New molecular insights into ferroptosis in lung adenocarcinoma progression and pharmacological compounds for targeted therapy.

BACKGROUND: The involvement of ferroptosis has been found in many pathological conditions of the lung. The genetic engineering of ferroptosis-related genes may provide a potential target for the treatment of lung adenocarcinoma (LUAD). METHODS: Nine ferroptosis regulators and markers were collected from FerrDb and their somatic mutations and expressions were analyzed based on The Cancer Genome Atlas (TCGA)-LUAD cohort data. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were performed to screen genes significantly associated with ferroptosis. The ferroptosis-related gene signature was constructed using TCGA-LUAD cohort data and was verified using the GSE cohort with pooled data for GSE30219, GSE31210, GSE37745 and GSE50081. Immune microenvironment component and mutation analysis were performed for genes in the ferroptosis-related gene signature. RESULTS: All nine ferroptosis regulators and markers were differentially expressed between normal LUAD tumor tissues and adjacent normal tissues and were related to copy number variation. The expression of 1329 genes were significantly associated with nine ferroptosis regulators and markers in the TCGA-LUAD dataset, five (ALDOA, PLK1, CD47, CENPC and TMOD3) of which were integrated into a ferroptosis-related gene signature to calculate the risk score of LUAD samples, showing a significant correlation with the abundance of immune cell infiltration and the immune score. Molecular docking showed the binding activity of natural active compound quercetin to target proteins ALDOA and CD47, as well as the binding activity of aristolochic acid to PLK1 protein and TMOD3 protein. CONCLUSIONS: In the present study, a ferroptosis-related gene signature with predictive value for LUAD prognosis was constructed, in which the gene was a potential therapeutic target for LUAD. Quercetin and aristolochic acid were potential candidates for inhibiting these targets by directly binding to them and showing high affinity and strong stability.

Usefulness of Therapeutic Drug Monitoring and Pharmacogenetics for a Patient Treated with Olanzapine, Buspirone, and Fluvoxamine: A Case Study.

BACKGROUND: A patient, with a mental disorder caused by an intracranial infection, treated with olanzapine, fluvoxamine, and buspirone. The plasma exposure of olanzapine was too high at standard doses, with evidence indicating that it was caused by drug-drug interactions. METHODS: Using pharmacogenomics and therapeutic drug monitoring to guide drug dose adjustment for a patient in clinical practice. RESULTS: The patient underwent pharmacogenetic testing in addition to therapeutic drug monitoring as part of a pharmacist-led comprehensive evaluation of medication therapy management in a clinical setting, resulting in improved clinical efficacy that allowed discharge from a psychiatric hospital. CONCLUSIONS: This case study demonstrates that therapeutic drug monitoring combined with pharmacogenetic-guided dose adjustment can aid in the management of patients receiving complex pharmacological treatments.

Synthesis and Properties of a Novel Thermally Conductive Pressure-Sensitive Adhesive with UV-Responsive Peelability.

Thermally conductive pressure-sensitive adhesive (PSA) has received a great amount of attention in recent years, but the traditional PSA hardly loses adhesion properties after UV irradiation or heating. Therefore, endowing thermally conductive adhesive with UV-responsive peelability becomes a design strategy. Herein, vinyl-functionalized graphene (AA-GMA-G) is prepared by modifying graphene with acrylic acid and subsequently reacting with glycidyl methacrylate. Then, the UV-curable acrylate copolymer is synthesized by grafting glycidyl methacrylate. Finally, the novel thermally conductivity PSA with UV-responsive peelability is obtained by blending the copolymer with AA-GMA-G and photoinitiator. The results show that the PSA at 2 wt% AA-GMA-G loading exhibits an excellent thermal conductivity (0.74 W m-1 K-1 ) and a relatively strong peel strength, increasing by 15% compared with pristine graphene/PSA. Interestingly, the peel strength of AA-GMA-G/PSA can achieve a dramatic drop after UV treatment, and the decrease rate is 96.7%. Therefore, the novel thermally conductive PSA with UV-responsive peelability has potential applications in certain electronic devices.

Effects of Age, Sex, and Comedication on the Plasma Concentrations of Olanzapine in Chinese Patients With Schizophrenia Based on Therapeutic Drug Monitoring Data.

BACKGROUND: Olanzapine (OLA) is an atypical second-generation antipsychotic that exhibits significant pharmacokinetic variability. We retrospectively investigated the effects of age, sex, and specific comedications on OLA pharmacokinetics in Chinese patients with schizophrenia. METHODS: Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed. The combined effects of dosage, age, sex, and comedication on OLA plasma levels were assessed via multiple linear regression analyses. RESULTS: A daily dose of OLA was positively correlated with the drug's plasma concentrations. Overall, the OLA plasma concentrations and concentration-to-dose ratio (C/D) of the studied patients varied by 53.6- and 64.1-fold, achieving median values of 42.7 ng/mL and 2.73 (ng/mL)/(mg/d), respectively. Furthermore, a 1.27-fold higher estimated C/D in patients 60 years or older than in those younger than 60 years was identified. Female patients demonstrated a 33.6% higher C/D than in male patients. When coadministered with mood stabilizers (valproate or lithium), the median OLA C/D was 24.1% to 26.1% lower than that of OLA monotherapy. Interestingly, the OLA plasma concentration and C/D were not significantly affected by a comedication with aripiprazole, haloperidol, amisulpride, risperidone, clozapine, ziprasidone, citalopram, or buspirone. CONCLUSIONS: The administered drug's dose was identified as an important determinant of the achieved OLA plasma concentration, with a positive correlation. The patients' sex and valproate (or lithium) comedication can significantly affect the C/D of OLA. Therapeutic drug monitoring should be routinely applied in cases of OLA-receiving patients with schizophrenia.

A sensitive fluorescence biosensor based on metal ion-mediated DNAzyme activity for amplified detection of acetylcholinesterase.

In this paper, we developed an amplified fluorescence biosensor for acetylcholinesterase (AChE) activity detection by taking advantage of the mercury ion-mediated Mgzyme (Mg2+-dependent DNAzyme) activity. The catalytic activity of Mgzyme can be inhibited by the formation of T-Hg2+-T base pairs between the Mgzyme and mercury ions. Therefore, the Mgzyme-Hg2+ complex has no activity on a molecular beacon (MB) substrate, which afforded a very weak fluorescence background for this biosensor. After the addition of acetylcholinesterase (AChE), the substrate acetylthiocholine could be hydrolyzed to thiocholine, which has a stronger binding power with mercury ions than T-Hg2+-T base pairs. Therefore, the Mgzyme activity was recovered. The activated Mgzyme could hybridize with the MB substrate and undergo many cleavage cycles, resulting in a significant increase of fluorescence intensity. This biosensor displayed high sensitivity with the detection limit as low as 0.01 mU mL-1. Moreover, this design did not require complex composition and sequence design; thus it is simple and convenient. This biosensor was also applied for the determination of AChE in human blood and showed satisfactory results.

Development of a Novel Analytical Method for Determining Trazodone in Human Plasma by Liquid Chromatography Coupled With Mass Spectrometry Coupled With Automatic 2-Dimensional Liquid Chromatograph-Mass Spectrometer Coupler 9500 and Its Application to Therapeutic Drug Monitoring.

BACKGROUND: Trazodone (TZD) is a tetracyclic serotonin antagonist and reuptake inhibitor that is used as a second-generation phenylpiperazine antidepressant. However, the plasma concentrations of TZD have shown individual variations in clinical practice. Quantification of TZD plasma concentrations may be an effective and valuable method to balance the clinical efficacy and adverse reactions. This study aimed to establish a novel liquid chromatography coupled with mass spectrometry (LC-MS) assay for measuring TZD concentrations in human plasma for therapeutic drug monitoring (TDM). METHODS: After protein precipitation with acetonitrile, LC-MS quantification of TZD was performed in the multiple reaction monitoring mode with chromatographic separation using a mobile phase of MeOH and 0.1% formic acid in water. This method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect, and stability according to United states food and drug administration guidelines. RESULTS: This method showed good selectivity because no interfering peaks were observed in the plasma samples during the 2-minute run time. The range of the calibration curve was 1-3000 ng/mL. The detection and quantification limits were 0.3 and 1 ng/mL, respectively. The intraday and interday accuracies were 96.5%-103.4%, with precision relative SD% values of <5%, except for the limit of quality. The mean TZD recovery from human plasma was 95.4%-104.5%. Finally, this method was successfully applied to TDM in 20 patients. The TZD plasma concentrations of the patients ranged between 21.5 and 2267.3 ng/mL. CONCLUSIONS: A novel analytical method was established to measure TZD by LC-MS coupled with an automatic 2-dimensional liquid chromatograph mass spectrometer coupler 9500 (LC-MS/MS-Mate 9500), which is superior to the ordinary LC-MS system in separation, transport, anti-interference, sensitivity, and quantitative analysis stability.

Preserving the topological properties of complex networks in network sampling.

Extremely large-scale networks have received increasing attention in recent years. The development of big data and network science provides an unprecedented opportunity for research on these networks. However, it is difficult to perform analysis directly on numerous real networks due to their large size. A solution is to sample a subnetwork instead for detailed research. Unfortunately, the properties of the subnetworks could be substantially different from those of the original networks. In this context, a comprehensive understanding of the sampling methods would be crucial for network-based big data analysis. In our work, we find that the sampling deviation is the collective effect of both the network heterogeneity and the biases caused by the sampling methods themselves. Here, we study the widely used random node sampling (RNS), breadth-first search, and a hybrid method that falls between these two. We empirically and analytically investigate the differences in topological properties between the sampled network and the original network under these sampling methods. Empirically, the hybrid method has the advantage of preserving structural properties in most cases, which suggests that this method performs better with no additional information needed. However, not all the biases caused by sampling methods follow the same pattern. For instance, properties, such as link density, are better preserved by RNS. Finally, models are constructed to explain the biases concerning the size of giant connected components and link density analytically.

Waterborne Polyurethane Enhanced, Adhesive, and Ionic Conductive Hydrogel for Multifunctional Sensors.

In the past two decades, ionic conductive hydrogel has attracted tremendous research interests for their intrinsic characteristics in the field of flexible sensor. However, synchronous achievement of high mechanical strength, satisfied ionic conductivity, and broad adhesion to various substrates is still a challenge. Herein, a novel zwitterionic composite hydrogel that displayed excited strechability (up to 900%), satisfied strength (about 30 kPa), high ionic conductivity (1.2 mS cm-1 ), and adhesion to polar and nonpolar materials is fabricated though the combination of waterborne polyurethanes (PU) and poly(sulfobetaine zwitterion-co-acrylamide) (SAm). Especially, this facile strategy demonstrates that PU has a synergistic effect on enhancing mechanical strength and ionic conductivity for ionic conductive hydrogel. Moreover, the hydrogel-based strain/stress sensor shows high sensitivity, wide sensing range, great stability, and accuracy for human body movements detecting and voice recognition. This novel ionic conductive hydrogel has promoted the development of wearable devices.

Silver-ion-mediated Mg2+-dependent DNAzyme activity for amplified fluorescence detection of cysteine.

In this paper, by taking advantage of the fact that silver ions could mediate the Mg2+-dependent DNAzyme (Mgzyme) activity, we for the first time developed a turn-on fluorescent biosensor for amplified cysteine (Cys) detection. Because Mgzyme can interact with the silver ion and form cytosine-Ag+-cytosine (C-Ag+-C) base pairs, the conformation of its catalytic core was changed. As a result, the catalytic activity of Mgzyme was suppressed and the Mgzyme-Ag+ complex could not initiate the cleavage reaction. Therefore, the background fluorescence of the biosensor was very low. In the presence of Cys, Cys can bind tightly to the silver ion and disrupt the C-Ag+-C base pairs in the Mgzyme-Ag+ complex, leading to the restoration of Mgzyme activity. The activated Mgzyme could hybridize with the MB substrate and undergo many cleavage cycles, resulting in a significant increase of fluorescence intensity. This designed strategy provided amplified fluorescence detection of cysteine, with a detection limit of 2 nM. Moreover, the strong binding between Cys and Ag+ ensured that the biosensor had a desirable selectivity for Cys. This sensing system was also used to detect Cys in human urine samples and displayed satisfying results.

Pigments accumulation via light and oxygen in Rhodobacter capsulatus strain XJ-1 isolated from saline soil.

A Rhodobacter capsulatus strain, designated XJ-1, isolated from saline soil, accumulated almost only one kind of bacteriochlorophyll a anaerobically in the light, aerobically in the light and dark, and the relative contents of the bacteriochlorophyll a were 44.61, 74.89, and 77.53% of the total pigments, respectively. A new purple pigment appeared only in aerobic-light grown cells, exhibited absorption maxima at 355, 389, 520, 621, and 755 nm, especially distinctly unusual peak at 621 nm, whereas vanished in anaerobic-light and in aerobic-dark culture. Spheroidene and OH-spheroidene predominated in anaerobic phototrophic cultures. Spheroidenone was the sole carotenoid when exposed to both light and oxygen. The second keto-carotenoids, OH-spheroidenone, presented only in aerobic-dark culture in addition to spheroidenone. Strain XJ-1 would be a good model organism for the further illustration of the regulation of bacteriochlorophyll biosynthesis gene expression in response to unique habitat.

Homotherapy for Heteropathy: A Molecular Mechanism of Poria Sini Decoction for Treatment of Liver Cancer and Chronic Heart Failure.

Poria sini decoction (PSD), a significant traditional Chinese herbal formula, is effective in liver cancer (LC) and chronic heart failure (CHF); however, little is known about its concurrent targeting mechanism. Methods. This study analyzed the potential molecular mechanism of PSD against the two distinct diseases using network pharmacology approaches, including multidatabase search, pharmacokinetic screening, network construction analysis, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking to elaborate the active components, signaling pathways, and potential mechanisms of PSD in the treatment of both LC and CHF. Results. A total of 155 active components and 193 potential targets in PSD were identified. Bioinformatics analysis revealed that quercetin, isorhamnetin, and naringenin, etc. may be potential candidate agents. TNF, AKT1, and IL6, etc. could become potential therapeutic targets. TNF-α, NF-κB, PI3K-AKT, and TRP signaling pathways might play an important role in PSD against LC and CHF. Molecular docking results showed that most screened active compounds could embed itself into target proteins with a high binding affinity, and the hydrogen bonds number ≥3 indicated a more stable conformation of the compounds and target proteins. Overall, quercetin and isorhamnetin were the main active components, and TNF and AKT1 were the primary targets for PSD treatment of LC and CHF. Conclusions. This study illustrated that quercetin contained in PSD played an important role in the treatment of LC and CHF by acting on the key gene of TP53 and downregulating the PI3K-AKT signaling pathway.

A retrospective study of clozapine and norclozapine concentration in patients with schizophrenia: Data from the Therapeutic Drug Monitoring Service, 2019-2022.

OBJECTIVE: The aim of this research was to assess the therapeutic drug monitoring (TDM) of clozapine (CLO) and norclozapine (NCLO). METHODS: TDM results of CLO and NCLO in patients obtained from the Xi'an Mental Health Center were retrospectively analyzed. RESULTS: TDM of CLO and NCLO was typically conducted only once in the majority of patients, particularly those receiving outpatient care. The CLO plasma concentrations were higher in inpatients and female patients. The interquartile (25th-75th) CLO concentrations ranged from 129.83 to 397.53 ng/mL, nearly 68.63% of the samples had subtherapeutic concentrations (<350 ng/mL). Receiver operating characteristic curve analysis showed that inpatients achieved the therapeutic level concentration of 350-600 ng/mL when their daily CLO dose was > 125 mg. CONCLUSIONS: It was surprising to find such a large number of patients with CLO levels below the therapeutic range, there is still a window of improvement for optimizing pharmacological treatments in clinical practice.

IL-32/NFκB/miR-205 loop sustains the high expression of IL-32 and enhances the motility of cervical cancer cells.

Human papillomavirus (HPV) infection is a major contributor to cervical cancer. Persistent HPV infection can trigger the expression of IL-32, yet the precise role of IL-32 in the occurrence and development of cervical cancer remains elusive. To investigate this, qRT‒PCR and western blotting were utilized to measure the mRNA and protein expression levels; bioinformatics analysis was used to screen differentially expressed miRNAs; wound healing and transwell assays were conducted to evaluate cell migration and invasion capabilities. Comparative analysis revealed significantly elevated IL-32 expression in cervical cancer tissues and cell lines compared to control groups. In SiHa and/or HeLa, overexpression of IL-32 and IL-32 exposure markedly upregulated miR-205, whereas its knockdown resulted in a substantial downregulation of miR-205. Furthermore, miR-205 also could significantly regulate the expression of IL-32 in HeLa and SiHa cells. Upregulation and downregulation of IL-32 led to a significant increase or decrease in NFκB expression, respectively. Treatment with BAY11-7082 (an NFκB inhibitor) notably decreased miR-205 expression but had no effect on IL-32 levels. qRT‒PCR and western blotting analyses demonstrated that both overexpression and underexpression of IL-32 and miR-205 significantly enhanced or reduced MMP2 and MMP9 expression in cervical cancer cells, respectively. Knockdown of IL-32 significantly inhibited the migration and invasion of HeLa and SiHa; conversely, treatment with rIL-32α and rIL-32γ notably promoted their migration and invasion. In brief, IL-32 is highly expressed via the formation of a positive regulatory loop with NFκB/miR-205, contributing to the persistence of inflammation and promoting the progression of cervical cancer.

A 5-year retrospective study of amisulpride steady-state plasma concentration in patients with schizophrenia in real-life settings based on therapeutic drug monitoring data.

OBJECTIVE: Here, we present a retrospective analysis of the last 5 years' data collected in real-life settings as direct evidence to evaluate the optimal therapeutic window of amisulpride (AMI) for psychiatric patients. METHODS: Retrospective analysis of the therapeutic drug monitoring (TDM) results of AMI in outpatients and inpatients were obtained from the Xi'an Mental Health Center from 2017 to 2021. RESULTS: The interquartile (P25-P75) AMI concentrations ranged 212.20-574.25 ng/mL. The results showed that the proportion of outpatients who received TDM once was significantly higher than that of inpatients who received TDM once (P < 0.001), whereas the reverse was true for those who experienced TDM more than twice (P < 0.001). Higher estimated plasma concentrations were identified in inpatients, female patients, and patients over 59 years of age. Nearly 57.21% of the samples had high concentrations (>320 ng/mL). CONCLUSIONS: The optimal therapeutic reference range for AMI may require reconstruction to guide the use of AMI for the treatment of schizophrenia.

Leading basic modes of spontaneous activity drive individual functional connectivity organization in the resting human brain.

Spontaneous activity of the human brain provides a window to explore intrinsic principles of functional organization. However, most studies have focused on interregional functional connectivity. The principles underlying rich repertoires of instantaneous activity remain largely unknown. We apply a recently proposed eigen-microstate analysis to three resting-state functional MRI datasets to identify basic modes that represent fundamental activity patterns that coexist over time. We identify five leading basic modes that dominate activity fluctuations. Each mode exhibits a distinct functional system-dependent coactivation pattern and corresponds to specific cognitive profiles. In particular, the spatial pattern of the first leading basis mode shows the separation of activity between the default-mode and primary and attention regions. Based on theoretical modelling, we further reconstruct individual functional connectivity as the weighted superposition of coactivation patterns corresponding to these leading basic modes. Moreover, these leading basic modes capture sleep deprivation-induced changes in brain activity and interregional connectivity, primarily involving the default-mode and task-positive regions. Our findings reveal a dominant set of basic modes of spontaneous activity that reflect multiplexed interregional coordination and drive conventional functional connectivity, furthering the understanding of the functional significance of spontaneous brain activity.

Therapeutic drug monitoring of perospirone: The lowest effective plasma concentration in patients with schizophrenia.

OBJECTIVES: This study investigated the effects of demographic factors such as age, sex and comedications on the plasma concentrations of perospirone in individuals diagnosed with schizophrenia. Additionally, the relationship between these plasma levels and the clinical efficacy of the medication was explored. METHODS: Data regarding the plasma concentration of perospirone in patients with schizophrenia were obtained from the Xi'an Mental Health Center and were retrospectively analysed. RESULTS: The study results revealed a range of 0.50-1.59 ng/mL for the 25th-75th percentile of perospirone concentration in the plasma, which ranged from 0.07 to 6.0 ng/mL. The plasma concentration of perospirone increased with the daily oral dose (r = 0.283, P < 0.05). Furthermore, patients with higher plasma perospirone concentrations and concentration-to-dose ratios (C/D) tended to be older or were women. Notably, the coadministration of valproate significantly reduced perospirone concentration and the C/D ratio by 54.7% and 35.3%, respectively (P < 0.01). Receiver operating characteristics curve analyses revealed that patients exhibited a good clinical response when their plasma perospirone concentrations were ≥ 1.17 ng/mL. CONCLUSION: The findings suggest that therapeutic drug monitoring of perospirone and adjustments to achieve steady-state concentrations of ≥ 1.17 ng/mL can be beneficial for optimising treatment for patients with schizophrenia.

Protective effect of mussel polysaccharide on cyclophosphamide-induced intestinal oxidative stress injury via Nrf2-Keap1 signaling pathway.

The hard-shelled mussel (Mytilus coruscus) has been used as a traditional Chinese medicine and health food in China for centuries. Polysaccharides from mussel has been reported to have multiple biological functions, however, it remains unclear whether mussel polysaccharide (MP) exerts protective effects in intestinal functions, and the underlying mechanisms of action remain unclear. The aim of this study was to investigate the protective effects and mechanism of MP on intestinal oxidative injury in mice. In this study, 40 male BALB/C mice were used, with 30 utilized to produce an animal model of intestinal oxidative injury with intraperitoneal injection of cyclophosphamide (Cy) for four consecutive days. The protective effects of two different doses of MP (300 and 600 mg/kg) were assessed by investigating the change in body weight, visceral index, and observing colon histomorphology. Moreover, the underlying molecular mechanisms were investigated by measuring the antioxidant enzymes and related signaling molecules through ELISA, real-time PCR, and western blot methods. The results showed that MP pretreatment effectively protected the intestinal from Cy-induced injury: improved the colon tissue morphology and villus structure, increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and reduced malondialdehyde (MDA) content in serum and colon tissues. Meanwhile, MP also significantly increased the expression levels of SOD, GSH-Px, heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) mRNA in colon tissues. Further, western blot results showed that the expression of Nrf2 protein was significantly upregulated while kelch-like ECH-associated protein 1 (Keap1) was significantly downregulated by MP in the colonic tissues. This study indicates that MP can ameliorate Cy-induced oxidative stress injury in mice, and Nrf2-Keap1 signaling pathway may mediate these protective effects.

Spark-induced sparks as a mechanism of intracellular calcium alternans in cardiac myocytes.

RATIONALE: Intracellular calcium (Ca) alternans has been widely studied in cardiac myocytes and tissue, yet the underlying mechanism remains controversial. OBJECTIVE: In this study, we used computational modeling and simulation to study how randomly occurring Ca sparks interact collectively to result in whole-cell Ca alternans. METHODS AND RESULTS: We developed a spatially distributed intracellular Ca cycling model in which Ca release units (CRUs) are locally coupled by Ca diffusion throughout the myoplasm and sarcoplasmic reticulum (SR) network. Ca sparks occur randomly in the CRU network when periodically paced with a clamped voltage waveform, but Ca alternans develops as the pacing speeds up. Combining computational simulation with theoretical analysis, we show that Ca alternans emerges as a collective behavior of Ca sparks, determined by 3 critical properties of the CRU network from which Ca sparks arise: "randomness" (of Ca spark activation), "refractoriness" (of a CRU after a Ca spark), and "recruitment" (Ca sparks inducing Ca sparks in adjacent CRUs). We also show that the steep nonlinear relationship between fractional SR Ca release and SR Ca load arises naturally as a collective behavior of Ca sparks, and Ca alternans can occur even when SR Ca is held constant. CONCLUSIONS: We present a general theory for the mechanisms of intracellular Ca alternans, which mechanistically links Ca sparks to whole-cell Ca alternans, and is applicable to Ca alternans in both physiological and pathophysiological conditions.

Time series reconstructing using calibrated reservoir computing.

Reservoir computing, a new method of machine learning, has recently been used to predict the state evolution of various chaotic dynamic systems. It has significant advantages in terms of training cost and adjusted parameters; however, the prediction length is limited. For classic reservoir computing, the prediction length can only reach five to six Lyapunov times. Here, we modified the method of reservoir computing by adding feedback, continuous or discrete, to "calibrate" the input of the reservoir and then reconstruct the entire dynamic systems. The reconstruction length appreciably increased and the training length obviously decreased. The reconstructing of dynamical systems is studied in detail under this method. The reconstruction can be significantly improved both in length and accuracy. Additionally, we summarized the effect of different kinds of input feedback. The more it interacts with others in dynamical equations, the better the reconstructions. Nonlinear terms can reveal more information than linear terms once the interaction terms are equal. This method has proven effective via several classical chaotic systems. It can be superior to traditional reservoir computing in reconstruction, provides new hints in computing promotion, and may be used in some real applications.

A novel and robust analytical method for the quantification of perospirone in human plasma using an LC-MS/MS system with self-internal standard calibration.

OBJECTIVES: This study aims to establish a novel method for measuring perospirone in human plasma for therapeutic drug monitoring (TDM) by liquid chromatography-mass spectrometry (LC-MS) coupled with an automatic liquid chromatograph mass spectrometer coupler 9500 (LC-MS/MS-Mate 9500), which has been equipped with self-internal standard (SIS) calibration technology. DESIGN & METHODS: A novel and attractive analytical calibration method designed for perospirone, calibration with SIS, was reported. After protein precipitation with acetonitrile-cyclopentanol (9:1, v/v) containing 1% NH3·H2O, LC-MS quantification of perospirone was performed by multiple reaction monitoring in the positive mode with quantitative and qualitative analysis of the ion pairs m/z 427.30 â†’ 177.15 and 427.30 â†’ 166.15 for perospirone and SIS. Chromatographic separation was accomplished in < 2.0 min on an Hypersil GOLDTM C18 column (2.1 mm × 50 mm, 3.0 µm) using a mobile methanol phase and 0.1% formic acid in water. RESULTS: This method showed good selectivity because no interfering peaks were observed in the plasma samples during the 2.0-min run time. The calibration curve range was 0.05-20 ng/mL, with a correlation coefficient of ≥ 0.9995. Intraday and interday accuracies were 98.3%-107.9%, respectively, with precision relative standard deviation values of < 10%. The matrix effects ranged from 92.7% to 96.1%, and extraction recoveries were between 97.3% and 108.8%. Finally, this method was successfully applied to routine clinical TDM for 142 patients. The perospirone plasma concentrations of the patients ranged between 0.07 and 10.96 ng/mL. CONCLUSIONS: This bioanalytical method can be used for the quantification of perospirone in human plasma by LC-MS/MS-Mate 9500 using perospirone itself as the SIS.