Simultaneous extraction and purification of alkaloids from Sophora flavescens Ait. by microwave-assisted aqueous two-phase extraction with ethanol/ammonia sulfate system

A rapid and effective method of integrating extraction and purification for alkaloids from Sophora flavescens Ait. was developed by microwave-assisted aqueous two-phase extraction (MAATPE) based on the high efficiency of microwave-assisted extraction (MAE) and the demixing effect of aqueous two-phase extraction (ATPE). The aqueous two-phase system (ATPS), ethanol/ammonia sulfate was chosen from seven combinations of ethanol/salt systems, and its extraction properties were investigated in detail. Key factors, namely, the compositions of ATPS, solvent-to-materials ratio, and the extraction temperature were selected for optimization of the experimental conditions using response surface methodology (RSM) on the basis of the results of the single-factor experiment. The final optimized conditions were, the compositions of ATPS: ethanol 28% (w/w) and (NH4)2SO4 18% (w/w), solvent-to-material ratio 60:1, temperature 90 C, extraction time 5 min, and microwave power 780 W. MAATPE was superior to MAE, the latter using a single solvent, not only in extraction yield but also in impurity content. Moreover, compared with the combination of MAE and ATPE in the two-step mode, MAATP demonstrated fewer impurities, a better yield (63.78 ± 0.45 mg/g) and a higher recovery (92.09 ± 0.14%) in the extraction and purification of alkaloids. A continuous multiphase-extraction model of MAATPE was proposed to explicate the extraction mechanism. MAATPE revealed that the interaction between microwave and ATPS cannot only cause plant cell rupture but also accelerate demixing, improving mass-transfer from solid–liquid extraction to liquid– liquid purification. MAATPE simplified procedures also contributed to the lower loss occurrence, better extraction efficiency, and reduced impurity to target constituents.The Science and Technology Project of Guangzhou (No. 2008Z1-E301) and Faculty Development fund Project of Guangdong Pharmaceutical University (No. 52104109

Association of CLDN molecules with sleep apnea hypopnea syndrome: new biomarker candidates

IntroductionObstructive sleep apnea (OSA) is a common sleep-related breathing disorder, and has become a serious threat to public health. Intermittent hypoxia caused by OSA results in a low-grade inflammatory response that leads to impaired mucosal barrier function. Claudin (CLDN) molecules are important for the permeability of the mucosal epithelium. This study aimed to explore whether CLDN molecules can be a potential biomarker of OSA.MethodsA total of 37 healthy controls and 40 OSA patients underwent a physical assessment for OSA and filled out the STOP-Bang Questionnaire (SBQ) and Epworth Sleepiness Scale (ESS). Clinical specimens of plasma and urine were obtained to observe the difference between OSA patients and healthy controls and diagnostic accuracy of CLDN molecules for OSA.ResultsCLDN1, CLDN2, and CLDN3 molecules in plasma and urine decreased in OSA patients (both p < 0.05). The areas under the receiver operating characteristic curve (AUCs) of urinary CLDN1, plasma CLDN1, urinary CLDN2, plasma CLDN2, urinary CLDN3, and plasma CLDN3 were 0.887, 0.724, 0.779, 0.676, 0.828, and 0.665, respectively. The AUC of urinary CLDN1 + CLDN2 + CLDN3 was 0.906 (95% confidence interval (CI), 0.831–0.981). The AUC of plasma CLDN1 + CLDN2 + CLDN3 was 0.776 (95% CI, 0.645–0.878). The AUC of urinary CLDN3 + SBQ was 0.899 (95% CI, 0.832–0.967). The AUC of urinary CLDN3 + ESS was 0.896 (95% CI, 0.826–0.966). In addition, Urinary CLDN-3 was negative associated with the severity of OSA.ConclusionCLDN molecules are promising as useful biomarkers for OSA, which may be related to the impaired barrier function related to OSA

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Objective: To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design: A retrospective single-institution cohort study. Patients: The perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November 2012 and June 2019 were retrospectively analyzed. Methods: The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results: The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations: The number of enrolled patients was relatively small and patients’ treatment options varied. Conclusions: A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target

Bio-oil based biorefinery strategy for the production of succinic acid

Background: Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid was investigated

Reducing the gap between streaming and non-streaming Transducer-based ASR by adaptive two-stage knowledge distillation

Transducer is one of the mainstream frameworks for streaming speech recognition. There is a performance gap between the streaming and non-streaming transducer models due to limited context. To reduce this gap, an effective way is to ensure that their hidden and output distributions are consistent, which can be achieved by hierarchical knowledge distillation. However, it is difficult to ensure the distribution consistency simultaneously because the learning of the output distribution depends on the hidden one. In this paper, we propose an adaptive two-stage knowledge distillation method consisting of hidden layer learning and output layer learning. In the former stage, we learn hidden representation with full context by applying mean square error loss function. In the latter stage, we design a power transformation based adaptive smoothness method to learn stable output distribution. It achieved 19\% relative reduction in word error rate, and a faster response for the first token compared with the original streaming model in LibriSpeech corpus

Multiple microRNAs regulate tacrolimus metabolism through CYP3A5

The CYP3A5 gene polymorphism accounts for the majority of inter-individual variability in tacmlimus pharmacokinetics. We found that the basal expression of CYP3A5 in donor grafts also played a significant role in tacrolimus metabolism under the same genetic conditions after pediatric liver transplantation. Thus, we hypothesized that some potential epigenetic factors could affect CYP3A5 expression and contributed to the variability. We used a high-throughput functional screening for miRNAs to identify miRNAs that had the most abundant expression in normal human liver and could regulate tacmlimus metabolism in HepaRG cells and HepLPCs. Four of these miRNAs (miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26-5p) were selected for testing. We found that these miRNAs inhibited tacmlimus metabolism that was dependent on CYP3A5. Putative miRNAs targeting key drug-metabolizing enzymes and transporters (DMETs) were selected using an in silico prediction algorithm. Luciferase reporter assays and functional studies showed that miR-26b-5p inhibited tacrolimus metabolism by directly regulating CYP3A5, while miR-29a-5p, miR-99a-5p, and miR-532-5p targeted HNF4a, NR1I3, and NR1I2, respectively, in turn regulating the downstream expression of CYP3A5; the corresponding target gene siRNAs markedly abolished the effects caused by miRNA inhibitors. Also, the expression of miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p in donor grafts were negatively correlated with tacmlimus C/D following pediatric liver transplantation. Taken together, our findings identify these miRNAs as novel regulators of tacrolimus metabolism

Predisposing factors for predicting the therapeutic response of adenomyosis after uterine artery embolization: serum CA125 levels and accompanying endometriosis

PURPOSE:We aimed to identify predisposing factors that could help predict the therapeutic response of adenomyosis after uterine artery embolization (UAE).METHODS:This was a retrospective, single-center study of patients admitted to the hospital for adenomyosis between 2013 and 2015. Sixty-eight patients with adenomyosis who underwent UAE with tris-acryl gelatin microspheres were divided into two groups based on their therapeutic response (complete or incomplete necrosis of lesions), and pre- and postprocedural pelvic magnetic resonance imaging (MRI) data. Patients were followed up for 12 months after UAE. Improvements in dysmenorrhea and menorrhagia were evaluated based on the symptom relief criteria. Improvement rates in both groups were analyzed and compared. Multivariate logistic regression analysis was used to identify the predisposing factors from retrospectively gathered baseline data that might affect the therapeutic response, including MRI features, clinical symptoms, biochemical index, and accompanying diseases of adenomyosis. Then, a prognostic model was established, and the receiver operating characteristic (ROC) curve of identified factors was drawn to determine their predictive value.RESULTS:Following UAE, 46 patients (67.6%) showed complete necrosis, while 22 patients (32.4%) showed incomplete necrosis. At 12-month follow-up, dysmenorrhea symptom improvement was seen in 94.7% of complete necrosis and 50% of incomplete necrosis group (P < 0.001); menorrhagia symptom improvement was seen in 96.2% of complete necrosis and 57.1% of incomplete necrosis groups (P = 0.004). Multivariate logistic regression analysis determined serum cancer antigen 125 (CA125) levels (odds ratio [OR], 1.006; 95% confidence interval [CI], 1.002–1.010; P = 0.005) and accompanying endometriosis (OR, 6.869; 95% CI, 1.881–25.016; P = 0.004) as predisposing factors. The areas under the ROC curve of CA125, endometriosis, and these two indicators combined were 0.785, 0.708, and 0.845, which corresponded to sensitivities of 95.5%, 66.7%, and 68.2% and specificities of 52.2%, 80.0%, and 87.0% at optimal cutoff values, respectively.CONCLUSION:Symptom relief of dysmenorrhea and menorrhagia for patients with complete necrosis was significantly better than that for patients with incomplete necrosis. Serum CA125 levels and accompanying endometriosis can effectively distinguish complete necrosis from incomplete necrosis

Determining the Best Sensing Coverage for 2-Dimensional Acoustic Target Tracking

Distributed acoustic target tracking is an important application area of wireless sensor networks. In this paper we use algebraic geometry to formally model 2-dimensional acoustic target tracking and then prove its best degree of required sensing coverage. We present the necessary conditions for three sensing coverage to accurately compute the spatio-temporal information of a target object. Simulations show that 3-coverage accurately locates a target object only in 53% of cases. Using 4-coverage, we present two different methods that yield correct answers in almost all cases and have time and memory usage complexity of Θ(1). Analytic 4-coverage tracking is our first proposed method that solves a simultaneous equation system using the sensing information of four sensor nodes. Redundant answer fusion is our second proposed method that solves at least two sets of simultaneous equations of target tracking using the sensing information of two different sets of three sensor nodes, and fusing the results using a new customized formal majority voter. We prove that 4-coverage guarantees accurate 2-dimensional acoustic target tracking under ideal conditions