Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC.

BACKGROUND AND AIMS: Cancer stem cells (CSCs) contribute to therapy resistance in HCC. Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs. APPROACH AND RESULTS: We found that HOIL-1, but not the other components of LUBAC, played a contributing role in LUBAC-mediated HCC sorafenib resistance, independent of its ubiquitin ligase activity. Both in vitro and in vivo assays revealed that the upregulated HOIL-1 expression enhanced the CSC properties of HCC. Mechanistically, HOIL-1 promoted sorafenib resistance and the CSC properties of HCC through Notch1 signaling. Mass spectrometry, co-immunoprecipitation, western blot, and immunofluorescence were used to determine that the A64/Q65 residues of HOIL-1 bound with the K78 residue of Numb, resulting in impaired Numb-mediated Notch1 lysosomal degradation. Notably, pixantrone was screened out by Autodock Vina, which was validated to disrupt HOIL-1/Numb interaction to inhibit Notch1 signaling and CSC properties by targeting the Q65 residue of HOIL-1. Moreover, pixantrone exerted synergistic effects with sorafenib for the treatment of HCC in different HCC mouse models. CONCLUSIONS: HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.

Decreased frontal lobe complexity in left-behind children during joint attention: a fNIRS study with multivariable and multiscale sample entropy analysis.

Human brain development is shaped by experiences, especially during preschool, the critical period for cognitive and socioemotional development. This study employed the functional Near-Infrared Spectroscopy technique to explore the neural differences between left-behind children (LBC) and non-left-behind children (NLBC) on joint attention. Through collecting brain image data of 50 children (26 boys, aged 65.08 ± 6.28 months) and conducting multivariable and multiscale sample entropy (MMSE) analysis, the present study found that: (i) LBC showed lower brain complexity than NLBC in right prefrontal cortex; (ii) all participants demonstrated higher brain complexity in responding to joint attention conditions, compared to initiating joint attention ones; (iii) their brain complexity during joint attention was negatively associated with their emotional abilities. The findings advance our understanding of early brain development in LBC by providing evidence for the neural process characteristics of joint attention. Implications for early intervention to promote their brain development are also addressed.

Sperm YOLOv8E-TrackEVD: A Novel Approach for Sperm Detection and Tracking.

Male infertility is a global health issue, with 40-50% attributed to sperm abnormalities. The subjectivity and irreproducibility of existing detection methods pose challenges to sperm assessment, making the design of automated semen analysis algorithms crucial for enhancing the reliability of sperm evaluations. This paper proposes a comprehensive sperm tracking algorithm (Sperm YOLOv8E-TrackEVD) that combines an enhanced YOLOv8 small object detection algorithm (SpermYOLOv8-E) with an improved DeepOCSORT tracking algorithm (SpermTrack-EVD) to detect human sperm in a microscopic field of view and track healthy sperm in a sample in a short period effectively. Firstly, we trained the improved YOLOv8 model on the VISEM-Tracking dataset for accurate sperm detection. To enhance the detection of small sperm objects, we introduced an attention mechanism, added a small object detection layer, and integrated the SPDConv and Detect_DyHead modules. Furthermore, we used a new distance metric method and chose IoU loss calculation. Ultimately, we achieved a 1.3% increase in precision, a 1.4% increase in recall rate, and a 2.0% improvement in mAP@0.5:0.95. We applied SpermYOLOv8-E combined with SpermTrack-EVD for sperm tracking. On the VISEM-Tracking dataset, we achieved 74.303% HOTA and 71.167% MOTA. These results show the effectiveness of the designed Sperm YOLOv8E-TrackEVD approach in sperm tracking scenarios.

HIGD2A silencing impairs hepatocellular carcinoma growth via inhibiting mitochondrial function and the MAPK/ERK pathway.

BACKGROUND: The Hypoxia inducible gene domain family member 2A (HIGD2A) protein is indispensable for the assembly of the mitochondrial respiratory supercomplex, which has been implicated in cell proliferation and cell survival under hypoxic conditions. Because the liver has a naturally low oxygen microenvironment, the role of HIGD2A in the development of hepatocellular carcinoma (HCC) remains largely unknown. METHODS: Gene expression data and clinical information were obtained from multiple public databases. A lentivirus-mediated gene knockdown approach was conducted to explore the function and mechanism of HIGD2A activity in HCC cells. In vivo and in vitro assays were performed to investigate the biological roles of HIGD2A. RESULTS: HIGD2A was overexpressed in HCC tissues and cell lines and was associated with a worse prognosis. Silencing HIGD2A expression significantly attenuated cell proliferation and migration, caused S-phase cell cycle arrest, and decreased tumor formation in nude mice. Mechanistically, HIGD2A depletion greatly decreased cellular ATP levels by disrupting mitochondrial ATP production. Moreover, HIGD2A knockdown cells displayed impaired mitochondrial function, such as mitochondrial fusion, increased expression of the mitochondrial stress response protein, and decreased oxygen consumption. Furthermore, knockdown of HIGD2A markedly attenuated the activation of the MAPK/ERK pathway. CONCLUSIONS: HIGD2A promoted liver cancer cell growth by fueling mitochondrial ATP synthesis and activating the MAPK/ERK pathway, suggested that targeting HIGD2A may represent a new strategy for HCC therapy.

A Novel Bearing Fault Diagnosis Method Based on Few-Shot Transfer Learning across Different Datasets.

At present, the success of most intelligent fault diagnosis methods is heavily dependent on large datasets of artificial simulation faults (ASF), which have not been widely used in practice because it is often costly to obtain a large number of samples in reality. Fortunately, various faults can be easily simulated in the laboratory, and these simulated faults contain a lot of fault diagnosis knowledge. In this study, based on a Siamese network framework, we propose a bearing fault diagnosis based on few-shot transfer learning across different datasets (cross-machine), using the knowledge of ASF to diagnose bearings with natural faults (NF). First of all, the model obtains a good feature encoder in the source domain, then defines a fault support set for comparison, and finally adjusts the support set with a very small number of target domain samples to improve the fault diagnosis performance of the model. We carried out experimental verification from many aspects on the ASF and NF datasets provided by Case Western Reserve University (CWRU) and Paderborn University (PU). The results show that the proposed method can fully learn diagnostic knowledge in different ASF datasets and sample numbers, and effectively use this knowledge to accurately identify the health state of the NF bearing, which has strong generalization and robustness. Our method does not need second training, which may be more convenient in some practical applications. Finally, we also discuss the possible limitations of this method.

Functional CYP3A variants affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients.

The aim of this study was to identify novel genetic variants affecting tacrolimus trough blood concentrations. We analyzed the association between 58 single nucleotide polymorphisms (SNPs) across the CYP3A gene cluster and the log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in 819 renal transplant recipients (Discovery cohort). Multivariate linear regression was used to test for associations between tacrolimus log (C0/D) and clinical factors. Luciferase reporter gene assays were used to evaluate the functions of select SNPs. Associations of putative functional SNPs with log (C0/D) were further tested in 631 renal transplant recipients (Replication cohort). Nine SNPs were significantly associated with tacrolimus log (C0/D) after adjustment for CYP3A5*3 and clinical factors. Dual luciferase reporter assays indicated that the rs4646450 G allele and rs3823812 T allele were significantly associated with increased normalized luciferase activity ratios (p < 0.01). Moreover, CYP3A7*2 was associated with higher TAC log(C0/D) in the group of CYP3A5 expressers. Age, serum creatinine and hematocrit were significantly associated with tacrolimus log (C0/D). CYP3A7*2, rs4646450, and rs3823812 are proposed as functional SNPs affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients. Clinical factors also significantly affect tacrolimus metabolism.

Extensively expanded murine-induced hepatic stem cells maintain high-efficient hepatic differentiation potential for repopulation of injured livers.

BACKGROUND & AIM: Shortage of donor hepatocytes limits hepatocyte transplantation for clinical application. Induced hepatic stem cells (iHepSCs) have capacities of self-renewal and bipotential differentiations. Here, we investigated whether iHepSCs could be extensively expanded, and whether they could differentiate into sufficient functional hepatocytes as donors for transplantation therapy after their extensive expansions. METHODS: Murine extensively expanded iHepSCs (50-55 passages) were induced to differentiate into iHepSC-Heps under a chemically defined condition. iHepSC-Heps were proved for carrying morphological hepatocyte characters and hepatocytic functions including low-density lipoprotein uptake, glycogen storage, CLF secretion, ICG uptake and release, Alb secretion, urea synthesis and metabolism-relative gene expressions respectively. Next, both iHepSCs and iHepSC-Heps were transplanted into Fah-/- mice respectively. Both liver repopulation and alleviation of liver function were compared between two transplantation groups. RESULTS: Murine iHepSCs still maintained the capacities of self-renewal and bipotential differentiations after extensive expansion. The efficiency for the functional hepatocyte differentiation from extensively expanded iHepSCs reached to 72.64%. Transplantations of both extensively expanded iHepSCs and iHepSC-Heps resulted in liver engraftment in Fah-/- mice. Survival rate of Fah-/- mice recipients and level of liver repopulation were 50% and 20.32 ± 4.58% respectively in iHepSC-Heps group, while 33% and 10.4 ± 4.3% in iHepSCs group. CONCLUSIONS: Extensively expanded iHepSCs can efficiently differentiate into hepatocytes in chemical defined medium. Transplantation of iHepSC-Heps was more effective and more efficient than transplantation of iHepSCs in Fah-/- mice. Our results suggested an innovative system to obtain sufficient hepatocytes through hepatic differentiation of iHepSCs generated by lineage reprogramming.

Two-dimensional type-II g-C3N4/SiP-GaS heterojunctions as water splitting photocatalysts: first-principles predictions.

Hydrogen production from water splitting by sunlight is a promising approach to solve the increasing energy and environmental crises, and the two-dimensional (2D) g-C3N4 monolayer is a red star in this realm. However, it suffers from low quantum efficiency caused by the fast combination of photogenerated electrons and holes. In this work, we investigate the electronic and photocatalytic properties of three newly proposed g-C3N4/SiP-GaS-α, -ß and -γ heterojunctions via first principles predictions. Theoretical results demonstrate that the three g-C3N4/SiP-GaS heterojunctions exhibit direct bandgaps of ∼2.2 eV, and have a type-II band alignment with the valence band maximum (VBM) located at the g-C3N4 layer and the conduction band minimum (CBM) at the SiP-GaS layer. Furthermore, their band edges straddle the redox potential of water in a wide range of biaxial strain. Their absorption coefficients are several times larger than that of most previously discovered 2D heterojunctions. Moreover, the in-built electric field adds a driving force to separate photogenerated electrons and holes. The oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) successfully take place on the g-C3N4 and SiP-GaS layers, respectively. Briefly, separated charge carriers, suitable band edges and strong visible-light absorbance, successful OER and HER enable the three g-C3N4/SiP-GaS heterojunctions to be promising water-splitting photocatalysts.

Electrolyte disorders are ERAS-associated in patients undergoing hepato-pancreato-biliary surgery.

PURPOSE: Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. METHODS: Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. RESULTS: The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76 mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41 mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. CONCLUSIONS: ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.

Design of a Low-Cost Indoor Navigation System for Food Delivery Robot Based on Multi-Sensor Information Fusion.

As the restaurant industry is facing labor shortage issues, the use of meal delivery robots instead of waiters/waitresses not only allows the customers to experience the impact of robot technology but also benefits the restaurant business financially by reducing labor costs. Most existing meal delivery robots employ magnetic navigation technologies, which require magnetic strip installation and changes to the restaurant decor. Once the moving path is changed, the magnetic strips need to be re-laid. This study proposes multisource information fusion, i.e., the fusion of ultra-wide band positioning technology with an odometer and a low-cost gyroscope accelerometer, to achieve the positioning of a non-rail meal delivery robot with navigation. By using a low-cost electronic compass and gyroscope accelerometer, the delivery robot can move along a fixed orbit in a flexible and cost-effective manner with steering control. Ultra-wide band (UWB) and track estimation algorithm are combined by extended Kalman filter (EKF), and the positioning error after fusion is about 15 cm, which is accepted by restaurants. In summary, the proposed approach has some potential for commercial applications.

A New Fuzzy Logic Classifier Based on Multiscale Permutation Entropy and Its Application in Bearing Fault Diagnosis.

The self-organizing fuzzy (SOF) logic classifier is an efficient and non-parametric classifier. Its classification process is divided into an offline training stage, an online training stage, and a testing stage. Representative samples of different categories are obtained through the first two stages, and these representative samples are called prototypes. However, in the testing stage, the classification of testing samples is completely dependent on the prototype with the maximum similarity, without considering the influence of other prototypes on the classification decision of testing samples. Aiming at the testing stage, this paper proposed a new SOF classifier based on the harmonic mean difference (HMDSOF). In the testing stage of HMDSOF, firstly, each prototype was sorted in descending order according to the similarity between each prototype in the same category and the testing sample. Secondly, multiple local mean vectors of the prototypes after sorting were calculated. Finally, the testing sample was classified into the category with the smallest harmonic mean difference. Based on the above new method, in this paper, the multiscale permutation entropy (MPE) was used to extract fault features, linear discriminant analysis (LDA) was used to reduce the dimension of fault features, and the proposed HMDSOF was further used to classify the features. At the end of this paper, the proposed fault diagnosis method was applied to the diagnosis examples of two groups of different rolling bearings. The results verify the superiority and generalization of the proposed fault diagnosis method.

Pericentral hepatocytes produce insulin-like growth factor-2 to promote liver regeneration during selected injuries in mice.

Liver regeneration (LR) happens after various types of injuries. Unlike the well-studied LR caused by partial hepatectomy (PHx), there is accumulating evidence suggesting that LR during other injuries may result from unknown mechanisms. In this study, we found that insulin-like growth factor 2 (IGF-2) was drastically induced following the liver injuries caused by tyrosinemia or long-term treatments of CCl4 . However, this was not observed during the early phase of acute liver injuries after PHx or single treatment of CCl4 . Remarkably, most IGF-2-expressing hepatocytes were located at the histological area around the central vein of the liver lobule after the liver injuries caused either in fumarylacetoacetate hydrolase-deficient mice or in CCl4 chronically treated mice. Hepatocyte proliferation in vivo was significantly promoted by induced IGF-2 overexpression, which could be inhibited by adeno-associated virus-delivered IGF-2 short hairpin RNAs or linsitinib, an inhibitor of IGF-2 signaling. Proliferating hepatocytes in vivo responded to IGF-2 through both insulin receptor and IGF-1 receptor. IGF-2 also significantly promoted DNA synthesis of primary hepatocytes in vitro. More interestingly, the significantly induced IGF-2 was also found to colocalize with glutamine synthetase in the region enriched with proliferating hepatocytes for the liver samples from patients with liver fibrosis. CONCLUSION: IGF-2 is produced by pericentral hepatocytes to promote hepatocyte proliferation and repair tissue damage in the setting of chronic liver injury, which is distinct from the signaling that occurs post-PHx. (Hepatology 2017;66:2002-2015).

PCA and deep learning based myoelectric grasping control of a prosthetic hand.

BACKGROUND: For the functional control of prosthetic hand, it is insufficient to obtain only the motion pattern information. As far as practicality is concerned, the control of the prosthetic hand force is indispensable. The application value of prosthetic hand will be greatly improved if the stable grip of prosthetic hand can be achieved. To address this problem, in this study, a bio-signal control method for grasping control of a prosthetic hand is proposed to improve patient's sense of using prosthetic hand and the thus improving the quality of life. METHODS: A MYO gesture control armband is used to collect the surface electromyographic (sEMG) signals from the upper limb. The overlapping sliding window scheme are applied for data segmentation and the correlated features are extracted from each segmented data. Principal component analysis (PCA) methods are then deployed for dimension reduction. Deep neural network is used to generate sEMG-force regression model for force prediction at different levels. The predicted force values are input to a fuzzy controller for the grasping control of a prosthetic hand. A vibration feedback device is used to feed grasping force value back to patient's arm to improve patient's sense of using prosthetic hand and realize accurate grasping. To test the effectiveness of the scheme, 15 able-bodied subjects participated in the experiments. RESULTS: The classification results indicated that 8-channel sEMG applying all four time-domain features, with PCA reduction from 32 to 8 dimensions results in the highest classification accuracy. Based on the experimental results from 15 participants, the average recognition rate is over 95%. On the other hand, from the statistical results of standard deviation, the between-subject variations ranges from 3.58 to 1.25%, proving that the robustness and stability of the proposed approach. CONCLUSIONS: The method proposed hereto control grasping power through the patient's own sEMG signal, which achieves a high recognition rate to improve the success rate of grip and increases the sense of operation and also brings the gospel for upper extremity amputation patients.

Resilient exponential tracking for disturbed systems with communication links faults.

Resilience is to appraise the ability of disturbed systems to recover cooperative performance after suffering from failures or disturbances. In this paper, the improvement on the exponential tracking resilience for disturbed Euler-Lagrange systems is explored by settling the unknown time-variant faults imposed on the communication interaction between agents. First, we transform the resilient exponential tracking problem into designing the trajectory and velocity observers for leaders, and showcase that the proposed observers are resilient to communication interaction malfunctions. Second, a disturbance observer is manifested to estimate disturbances precisely, which is needless to know the upper bound of disturbance. The reliable observers and estimator are incorporated into the resilient tracking control frame. Further, the global exponential stabilization of the tracking systems is performed by utilizing the Lyapunov theory. Moreover, benefiting from feasible and reliable observation and estimation results, the proposed control framework enables to realize a satisfactory resilient exponential tracking performance even in the case of communication links faults (CLFs) and disturbances. Comprehensive studies are executed on a group of satellite systems, and the simulations results verify the effectiveness of the proposed resilient approaches in a time-variant tracking case.

miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions.

BACKGROUND & AIMS: Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS: We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS: miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS: miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.

Partner's emotions are associated with preschoolers' prefrontal activation under joint attention: An fNIRS evidence.

Emotions and joint attention are highly associated and mutually influenced during preschool, the critical period for early emotional and cognitive development. However, few studies have explored the neuropsychological mechanism of joint attention with preschoolers and their partners under different emotions. This study has examined the prefrontal activation under a comprehensive emotional joint attention task in 45 preschoolers (25 boys, Mage = 58 ± 9.02 months) to compare the different influences of partners' positive, neutral, and negative emotions. Analysis of the functional near-infrared spectroscopy data indicated that the participants' prefrontal activation triggered by joint attention in positive and negative emotions was significantly higher than in neutral emotions. Moreover, their brain synchronization intensity was significantly higher in positive emotions of joint attention than in negative emotions. These findings advance our understanding of the neural mechanism of early childhood emotional processing under joint attention and provide a neural perspective to explain the effects of different emotions on preschoolers' social cognition.

A Hybrid Design of Fault Detection for Nonlinear Systems Based on Dynamic Optimization.

To ensure the safety of an automation system, fault detection (FD) has become an active research topic. With the development of artificial intelligence, model-free FD strategies have been widely investigated over the past 20 years. In this work, a hybrid FD design approach that combines data-driven and model-based is developed for nonlinear dynamic systems whose information is not known beforehand. With the aid of a Takagi-Sugeno (T-S) fuzzy model, the nonlinear system can be identified through a group of least-squares-based optimization. The associated modeling errors are taken into account when designing residual generators. In addition, statistical learning is adopted to obtain an upper bound of modeling errors, based on which an optimization problem is formulated to determine a reliable FD threshold. In the online FD decision, an event-triggered strategy is also involved in saving computational costs and network resources. The effectiveness and feasibility of the proposed hybrid FD method are illustrated through two simulation studies on nonlinear systems.

Inhibitory control associated with the neural mechanism of joint attention in preschoolers: An fNIRS evidence.

Joint attention (JA) is fundamental to the development of children's social functioning; both its response and initiation are closely related to executive function (EF), but the relationship between JA and EF has been relatively rarely studied. The present study aimed to investigate the between-condition differences in brain activation and synchronization of JA under four conditions: (1) stranger-Initiating Joint Attention (Stranger-IJA); (2) teacher-Initiating Joint Attention (Teacher-IJA); (3) stranger-Responding to Joint Attention (Stranger-RJA); and (4) teacher-Responding to Joint Attention (Teacher-RJA). It also aimed to explore the relationships between neuroimaging data and children's inhibitory control levels. To address these two goals, the present study employed 41 (aged 58.61 ± 8.64 months, 24 boys) preschool children through behavioral and functional Near-Infrared Spectroscopy (fNIRS) brain imaging assessment to measure children's EF and brain function under JA, respectively. The results revealed that: (1) a significantly higher prefrontal cortex (PFC) activation was triggered in IJA than RJA; (2) a significantly higher brain activation was triggered in JA with a stranger than with a teacher; (3) a significantly higher index of synchronization asymmetry was evoked in the left and right PFC during interaction with the teacher than with the stranger; and (4) preschoolers' brain activation and synchronization were correlated with their inhibitory control level. The findings advance our understanding of preschoolers' social cognitive development with a biological aspect, offer an opportunity to understand the potential risk of the neural disorder in preschoolers, and provide a basis and insight for preventing neural developmental disorders.

Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients.

Purpose: The aim of this study was to analyze the effects of various genetic polymorphisms and clinical factors on tacrolimus (TAC) concentration in the convalescence period (CP) and stabilization period (SP) post-liver transplantation. Patients & methods: A total of 13 SNPs were genotyped in 97 Chinese liver transplant recipients. Associations between SNPs and TAC trough blood concentration/dose ratio (C0/D) were analyzed using different genetic models in both CP and SP. Results: Only five SNPs were significantly associated with TAC log (C0/D) in the CP, and none showed a significant association in the SP. We identified rs15524 (CYP3A5), rs9200 (C6), albumin and creatinine as independent predictors of TAC C0/D in the CP. Furthermore, a final model in the CP explained a total of 30.5% TAC variation. Conclusion: Our study results suggest that in the early stages post-transplantation surgery, recipients' genetic and clinical factors exert a short-term impact on TAC metabolism that gradually decreases with time.