A bivalent ß-carboline derivative inhibits macropinocytosis-dependent entry of pseudorabies virus by targeting the kinase DYRK1A.

Pseudorabies virus (PRV) has become a "new life-threatening zoonosis" since the human-originated PRV strain was first isolated in 2020. To identify novel anti-PRV agents, we screened a total of 107 ß-carboline derivatives and found 20 compounds displaying antiviral activity against PRV. Among them, 14 compounds showed better antiviral activity than acyclovir. We found that compound 45 exhibited the strongest anti-PRV activity with an IC50 value of less than 40 nM. Our in vivo studies showed that treatment with 45 significantly reduced the viral loads and protected mice challenged with PRV. To clarify the mode of action of 45, we conducted a time of addition assay, an adsorption assay, and an entry assay. Our results indicated that 45 neither had a virucidal effect nor affected viral adsorption while significantly inhibiting PRV entry. Using the FITC-dextran uptake assay, we determined that 45 inhibits macropinocytosis. The actin-dependent plasma membrane protrusion, which is important for macropinocytosis, was also suppressed by 45. Furthermore, the kinase DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) was predicted to be a potential target for 45. The binding of 45 to DYRK1A was confirmed by drug affinity responsive target stability and cellular thermal shift assay. Further analysis revealed that knockdown of DYRK1A by siRNA suppressed PRV macropinocytosis and the tumor necrosis factor alpha-TNF-induced formation of protrusions. These results suggested that 45 could restrain PRV macropinocytosis by targeting DYRK1A. Together, these findings reveal a unique mechanism through which ß-carboline derivatives restrain PRV infection, pointing to their potential value in the development of anti-PRV agents.

9-Butyl-Harmol Exerts Antiviral Activity against Newcastle Disease Virus through Targeting GSK-3ß and HSP90ß.

The paramyxoviruses represent a large family of human and animal pathogens that cause significant health and economic burdens worldwide. However, there are no available drugs against the virus. ß-carboline alkaloids are a family of naturally occurring and synthetic products with outstanding antiviral activities. Here, we examined the antiviral effect of a series of ß-carboline derivatives against several paramyxoviruses, including Newcastle disease virus (NDV), peste des petits ruminants virus (PPRV), and canine distemper virus (CDV). Among these derivatives, 9-butyl-harmol was identified as an effective antiviral agent against these paramyxoviruses. Further, a genome-wide transcriptome analysis in combination with target validation strategies reveals a unique antiviral mechanism of 9-butyl-harmol through the targeting of GSK-3ß and HSP90ß. On one hand, NDV infection blocks the Wnt/ß-catenin pathway to suppress the host immune response. 9-butyl-harmol targeting GSK-3ß dramatically activates the Wnt/ß-catenin pathway, which results in the boosting of a robust immune response. On the other hand, NDV proliferation depends on the activity of HSP90. The L protein, but not the NP protein or the P protein, is proven to be a client protein of HSP90ß, rather than HSP90α. 9-butyl-harmol targeting HSP90ß decreases the stability of the NDV L protein. Our findings identify 9-butyl-harmol as a potential antiviral agent, provide mechanistic insights into the antiviral mechanism of 9-butyl-harmol, and illustrate the role of ß-catenin and HSP90 during NDV infection. IMPORTANCE Paramyxoviruses cause devastating impacts on health and the economy worldwide. However, there are no suitable drugs with which to counteract the viruses. We determined that 9-butyl-harmol could serve as a potential antiviral agent against paramyxoviruses. Until now, the antiviral mechanism of ß-carboline derivatives against RNA viruses has rarely been studied. Here, we found that 9-butyl-harmol exerts dual mechanisms of antiviral action, with its antiviral activities being mediated by two targets: GSK-3ß and HSP90ß. Correspondingly, the interaction between NDV infection and the Wnt/ß-catenin pathway or HSP90 is demonstrated in this study. Taken together, our findings shed light on the development of antiviral agents against paramyxoviruses, based on the ß-carboline scaffold. These results present mechanistic insights into the polypharmacology of 9-butyl-harmol. Understanding this mechanism also deepens the host-virus interaction and reveals new drug targets for anti-paramyxoviruses.

Lineage 1 PRRSVs infection induces hemorrhagic injury in intestines of piglets: Effects on complement and coagulation cascades.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.

Genetic and pathogenic characterization of an NADC-34-like isolate of porcine reproductive and respiratory syndrome virus.

In this study, an NADC34-like strain of porcine reproductive and respiratory syndrome virus (PRRSV), YC-2020, was isolated from a pig farm in Yuncheng, Shanxi Province, China. Phylogenetic and molecular evolutionary analysis showed that the genome sequence of YC-2020 was very similar to those of NADC34-like PRRSV strains in the ORF2-7 region. However, it was more closely related to NADC30-like PRRSV and highly pathogenic (HP) PRRSV in the NSP2 and NSP3-9 coding regions, respectively, suggesting that recombination had occurred between viruses belonging to lineages 1 and 8. Piglets infected with YC-2020 exhibited mild clinical signs, but they had severe histopathological lesions in their lungs. These findings reveal novel genetic and pathogenic features of this isolate.

Canthin-6-one analogs block Newcastle disease virus proliferation via suppressing the Akt and ERK pathways.

Newcastle disease virus, a member of the Paramyxoviridae family, causes significant economic losses in poultry worldwide. To identify novel antiviral agents against NDV, 36 canthin-6-one analogs were evaluated in this study. Our data showed that 8 compounds exhibited excellent inhibitory effects on NDV replication with IC50 values in the range of 5.26 to 11.76 µM. Besides, these analogs inhibited multiple NDV strains with IC50 values within 12 µM and exerted antiviral activity against peste des petits ruminants virus (PPRV) and canine distemper virus (CDV). Among these analogs, 16 presented the strongest anti-NDV activity (IC50 = 5.26 µM) and minimum cytotoxicity (CC50 > 200 µM) in DF-1 cells. Furthermore, 16 displayed antiviral activity in different cell lines. Our results showed that 16 did not affect the viral adsorption while it can inhibit the entry of NDV by suppressing the Akt pathway. Further study found that 16-treatment inhibited the NDV-activated ERK pathway, thereby promoting the expression of interferon-related genes. Our findings reveal an antiviral mechanism of canthin-6-one analogs through inhibition of the Akt and ERK signaling pathways. These results point to the potential value of canthin-6-one analogs to serve as candidate antiviral agents for NDV.

A sub-region combination scheme for spatial coding in a high-frequency SSVEP-based BCI.

Objective.In studying the spatial coding mechanism of visual evoked potentials, it is significant to construct a model that shows the relationship between steady-state visual evoked potential (SSVEP) responses to the local and global visual field stimulation. In order to investigate whether SSVEPs produced by sub-region stimulation can predict that produced by joint region stimulation, a sub-region combination scheme for spatial coding in a high-frequency SSVEP-based brain-computer interface (BCI) is developed innovatively.Approach.An annular visual field is divided equally into eight sub-regions. The 60 Hz visual stimuli in different sub-regions and joint regions are presented separately to participants. The SSVEP produced by the sub-region stimulation is superimposed to simulate the SSVEP produced by the joint region stimulation with different spatial combinations. A four-class spatially-coded BCI paradigm is used to evaluate the simulated classification performance, and the performance ranking of all simulated SSVEPs is obtained. Six representative stimulus patterns from two performance levels and three stimulus areas are applied to the online BCI system for each participant.Main results.The experimental result shows that the proposed scheme can implement a spatially-coded visual BCI system and realize satisfactory performance with imperceptible flicker. Offline analysis indicates that the classification accuracy and information transfer rate (ITR) are 89.69 ± 8.75% and 24.35 ± 7.09 bits min-1with 3 s data length under the 3/8 stimulus area. The online BCI system reaches an average classification accuracy of 87.50 ± 9.13% with 3 s data length, resulting in an ITR of 22.48 ± 6.71 bits min-1under the 3/8 stimulus area.Significance.This study proves the feasibility of using the sub-region's response to predict the joint region's response. It has the potential to extend to other frequency bands and lays a foundation for future research on more complex spatial coding methods.

ß-catenin facilitates fowl adenovirus serotype 4 replication through enhancing virus-induced autophagy.

ß-catenin is a key component of the Wnt/ß-catenin signal transduction cascade which is a highly conserved signaling pathway in eukaryotes. Increasing evidence suggests that the Wnt/ß-catenin signaling pathway is involved in the infection of many viruses. However, its role in fowl adenovirus serotype 4 (FAdV-4) replication remains unclear. In the present study, we showed that FAdV-4 infection increased the expression of ß-catenin and promoted the nuclear translocation of ß-catenin. Overexpression of ß-catenin and LiCl treatment stimulated the accumulation of ß-catenin in the nucleus, and then facilitated FAdV-4 replication. Conversely, repression of ß-catenin by inhibitors and siRNA significantly inhibited FAdV-4 replication. Furthermore, inhibition of autophagy by 3-Methyladenine (3-MA) suppressed the FAdV-4 replication, and repression of ß-catenin inhibited the FAdV-4-triggered autophagy. In conclusion, the nuclear translocation of ß-catenin benefits FAdV-4 replication, and suppression of ß-catenin limits FAdV-4 production by inhibiting FAdV-4-induced autophagy. These findings indicated that ß-catenin is an important regulator of FAdV-4 replication which can serve as a potential target for anti-FAdV-4 agents.

Newcastle disease virus forms inclusion bodies with features of liquid-liquid phase separation.

Formation of inclusion bodies (IBs) is a hallmark of infections with negative-strand RNA viruses. Although the Newcastle disease virus (NDV) IBs had been observed in the 1950s, the characteristics of NDV IBs remained largely unknown. Here, we show that NDV infection triggers the formation of IBs that contain newly synthesized viral RNA. The structures of NDV IBs, observed by electron microscopy, were not membrane-bound. Fluorescence recovery after photobleaching a region of NDV IBs occurred rapidly, and IBs were dissolved by 1,6-hexanediol treatment, demonstrating they exhibited properties consistent with liquid-liquid phase separation (LLPS). We find the nucleoprotein (NP) and phosphoprotein (P) are sufficient to generate IB-like puncta, with the N arm domain and N core region of NP and the C terminus of P playing important roles in this process. In summary, our findings suggest that NDV forms IBs containing viral RNA, and provide insights into the formation of NDV IBs.

A Novel Myoelectric Control Scheme Supporting Synchronous Gesture Recognition and Muscle Force Estimation.

Aiming to provide feasible solutions for the realization of the robust and natural myoelectric control systems, a novel myoelectric control scheme supporting gesture recognition and muscle force estimation is proposed in this study. Eleven grasping gestures abstracted from daily life are selected as the target gesture set. The high-density surface electromyography (HD-sEMG) of the forearm flexor and the grasping force signal are collected simultaneously. The synchronous prediction of gesture category and instantaneous force is realized by the multi-task learning (MTL) technique. Especially, a post-processing algorithm based on threshold method is conducted to overcome the influence of force variation on the accuracy of gesture recognition. The experimental results show that the proposed post-processing method can decrease the classification error significantly. Specifically, the overall gesture classification error is reduced by 27 ~ 30 percent compared with not using the post-processing method; and 16 ~ 24 percent compared with using classical post-processing methods. The whole scheme can realize the synchronous gesture recognition and force estimation with 9.35 ± 11.48% gesture classification error and 0.1479 ± 0.0436 root-mean-square deviation force estimation accuracy. Meanwhile, it is feasible in different number of electrodes and well meets the real-time requirement of the EMG control system in response time delay (about 28.22 ~ 113.16ms on average). The proposed framework provides the possibility for myoelectric control supporting synchronous gesture recognition and force estimation, which can be extended and applied in the fields of myoelectric prosthesis and exoskeleton devices.

The transcriptional characteristics of NADC34-like PRRSV in porcine alveolar macrophages.

The widespread and endemic circulation of porcine reproductive and respiratory syndrome virus (PRRSV) cause persistent financial losses to the swine industry worldwide. In 2017, NADC34-like PRRSV-2 emerged in northeastern China and spread rapidly. The dynamics analysis of immune perturbations associated with novel PRRSV lineage is still incomplete. This study performed a time-course transcriptome sequencing of NADC34-like PRRSV strain YC-2020-infected porcine alveolar macrophages (PAMs) and compared them with JXA1-infected PAMs. The results illustrated dramatic changes in the host's differentially expressed genes (DEGs) presented at different timepoints after PRRSV infection, and the expression profile of YC-2020 group is distinct from that of JXA1 group. Functional enrichment analysis showed that the expression of many inflammatory cytokines was up-regulated following YC-2020 infection but at a significantly lower magnitude than JXA1 group, in line with the trends for most interferon-stimulated genes (ISGs) and their regulators. Meanwhile, numerous components of histocompatibility complex (MHC) class II and phagosome presented a stronger transcription suppression after the YC-2020 infection. All results imply that YC-2020 may induce milder inflammatory responses, weaker antiviral processes, and more severe disturbance of antigen processing and presentation compared with HP-PRRSV. Additionally, LAPTM4A, GLMP, and LITAF, which were selected from weighted gene co-expression network analysis (WGCNA), could significantly inhibit PRRSV proliferation. This study provides fundamental data for understanding the biological characteristics of NADC34-like PRRSV and new insights into PRRSV evolution and prevention.

The canonical Wnt/ß-catenin signaling pathway facilitates pseudorabies virus proliferation and enhances virus-induced autophagy.

Pseudorabies virus (PRV) is a swine herpesvirus with a broad host range that causes significant economic losses worldwide. The Wnt/ß-catenin signaling pathway is reportedly involved in multiple viruses' proliferation. In this study, we demonstrated that PRV infection significantly activated the Wnt/ß-catenin signaling and promoted the nuclear translocation of ß-catenin. Applying specific chemical inhibitors (FH535 and iCRT14) caused a remarkable decrease in PRV titers in various cell lines. Knockdown of ß-catenin by siRNA also reduced the proliferation of PRV. On the contrary, treatment with lithium chloride (LiCl), an inhibitor of GSK3ß, stimulated the Wnt/ß-catenin signaling pathway and enhanced the PRV proliferation. Similarly, overexpression of ß-catenin promoted PRV proliferation and reversed the antiviral effect of FH535. Moreover, LiCl promoted PRV-induced autophagy, whereas FH535 and iCRT14 showed converse effects. These findings suggest that PRV infection stimulates the canonical Wnt/ß-catenin signaling pathway, facilitating PRV proliferation and regulating virus-induced autophagy. These data also provide potential targets for developing antiviral agents against PRV.

Adaptive Electrode Calibration Method Based on Muscle Core Activation Regions and Its Application in Myoelectric Pattern Recognition.

To reduce the bad effect of electrode shifts on myoelectric pattern recognition, this paper presents an adaptive electrode calibration method based on core activation regions of muscles. In the proposed method, the high-density surface electromyography (HD-sEMG) matrix collected during hand gesture execution is decomposed into source signal matrix and mixed coefficient matrix by fast independent component analysis algorithm firstly. The mixed coefficient vector whose source signal has the largest two-norm energy is selected as the major pattern, and core activation region of muscles is extracted by traversing the major pattern periodically using a sliding window. The electrode calibration is realized by aligning the core activation regions in unsupervised way. Gestural HD-sEMG data collection experiments with known and unknown electrode shifts are carried out on 9 gestures and 11 participants. A CNN+LSTM-based network is constructed and two network training strategies are adopted for the recognition task. The experimental results demonstrate the effectiveness of the proposed method in mitigating the bad effect of electrode shifts on gesture recognition accuracy and the potentials in reducing user training burden of myoelectric control systems. With the proposed electrode calibration method, the overall gesture recognition accuracies increase about (5.72~7.69)%. In specific, the average recognition accuracy increases (13.32~17.30)% when using only one batch of data in data diversity strategy, and increases (12.01~13.75)% when using only one repetition of each gesture in model update strategy. The proposed electrode calibration algorithm can be extended and applied to improve the robustness of myoelectric control system.

Hand Gesture Recognition based on Surface Electromyography using Convolutional Neural Network with Transfer Learning Method.

This paper presents an effective transfer learning (TL) strategy for the realization of surface electromyography (sEMG)-based gesture recognition with high generalization and low training burden. To realize the idea of taking a well-trained model as the feature extractor of the target networks, 30 hand gestures involving various states of finger joints, elbow joint and wrist joint are selected to compose the source task, and a convolutional neural network (CNN)-based source network is designed and trained as the general gesture EMG feature extraction network. Then, two types of target networks, in the forms of CNN-only and CNN+LSTM (long short-term memory) respectively, are designed with the same CNN architecture as the feature extraction network. Finally, gesture recognition experiments on three different target gesture datasets are carried out under TL and Non-TL strategies respectively. The experimental results verify the validity of the proposed TL strategy in improving hand gesture recognition accuracy and reducing training burden. For both the CNN-only and the CNN+LSTM target networks, on the three target datasets from new users, new gestures and different collection scheme, the proposed TL strategy improves the recognition accuracy by 10%∼38%, reduces the training time to tens of times, and guarantees the recognition accuracy of more than 90% when only 2 repetitions of each gesture are used to fine-tune the parameters of target networks. The proposed TL strategy has important application value for promoting the development of myoelectric control systems.

1-Formyl-ß-carboline Derivatives Block Newcastle Disease Virus Proliferation through Suppressing Viral Adsorption and Entry Processes.

Newcastle disease virus (NDV) is one of the highly contagious pathogens causing devastating economic effects on the global poultry industry. In the present study, three 1-formyl-ß-carboline derivatives (compounds 6, 7, and 9) were found to be potent inhibitors of different genotypes of NDV with IC50 values within 10 µM, which are similar to ribavirin. The virus titers were decreased by the presence of 1-formyl-ß-carboline derivatives in a dose-dependent manner, and the inhibition rate was found to exceed 90% at the concentration of 20 µM. These compounds mainly suppressed the adsorption and entry processes of NDV lifecycle. Through DARTS, CETSA, and RBC binding assay, these compounds were identified as novel HN inhibitors, which could directly interact with the NDV HN protein to affect the adsorption of NDV. Furthermore, they could inhibit the entry of NDV through suppressing the PI3K/Akt pathway rather than the ERK pathway. The PI3K/Akt pathway was proved to be involved in NDV entry. Our findings reveal a unique mechanism through which 1-formyl-ß-carboline derivatives restrain NDV infection. Moreover, these compounds represent suitable scaffolds for designing novel HN inhibitors.

Evasion of Host Antiviral Innate Immunity by Paramyxovirus Accessory Proteins.

For efficient replication, viruses have developed multiple strategies to evade host antiviral innate immunity. Paramyxoviruses are a large family of enveloped RNA viruses that comprises diverse human and animal pathogens which jeopardize global public health and the economy. The accessory proteins expressed from the P gene by RNA editing or overlapping open reading frames (ORFs) are major viral immune evasion factors antagonizing type I interferon (IFN-I) production and other antiviral innate immune responses. However, the antagonistic mechanisms against antiviral innate immunity by accessory proteins differ among viruses. Here, we summarize the current understandings of immune evasion mechanisms by paramyxovirus accessory proteins, specifically how accessory proteins directly or indirectly target the adaptors in the antiviral innate immune signaling pathway to facilitate virus replication. Additionally, some cellular responses, which are also involved in viral replication, will be briefly summarized.

Upper Limb End-Effector Force Estimation During Multi-Muscle Isometric Contraction Tasks Using HD-sEMG and Deep Belief Network.

In this study, research was carried out on the end-effector force estimation of two representative multi-muscle contraction tasks: elbow flexion and palm-pressing. The aim was to ascertain whether an individual muscle or a combination of muscles is more suitable for the end-effector force estimation. High-density surface electromyography (HD-sEMG) signals were collected from four primary muscle areas of the upper arm and forearm: the biceps brachii (BB), brachialis (BR), triceps brachii (TB), brachioradialis (BRD), and extensor digitorum communis (EDC). The wrist pulling and palm-pressing forces were measured in elbow flexion and palm-pressing tasks, respectively. The deep belief network (DBN) was adopted to establish the relation between HD-sEMG and the measured force. The representative signals of the four primary areas, which were considered as the input signal of the force estimation model, were extracted by HD-sEMG using the principle component analysis (PCA) algorithm, and fed separately or together into the DBN. An index termed mean impact value (MIV) was proposed to describe the priority of different muscle groups for estimating the end-effector force. The experimental results demonstrated that, in multi-muscle isometric contraction tasks, the dominant muscles with the highest activation degree could track variations in the end-effector force more effectively, and are more suitable than a combination of muscles. The main contributions of this research are as follows: (1) To fuse the activation information from different muscles effectively, DBN was adopted to establish the relationship between HD-sEMG and the generated force, and achieved highly accurate force estimation. (2) Based on the well-trained DBN force estimation model, an index termed MIV was presented to evaluate the priority of muscles for estimating the generated force.

Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity.

Cyclooxygenase-2 (COX-2), one of the mediators of inflammation in response to viral infection, plays an important role in host antiviral defense system. But its role in Newcastle disease virus (NDV) proliferation process remains unclear. This study revealed that inhibition of COX-2 could benefit NDV proliferation and overexpression of COX-2 dose-dependently suppressed NDV proliferation. Overexpression of COX-2 also showed inhibitory effect on NDV-induced endoplasmic reticulum (ER)-stress and autophagy, also promoted the expression of antiviral genes. However, prostaglandin E2 (PGE2), the major product of COX-2, had indistinctive effects on NDV proliferation. At variant time point post viral infection, a tight regulation pattern of COX-2 by NDV was observed. Using inhibitors and siRNA against signaling molecules, the nuclear factor-κB (NF-κB) and melanoma differentiation-associated gene 5 (MDA5) were identified as critical factors for NDV induced COX-2 expression. Nonetheless, at late stage of NDV proliferation, substantial suppression of COX-2 protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Furthermore, three C ring-truncated canthin-6-one analogs were used to activate COX-2 expression and showed inhibitory effect on NDV proliferation with the effective concentrations on µM level. Taken together, these results illustrated a novel NDV-regulated cellular mechanism and indicated that COX-2 is an important regulator of NDV proliferation which can serve as a potential target for anti-NDV agents.

Investigation on the Contributions of Different Muscles to the Generated Force based on HD-sEMG and DBN.

In this study, we proposed a multi-muscle contraction force estimation framework and implemented it on the elbow flexion task to explore the contributions of different muscles to integrated force at different force levels. High density surface electromyography (HD-sEMG) signals were collected from four muscle groups and the wrist pulling force was measured synchronously. The deep belief network (DBN) was adopted to establish the relationship between HD-sEMG and force. The representative signals of four primary areas, which were considered as the input signal of the force estimation model, were extracted from HD-sEMG by principle component analysis (PCA) algorithm, then fed separately or in common to the DBN to estimate the generated force. And the contributions of different muscle groups to the generated force was analyzed with an index called mean impact value (MIV). The experimental result demonstrates that in multi-muscle contraction task, not all muscles are suitable for force estimation, the force estimation accuracy obtained using only one muscle approximates even exceeds that obtained using multiple muscles, and the relative contributions of different muscle groups to the force can be obtained according to the ranking of MIVs. This scheme provides an effective method for muscle force estimation in multi-muscle contraction tasks, and can be further applied to biomechanics, sports and rehabilitation medicine.

Elbow-flexion force estimation during arm posture dynamically changing between pronation and supination.

OBJECTIVE: In this study, we proposed a dynamic voluntary contraction force estimation framework and implemented it for elbow-flexion force estimation during arm posture dynamically changing between pronation and supination. APPROACH: High-density surface electromyography (HD-sEMG) from biceps brachii and brachialis muscles and the elbow-flexion force were measured synchronously. The simplified Hill model was adopted to establish the relation between HD-sEMG and the elbow-flexion force. In the training process of the force estimation model, HD-sEMG data from static isometric elbow flexion tasks in two force modes (staircase and sinusoidal) and two postures (supination or pronation) were used. The nonnegative matrix factorization (NMF) algorithm was adopted to decompose HD-sEMG into activation patterns and the corresponding time-varying coefficient vectors. The major activation pattern was used to select the appropriate sEMG channels for extracting the input signal of the force estimation model. In the testing phase, the elbow-flexion force estimation during arm posture dynamically changing between pronation and supination was conducted. HD-sEMG was also decomposed using NMF algorithm. In this case, the concept of the major activation pattern is no longer applicable because the activation areas of biceps brachii and brachialis vary with the change of arm posture. An improved channel selection scheme based on the ratio of activation intensities was presented to extract the input signal of the well-trained simplified Hill model. MAIN RESULTS: (1) the improved channel selection scheme could locate effectively the primary muscle activation areas related to the change of arm posture; (2) the input signal extraction method based on the ratio of activation intensities obtained the best force estimation performance compared to the method based on all channels of HD-sEMG array and the method based on major activation pattern; (3) the force estimation performance was better when the simplified Hill model was calibrated with the sinusoidal force data rather than staircase data. SIGNIFICANCE: This research provides an effective solution to realize muscle force estimation during a dynamic voluntary contraction task. It can be further extended to the research fields of biomechanics, sports, and rehabilitation medicine.