV, 0.02 Hz to 0.05 Hz) was analyzed using wavelet coherence method. The Δ[HbO2] oscillations showed significant wavelet coherence (WCO) in intervals I and III, and significant wavelet phase coherence (WPCO) in intervals from I to IV. Remarkably, in elderly subjects with hypertension, the WCO and WPCO in interval III were significantly lower in the left and right prefrontal regions than in healthy elderly subjects (p = 0.014 for WCO, p = 0.007 for WPCO). The lower coherence in interval III indicates a decreased synchronization of neural control in the left and right prefrontal regions in elderly subjects with hypertension. This might suggest a weakened brain functional connectivity in the elderly subjects with hypertension.