Bulge-Free and Homogeneous Metal Line Jet Printing with StarJet Technology.

The technology to jet print metal lines with precise shape fidelity on diverse substrates is gaining higher interest across multiple research fields. It finds applications in additively manufactured flexible electronics, environmentally friendly and sustainable electronics, sensor devices for medical applications, and fabricating electrodes for solar cells. This paper provides an experimental investigation to deepen insights into the non-contact printing of solder lines using StarJet technology, eliminating the need for surface activation, substrate heating, curing, or post-processing. Moreover, it employs bulk metal instead of conventional inks or pastes, leading to cost-effective production and enhanced conductivity. The effect of molten metal temperature, substrate temperature, standoff distance, and printing velocity was investigated on polymer foils (i.e., PET sheets). Robust printing parameters were derived to print uniform, bulge-free, bulk metal lines suitable for additive manufacturing applications. The applicability of the derived parameters was extended to 3D-printed PLA, TPU, PA-GF, and PETG substrates having a much higher surface roughness. Additionally, a high aspect ratio of approx. 16:1 wall structure has been demonstrated by printing multiple metal lines on top of each other. While challenges persist, this study contributes to advancing additively manufactured electronic devices, highlighting the capabilities of StarJet metal jet-printing technology.

Hybrid Printing of Conductive Traces from Bulk Metal for Digital Signals in Intelligent Devices.

In this article, we explore multi-material additive manufacturing (MMAM) for conductive trace printing using molten metal microdroplets on polymer substrates to enhance digital signal transmission. Investigating microdroplet spread informs design rules for adjacent trace printing. We studied the effects of print distance on trace morphology and resolution, noting that printing distance showed almost no change in the printed trace pitch. Crosstalk interference between adjacent signal traces was analyzed across frequencies and validated both experimentally and through simulation; no crosstalk was visible for printed traces at input frequencies below 600 kHz. Moreover, we demonstrate printed trace reliability against thermal shock, whereby no discontinuation in conductive traces was observed. Our findings establish design guidelines for MMAM electronics, advancing digital signal transmission capabilities.

Reversibly Cross-Linked Isoporous Membranes Fabricated by the Recyclable Block Copolymer with Pendent Dithiolane Groups.

The reversible formation and cleavage of disulfide bonds under physical/chemical stimuli make it a valuable motif in constructing dynamically cross-linked materials. In the present work, the block copolymer bearing pendent dithiolanes was synthesized and fabricated into isoporous membranes by the combination of self-assembly and nonsolvent-induced phase separation strategy. The cross-linking within the membrane was realized by the thiol-initiated ring-opening cascades of cyclic disulfides. Successful formation of disulfide bond networks within the isoporous membranes was proved by the Raman spectra, UV-vis diffuse reflectance spectroscopy, differential scanning calorimetry, and rheological analysis. The cross-linking in membranes was further demonstrated by the notably improved toughness and obviously enhanced swelling resistance to acid/alkaline solution as well as organic solvents. Importantly, the cross-linked isoporous membranes were fully dissolvable in solution containing dithiothreitol, which enabled the complete cleavage of disulfide bonds and successful recovery of the block copolymer that was able to be repeatedly fabricated into isoporous membranes with pore sizes identical to membranes prepared from the freshly synthesized copolymer. Our results indicate that dynamically cross-linked isoporous membranes with improved durability and good recyclability can be custom-made by simply incorporating active dithiolane moieties into self-assembling block copolymers.

Hyper-crosslinked Isoporous Block Copolymer Membranes with Robust Solvent Resistance and Customized Pore Sizes for Precise Separation.

Isoporous block copolymer membranes are viewed as the next-generation separation membranes for their unique structures and urgent application in precise separation. However, an obvious weakness for such membranes is their poor solvent-resistance which limits their applications to aqueous solution, and isoporous membranes with superior solvent-resistance and tunable pore size have been rarely prepared before. Herein, self-supporting isoporous membranes with excellent solvent resistance are prepared by the facile yet robust hyper-crosslinking approach which is able to create a rigid network in whole membranes. The hyper-crosslinking is found to be a novel and non-destructive approach that does not change pore size and isoporous structure during the reaction, and the resulting hyper-crosslinked isoporous membranes display superior structural and separation stability to a broad range of solvents with varied polarities for months to years. More importantly, hyper-crosslinking has proved to be a universal strategy that is applicable to isoporous membranes with varied pore size and pore chemistry, offering an important opportunity to prepare solvent-resistant isoporous membranes with customizable pore size and pore functionality that are important to realize their accurate separations in organic solvents. This concept is demonstrated finally by precise and on-demand separation of nanoparticles with the prepared membranes.

Association of trajectories of non-high-density lipoprotein cholesterol concentration with risk of cardiovascular disease: the Kailuan Study.

OBJECTIVES: This study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk. DESIGN: A retrospective study. SETTING: Data were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China. PARTICIPANTS: The current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006-2012 surveys to predict the CVD risk from 2012 to 2020. PRIMARY OUTCOME MEASURES: CVD events included myocardial infarction and stroke. RESULTS: 3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications. CONCLUSIONS: Changes in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-1100148.

Co-catalysis of rhodium/phosphoramidite catalyst and ZSM-35(10) for the tandem hydroformylation-acetalization of olefins.

The Rh/BINAPa and ZSM-35(10) co-catalyzed tandem hydroformylation-acetalization of olefins has been developed. A series of olefins with various alcohols performed well in the process, affording the corresponding acetals with high regioselectivities (l/b ≥ 30.5) and excellent catalytic activities (TON of the Rh catalyst up to 4.3 × 104). Control experiments and DFT calculations indicated that the Rh/L11-catalyzed hydroformylation occurred in the solvent outside the molecular sieve, while the acetalization of intermediate aldehydes with alcohols takes place mainly in the interior of the molecular sieve.

The Mediating Role of Systemic Inflammation in the Effects of Fetal Famine Exposure on Cardiovascular Disease in Adults: A Cohort Study.

BACKGROUND: A few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. OBJECTIVES: The objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. METHODS: A total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. RESULTS: During a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). CONCLUSIONS: Fetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.

Selectively retaining nutrients in biochar in magnesium added two-zone staged copyrolysis of blue algae and corn gluten wastes.

The disposal of blue algae (BA) and corn gluten (CG) wastes and the simultaneous recovery of abundant phosphorus (P) and nitrogen (N) by pyrolysis to obtain biochars with high fertility is a promising strategy. However, pyrolysis of BA or CG alone by a conventional reactor cannot reach the target. Herein, we propose a novel MgO-enhanced N and P recovery method by designing a two-zone staged pyrolysis reactor to highly efficiently recover N and P with easily available plant forms in BA and CG. The results show that a 94.58% total phosphorus (TP) retention rate was achieved by means of the special two-zone staged pyrolysis method, in which the effective P (Mg2PO4(OH) and R-NH-P) accounted for 52.9% of TP, while the total nitrogen (TN) reached 4.1 wt%. In this process, stable P was formed first at 400 °C to avoid rapid volatilization and then to form hydroxyl P at 800 °C. Meanwhile, Mg-BA char in the lower zone can efficiently absorb N-containing gas generated by the upper CG, forming dispersible N. This work is of great significance for improving the green utilization value of P and N in BA and CG.

Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study.

BACKGROUND: Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown. METHODS: Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group. RESULTS: We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls. CONCLUSIONS: Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Effects of fetal famine exposure on the cardiovascular disease risk in the metabolic syndrome individuals.

BACKGROUND: Patients with metabolic syndrome (MS) have a higher incidence of cardiovascular disease (CVD), but the possible mechanisms are not fully understood and further exploration of the possible factors influencing the high incidence of CVD in patients with MS is still needed. OBJECTIVES: This study aims to examine the association between fetal famine exposure and the risk of CVD in adulthood with MS. METHODS: Of 13,744 MS patients free of CVD selected from the Kailuan Study in 2006 (referred as the baseline survey) were included in the study. China suffered a severe famine from 1959 to 1962, so the participants born during this period were classified as the uterine famine exposed group. All patients were born between January 1, 1949, and December 31, 1974. Based on the date of birth, all patients were divided into the no-exposed group (born between January 1, 1963, and December 31, 1974), uterine famine exposed group (born between January 1, 1959 and December 31, 1962), and childhood famine exposed group (born between January 1, 1949 and December 31, 1958). After following up to December 31, 2019, the weighted Cox regression analysis model was used to calculate the effect of early life famine exposure in MS individuals on the risk of CVD in adulthood. RESULTS: During the 12.12 years of follow-up, the incidence of CVD was 5.87%, 10.13%, and 10.90% in the no-exposed group, uterine famine exposed group, and childhood famine exposed group, respectively. Compared with participants in the no-exposed group, the CVD risk and stroke risk increased in participants in the uterine famine exposed group (for CVD, HR: 1.32, 95% CI 1.04-1.67; for stroke, HR:1.37, 95% CI 1.05-1.79), but not in childhood famine exposed group. However, the increased CVD risks were only observed in females or smokers. No increased MI risks were observed for participants in the uterine famine exposed group or childhood famine exposed group. CONCLUSIONS: Our findings suggested that exposure to famine during uterine life might increase the risk of CVD in adulthood in participants with MS.

A back propagation neural network model for accurately predicting the removal efficiency of ammonia nitrogen in wastewater treatment plants using different biological processes.

Accurately predicting the water quality of treated water from a water treatment plant (WWTP) based on the obtained operating database is of great significance. However, it is difficult for common mechanistic models to work well. In this study, a back propagation artificial neural network (BPANN) model with high accuracy was developed to predict the denitrification efficiency based on a 1-year operating database. Standardized principal component analysis (PCA) methods were used to address the data, and the PCA processed data exhibited the best accuracy. In three WWTPs adopting the anaerobic/anoxic/oxic (A2O) process, the ammonia nitrogen removal efficiency of WWTPs was successfully predicted by using five variables: inlet flow rate, pH value, original ammonia nitrogen concentration, Chemical oxygen demand (COD) concentration, and total phosphorus concentration. Importantly, the obtained BPANN model can be effectively used for other widely used treatment processes, such as oxidation ditch (OD), sequencing batch reactor activated sludge process (SBR), membrane bioreactor (MBR), and cyclic activated sludge technology (CAST), by simply optimizing the training data ratios between 50/50 and 90/10. This is the first trial to set up a universal model for predicting the denitrification efficiency of WWTPs adopting common biological processes. The model could be used to choose the optimum treatment process in the new WWTP design or take action in advance to avoid the risk of excessive emissions when the already built WWTPs are subjected to sudden shocks.

Hub-connected functional connectivity within social brain network weakens the association with real-life social network in schizophrenia patients.

Hubs in the brain network are the regions with high centrality and are crucial in the network communication and information integration. Patients with schizophrenia (SCZ) exhibit wide range of abnormality in the hub regions and their connected functional connectivity (FC) at the whole-brain network level. Study of the hubs in the brain networks supporting complex social behavior (social brain network, SBN) would contribute to understand the social dysfunction in patients with SCZ. Forty-nine patients with SCZ and 27 healthy controls (HC) were recruited to undertake the resting-state magnetic resonance imaging scanning and completed a social network (SN) questionnaire. The resting-state SBN was constructed based on the automatic analysis results from the NeuroSynth. Our results showed that the left temporal lobe was the only hub of SBN, and its connected FCs strength was higher than the remaining FCs in both two groups. SCZ patients showed the lower association between the hub-connected FCs (compared to the FCs not connected to the hub regions) with the real-life SN characteristics. These results were replicated in another independent sample (30 SCZ and 28 HC). These preliminary findings suggested that the hub-connected FCs of SBN in SCZ patients exhibit the abnormality in predicting real-life SN characteristics.

Altered empathy-related resting-state functional connectivity in patients with bipolar disorder.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people's emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal-parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

Paper-based open microfluidic platform for protein electrophoresis and immunoprobing.

Protein electrophoresis and immunoblotting are indispensable analytical tools for the characterization of proteins and posttranslational modifications in complex sample matrices. Owing to the lack of automation, commonly employed slab-gel systems suffer from high time demand, significant sample/antibody consumption, and limited reproducibility. To overcome these limitations, we developed a paper-based open microfluidic platform for electrophoretic protein separation and subsequent transfer to protein-binding membranes for immunoprobing. Electrophoresis microstructures were digitally printed into cellulose acetate membranes that provide mechanical stability while maintaining full accessibility of the microstructures for consecutive immunological analysis. As a proof-of-concept, we demonstrate separation of fluorescently labeled marker proteins in a wide molecular weight range (15-120 kDa) within only 15 min, reducing the time demand for the entire workflow (from sample preparation to immunoassay) to approximately one hour. Sample consumption was reduced 10- to 150-fold compared to slab-gel systems, owing to system miniaturization. Moreover, we successfully applied the paper-based approach to complex samples such as crude bacterial cell extracts. We envisage that this platform will find its use in protein analysis workflows for scarce and precious samples, providing a unique opportunity to extract profound immunological information from limited sample amounts in a fast fashion with minimal hands-on time.

Improvement in Midline Shift Is a Positive Prognostic Predictor for Malignant Middle Cerebral Artery Infarction Patients Undergoing Decompressive Craniectomy.

Objective: The aim of this retrospective study is to evaluate the risk factors of malignant middle cerebral artery infarction (MMCAI) patients and explore an applicable prognostic predictor for MMCAI patients undergoing decompressive craniectomy (DC). Methods: Clinical data from the period 2012-2017 were retrospectively evaluated. Forty-three consecutive MMCAI patients undergoing DC were enrolled in this study. The 30-day mortality was assessed, and age, location, hypertension, pupil dilation, onset to operation duration, midline shift, and Glasgow Coma Scale (GCS) score were identified by univariate analysis and binary logistic regression. Results: In this retrospective study for DC patients, the 30-day mortality was 44.2%. In the univariate analysis, advanced age (≥60 years), right hemispheric location, hypertension, pupil dilation, shorter onset to operation duration (<48 h), improved midline shift (t = 4.214, p < 0.01), and lower pre-operation GCS score were significant predictors of death within 30 days. In binary logistic regression analysis, age [odds ratio (OR) = 1.141, 95% CI 1.011-1.287], the improvement of the midline shift (OR = 0.764, 95% CI 0.59-0.988), and pupillary dilation (OR = 15.10, 95% CI 1.374-165.954) were independent influencing factors. For the receiver operating characteristic (ROC) analysis of the relationship between post-operation outcomes and midline shift improvement, the area under the curve (AUC) was 0.844, and the cutoff point of midline shift improvement was 0.83 cm. Conclusion: Improved midline shift was a significant predictor of 30-day mortality. The improved midline shift of >0.83 cm indicated survival at 30 days.

Social brain network correlates with real-life social network in individuals with schizophrenia and social anhedonia.

Social behaviour requires the brain to efficiently integrate multiple social processes, but it is not clear what neural substrates underlie general social behaviour. While psychosis patients and individuals with subclinical symptoms are characterized by social dysfunction, the neural mechanisms underlying social dysfunctions in schizophrenia spectrum disorders remains unclear. We first constructed a general social brain network (SBN) using resting-state functional connectivity (FC) with regions of interest based on the automatic meta-analysis results from NeuroSynth. We then examined the general SBN and its relationship with social network (SN) characteristics in 30 individuals with schizophrenia (SCZ) and 33 individuals with social anhedonia (SA). We found that patients with SCZ exhibited deficits in their SN, while SA individuals did not. SCZ patients showed decreased segregation and functional connectivity in their SBN, while SA individuals showed a reversed pattern with increased segregation and functional connectivity of their SBN. Sparse canonical correlation analysis showed that both SCZ patients and SA individuals exhibited reduced correlation between SBN and SN characteristics compared with their corresponding healthy control groups. These preliminary findings suggest that both SCZ and SA participants exhibit abnormality in segregation and functional connectivity within the general SBN and reduced correlation with SN characteristics. These findings could guide the development of non-pharmacological interventions for social dysfunction in SCZ spectrum disorders.

The diagnostic threshold of Cornell assessment of pediatric delirium in detection of postoperative delirium in pediatric surgical patients.

BACKGROUND: Cornell assessment of pediatric delirium (CAPD) showed advantage in diagnosis of pediatric delirium in Chinese critically ill patients. But its performance in surgical patients is still unclear. The present study was designed to validate the diagnostic performance of CAPD in surgical pediatric patients. METHODS: This is a prospective validation study. Pediatric patients who underwent selective surgery and general anesthesia were enrolled. Primary outcome was the incidence of delirium within postoperative three days. CAPD Chinese version was used to evaluate if the patient had delirium one time per day. At the meantime, a psychiatrist employed Diagnostic and Statistical Manual of Mental Disorders fifth edition to diagnose delirium, which was the "gold standard", and the result was considered as reference standard. Sensitivity, specificity and area under receiver operating characteristic (ROC) curve were calculated to investigate the performance of CAPD. RESULTS: A total of 170 patients were enrolled. Median age was 4 years old. As diagnosed by psychiatrist, 23 (13.5 %) patients experienced at least one episode of delirium during the follow-up period. When diagnostic threshold was set at 9, CAPD showed the optimal sensitivity (87.0 %, 95 %CI 65.3 %-96.6 %) and specificity (98.0 %, 95 %CI 93.7 %-99.5 %) in comparison with other diagnostic thresholds. ROC analysis showed that CAPD was a good delirium assessment instrument with area under curve of 0.911 (95 % CI 0.812 to 1.000, P < 0.001). Agreement between CAPD and reference standard was 0.849 (Kappa coefficient, P < 0.001). CONCLUSIONS: This study found that Cornell assessment of pediatric delirium could be used as an effective instrument in diagnosis of delirium in pediatric surgical patients. TRIAL REGISTRATION: www.chictr.org.cn Identifier: ChiCTR-DDD-17,012,231, August 3, 2017.

Validation of the Questionnaire of Cognitive and Affective Empathy in patients with schizophrenia, major depressive disorder and bipolar disorder.

INTRODUCTION: Alteration of empathy is common in patients with psychiatric disorders. Reliable and valid assessment tools for measuring empathy of clinical samples is needed. The Questionnaire of Cognitive and Affective Empathy (QCAE) is a newly-developed instrument to capture cognitive and affective components of empathy. This study aimed to validate the QCAE and compared self-reported empathy between clinical groups with varied psychiatric diagnoses and healthy sample. METHODS: The present study performed factor analysis for the QCAE on clinical samples in the Chinese setting (n = 534), including patients with schizophrenia (n = 158), bipolar disorder (n = 213) and major depressive disorder (n = 163). Internal consistency, internal correlation and convergent validity was examined in the subsample (n = 361). Group comparison among patients with schizophrenia, bipolar disorder, major depressive disorder and healthy controls (n = 107) was conducted to assess the discriminant validity. RESULTS: Our results indicated acceptable factor model, good reliability and validity of the QCAE. Impaired cognitive empathy was found in clinical samples, especially in patients with schizophrenia, while higher affective empathy was found in patients with bipolar disorder and major depressive disorder. CONCLUSION: The QCAE is a useful tool in assessing empathy in patients with varied psychiatric diagnoses.

Torin2 overcomes sorafenib resistance via suppressing mTORC2-AKT-BAD pathway in hepatocellular carcinoma cells.

BACKGROUND: Sorafenib is an oral multi-kinase inhibitor that was approved by the US Food and Drug Administration for the treatment of patients with advanced hepatocellular carcinoma (HCC). However, resistance to sorafenib is an urgent problem to be resolved to improve the therapeutic efficacy of sorafenib. As the activation of AKT/mTOR played a pivotal role in sorafenib resistance, we evaluated the effect of a dual mTOR complex 1/2 inhibitor Torin2 on overcoming the sorafenib resistance in HCC cells. METHODS: The sorafenib-resistant Huh7 and Hep3B cell lines were established from their parental cell lines. The synergistic effect of sorafenib and Torin2 on these cells was measured by cell viability assay and quantified using the Chou-Talalay method. Apoptosis induced by the combination of sorafenib and Torin2 and the alteration in the specific signaling pathways of interest were detected by Western blotting. RESULTS: Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant Huh7 and Hep3B HCC cells, which underscores the significance of AKT activation. Torin2 and sorafenib synergistically suppressed the viability of sorafenib-resistant cells via apoptosis induction. Torin2 successfully suppressed the sorafenib-activated mTORC2-AKT axis, leading to the dephosphorylation of Ser136 in BAD protein, and increased the expression of total BAD, which contributed to the apoptosis in sorafenib-resistant HCC cells. CONCLUSIONS: In this study, Torin2 and sorafenib showed synergistic cytostatic capacity in sorafenib-resistant HCC cells, via the suppression of mTORC2-AKT-BAD pathway. Our results suggest a novel strategy of drug combination for overcoming sorafenib resistance in HCC.

Cross-cultural adaptation and validation of the 3D-CAM Chinese version in surgical ICU patients.

BACKGROUND: Accurate diagnosis of delirium is very important for prevention and treatment. Present study was designed to validate the 3-Minute Diagnostic Interview for CAM-defined Delirium Chinese version (3D-CAM-CN) in surgical ICU patients. METHODS: In this prospective diagnostic study, the 3D-CAM was translated into Chinese with culture adaption. Two interviewers (Roles A and B) independently administrated 3D-CAM-CN assessment in adult patients from postoperative days 1 to day 3. At the meantime, a panel of psychiatrists diagnosed delirium according to the Diagnostic and Statistical Manual of Mental Disorders-fifth edition as the reference standard. The sensitivity and specificity were calculated to analyze the diagnostic character of the 3D-CAM-CN. Kappa coefficient was used to evaluate interrater reliability. RESULTS: Two hundred forty-five adult patients were assessed for at least 2 days, resulting a total of 647 paired-assessments. When compared with the reference standard, the sensitivity and specificity of the 3D-CAM-CN assessment were 87.2 and 96.7%, respectively, by Role A and 84.6 and 97.4%, respectively, by Role B, with good interrater reliability (Kappa coefficient = 0.82, P < 0.001). It also performed well in patients with mild cognitive impairment, with the sensitivity from 85.7 to 100% and the specificity from 95.7 to 96.4%. CONCLUSION: Our results showed that the 3D-CAM-CN can be used as a reliable and accurate instrument for delirium assessment in surgical patients. TRIAL REGISTRATION: This trail was approved by the Clinical Research Ethic Committee of Peking University First Hospital (No. 2017-1321) and registered on Chinese clinical trial registry on July 6, 2017 (ChiCTR-OOC-17011887).