Design of surface nanostructures for chirality sensing based on quartz crystal microbalance.

Quartz crystal microbalance (QCM) has been widely used for various sensing applications, including chirality detection due to the high sensitivity to nanogram or picogram mass changes, fast response, real-time detection, easy operation, suitability in different media, and low experimental cost. The sensing performance of QCM is dependent on the surface design of the recognition layers. Various strategies have been employed for studying the relationship between the structural features and the specific detection of chiral isomers. This review provides an overview of the construction of chiral sensing layers by various nanostructures and materials in the QCM system, which include organic molecules, supermolecular assemblies, inorganic nanostructures, and metal surfaces. The sensing mechanisms based on these surface nanostructures and the related potentials for chiral detection by the QCM system are also summarized.

Inferences of carboplatin response-related signature by integrating multiomics data in ovarian serous cystadenocarcinoma.

Platinum-based chemotherapy, especially carboplatin, is the primary measure to treat patients with ovarian cancer (OC). However, OC patients still have an adverse prognosis due to emergency of chemotherapy resistance. Ovarian serous cystadenocarcinoma (OSC) is the most common histological subtype of OC. Therefore, identifying the key factors that affect chemotherapy resistance and searching novel treatments had become a top priority. In this study, we analyzed carboplatin response-related mRNA, miRNA, DNA methylation, and alternative splicing (AS) and established a drug-resistant signature for carboplatin in OSC. This drug-resistant signature was obviously higher in resistant group than in non-resistant group and had accuracy predictive performance, which demonstrated that this signature could be considered as a superior indicator for OSC patients with carboplatin resistance. Furthermore, we selected three potential small molecule drugs including liranaftate, siguazodan, and tramiprostate to inhibit carboplatin resistance of OSC. In addition, we also identified ZINC00000205417, ZINC00000140928, and ZINC00021908260 were potential small molecule compounds for SLC17A7 based on Molecular Operating Environment (MOE) virtual screening. Finally, we confirmed the drug-like properties of these small molecule drugs via evaluating absorption, distribution, metabolism, elimination, and toxicity (ADMET) property. In summary, the signature could be used as biomarker for carboplatin resistance and small molecule drugs targeting these genes could improve clinical treatment for OSC in the future.

Gene polymorphism-related differences in the outcomes of abiraterone for prostate cancer: a systematic overview.

Numerous prostate cancer (PC) associated genes have been reported in previous genome-wide association studies. Elucidation of prostate cancer pharmacogenomics have enhanced studies into the impact of germline genetic changes on treatment, in addition to evaluating related genomic alterations and biomarkers in prostate tumor tissues. Currently, Abiraterone (Abi) is used as one of the therapeutic options for PC. In this article, germline variants that have been associated with responses to Abi in patients with advanced PC are summarized. These include biomarker genes such as CYP17A1, AR-V7, HSD3B1, SLCO2B1, SULT1E1, and SRD5A2 that are involved in homologous recombination, as well as in gene expression mutations in important signaling pathways, such as WNT and Abi metabolic pathways.

Online monitoring of air activation at the China spallation neutron source.

During the operation of high-energy proton accelerators, the air in the tunnel is activated with the production of radionuclides. For CSNS (China Spallation Neutron Source), the first pulsed neutron source in China for multidisciplinary research, an online air activation monitoring system was developed to evaluate the radiation safety of the staff and the public, which consisted of a NaI detector, Pb shielding, an MB container and a control system. With the monitoring system, gamma spectra of the activated air from controlled areas are measured, and the activity concentration and immersion dose rates of radionuclides in air are calculated and displayed in real time. The system has been in stable operation since February 2020, and results have been obtained for the evaluation of the radiation risk from activated air.

Development of alternative splicing signature in lung squamous cell carcinoma.

Increasing evidence demonstrated that alternative splicing (AS) plays a vital role in tumorigenesis and clinical outcome of patient. However, systematical analysis of AS in lung squamous cell carcinoma (LUSC) is lacking and greatly necessary. Thus, this study was to systematically estimate the function of AS events served as prognostic indicators in LUSC. Among 31,345 mRNA AS events in 9633 genes, we detected 1996 AS in 1409 genes which have significant connection with overall survival (OS) of LUSC patients. Then, prognostic model based on seven types of AS events was established and we further constructed a combined prognostic model. The Kaplan-Meier curve results suggested that seven types of AS signatures and the combined prognostic model could exhibit robust performance in predicting prognosis. Patients in the high-risk group had significantly shorter OS than those in the low-risk group. The ROC showed all prognostic models had high accuracy and powerful predictive performance with different AUC ranging from 0.837 to 0.978. Moreover, the combined prognostic model had highest performance in risk stratification and predictive accuracy than single prognostic models and had higher accuracy than other mRNA model. Finally, a significant correlation network between survival-related AS genes and prognostic splicing factors (SFs) was established. In conclusion, our study provided several potential prognostic AS models and constructed splicing network between AS and SFs in LUSC, which could be used as potential indicators and treatment targets for LUSC patients.

Radionuclides in target station coolant in the China Spallation Neutron Source.

The China Spallation Neutron Source (CSNS) is the first pulsed neutron source in China for multidisciplinary research. After operation with 80 kW proton beam for 4 months, 3 circuits of target station coolant, light water 1/2/3 were sampled, and radionuclides in coolants were measured. The results showed that, activity concentration of H-3 in coolant can be up to the magnitude of 1.00E+06 Bq/L, and the H-3 amount in light water 1 was the highest and the amount in light water 3 was the lowest, agreeing with the radiation field exposed by coolants. For Be-7, due to the complicated filtering and trapping process, amount of Be-7 in coolant differed from a minimum of 7.15E+01 Bq/L to a maximum of 4.58E+03 Bq/L. Comparison of the results with former measurements and simulated results were conducted. Permitted volumes for coolant discharge were presented. And the work time in the equipment room of cooling system after the beam is shut off is safe. Results in this research could provide reference data and measurement methods for similar accelerator devices.

Population Pharmacokinetics and Exposure-Safety Relationship of Paclitaxel Liposome in Patients With Non-small Cell Lung Cancer.

PURPOSE: Paclitaxel liposome (Lipusu) is the first commercialized liposomal formulation of paclitaxel. There has been little data collected on the pharmacokinetics (PK) of paclitaxel liposome, especially in relation to patient use. This study aimed to build a population pharmacokinetic (PopPK) model and further explore the exposure-safety relationship for paclitaxel liposome in patients with non-small cell lung cancer (NSCLC). METHODS: Data from 45 patients with a total of 349 plasma concentrations were analyzed. The PopPK model was built using the non-linear mixed effect modeling technique. RESULTS: The PK of paclitaxel liposome were well described by a three-compartment model with first-order elimination. For a dose of 175 mg m-2, the estimated clearance of total plasma paclitaxel was 21.55 L h-1. Age, sex, body weight, total bilirubin, albumin, serum creatinine, and creatinine clearance did not influence the paclitaxel PK. Exposure to paclitaxel had no significant change in the presence of the traditional Chinese medicine, aidi injection. The exploratory exposure-safety relationship was well described by a generalized linear regression model. Higher probabilities of grade >1 neutropenia were observed in patients with higher exposure to paclitaxel. CONCLUSION: This PopPK model adequately described the PK of paclitaxel liposome in patients with NSCLC. Predicted exposure of paclitaxel did not change in the presence of the traditional Chinese medicine, aidi injection. The exposure-safety analysis suggested that a higher risk of neutropenia was correlated with higher exposure to paclitaxel.

Neuroprotective effects of pramipexole transdermal patch in the MPTP-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons. To avoid inconvenience of frequent administration caused by short half life and recurrence of symptoms such as tremor and bradykinesia incurred by drug elimination, a novel long-acting pramipexole transdermal patch has been made. In the present study, we evaluated the neuroprotective effects and underlying mechanisms of pramipexole patch (PPX patch) in a subacute PD mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PPX patch treatment improved dyskinesia. MPTP-induced reduction of DA as well as its metabolites DOPAC and HVA in the striatum were prevented by PPX patch in a dose-dependent manner. PPX patch also restored the activity of antioxidant enzymes including SOD, GSH-Px and CAT in the striatum while reduced the content of MDA. Furthermore, PPX patch upregulated Nrf2/HO-1 expression. The protective effects of PPX patch was also associated with downregulation of the Bax/Bcl-2 ratio and Apaf-1, inhibition of cytochrome c release and inactivation of caspase-9 and caspase-3. In conclusion, our studies demonstrated that the long-acting pramipexole patch exerts its neuroprotective effects, at least in part, by inhibiting oxidative stress and mitochondrial apoptosis pathway and holds promise as a candidate drug.

Upregulation of UDP-Glucuronosyltransferases 1a1 and 1a7 Are Involved in Altered Puerarin Pharmacokinetics in Type II Diabetic Rats.

Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of puerarin in normal rats and rats with diabetes mellitus (DM), and the mechanism involved. DM was induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection. Plasma concentrations of puerarin in DM, HFD, and control rats were determined after intravenous (20 mg/kg) and oral administration (500 mg/kg) of puerarin, and pharmacokinetic parameters were estimated. The messenger RNA (mRNA) and protein expression levels of Ugt1a1 and Ugt1a7 in rat livers and intestines were measured using qRT-PCR and western blot, respectively. The area under the concentration⁻time curve and the clearance of puerarin in the DM rats statistically differed from those in the control rats (p <0.05) with both administration routes. The hepatic and intestinal gene and protein expressions of Ugt1a1 and Ugt1a7 were significantly increased in the DM rats (p <0.05). Therefore, the metabolic changes in diabetes could alter the pharmacokinetics of puerarin. This change could be caused by upregulated uridine diphosphate (UDP)-glucuronosyltransferase activity, which may enhance puerarin clearance, and alter its therapeutic effects.

A Review of the Extraction and Determination Methods of Thirteen Essential Vitamins to the Human Body: An Update from 2010.

Vitamins are a class of essential nutrients in the body; thus, they play important roles in human health. The chemicals are involved in many physiological functions and both their lack and excess can put health at risk. Therefore, the establishment of methods for monitoring vitamin concentrations in different matrices is necessary. In this review, an updated overview of the main pretreatments and determination methods that have been used since 2010 is given. Ultrasonic assisted extraction, liquid⁻liquid extraction, solid phase extraction and dispersive liquid⁻liquid microextraction are the most common pretreatment methods, while the determination methods involve chromatography methods, electrophoretic methods, microbiological assays, immunoassays, biosensors and several other methods. Different pretreatments and determination methods are discussed.

Study on patient-induced radioactivity during proton treatment in hengjian proton medical facility.

At present, increasingly more proton medical facilities have been established globally for better curative effect and less side effect in tumor treatment. Compared with electron and photon, proton delivers more energy and dose at its end of range (Bragg peak), and has less lateral scattering for its much larger mass. However, proton is much easier to produce neutron and induced radioactivity, which makes radiation protection for proton accelerators more difficult than for electron accelerators. This study focuses on the problem of patient-induced radioactivity during proton treatment, which has been ignored for years. However, we confirmed it is a vital factor for radiation protection to both patient escort and positioning technician, by FLUKA's simulation and activation formula calculation of Hengjian Proton Medical Facility (HJPMF), whose energy ranges from 130 to 230MeV. Furthermore, new formulas for calculating the activity buildup process of periodic irradiation were derived and used to study the relationship between saturation degree and half-life of nuclides. Finally, suggestions are put forward to lessen the radiation hazard from patient-induced radioactivity.

Mindful learning can promote connectedness to nature: Implicit and explicit evidence.

Environmental problems have attracted increasing attention, yet individuals' connectedness to nature remains a significant concern for potential solutions to these problems. In this article, we propose a novel method to promote connectedness to nature: mindful learning. One hundred and thirty-four students participated in the experiment. First, baseline measurements using the Connectedness to Nature Scale were obtained. Participants were then assigned to either a mindful or mindless learning condition. Finally, as a posttest, participants completed the Implicit Association Test and the Inclusion of Nature in the Self Scale. The performance of the mindful-learning group was better for both measures. Participants in the mindful-learning condition performed better on the Implicit Association Test and scored higher on the Inclusion of Nature in the Self Scale. These results provide empirical evidence that mindful learning may promote connectedness to nature, both implicitly and explicitly.

Sulfonation of curcuminoids: characterization and contribution of individual SULT enzymes.

SCOPE: Poor oral bioavailability of curcuminoids limited their various applications, and one of the main reasons is their rapid metabolism in vivo. Sulfonation via sulfotransferases (SULTs) is an important metabolic pathway for such compounds. The objective of this study is to determine the SULT-isoform-specific metabolic fingerprint, tissue-specific rate, and reaction kinetic profiles to describe the characterization and contribution of curcuminoids sulfonation. METHODS AND RESULTS: Sulfonation of curcuminoids was investigated by using nine expressed SULT isoforms and four pooled human tissue S9 fractions. The results showed that human small intestine is the predominant tissue responsible for sulfonation of curcuminoids. SULT1A3 is a major isoform catalyzing sulfonation of curcumin and demethoxycurcumin, but not for bisdemethoxycurcumin. SULT1B1 is only responsible for sulfonation of curcumin. Although SULT1C4 and 1E1 could highly catalyze the sulfate conjugations toward all the three compounds, the correlativities with human small intestine S9 fractions were much weaker (R(2) = 0.100-0.482). Almost all the kinetic profiles of the SULT isoforms for curcuminoids exhibited substrate inhibition kinetics. CONCLUSION: This investigation contributed to elucidate the SULT-mediated metabolism and detoxication of curcuminoids at molecular levels and in different organs.