Phase II study of fezolinetant for treatment of vasomotor symptoms associated with menopause in Japan.

OBJECTIVE: The phase II STARLIGHT study was conducted to investigate the efficacy/safety of fezolinetant in Japanese women and identify the optimal dose for future evaluation. METHOD: Participants were perimenopausal/postmenopausal women aged ≥40 to ≤65 years from 36 centers in Japan seeking treatment/relief for vasomotor symptoms (VMS) associated with menopause. After screening, participants were randomized 1:1:1, stratified by menopausal status, to receive fezolinetant 15 or 30 mg or placebo orally once daily for 12 weeks. Participants completed a daily VMS diary. The primary endpoint was mean change in frequency of VMS of any severity from baseline to week 8. Secondary endpoints included mean change in VMS frequency from baseline each week up to week 12 and frequency/severity of adverse events. RESULTS: A total of 147 participants were randomized (placebo, n = 47; fezolinetant 15 mg, n = 53; fezolinetant 30 mg, n = 47). Fezolinetant 15 and 30 mg demonstrated statistically significant reductions in mean VMS frequency at week 8 versus placebo. Least-squares mean estimates of mean change in frequency of VMS from baseline to week 8 were -7.04 for fezolinetant 15mg, -6.31 for fezolinetant 30mg, and -4.55 for placebo. The difference in least-squares mean estimates was -2.50 (95% CI: -4.03, -0.96), p = 0.002 for fezolinetant 15mg and placebo, and was -1.76 (95% confidence interval [CI]: -3.35, -0.17), p = 0.030 for fezolinetant 30mg and placebo. Reductions from baseline in mean VMS frequency versus placebo were seen after week 1 of treatment, maintained throughout 12 weeks. Fezolinetant was well tolerated, with no safety signals of concern for either dose to week 12. CONCLUSION: Oral fezolinetant at once-daily doses of 15 or 30 mg was efficacious and well tolerated for treatment of mild, moderate and severe VMS associated with menopause in this Japanese study.

Preparation and Performance Evaluation of a Temperature and Salt Resistant Hydrophobic Associative Weak Polymer Gel System.

We targeted high-temperature and highly saline old oil fields, whose environmental conditions could be attributed to the significantly high heterogeneity cause by long-term water flooding. The Huabei Oilfield was chosen as the research object. We developed a hydrophobic functional monomer-polymer with temperature and salt resistance by introducing the temperature-resistant and salt-resistant monomer NVP and a hydrophobic functional monomer into the main chain for copolymerization. We used a crosslinking agent with phenolic resin to prepare a weak gel system that showed temperature and salt resistance and investigated its temperature and salt resistance, infective property, plugging performance, liquid flow ability, micropore throat migration, and plugging characteristics. The results obtained using the infrared spectroscopy technique revealed the successful preparation of the phenolic resin crosslinker. The weak gel exhibited good temperature and salt resistance when the polymer concentration was 2000 mg/L, the cohesion ratio was 1:1.5, the additive concentration was 2000 mg/L, the reservoir temperature was 120 °C, and the injected water salinity was 40,300.86 mg/L. The average viscosity retention rate of the 90-day weak gel reached more than 80% and its microstructure was examined. The coreflow experiment results revealed that the weak gel system was characterized by good infectivity. After plugging the weak gel, the effect on the direction of the liquid flow was evident and the flow rate of the low permeability layer increased to a maximum of 48.63% under conditions of varying permeability levels. A significant improvement in the water absorption profile was achieved. The plugging was carried out through a sand-filling pipe under varying permeability conditions and the pressure measuring points in the sand-filling pipe were sucessfully pressurized. The migration ability of the weak gel was good and the blocking rate was >85%.

Integrated Transcriptome and Metabolome Analysis to Identify Sugarcane Gene Defense against Fall Armyworm (Spodoptera frugiperda) Herbivory.

Sugarcane is the most important sugar crop, contributing ≥80% to total sugar production around the world. Spodoptera frugiperda is one of the main pests of sugarcane, potentially causing severe yield and sugar loss. The identification of key defense factors against S. frugiperda herbivory can provide targets for improving sugarcane resistance to insect pests by molecular breeding. In this work, we used one of the main sugarcane pests, S. frugiperda, as the tested insect to attack sugarcane. Integrated transcriptome and metabolomic analyses were performed to explore the changes in gene expression and metabolic processes that occurred in sugarcane leaf after continuous herbivory by S. frugiperda larvae for 72 h. The transcriptome analysis demonstrated that sugarcane pest herbivory enhanced several herbivory-induced responses, including carbohydrate metabolism, secondary metabolites and amino acid metabolism, plant hormone signaling transduction, pathogen responses, and transcription factors. Further metabolome analysis verified the inducement of specific metabolites of amino acids and secondary metabolites by insect herbivory. Finally, association analysis of the transcriptome and metabolome by the Pearson correlation coefficient method brought into focus the target defense genes against insect herbivory in sugarcane. These genes include amidase and lipoxygenase in amino acid metabolism, peroxidase in phenylpropanoid biosynthesis, and pathogenesis-related protein 1 in plant hormone signal transduction. A putative regulatory model was proposed to illustrate the sugarcane defense mechanism against insect attack. This work will accelerate the dissection of the mechanism underlying insect herbivory in sugarcane and provide targets for improving sugarcane variety resistance to insect herbivory by molecular breeding.

Inhibitory Effect and Mechanism of Chitosan-Ag Complex Hydrogel on Fungal Disease in Grape.

Hydrogel antibacterial agent is an ideal antibacterial material because of its ability to diffuse antibacterial molecules into the decayed area by providing a suitable microenvironment and acting as a protective barrier on the decay interface. The biocompatibility and biodegradation make the removal process easy and it is already widely used in medical fields. However, there have been few reports on its application for controlling postharvest diseases in fruit. In this study, the Chitosan-silver (CS-Ag) complex hydrogels were prepared using the physical crosslinking method, which is used for controlling postharvest diseases in grape. The prepared hydrogels were stable for a long period at room temperature. The structure and surface morphology of CS-Ag composite hydrogels were characterized by UV-Vis, FTIR, SEM, and XRD. The inhibitory effects of CS-Ag hydrogel on disease in grape caused by P. expansum, A. niger, and B. cinerea were investigated both in vivo and in vitro. The remarkable antibacterial activity of CS-Ag hydrogels was mainly due to the combined antibacterial and antioxidant effects of CS and Ag. Preservation tests showed that the CS-Ag hydrogel had positive fresh-keeping effect. This revealed that CS-Ag hydrogels can play a critical role in controlling fungal disease in grapes.

Screening the Key Region of Sunlight Regulating the Flavonoid Profiles of Young Shoots in Tea Plants (Camellia sinensis L.) Based on a Field Experiment.

Both UV and blue light have been reported to regulate the biosynthesis of flavonoids in tea plants; however, the respective contributions of the corresponding regions of sunlight are unclear. Additionally, different tea cultivars may respond differently to altered light conditions. We investigated the responses of different cultivars ('Longjing 43', 'Zhongming 192', 'Wanghai 1', 'Jingning 1' and 'Zhonghuang 2') to the shade treatments (black and colored nets) regarding the biosynthesis of flavonoids. For all cultivars, flavonol glycosides showed higher sensitivity to light conditions compared with catechins. The levels of total flavonol glycosides in the young shoots of different tea cultivars decreased with the shade percentages of polyethylene nets increasing from 70% to 95%. Myricetin glycosides and quercetin glycosides were more sensitive to light conditions than kaempferol glycosides. The principal component analysis (PCA) result indicated that shade treatment greatly impacted the profiles of flavonoids in different tea samples based on the cultivar characteristics. UV is the crucial region of sunlight enhancing flavonol glycoside biosynthesis in tea shoots, which is also slight impacted by light quality according to the results of the weighted correlation network analysis (WGCNA). This study clarified the contributions of different wavelength regions of sunlight in a field experiment, providing a potential direction for slightly bitter and astringent tea cultivar breeding and instructive guidance for practical field production of premium teas based on light regimes.

A Phase I, Randomized, Double-Blind, Laser-Evoked Potential Study to Evaluate the Analgesic/Antihyperalgesic Effect of ASP9226, a State-Dependent N-Type Voltage-Gated Calcium Channel Inhibitor, in Healthy Male Subjects.

Objective: Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects. Design: Randomized, double-blind, double-dummy, placebo- and active comparator-controlled crossover study. Setting: HPR Dr. Schaffler GmbH, Munich, Germany. Subject: Healthy male subjects aged 18-55 years. Methods: Twenty-four eligible subjects were randomly assigned to one of four treatment sequences and received single doses of ASP9226 (30 mg or 50 mg), pregabalin (150 mg), or placebo during four treatment periods. Laser-evoked potentials (LEP) and postlaser pain visual analog scales (VAS) on capsaicin-treated skin were assessed during main assessment days (the first day of each study period). Primary and secondary end points were the differences in LEP N2-P2 peak-to-peak (PtP) amplitudes and VAS score, respectively, in all subjects. Results: Overall, treatment with pregabalin resulted in a significantly lower LEP N2-P2 PtP amplitude vs placebo (-3.30 µV, P < 0.0001). There were no clinically relevant differences in N2-P2 PtP amplitudes between placebo and either ASP9226 dose (-0.31 µV and -0.27 µV). Furthermore, subjects reported significantly lower VAS pain scores with pregabalin vs placebo (-9.90%, P < 0.0001) in contrast to ASP9226 30 mg (-2.1%) and ASP9226 50 mg (1.2%) vs placebo. Subgroup analysis of LEP and VAS pain in participants with positive prestudy capsaicin response (n = 13) were in keeping with results in all subjects. Conclusions: ASP9226 was well tolerated; however, there was no improvement in LEP and VAS pain scores with ASP9226 at either dose vs placebo.

Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval)).

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval)) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides.

A randomized, double-blind, solifenacin succinate versus placebo control, phase 4, multicenter study evaluating urinary continence after robotic assisted radical prostatectomy.

PURPOSE: Bladder dysfunction influences recovery of urinary continence after radical prostatectomy. We performed a multicenter, randomized, double-blind study evaluating solifenacin vs placebo on return to continence in patients who were still incontinent 7 to 21 days after catheter removal after robot-assisted radical prostatectomy. MATERIALS AND METHODS: A wireless personal digital assistant was given to patients the day of catheter removal. Encrypted answers were transmitted daily to dedicated servers. After a 7 to 21-day treatment-free washout period, patients requiring 2 to 10 pads per day for 7 consecutive days were randomized (1:1) to 5 mg solifenacin daily or placebo. The primary end point was time from first dose to continence defined as 0 pads per day or a dry security pad for 3 consecutive days. Secondary end points included proportion of patients continent at end of study, average change in pads per day number and quality of life assessments. RESULTS: A total of 1,086 screened patients recorded personal digital assistant information. Overall 640 patients were randomized to solifenacin vs placebo and 17 failed to take medication. There was no difference in time to continence (p=0.17). Continence was achieved by study end in 91 of 313 (29%) vs 66 of 309 (21%), respectively (p=0.04). Pads per day change from baseline was -3.2 and -2.9, respectively (p=0.03). Dry mouth was the only common adverse event seen in 6.1% and 0.6%, respectively. Constipation rates were similar. The overall rate of continence in the entire population from screening to end of study was 73%. CONCLUSIONS: There was no effect on primary outcome but some secondary end points benefited the solifenacin arm. The study provides level 1B clinical evidence for continence outcomes after robot-assisted radical prostatectomy.

Time-Series Transcriptome of Cucumis melo Reveals Extensive Transcriptomic Differences with Different Maturity.

As the most important melon cultivar grown in the north-western provinces of China, Hami melon (Cucumis melo) produces large edible fruits that serve as an important dietary component in the world. In general, as a climacteric plant, melon harvested at 60% maturity results in a product with bad quality, while the highest-quality product can be guaranteed when harvesting at 90% maturity. In order to clarify the genetic basis of their distinct profiles of metabolite accumulation, we performed systematic transcriptome analyses between 60% and 90% maturity melons. A total of 36 samples were sequenced and over 1.7 billion reads were generated. Differentially expressed genes in 60% and 90% maturity melons were detected. Hundreds of these genes were functionally enriched in the sucrose and citric acid accumulation process of C. melo. We also detected a number of distinct splicing events between 60% and 90% maturity melons. Many genes associated with sucrose and citric acid accumulation displayed as differentially expressed or differentially spliced between different degrees of maturity of Hami melons, including CmCIN2, CmSPS2, CmBGAL3, and CmSPS2. These results demonstrate that the phenotype pattern differences between 60% and 90% maturity melons may be largely resulted from the significant transcriptome regulation.

Combined metabolome and transcriptome analyses reveal that growing under Red shade affects secondary metabolite content in Huangjinya green tea.

Shading treatments impact the tea (Camellia sinensis L.) quality. The sunlight sensitive varieties can be grown under shading nets for better growth and secondary metabolite content. Here, we studied the responses of a sunlight sensitive green tea variety "Huangjinya" by growing under colored shading nets (red, yellow, blue, and black (75% and 95%) shading rates) to find out the most suitable color of the shading net. Red shading was the most promising treatment as it positively affected the weight and length of 100 one-bud-three leaves and reduced the degree and rate of new shoots burn compared to control (natural sunlight). We then explored the comparative metabolomic changes in response to red shading by using UPLC-ESI-MS/MS system. The amino acids and derivatives, flavonoids, and alkaloids were downaccumulated whereas lipids, organic acids, and lignans were upaccumulated in Red shade grown tea samples. The red shading nets caused a decreased catechin, epicatechin, dopamine, and L-tyramine contents but increased caffeine content. We then employed transcriptome sequencing to find key changes in expressions of related genes and pathways. Notably, key genes associated with the phenylpropanoid and flavonoid biosynthesis pathways exhibited complex regulation. These expression changes suggested a potential trend of polymerization or condensation of simple molecules like catechin or pelargonidin into larger molecules like glucoside or proanthocyanidins. Here, Red shading net triggered higher expression of genes enriched in lipid biosynthesis and jasmonic acid biosynthesis, suggesting an interplay of fatty acids and JA in improving tea performance. These findings contribute to the metabolic responses of Huangjinya tea to red shading nets which might have implications for flavor and health benefits. Our data provide a foundation for further exploration and optimization of cultivation practices for this unique tea variety.

Long-term safety of fezolinetant in Chinese women with vasomotor symptoms associated with menopause: the phase 3 open-label MOONLIGHT 3 clinical trial.

OBJECTIVE: We aimed to assess long-term safety and tolerability of fezolinetant, a nonhormonal neurokinin 3 receptor antagonist, among Chinese women with vasomotor symptoms associated with menopause participating in the MOONLIGHT 3 trial. METHODS: In this phase 3 open-label study, women in menopause aged 40-65 years received fezolinetant 30 mg once daily for 52 weeks. The primary endpoint was frequency and severity of treatment-emergent adverse events (TEAEs), assessed at every visit through week 52 and one follow-up visit at week 55. RESULTS: Overall, 150 women were enrolled (mean age, 54 years) and 105 completed treatment. The frequency of TEAEs was 88.7%. Most TEAEs were mild (63.3%) or moderate (22.7%). The most common TEAE was upper respiratory tract infection (16.0%), followed by dizziness, headache, and protein urine present (10.7% each). There was no clinically relevant change (mean ± standard deviation) in endometrial thickness (baseline, 2.95 ± 1.11 mm; week 52, 2.94 ± 1.18 mm). Alanine aminotransferase and/or aspartate aminotransferase levels >3 times the upper limit of normal were reported in 1.4% of women; no Hy's Law cases occurred. CONCLUSIONS: Fezolinetant 30 mg once daily was generally safe and well tolerated over a 52-week period among women in China with vasomotor symptoms associated with menopause.ClinicalTrials.gov Identifier: NCT04451226.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Safety and tolerability of solifenacin add-on therapy to α-blocker treated men with residual urgency and frequency.

PURPOSE: VICTOR was a 12-week, double-blind, placebo controlled trial assessing the safety and tolerability of solifenacin plus tamsulosin in men with residual overactive bladder symptoms after tamsulosin monotherapy. Efficacy of solifenacin plus tamsulosin vs placebo plus tamsulosin was also evaluated. MATERIALS AND METHODS: A total of 398 men 45 years old or older were randomized to 12 weeks of solifenacin plus tamsulosin or placebo plus tamsulosin once daily. The study population had 8 or more micturitions per 24 hours and 1 or more urgency episode per 24 hours after taking tamsulosin for 4 or more weeks, a total International Prostate Symptom Score of 13 or greater, a Patient Perception of Bladder Condition score of 3 or greater, a post-void residual of 200 ml or less and a peak flow rate of 5 ml per second or greater. Adverse events were monitored throughout the study. The primary efficacy end point was mean change from baseline to week 12 in micturitions per 24 hours. Secondary measures included mean change in urgency episodes per 24 hours, and changes in Patient Perception of Bladder Condition, Urgency Perception Scale and total International Prostate Symptom Scores. RESULTS: The most frequent adverse events in the solifenacin plus tamsulosin and placebo plus tamsulosin groups were dry mouth (7% and 3%, respectively) and dizziness (3% and 2%, respectively). Of the patients on solifenacin plus tamsulosin 7 (3%) reported retention and 3 required catheterization. No patients on placebo plus tamsulosin reported retention. Patients on solifenacin plus tamsulosin vs placebo plus tamsulosin showed larger reductions in frequency but not of statistical significance (-1.05 vs -0.67, p = 0.135). However, patients on solifenacin plus tamsulosin vs placebo plus tamsulosin did show statistically significant reductions in urgency (-2.18 vs -1.10, p <0.001). Patient reported outcome measures showed no significant between group differences. CONCLUSIONS: Solifenacin plus tamsulosin was well tolerated. There was a low incidence of urinary retention requiring catheterization. At week 12 solifenacin plus tamsulosin decreased daily micturitions and urgency episodes. Only urgency reached statistical significance vs placebo plus tamsulosin.

Urodynamics and safety of the ß3-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction often presents as storage and voiding symptoms. We investigated urodynamic parameters in men with lower urinary tract symptoms and bladder outlet obstruction treated with the ß3 agonist mirabegron, a new therapy for overactive bladder symptoms. MATERIALS AND METHODS: A total of 200 men 45 years old or older with lower urinary tract symptoms and bladder outlet obstruction were randomized to receive once daily mirabegron 50 mg (70) or 100 mg (65), or placebo (65) for 12 weeks. The primary urodynamic parameters assessed were change from baseline to end of treatment in maximum urinary flow and detrusor pressure at maximum urinary flow (noninferiority margins -3 ml per second and 15 cm H2O, respectively). We evaluated adverse events and vital signs. RESULTS: Treatment with mirabegron 50 and 100 mg was noninferior to placebo based on the lower and upper limits of the 95% CI, respectively, for maximum urinary flow and detrusor pressure at maximum urinary flow. The adjusted mean difference vs placebo was 0.40 (95% CI -0.63, 1.42) and 0.62 ml per second (95% CI -0.43, 1.68) for maximum urinary flow, and -5.94 (95% CI -13.98, 2.09) and -1.39 cm H2O (95% CI -9.73, 6.96), respectively, for detrusor pressure at maximum urinary flow. The incidence of adverse events was similar for mirabegron and placebo. CONCLUSIONS: Mirabegron did not adversely affect voiding urodynamics (maximum urinary flow and detrusor pressure at maximum urinary flow) compared with placebo after 12 weeks of treatment.

Finding unrecognized information in overactive bladder clinical trial data: a new approach to understanding placebo and treatment effects.

AIMS: To identify combinations of variables among overactive bladder (OAB) clinical trial subjects that allow prediction of those who are more--or less--likely to respond strongly to placebo, or to medication. METHODS: Data from two Phase IIIb clinical trials of solifenacin in OAB were combined. Predictive models for placebo and treatment responses were constructed using baseline variables including individual items from the OAB questionnaire. These models were reduced to an essential subset of predictor variables. Two outcome measures are reported: urgency and incontinence. RESULTS: In placebo subjects, 14 selected variables permitted distinction between those who responded with significant reductions in urgency and those who did not. A subset of nine variables in treated subjects permitted distinction between those more--or less--likely to respond to medication. Data for urgency were combined from both placebo and actively treated subjects to identify those who had one of the previously identified clusters of variables. It was possible to predict, among all subjects, who would be likely to experience a strong placebo or active treatment response and who would not. This process was also applied to incontinence data. CONCLUSIONS: We have developed a new process to help understand placebo and treatment responses and their relationships to baseline conditions. The effectiveness of these methods was indicated using data from two solifenacin clinical trials and would benefit from future validation using other data sets. Methods used here are suitable for predicting the placebo effect in other clinical trials.

Comparison of Volatile and Nonvolatile Metabolites in Black Tea under Four Second-Drying Methods Using Widely Targeted Metabolomics.

Second-drying has an impact on the development of flavor and aroma in black tea. However, the effect of the shape changes of the tea leaves during second-drying on the quality of black tea has yet to be evaluated. In this study, GC-TOFMS and UPLC-HRMS identified 411 volatile metabolites and 253 nonvolatile metabolites. Additionally, 107 nonvolatile compounds and 21 different volatiles were screened. Significant alterations (p < 0.01) were found in 18 amino acid derivatives, 17 carbohydrates, 20 catechins, 19 flavonoids, 13 phenolic acids, and 4 organic acids. The content of certain amino acids and carbohydrates correlated with the shape of black tea. Furthermore, sweet aroma compound formation was facilitated by hot-air second-drying while the remaining second-drying approaches encouraged the formation of the fruity aroma compound. The results of the study provide a theoretical basis and technical instructions for the accurate and precise processing of premium black tea.

Comparison of volatile and nonvolatile metabolites in green tea under hot-air drying and four heat-conduction drying patterns using widely targeted metabolomics.

Hot-air and heat-conduction drying are the most common drying patterns in green tea production. However, the differences between them in terms of the resulting green tea chemical compounds have not been illustrated systematically. In this study, 515 volatile and 204 nonvolatile metabolites were selected to compare the differences between hot-air drying green tea (HAGT) and four heat-conduction drying green teas (HCDGTs) using widely targeted metabolomics. The results showed notable changes in volatile compounds; for example, two kinds of HCDGTs preferred to form chestnut-like and caramel-like key odorants. In addition, 14 flavonol glycosides, 10 catechins, 9 phenolic acids, 8 amino acids, 7 flavonols, and 3 sugars were significantly changed between HAGT and HCDGTs (p < 0.05), presenting a tremendous discrepancy in the transformation of nonvolatile compounds. Our results provide clear guidance for the precise manufacturing of green tea by four common heat-drying patterns and hot air-drying patterns.

Neural signals-based respiratory motion tracking: a proof-of-concept study.

Objective.Respiratory motion tracking techniques can provide optimal treatment accuracy for thoracoabdominal radiotherapy and robotic surgery. However, conventional imaging-based respiratory motion tracking techniques are time-lagged owing to the system latency of medical linear accelerators and surgical robots. This study aims to investigate the precursor time of respiratory-related neural signals and analyze the potential of neural signals-based respiratory motion tracking.Approach.The neural signals and respiratory motion from eighteen healthy volunteers were acquired simultaneously using a 256-channel scalp electroencephalography (EEG) system. The neural signals were preprocessed using the MNE python package to extract respiratory-related EEG neural signals. Cross-correlation analysis was performed to assess the precursor time and cross-correlation coefficient between respiratory-related EEG neural signals and respiratory motion.Main results.Respiratory-related neural signals that precede the emergence of respiratory motion are detectable via non-invasive EEG. On average, the precursor time of respiratory-related EEG neural signals was 0.68 s. The representative cross-correlation coefficients between EEG neural signals and respiratory motion of the eighteen healthy subjects varied from 0.22 to 0.87.Significance.Our findings suggest that neural signals have the potential to compensate for the system latency of medical linear accelerators and surgical robots. This indicates that neural signals-based respiratory motion tracking is a potential promising solution to respiratory motion and could be useful in thoracoabdominal radiotherapy and robotic surgery.

Caregiver-child interaction as an effective tool for identifying autism spectrum disorder: evidence from EEG analysis.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. METHODS: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. RESULTS: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). CONCLUSION: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.