Initial dosage optimization of olanzapine in patients with bipolar disorder based on model-informed precision dosing: a study from the real world.

Objectives: Olanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study. Methods: Thirty-nine patients with BPD from the real-world study were collected to construct the MIPD model. Results: Weight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60 mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05 mg/kg/day was suitable for 40- to 100-kg BPD patients. Conclusion: This study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients.

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model.

OBJECTIVE: The method of administering the initial doses of tacrolimus in recipients of pediatric lung transplantation, especially in patients with low hematocrit, is not clear. The present study aims to explore whether weight, CYP3A5 genotype, and voriconazole co-administration influence tacrolimus initial dosage in recipients of pediatric lung transplantation with low hematocrit based on safety and efficacy using a simulation model. METHODS: The present study utilized the tacrolimus population pharmacokinetic model, which was employed in lung transplantation recipients with low hematocrit. RESULTS: For pediatric lung transplantation recipients not carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-13, 13-19, 19-22, 22-35, 35-38, and 38-40 kg are 0.03, 0.04, 0.05, 0.06, 0.07, and 0.08 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-18, 18-30, and 30-40 kg are 0.06, 0.08, 0.11 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients not carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20 and 20-40 kg are 0.02 and 0.03 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20, 20-33, and 33-40 kg are 0.03, 0.04, and 0.05 mg/kg/day, which are split into two doses, respectively. CONCLUSION: The present study is the first to recommend the initial dosages of tacrolimus in recipients of pediatric lung transplantation with low hematocrit using a simulation model.

Application of Facial Expression Analysis Technology in Violence Risk Assessment of Individuals with Mental Disorders in Supervised Settings.

OBJECTIVES: To explore the association between violent behaviors and emotions in individuals with mental disorders, to evaluate the application value of facial expression analysis technology in violence risk assessment of individuals with mental disorders in supervised settings, and to provide a reference for violence risk assessment. METHODS: Thirty-nine male individuals with mental disorders in supervised settings were selected, the participant risk of violence, cognitive function, psychiatric symptoms and severity were assessed using the Modified Overt Aggression Scale (MOAS), the Historical, Clinical, Risk Management-Chinese version(HCR-CV), the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). An emotional arousal was performed on the participants and the intensity of their emotions and facial expression action units was recorded before, during and after the arousal. One-way analysis of variance (ANOVA) was used to compare the differences in the intensity of emotions and facial expression action units before, during and after the arousal. Pearson correlation analysis was used to calculate the correlations between the intensity of the seven basic emotional facial expressions and the scores of the assessment scales. RESULTS: The intensity difference of sadness, surprise and fear in different time periods was statistically significant (P<0.05). The intensity of the left medial eyebrow lift action unit was found significantly different before and after the emotional arousal (P<0.05). The intensity of anger was positively correlated with the Modified Overt Aggression Scale score throughout the experiment (P<0.05). CONCLUSIONS: Eye action units such as eyebrow lifting, eyelid tightening and upper eyelid lifting can be used as effective action units to identify sadness, anger and other negative emotions associated with violent behaviors. Facial expression analysis technology can be used as an auxiliary tool to assess the potential risk of violence in individuals with mental disorders in supervised settings.

Polyfluoride Acceptor with Limited Molecular Diffusion Enables Efficient and Stable Ternary Organic Solar Cells.

Due to the slow diffusion of photovoltaic molecules, in particular, small-molecule acceptors (SMAs), under light and heating, the morphology of the active layer in organic solar cells (OSCs) prefers to deviate from the favorably metastable status, leading to the challenge of stability during long-term operation. Employing materials with a high glass transition temperature (Tg) as the third component to suppress molecular diffusion is an efficient method to achieve the balance of efficiency and stability of OSCs. Herein, a dimerized small-molecule acceptor denoted as F6D is synthesized by introducing a polyfluoride moiety as the linker to enhance the Tg. Benefitting from a rational molecular design, F6D not only exhibits a higher Tg, complementary absorption, and cascade energy levels with the host materials of the polymer donor PM6 and the SMA Y6 but also has excellent miscibility and multiple intermolecular interactions with Y6. As a result, a champion power conversion efficiency of 17.52% is achieved in the optimal PM6:Y6:F6D-based device. More importantly, the ternary device exhibits superior stability under continuous heating and lighting compared with the binary device.

Drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics.

Background: The present study aimed to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics. Research design and methods: A total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects. Results: The weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg-1 day-1 were recommended for patients with schizophrenia weighing 40-95 and 95-120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg-1 day-1 was recommended for those weighing 40-120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg-1 day-1 was recommended for patients with schizophrenia weighing 40-120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg-1 day-1 were recommended for those weighing 40-60 and 60-120 kg, respectively. Conclusion: This is the first investigation of the effects of fluoxetine on aripiprazole via drug-drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia.

Effects of Sex Differences and Combined Use of Clozapine on Initial Dosage Optimization of Valproic Acid in Patients with Bipolar Disorder.

BACKGROUND: Due to the narrow therapeutic window and large pharmacokinetic variation of valproic acid (VPA), it is difficult to make an optimal dosage regimen. The present study aims to optimize the initial dosage of VPA in patients with bipolar disorder. METHODS: A total of 126 patients with bipolar disorder treated by VPA were included to construct the VPA population pharmacokinetic model retrospectively. Sex differences and combined use of clozapine were found to significantly affect VPA clearance in patients with bipolar disorder. The initial dosage of VPA was further optimized in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. RESULTS: The CL/F and V/F of VPA in patients with bipolar disorder were 11.3 L/h and 36.4 L, respectively. It was found that sex differences and combined use of clozapine significantly affected VPA clearance in patients with bipolar disorder. At the same weight, the VPA clearance rates were 1.134, 1, 1.276884, and 1.126 in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. This study further optimized the initial dosage of VPA in male patients without the combined use of clozapine, female patients without the combined use of clozapine, male patients with the combined use of clozapine, and female patients with the combined use of clozapine, respectively. CONCLUSION: This study is the first to investigate the initial dosage optimization of VPA in patients with bipolar disorder based on sex differences and the combined use of clozapine. Male patients had higher clearance, and the recommended initial dose decreased with increasing weight, providing a reference for the precision drug use of VPA in clinical patients with bipolar disorder.

Unilateral Biportal Endoscopic Discectomy versus Percutaneous Endoscopic Interlaminar Discectomy for Lumbar Disc Herniation.

Background: As the latest endoscopic spine surgery, percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) discectomy have distinct technical characteristics. This study aimed to evaluate the clinical outcomes of PEID and UBE discectomy in the treatment of single-level lumbar disc herniation (LDH). Methods: Between February 2019 and April 2022, 115 patients with single-level LDH at L4-5 or L5-S1 received PEID or UBE discectomy. The patients were separated into two groups based on the surgical method used: Group 1 (the PEID group) (n = 60) and Group 2 (the UBE group) (n = 55). Various parameters, including operative time, hospitalization time, fluoroscopy frequency, total costs, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI), were evaluated and compared between the two groups. Results: There were no significant differences in the VAS and ODI scores in 12 months after the operation between two groups (P > 0.05). However, the VAS of lower back pain on the first day after the operation in Group 2 (2.53±0.89) was higher than that in Group 1 (2.19±0.74) (P < 0.05). There were no significant differences in the operation time and incidence of complications between two groups (P > 0.05). But total costs in Group 2 (43,121±4280) were significantly higher than those in Group 1 (30,069±3551) (P < 0.05). Conclusion: Both UBE and PEID procedures have similar efficacy in alleviating pain and improving functional ability in patients with LDH. However, UBE surgery results in higher costs than PEID surgery.

Stimuli­Responsive Hydrogels for Antibacterial Applications.

Hydrogels have emerged as promising candidates for biomedical applications, especially in the field of antibacterial therapeutics, due to their unique structural properties, highly tunable physicochemical properties, and excellent biocompatibility. The integration of stimuli-responsive functions into antibacterial hydrogels holds the potential to enhance their antibacterial properties and therapeutic efficacy, dynamically responding to different external or internal stimuli, such as pH, temperature, enzymes, and light. Therefore, this review describes the applications of hydrogel dressings responsive to different stimuli in antibacterial therapy. The collaborative interaction between stimuli-responsive hydrogels and antibacterial materials is discussed. This synergistic approach, in contrast to conventional antibacterial materials, not only amplifies the antibacterial effect but also alleviates adverse side effects and diminishes the incidence of multiple infections and drug resistance. The review provides a comprehensive overview of the current challenges and outlines future research directions for stimuli-responsive antibacterial hydrogels. It underscores the imperative for ongoing interdisciplinary research aimed at unraveling the mechanisms of wound healing. This understanding is crucial for optimizing the design and implementation of stimuli-responsive antibacterial hydrogels. Ultimately, this review aims to offer scientific guidance for the development and practical clinical application of stimuli-responsive antibacterial hydrogel dressings.

Binary Organic Solar Cells with Exceeding 19% Efficiency via the Synergy of Polyfluoride Polymer and Fluorous Solvent.

Rational molecular design and suitable device engineering are two important strategies to boost the efficiencies in organic solar cells (OSCs). Yet these two approaches are independently developed, while their synergy is believed to be more productive. Herein, a branched polyfluoride moiety, heptafluoroisopropoxyl group, is introduced into the side chains of conjugated polymers for the first time. Compared with the conventional alkyl chain, this polyfluoride chain can endow the resulting polymer namely PF7 with highly packing order and strong crystallinity owing to the strong polarization and fluorine-induced interactions, while good solubility and moderate miscibility are retained. As a result, PF7 comprehensively outperforms the state-of-the-art polymer PM6 in photovoltaic properties. More importantly, based on the solubility of heptafluoroisopropoxyl groups in fluorous solvents, a new post-treatment denoted as fluorous solvent vapor annealing (FSVA) is proposed to match PF7. Differing from the existing post-treatments, FSVA can selectively reorganize fluoropolymer molecules but less impact small molecules in blend films. By employing the synergy of fluoropolymer and fluorous solvent, the device achieves a remarkable efficiency of 19.09%, which is among the best efficiencies in binary OSCs. The polymer PF7 and the FSVA treatment exhibit excellent universality in various OSCs with different material combinations or device architectures.

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients.

Objective: Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients. Methods: In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM). Results: Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively. Conclusion: Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.

Background: The appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels. Methods: The present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels. Results: Within normal hematocrit levels, for children with lung transplantation who do not carry the CYP3A5*1 gene and have no coadministration with voriconazole, it is recommended to administer tacrolimus at a dosage of 0.02 mg/kg/day, divided into two doses, for children weighing 10-32 kg, and a dosage of 0.03 mg/kg/day, also divided into two doses, for children weighing 32-40 kg. For children with lung transplantation who carry the CYP3A5*1 gene and have no coadministration with voriconazole, tacrolimus dosages of 0.02, 0.03, and 0.04 mg/kg/day split into two doses are recommended for children weighing 10-15, 15-32, and 32-40 kg, respectively. For children with lung transplantation who do not carry the CYP3A5*1 gene and have coadministration with voriconazole, tacrolimus dosages of 0.01 and 0.02 mg/kg/day split into two doses are recommended for children weighing 10-17 and 17-40 kg, respectively. For children with lung transplantation who carry the CYP3A5*1 gene and have coadministration with voriconazole, a tacrolimus dosage of 0.02 mg/kg/day split into two doses is recommended for children weighing 10-40 kg. Conclusions: It is the first time to optimize the initial dosage of tacrolimus in Chinese children undergoing lung transplantation within normal hematocrit.

High-fidelity intracellular imaging of multiple miRNAs via stimulus-responsive nanocarriers and catalytic hairpin assembly.

An advanced nanoplatform was developed by integrating catalytic hairpin assembly (CHA) with glutathione-responsive nanocarriers, enabling superior imaging of dual cancer-related miRNAs. Two distinct CHA circuits for the sensing of miRNA-21 and miRNA-155 were functionalized on biodegraded MnO2. In the presence of GSH and the corresponding miRNAs, the degraded MnO2 released the DNA cargos, activating the CHA circuits and recovering the fluorescence. This approach offers a reliable sensing performance with highly selective cell-identification capacity, positioning it as a pivotal tool for imaging multiple biomarkers in living cells.

Dynamic Optical Encryption Fueled via Tunable Mechanical Composite Micrograting Systems.

Optical grating devices based on micro/nanostructured functional surfaces are widely employed to precisely manipulate light propagation, which is significant for information technologies, optical data storage, and light sensors. However, the parameters of rigid periodic structures are difficult to tune after manufacturing, which seriously limits their capacity for in situ light manipulation. Here, a novel anti-eavesdropping, anti-damage, and anti-tamper dynamic optical encryption strategy are reported via tunable mechanical composite wrinkle micrograting encryption systems (MCWGES). By mechanically composing multiple in-situ tunable ordered wrinkle gratings, the dynamic keys with large space capacity are generated to obtain encrypted diffraction patterns, which can provide a higher level of security for the encrypted systems. Furthermore, a multiple grating cone diffraction model is proposed to reveal the dynamic optical encryption principle of MCWGES. Optical encryption communication using dynamic keys has the effect of preventing eavesdropping, damage, and tampering. This dynamic encryption method based on optical manipulation of wrinkle grating demonstrates the potential applications of micro/nanostructured functional surfaces in the field of information security.

Evodiamine inhibits EPRS expression to regulate glutamate metabolism and proliferation of oral squamous cell carcinoma cells.

The effects of evodiamine (EVO) on oral squamous cell carcinoma (OSCC) are not yet understood. Based on our earlier findings, we hypothesized that evodiamine may affect OSCC cell proliferation and glutamate metabolism by modulating the expression of EPRS (glutamyl-prolyl-tRNA synthetase 1). From GEPIA, we obtained EPRS expression data in patients with OSCC as well as survival prognosis data. An animal model using Cal27 cells in BALB/c nude mice was established. The expression of EPRS was assessed by immunofluorescence, Western blotting, and quantitative PCR. Glutamate measurements were performed to evaluate the impact of evodiamine on glutamate metabolism of Cal27 and SAS tumor cells. transient transfection techniques were used to knock down and modulate EPRS in these cells. EPRS is expressed at higher levels in OSCC than in normal tissues, and it predicts poor prognosis in patients. In a nude mouse xenograft model, evodiamine inhibited tumor growth and the expression of EPRS. Evodiamine impacted cell proliferation, glutamine metabolism, and EPRS expression on Cal27 and SAS cell lines. In EPRS knockdown cell lines, both cell proliferation and glutamine metabolism are suppressed. EPRS's overexpression partially restores evodiamine's inhibitory effects on cell proliferation and glutamine metabolism. This study provides crucial experimental evidence supporting the potential therapeutic application of evodiamine in treating OSCC. Evodiamine exhibits promising anti-tumor effects by targeting EPRS to regulate glutamate metabolism.

Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin.

BACKGROUND: The treatment of tacrolimus-induced post-transplantation diabetes mellitus (PTDM) has become a hot topic to improve the long-term survival of organ transplant patients, however whose pathogenesis has not been fully elucidated. In pancreas, the up-regulation of NF-κB has been reported to stimulate cytokine IL-1ß/TNF-α secretion, inducing pancreatic injury, meanwhile other studies have reported the inhibitory effect of rapamycin on NF-κB. PURPOSE: The aim of this study was to clarify the mechanism of tacrolimus-induced pancreatic injury and to explore the potential effect from small dose of sirolimus. METHODS: Wistar rats were randomly divided normal control (NC) group, PTDM group, sirolimus intervention (SIR) group. Transcriptomic analysis was used to screen potential mechanism of PTDM. Biochemical index detections were used to test the indicators of pancreatic injury. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot were used to verify the underlying mechanism. RESULTS: Compared with NC group, the level of insulin was significant reduction (P < 0.01), inversely the level of glucagon was significantly increase (P < 0.01) in PTDM group. Transcriptomic analysis indicated Syk/BLNK/NF-κB signaling was significantly up-regulated in PTDM group. Pathological staining, immumohistochemical staining, immunofluorescent staining, western blot verified Syk/BLNK/NF-κB and TNF-α/IL-1ß were all significantly increased (P < 0.05 or P < 0.01), demonstrating the mechanism of tacrolimus-induced pancreatic injury via Syk/BLNK/NF-κB signaling. In addition, compared with PTDM group, the levels of weight, FPG, AMY, and GSP in SIR group were significant ameliorative (P < 0.05 or P < 0.01), and the expressions of p-NF-κB, TNF-α/IL-1ß in SIR group were significantly reduction (P < 0.05 or P < 0.01), showing Syk/BLNK/NF-κB signaling promoted pancreatic injury induced by tacrolimus and potential protective effect from rapamycin reducing NF-κB. CONCLUSION: Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and rapamycin has a potentially protective effect by down-regulating NF-κB. Further validation and clinical studies are needed in the future.

Human-influenced changes in pollution status and potential risk of sediment heavy metals in Xincun Bay, a typical lagoon of Hainan, China.

Pollution status and ecological risks associated with sediment heavy metals (Cu, Pb, Zn, Cd, and Cr) were investigated around Xincun Bay, assessing their spatial variations and relationship with sediment physiochemical factors. Higher concentrations and associated risks were observed in the central region, where mariculture activities were concentrated, compared to non-maricultured areas. Despite with overall low concentrations, Cd had a higher ecological risk. Correlation and principal component analyses revealed similar sources for all metals in Xincun Bay. Heavy metal concentrations varied with expansion of mariculture operations in terms of quantity and scale, confirming the influence of mariculture activities. Sediments around mariculture had higher contents of clay, silt, and total organic carbon (TOC), and finer particle sizes. Quantitative analyses through correlation and linear regression indicated that TOC significantly regulated heavy metal concentration and distribution (p < 0.05). Considering its significant association with TOC, the influence of mean grain size should not be overlooked.

Development and validation of a predictive models for predicting the cardiac events within one year for patients underwent percutaneous coronary intervention procedure at IJN.

PURPOSE: Percutaneous coronary intervention (PCI) is a common treatment modality for coronary artery disease. Accurate prediction of patients at risk for complications and hospital readmission after PCI could improve the overall clinical management. We aimed to develop and validate predictive models to predict any cardiac event within a year post PCI procedure. METHODS: This is a retrospective cohort study utilizing data from the National Cardiovascular Disease (NCVD)-PCI registry. The data collected (N = 28,007) were split into training set (n = 24,409) and testing set (n = 3598). Four predictive models (logistic regression [LR], random forest method, support vector machine [SVM], and artificial neural network) were developed and validated. The outcome on risk prediction were compared. RESULTS: The demographic and clinical features of patients in the training and testing cohorts were similar. Patients had mean age ± standard deviation of 58.15 ± 10.13 years at admission with a male majority (82.66%). In over half of the procedures (50.61%), patients had chronic stable angina. Within 1 year of follow up mortality, target vessel revascularization (TVR), and composite event of mortality and TVR were 3.92%, 9.48%, and 12.98% respectively. LR was the best model in predicting mortality event within 1-year post-PCI (AUC: 0.820). SVM had the highest discrimination power for both TVR event (AUC: 0.720) and composite event of mortality and TVR (AUC: 0.720). CONCLUSIONS: This study successfully identified optimal prediction models with the good discriminatory ability for mortality outcome and good discrimination ability for TVR and composite event of mortality and TVR with a simple machine learning framework.

Research Progress and Application Prospect of Facial Micro-Expression Analysis in Forensic Psychiatry.

Research on facial micro-expression analysis has been going on for decades. Micro-expression can reflect the true emotions of individuals, and it has important application value in assisting auxiliary diagnosis and disease monitoring of mental disorders. In recent years, the development of artificial intelligence and big data technology has made the automatic recognition of micro-expressions possible, which will make micro-expression analysis more convenient and more widely used. This paper reviews the development of facial micro-expression analysis and its application in forensic psychiatry, to look into further application prospects and development direction.

Determination of niclosamide and its two metabolites in fish by molecularly imprinted microsphere-based pseudo-ELISA.

Niclosamide is usually used for the treatment of parasite infections in animals. However, niclosamide and one of its metabolites 2-chloro-4-nitroaniline are mutagenic substances, and their residues in animal-derived foods are potential risks to consumers. As far as we know, there has been no immunoassay or pseudo immunoassay reported to determine niclosamide and its metabolites in animal-derived foods. In this study, a molecularly imprinted microsphere for niclosamide was first synthesized, and a streptavidin-horseradish peroxidase labelled conjugate was also synthesized. The two reagents were used to develop a pseudo enzyme-linked immunosorbent assay on conventional microplates for the determination of niclosamide and its two metabolites (2-chloro-4-nitroaniline and 5-chlorosalicylic acid) in fish. Because biotinylated horseradish peroxidase was used to amplify the signal, the method sensitivities for the three analytes were increased fivefold to 27.5-fold (limits of detection of 0.004-0.03 ng/mL) in comparison with the use of single horseradish peroxidase labelled conjugate (limits of detection of 0.11-0.16 ng/mL). Their recoveries from the standards fortified blank fish samples were in the range of 70.6-95.5%. This is the first study reporting a molecularly imprinted polymer-based pseudo immunoassay for screening of niclosamide and its metabolites in food sample.

E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.

OBJECTIVE: The role E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) has not been studied in pancreatic cancer. METHOD: Pancreatic cancer cell lines and the normal pancreatic cells were tested in vitro studies and male athymic nude mice were tested in vivo studies. Measuring cell viability by Cell Counting Kit-8 assay (CCK8), 5-ethynyl-2'- deoxyuridine (Edu) staining, and colony formation assay. Wound healing assay was implemented for cell migration and Transwell assay was performed for cell invasion to evaluate the histological status by hematoxylin and eosin staining and to detect the protein ubiquitination by ubiquitination assay. The protein expression was determined by immunohistochemistry staining and western blotting, and mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. RESULT: The expression of MARCH8 was increased whereas PTPN4 was decreased in pancreatic cancer cells. Overexpression of MARCH8 promoted the growth, migration, and invasion of cells, and knockdown of PTPN4 had the similar effects both in vitro and in vivo. MARCH8 promoted PTPN4 protein degradation through ubiquitination. Moreover, PTPN4 suppressed the transcription activities of STAT3 by impairing the level of pSTAT3 (705), while inhibition of PTPN4 activated phosphorylation of STAT3. CONCLUSIONS: MARCH8 promoted pancreatic cancer growth and invasion through mediating the degradation of PTPN4 and activated the phosphorylation of STAT3.