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.

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.

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.

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.

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.

Activation of Sphingomyelin Phosphodiesterase 3 in Liver Regeneration Impedes the Progression of Colorectal Cancer Liver Metastasis Via Exosome-Bound Intercellular Transfer of Ceramides.

BACKGROUND & AIMS: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR. METHODS: Mice were intrasplenically injected with CRC cells. LR was induced by 2/3 partial hepatectomy (PH) to mimic the CRLM in the context of LR. The alteration of corresponding CER-metabolizing genes was examined. The biological roles of CER metabolism in vitro and in vivo were examined by performing a series of functional experiments. RESULTS: Induction of LR augmented apoptosis but promoted matrix metalloproteinase 2 (MMP2) expression and epithelial-mesenchymal transition (EMT) to increase the invasiveness of metastatic CRC cells, resulting in aggressive CRLM. Up-regulation of sphingomyelin phosphodiesterase 3 (SMPD3) was determined in the regenerating hepatocytes after LR induction and persisted in the CRLM-adjacent hepatocytes after CRLM formation. Hepatic Smpd3 knockdown was found to further promote CRLM in the context of LR by abolishing mitochondrial apoptosis and augmenting the invasiveness in metastatic CRC cells by up-regulating MMP2 and EMT through promoting the nuclear translocation of ß-catenin. Mechanistically, we found that hepatic SMPD3 controlled the generation of exosomal CER in the regenerating hepatocytes and the CRLM-adjacent hepatocytes. The SMPD3-produced exosomal CER critically conducted the intercellular transfer of CER from the hepatocytes to metastatic CRC cells and impeded CRLM by inducing mitochondrial apoptosis and restricting the invasiveness in metastatic CRC cells. The administration of nanoliposomal CER was found to suppress CRLM in the context of LR substantially. CONCLUSIONS: SMPD3-produced exosomal CER constitutes a critical anti-CRLM mechanism in LR to impede CRLM, offering the promise of using CER as a therapeutic agent to prevent the recurrence of CRLM after PH.

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.

Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified. Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury. Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry. The pathology associated with the dysregulated lipids was examined. Results: Lipidomics analyses identified cardiolipins (CL) and sphingolipids (SL), including ceramides (CER), glycosphingolipids, sphingosines, and sphingomyelins, as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury. CER were increased in normal livers with I/R injury, and the I/R-induced increase of CER was further augmented in NASH livers. Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury, including serine palmitoyltransferase 3 (Sptlc3), ceramide synthase 2 (Cers2), neutral sphingomyelinase 2 (Smpd3), and glucosylceramidase beta 2 (Gba2) that produced CER, and alkaline ceramidase 2 (Acer2), alkaline ceramidase 3 (Acer3), sphingosine kinase 1 (Sphk1), sphingosine-1-phosphate lyase (Sgpl1), and sphingosine-1-phosphate phosphatase 1 (Sgpp1) that catalyzed the degradation of CER. CL were not affected by I/R challenge in normal livers, but CL was dramatically reduced in NASH livers with I/R injury. Consistently, metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury, including cardiolipin synthase (Crls1) and tafazzin (Taz). Notably, the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers, which were possibly mediated by the reduction of CL and accumulation of CER. Conclusions: The I/R-induced dysregulation of CL and SL were critically rewired by NASH, which might potentially mediate the aggressive I/R injury in NASH livers.

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.

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.

Inertial imitation method of MMC with hybrid topology for VSC-HVDC.

A new virtual synchronous generator (VSG) control strategy was researched and proposed for a VSC-HVDC (High Voltage Direct Current Based on Voltage Source Converter) transmission system. It can be applied to half-bridge or full-half-bridge hybrid topology modular multi-level converter (MMC) to improve the stability and reliability of the system. First, it is proposed that the energy stored in the equivalent capacitor of MMC power module was used to imitate the rotor inertial of synchronous generator. It can buffer transient power fluctuations and synchronize autonomously with the grid. Then the impedance characteristics of the proposed control method have been deduced and analyzed. The results show that the VSG control loop mainly improves the low frequency characteristics of the converter. Secondly, the ability to suppress transient fault current is weak. So, a method, that the given values of inner current loop are calculated by grid impedance matrix, was used. A double closed loop control structure composed by a power outer loop based on VSG control and a current inner loop is obtained. The simulation results show that it can effectively improve the current control capability during the transient process for systems with a 1:2 ratio of converter capacity to grid capacity (The grid short-circuit capacity is 60MW and the MMC is 30 MW). Finally, a hybrid MMC simulation model was built based on PSCAD and the steady-state and transient fault ride-through simulations were performed. The power adjustment time of MMC under the proposed VSG control is about 1s, while the adjustment time under the conventional control strategy is greater than 4s.

Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5.

The cytochrome P450 3As (CYP3As) are abundantly expressed in the liver and metabolize many commonly prescribed medications. Their expression is highly variable between individuals with little known genetic cause. Despite extensive investigation, cis-acting genetic elements that control the expression of the CYP3As remain uncharacterized. Using chromatin conformation capture (4C assays), we detected reciprocal interaction between a distal regulatory region (DRR) and the CYP3A4 promoter. The DRR colocalizes with a variety of enhancer marks and was found to promote transcription in reporter assays. CRISPR-mediated deletion of the DRR decreased expression of CYP3A4, CYP3A5, and CYP3A7, supporting its role as a shared enhancer regulating the expression of three CYP3A genes. Using reporter gene assays, we identified two single-nucleotide polymorphisms (rs115025140 and rs776744/rs776742) that increased DRR-driven luciferase reporter expression. In a liver cohort (n = 246), rs115025140 was associated with increased expression of CYP3A4 mRNA (1.8-fold) and protein (1.6-fold) and rs776744/rs776742 was associated with 1.39-fold increased expression of CYP3A5 mRNA. The rs115025140 is unique to the African population and in a clinical cohort of African Americans taking statins for lipid control rs115025140 carriers showed a trend toward reduced statin-mediated lipid reduction. In addition, using a published cohort of Chinese patients who underwent renal transplantation taking tacrolimus, rs776744/rs776742 carriers were associated with reduced tacrolimus concentration after adjusting for CYP3A5*3. Our results elucidate a complex regulatory network controlling expression of three CYP3A genes and identify two novel regulatory variants with potential clinical relevance for predicting CYP3A4 and CYP3A5 expression.

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.

Genomewide association study identifies a novel variant associated with tacrolimus trough concentration in Chinese renal transplant recipients.

Tacrolimus (TAC) is an immunosuppressant widely used in kidney transplantation. TAC displays considerable interindividual variability in pharmacokinetics (PKs). Genetic and clinical factors play important roles in TAC PKs. We enrolled a total of 251 Chinese renal transplant recipients and conducted a genomewide association study (GWAS), linkage disequilibrium (LD), and one-way analysis of variance (ANOVA) to find genetic variants affecting log-transformed TAC trough blood concentration/dose ratio (log[C0 /D]). In addition, we performed dual luciferase reporter gene assays and multivariate regression models to evaluate the effect of the genetic variants. The GWAS results showed that all 23 genomewide significant single-nucleotide polymorphisms (p < 5 × 10-8 ) were located on chromosome 7, including CYP3A5*3. LD, conditional association analysis, and one-way ANOVA showed that rs75125371 T > C independently influenced TAC log(C0 /D). Dual luciferase reporter gene assays indicated that rs75125371 minor allele (C) was significantly associated with increased normalized luciferase activity than the major allele (T) in the Huh7 cells (p = 1.2 × 10-5 ) and HepaRG cells (p = 0.0097). A model inclusive of age, sex, hematocrit, CYP3A5*3, and rs75125371 explained 37.34% variance in TAC C0 . These results suggest that rs75125371 T > C is a functional and population-specific variant affecting TAC C0 in Chinese renal transplant recipients.

A Hybrid Matching Network for Fault Diagnosis under Different Working Conditions with Limited Data.

Intelligent fault diagnosis methods based on deep learning have achieved much progress in recent years. However, there are two major factors causing serious degradation of the performance of these algorithms in real industrial applications, i.e., limited labeled training data and complex working conditions. To solve these problems, this study proposed a domain generalization-based hybrid matching network utilizing a matching network to diagnose the faults using features encoded by an autoencoder. The main idea was to regularize the feature extractor of the network with an autoencoder in order to reduce the risk of overfitting with limited training samples. In addition, a training strategy using dropout with random changing rates on inputs was implemented to enhance the model's generalization on unseen domains. The proposed method was validated on two different datasets containing artificial and real faults. The results showed that considerable performance was achieved by the proposed method under cross-domain tasks with limited training samples.

Motor Imagery EEG Classification Based on Transfer Learning and Multi-Scale Convolution Network.

For the successful application of brain-computer interface (BCI) systems, accurate recognition of electroencephalography (EEG) signals is one of the core issues. To solve the differences in individual EEG signals and the problem of less EEG data in classification and recognition, an attention mechanism-based multi-scale convolution network was designed; the transfer learning data alignment algorithm was then introduced to explore the application of transfer learning for analyzing motor imagery EEG signals. The data set 2a of BCI Competition IV was used to verify the designed dual channel attention module migration alignment with convolution neural network (MS-AFM). Experimental results showed that the classification recognition rate improved with the addition of the alignment algorithm and adaptive adjustment in transfer learning; the average classification recognition rate of nine subjects was 86.03%.

RGB-D Visual SLAM Based on Yolov4-Tiny in Indoor Dynamic Environment.

For a SLAM system operating in a dynamic indoor environment, its position estimation accuracy and visual odometer stability could be reduced because the system can be easily affected by moving obstacles. In this paper, a visual SLAM algorithm based on the Yolov4-Tiny network is proposed. Meanwhile, a dynamic feature point elimination strategy based on the traditional ORBSLAM is proposed. Besides this, to obtain semantic information, object detection is carried out when the feature points of the image are extracted. In addition, the epipolar geometry algorithm and the LK optical flow method are employed to detect dynamic objects. The dynamic feature points are removed in the tracking thread, and only the static feature points are used to estimate the position of the camera. The proposed method is evaluated on the TUM dataset. The experimental results show that, compared with ORB-SLAM2, our algorithm improves the camera position estimation accuracy by 93.35% in a highly dynamic environment. Additionally, the average time needed by our algorithm to process an image frame in the tracking thread is 21.49 ms, achieving real-time performance.

Distributed Formation Control of Multiple Euler-Lagrange Systems: A Multilayer Framework.

In this technical correspondence, a multilayer formation (MLF) control problem is considered and solved by a unified framework. The agents in each layer present a sort of hierarchical distinction: receive information from former layers, communicate inside the current layer, and send information to subsequent layers. With an arbitrary number of layers, we extend the previous result from undirected graphs to directed ones. The proposed controller achieves MLF without using the distributed estimators and the acceleration information. This removes the induced discontinuities and alleviates the system complexity. It is then proved that the closed-loop errors are semiglobally uniformly ultimately bounded. Simulations are presented to illustrate the effectiveness of this approach.

Formation-containment control of multi-agent systems with communication delays.

This paper designs formation-containment control algorithms for a class of second-order nonlinear multi-agent systems governed by Euler-Lagrange dynamics with communication delays. The formation-containment problem consists of leader agents' formation control and follower agents' containment control. Firstly, to make the leaders form a desired formation and move collectively with a constant velocity, a coordinated formation control algorithm is designed and the variable-gain technique is used to eliminate the effect of communication delays on the leaders' formation control. Secondly, considering that only the leaders have access to the desired moving velocity, we propose distributed velocity estimators for followers in which the communication delays also exist in the followers' information interaction. By using the estimated velocity information, coordinated containment control laws are designed for the followers to drive them asymptotically converge to the convex hull spanned by all leaders. Furthermore, to increase the system robustness against uncertainties and external disturbances, the adaptive updating laws are designed for all agents. Finally, simulations are given to demonstrate these obtained results.