A Modular Neural Motion Retargeting System Decoupling Skeleton and Shape Perception.

Motion mapping between characters with different structures but corresponding to homeomorphic graphs, meanwhile preserving motion semantics and perceiving shape geometries, poses significant challenges in skinned motion retargeting. We propose M-R2ET, a modular neural motion retargeting system to comprehensively address these challenges. The key insight driving M-R2ET is its capacity to learn residual motion modifications within a canonical skeleton space. Specifically, a cross-structure alignment module is designed to learn joint correspondences among diverse skeletons, enabling motion copy and forming a reliable initial motion for semantics and geometry perception. Besides, two residual modification modules, i.e., the skeleton-aware module and shape-aware module, preserving source motion semantics and perceiving target character geometries, effectively reduce interpenetration and contact-missing. Driven by our distance-based losses that explicitly model the semantics and geometry, these two modules learn residual motion modifications to the initial motion in a single inference without post-processing. To balance these two motion modifications, we further present a balancing gate to conduct linear interpolation between them. Extensive experiments on the public dataset Mixamo demonstrate that our M-R2ET achieves the state-of-the-art performance, enabling cross-structure motion retargeting, and providing a good balance among the preservation of motion semantics as well as the attenuation of interpenetration and contact-missing.

The analysis of complete genome sequence and comparative genomics of Vibrio parahaemolyticus LF1113 in Hainan.

Vibrio parahaemolyticus is a Gram-negative, halophilic and polymorphic coccobacillus. It is world-widely distributed and has resulted in great economic losses since its first appearance. In this study, a pathogenic strain was isolated from diseased pearl gentian grouper and identified as V. parahaemolyticus based on the sequencing results of 16S rDNA gene. In order to gain a comprehensive understanding of this isolation, the whole genome sequencing was conducted. Phylogenetic analysis of the complete genomes of 16 Vibrio species showed that LF1113, ATCC17802, ATCC33787, 2210633, FORC 004, and 160807 were the most closely related. Animal experiments demonstrated that the isolated LF1113 strain was pathogenic in a fish model. This study is the first study to describe the complete genome sequence of a V. parahaemolyticus isolate, which infected pearl gentian grouper from an outbreak in a fish factory farm in Hainan. The results will expand our understanding of genetic characteristics, pathogenesis, diagnostics and disease prevention of V. parahaemolyticus, and lay the foundation for further study.

Improving Blueberry Anthocyanins' Stability Using a Ferritin Nanocarrier.

Blueberries are fruits known for their high level of anthocyanins, which have high nutritional value and several biological properties. However, the chemical instability of anthocyanins is one of the major limitations of their application. The stability of blueberry anthocyanin extracts (BAEs) encapsulated in a ferritin nanocarrier was investigated in this study for several influencing parameters, including pH, temperature, UV-visible light, redox agents, and various metal ions. The outcomes supported the positive role of protein nanoparticles in enhancing the stability of blueberry anthocyanins by demonstrating that the stability of encapsulated BAE nanoparticles with ferritin carriers was significantly higher than that of free BAEs and a mixture of BAEs and ferritin carriers. This study provides an alternative approach for enhancing blueberry anthocyanin stability using ferritin nanocarrier encapsulation.

DTCM: Joint Optimization of Dark Enhancement and Action Recognition in Videos.

Recognizing human actions in dark videos is a useful yet challenging visual task in reality. Existing augmentation-based methods separate action recognition and dark enhancement in a two-stage pipeline, which leads to inconsistently learning of temporal representation for action recognition. To address this issue, we propose a novel end-to-end framework termed Dark Temporal Consistency Model (DTCM), which is able to jointly optimize dark enhancement and action recognition, and force the temporal consistency to guide downstream dark feature learning. Specifically, DTCM cascades the action classification head with the dark augmentation network to perform dark video action recognition in a one-stage pipeline. Our explored spatio-temporal consistency loss, which utilizes the RGB-Difference of dark video frames to encourage temporal coherence of the enhanced video frames, is effective for boosting spatio-temporal representation learning. Extensive experiments demonstrated that our DTCM has remarkable performance: 1) Competitive accuracy, which outperforms the state-of-the-arts on the ARID dataset by 2.32% and the UAVHuman-Fisheye dataset by 4.19% in accuracy, respectively; 2) High efficiency, which surpasses the current most advanced method (Chen et al., 2021) with only 6.4% GFLOPs and 71.3% number of parameters; 3) Strong generalization, which can be used in various action recognition methods (e.g., TSM, I3D, 3D-ResNext-101, Video-Swin) to promote their performance significantly.

Pro-inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease, and aging is a major risk factor. The accumulation of senescent vascular endothelial cells (VECs) often leads to chronic inflammation and oxidative stress and induces endothelial dysfunction, contributing to the occurrence and development of AS. Senescent cells can secrete a variety of pro-inflammatory cytokines to induce the senescence of adjacent cells in a paracrine manner, leading to the transmission of signaling of cellular senescence to neighboring cells and the accumulation of senescent cells. Recent studies have demonstrated that several pro-inflammatory cytokines, including IL-17, TNF-α, and IFN-γ, can induce the senescence of VECs. This review summarizes and focuses on the pro-inflammatory cytokines that often induce the senescence of VECs and the molecular mechanisms of these pro-inflammatory cytokines inducing senescence of VECs. Targeting the senescence of VECs induced by pro-inflammatory cytokines may provide a potential and novel strategy for the prevention and treatment of AS.

Consistent 3D Hand Reconstruction in Video via Self-Supervised Learning.

We present a method for reconstructing accurate and consistent 3D hands from a monocular video. We observe that the detected 2D hand keypoints and the image texture provide important cues about the geometry and texture of the 3D hand, which can reduce or even eliminate the requirement on 3D hand annotation. Accordingly, in this work, we propose S2HAND, a self-supervised 3D hand reconstruction model, that can jointly estimate pose, shape, texture, and the camera viewpoint from a single RGB input through the supervision of easily accessible 2D detected keypoints. We leverage the continuous hand motion information contained in the unlabeled video data and explore S2HAND(V), which uses a set of weights shared S2HAND to process each frame and exploits additional motion, texture, and shape consistency constrains to obtain more accurate hand poses, and more consistent shapes and textures. Experiments on benchmark datasets demonstrate that our self-supervised method produces comparable hand reconstruction performance compared with the recent full-supervised methods in single-frame as input setup, and notably improves the reconstruction accuracy and consistency when using the video training data.

Research on the Sustainable Renewal of Architectural Heritage Sites from the Perspective of Extenics-Using the Example of Tulou Renovations in LantianVillage, Longyan City.

Fujian Tulous in China are important international architectural heritage sites that reflect precious human cultural heritage. Currently, only a small number of Tulou buildings have been listed as world cultural heritage sites, resulting in a lack of attention and financial support for most Tulou buildings. Thus, it is difficult to effectively renovate and repair Tulou buildings to adapt to modern life, and therefore they are facing the severe challenge of abandonment and desolation. Due to the special conditions of Tulou buildings, there are significant limitations in renovation and repair work, with a number of problems such as the lack of innovative renovations. Therefore, through a problem model analysis of a design system for Tulou renovations, in this study, we adopt the methods of divergent tree, conjugate pair, correlative net, implied system, and split-merge chain analyses in extenics to carry out extension transformation and solve the problem and we verify its feasibility using the example of the Tulou renovation projects in Lantian Village, Longyan City. We explore an innovative methodology for scientific renovation of Tulou buildings, and we establish a design system for Tulou building renovations that enriches and supplements original renovation methods; thus, we provide a basis for the repair and reuse of Tulou buildings, to extend their service life and to realize the sustainable development of Tulou buildings. The research results show that extenics can be implemented in innovative renovations of Tulou buildings, and it is concluded that the essence of achieving sustainable renewal in Tulou building renovations is to solve contradictory problems, including contradictions in conditions, objectives, and design. This study verifies the possibility of applying extenics in the design of Tulou building renovations, makes corresponding contributions to the application of extension methods in the renovation and renewal of Tulou buildings, and also contributes to the renovation, renewal, and protection of other types of architectural heritage sites.

Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers.

The susceptibility of cells to DNA damage and their DNA repair ability are crucial for cancer therapy. Homologous recombination is one of the major repairing mechanisms for DNA double-strand breaks. Approximately half of ovarian cancer (OvCa) cells harbor homologous recombination deficiency (HRD). Considering that HRD is a major hallmark of OvCas, scholars proposed HRD scoring to evaluate the HRD degree and guide the choice of therapeutic strategies for OvCas. In the last decade, synthetic lethal strategy by targeting poly (ADP-ribose) polymerase (PARP) in HR-deficient OvCas has attracted considerable attention in view of its favorable clinical effort. We therefore suggested that the uses of other DNA damage/repair-targeted drugs in HR-deficient OvCas might also offer better clinical outcome. Here, we reviewed the current small molecule compounds that targeted DNA damage/repair pathways and discussed the HRD scoring system to guide their clinical uses.

Inhibitory effects and molecular mechanisms of ginsenoside Rg1 on the senescence of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) produce all blood cell lineages and maintain life-long hematopoiesis. However, the self-renewal ability and differentiation capacity of HSCs reduces with age. The senescence of HSCs can lead to the imbalance of hematopoietic homeostasis and immune disorder and induce a variety of age-related diseases. Recent studies have shown that therapeutic interventions targeting the senescence of HSCs may prevent disease progression. Ginsenoside Rg1 (Rg1), extracted from roots or stems of ginseng, has beneficial antiaging activities. It has been reported that Rg1 can inhibit the senescence of HSCs. Here, we reviewed recent advances of Rg1 in inhibiting the senescence of HSCs and discussed related molecular mechanisms. Bioinformatics and network databases have been widely applied to drug discoveries. Here, we predicted potential antiaging targets of Rg1 explored by bioinformatic methods, which may help discover new targets of Rg1 and provide novel strategies for delaying the aging process of HSCs.

A General Dynamic Knowledge Distillation Method for Visual Analytics.

Existing knowledge distillation (KD) method normally fixes the weight of the teacher network, and uses the knowledge from the teacher network to guide the training of the student network no-ninteractively, thus it is called static knowledge distillation (SKD). SKD is widely used in model compression on the homologous data and knowledge transfer on the heterogeneous data. However, the teacher network that with fixed-weight constrains the student network to learn knowledge from it. It is worth expecting that the teacher network itself can be continuously optimized to promote the learning ability of the student network dynamically. To overcome this limitation, we propose a novel dynamic knowledge distillation (DKD) method, in which the teacher network and the student network can learn from each other interactively. Importantly, we analyzed the effectiveness of DKD mathematically (see Eq. 4), and addressed one crucial issue caused by the continuous change of the teacher network in the dynamic distillation process via designing a valid loss function. We verified the practicality of our DKD by extensive experiments on various visual tasks, e.g. for model compression, we conducted experiments on image classification and object detection. For knowledge transfer, video-based human action recognition is chosen for analysis. The experimental results on benchmark datasets (i.e. ILSVRC2012, COCO2017, HMDB51, UCF101) demonstrated that the proposed DKD is valid to improve the performance of these visual tasks for a large margin. The source code is publicly available online at1.

RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors.

Synthetic lethal targeting of homologous recombination (HR)-deficient ovarian cancers (OvCas) with poly(ADP-ribose) polymerase inhibitors (PARPis) has attracted considerable attention. Olaparib was the first PARPi approved by the Food and Drug Administration, offering significant clinical benefits in BRCA1/2-deficient OvCas. However, only approximately 20% of OvCa patients harbor BRCA1/2 mutations. Given the shared roles that BRCA1/2 have with other HR regulators, alterations in HR genes may also contribute to "BRCAness profiles" in OvCas. RAD54B has been considered a key player in HR repair, although its roles and therapeutic potential in cancers need further investigation. Here, we identified 22 frequently mutated HR genes by whole-exome sequencing of OvCa tissues from 82 patients. To our surprise, 7.3% of patients were found to harbor mutations of RAD54B, the third-highest mutated gene among patients. We determined that RAD54B-mutated tumor tissues harbored more DNA double-strand breaks than normal tissues. Additionally, we found that RAD54B knockdown inhibited HR repair, enhanced sensitivities of OvCa cells with increased DNA double-strand breaks to olaparib, and induced apoptosis. Enhanced inhibitory effects of olaparib on the growth of ES2 xenograft tumors were further demonstrated by RAD54B knockdown. Finally, we show that restoration with wildtype RAD54B rather than RAD54BN593S and RAD54BH219Y, identified in patients, abolished the effects of RAD54B knockdown, indicating these RAD54B mutants probably malfunctioned in HR repair. Our investigations may offer insight into the contributions of RAD54B mutations to synthetic lethality with olaparib treatment in OvCas, enrich the gene list for "HR deficiency scoring," and expand the applications of PARPis.

Motion-Driven Visual Tempo Learning for Video-Based Action Recognition.

Action visual tempo characterizes the dynamics and the temporal scale of an action, which is helpful to distinguish human actions that share high similarities in visual dynamics and appearance. Previous methods capture the visual tempo either by sampling raw videos with multiple rates, which require a costly multi-layer network to handle each rate, or by hierarchically sampling backbone features, which rely heavily on high-level features that miss fine-grained temporal dynamics. In this work, we propose a Temporal Correlation Module (TCM), which can be easily embedded into the current action recognition backbones in a plug-in-and-play manner, to extract action visual tempo from low-level backbone features at single-layer remarkably. Specifically, our TCM contains two main components: a Multi-scale Temporal Dynamics Module (MTDM) and a Temporal Attention Module (TAM). MTDM applies a correlation operation to learn pixel-wise fine-grained temporal dynamics for both fast-tempo and slow-tempo. TAM adaptively emphasizes expressive features and suppresses inessential ones via analyzing the global information across various tempos. Extensive experiments conducted on several action recognition benchmarks, e.g. Something-Something V1&V2, Kinetics-400, UCF-101, and HMDB-51, have demonstrated that the proposed TCM is effective to promote the performance of the existing video-based action recognition models for a large margin. The source code is publicly released at https://github.com/zphyix/TCM.

HSP90 Inhibitor Ganetespib Enhances the Sensitivity of Mantle Cell Lymphoma to Bruton's Tyrosine Kinase Inhibitor Ibrutinib.

Mantle cell lymphoma (MCL) is a highly aggressive and heterogeneous B-cell lymphoma. Though Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has shown great efficacy as a single agent for MCL treatment, the real-world use of ibrutinib is still subject to limitations. Our previous study has shown the treatment with HSP90 inhibitor ganetespib can attack major targets of MCL, luckily complementary to ibrutinib's targets. In this study, transient ganetespib treatment sensitizes MCL cells to ibrutinib as manifested by the significant decrease of IC50 values, percentages of EdU (5-Ethynyl-2'-deoxyuridine) positive cells, and levels of p-AKT and NF-κB after combinational treatment. Additionally, pretreatment with ganetespib enhanced cell cycle arrest induced by ibrutinib at G0/G1 phase and significantly decreased levels of cell cycle promoting proteins CDK2, 4, and 6. Pretreatment with ganetespib also enhanced cell apoptosis induced by ibrutinib through the upregulation of cleaved-caspase 9 and downregulation of BCL-2 in MCL cells at the molecular level. The sequential administration of ganetespib and ibrutinib had similar effects on increasing DNA damage as the transient treatment with ganetespib as demonstrated by the improved percentage of γH2AX and 53BP1 foci. Furthermore, ganetespib significantly increased inhibition of tumor growth mediated by ibrutinib in vivo, confirmed by the changes of the expression levels of Ki-67 and BCL-2 through immunohistochemistry assays. This study indicates that HSP90 inhibitor ganetespib maybe ideal for the combinational use with BTK inhibitor ibrutinib to target major pathogenesis-associated signaling pathways for MCL treatment which may help identify new possibilities for clinical trials.

Molecular dissection on inhibition of Ras-induced cellular senescence by small t antigen of SV40.

Simian virus 40 (SV40) is a potentially oncogenic virus of monkey origin. Transmission, prevalence, and pathogenicity rates of SV40 are unclear, but infection can occur in humans, for example individuals with high contact with rhesus macaques and individuals that received contaminated early batches of polio vaccines in 1950-1963. In addition, several human polyomaviruses, proven carcinogenic, are also highly common in global populations. Cellular senescence is a major mechanism of cancer prevention in vivo. Hyperactivation of Ras usually induces cellular senescence rather than cell transformation. Previous studies suggest small t antigen (ST) of SV40 may interfere with cellular senescence induced by Ras. In the current study, ST was demonstrated to inhibit Ras-induced cellular senescence (RIS) and accumulation of DNA damage in Ras-activated cells. In addition, ST suppressed the signal transmission from BRaf to MEK and thus blocked the downstream transmission of the activated Ras signal. B56γ knockdown mimicked the inhibitory effects of ST overexpression on RIS. Furthermore, KSR1 knockdown inhibited Ras activation and the subsequent cellular senescence. Further mechanism studies indicated that the phosphorylation level of KSR1 rather than the levels of the total protein regulates the activation of Ras signaling pathway. In sum, ST inhibits the continuous hyperactivation of Ras signals by interfering with the normal functions of PP2A-B56γ of dephosphorylating KSR1, thus inhibiting the occurrence of cellular senescence. Although the roles of SV40 in human carcinogenesis are controversial so far, our study has shown that ST of polyomaviruses has tumorigenic potential by inhibiting oncogene-induced senescence (OIS) as a proof of concept.

Partitioning defective 6 homolog alpha (PARD6A) promotes epithelial-mesenchymal transition via integrin ß1-ILK-SNAIL1 pathway in ovarian cancer.

Partitioning-defective protein 6 (Par6) family proteins have been demonstrated to be closely associated with the occurrence and development of cancers. It is well accepted that dysregulation of epithelial-mesenchymal transition (EMT) greatly contributes to carcinogenesis and metastases of ovarian cancer. So far, the roles of Par6 in EMT of ovarian cancer are not clear. Functional experiments were carried out to study the roles of PARD6A in EMT of ovarian cancer in vitro and in vivo, and EMT pathways potentially affected by PARD6A expression were screened. We found that PARD6A was significantly highly expressed in tissues of ovarian cancer patients in III-IV stages, poorly differentiated or with lymphatic metastases versus I-II stages, moderately or well differentiated, or without lymphatic metastases, respectively. PARD6A knockdown suppressed EMT of SKOV3 and A2780 cells in vitro and ovarian cancer metastasis in vivo, while overexpression of PARD6A promoted EMT in HO8910 and OVCAR8 cells. It was indicated that PARD6A affected EMT of ovarian cancer cells through SNAIL1 signaling pathway and subsequently modulated the expression of VIMENTIN and E-cadherin, which was further confirmed by knockdown and overexpression of SNAIL1 experiments. PARD6A was also demonstrated to regulate expression of SNAIL1 by modulating integrin ß1 and ILK proteins, specifically it was shown that the transcription of SNAIL1 was regulated by ILK in this study. In addition, expression of ILK in ovarian cancer tissues was demonstrated to be correlated with tumor stages and lymphatic metastases clinically. In this study, we identified a novel role of PARD6A as an inducer of cell migration and invasion, which is likely to play an important role in metastasis of ovarian cancer. The molecular pathways of EMT mediated by PARD6A-Integrin ß1-ILK-SNAIL1 and finally implemented by E-cadherin and VIMENTIN may provide a novel strategy for drug development for ovarian cancer therapy in the near future.

DnaK Functions as a Moonlighting Protein on the Surface of Mycoplasma hyorhinis Cells.

Mycoplasma hyorhinis is a common pathogen of swine and is also associated with various human tumors. It causes systemic inflammation, typically polyserositis and polyarthritis, in some infected pigs. However, the pathogenic mechanism of M. hyorhinis remains unclear. DnaK is a highly conserved protein belonging to the heat-shock protein 70 family of molecular chaperones, which plays important roles as a moonlighting protein in various bacteria. In the present study, we identified the surface exposure of M. hyorhinis DnaK. Two virulent strains expressed more DnaK on their surface than the avirulent strain. Thereafter, the potential moonlighting functions of DnaK were investigated. Recombinant M. hyorhinis DnaK (rMhr-DnaK) was found to be able to adhere to swine PK-15 cells and human NCI-H292 cells. It also bound to four extracellular matrix components-fibronectin, laminin, type IV collagen, and vitronectin-in a dose-dependent manner. ELISA demonstrated an interaction between rMhr-DnaK and plasminogen, which was significantly inhibited by a lysine analog, ε-aminocaproic acid. rMhr-DnaK-bound plasminogen was activated by tissue-type plasminogen activator (tPA), and the addition of rMhr-DnaK significantly enhanced the activation. Finally, a DnaK-specific antibody was detected in the serum of pigs immunized with inactivated vaccines, which indicated good immunogenicity of it. In summary, our findings imply that DnaK is an important multifunctional moonlighting protein in M. hyorhinis and likely participates extensively in the infection and pathogenesis processes of M. hyorhinis.

Regulatory network of metformin on adipogenesis determined by combining high-throughput sequencing and GEO database.

Adipose differentiation and excessive lipid accumulation are the important characteristics of obesity. Metformin, as a classic hypoglycaemic drug, has been proved to reduce body weight in type 2 diabetes, the specific mechanism has not been completely clear. A few studies have explored its effect on adipogenesis in vitro, but the existing experimental results are ambiguous. 3T3-L1 preadipocytes were used to explore the effects of metformin on the morphological and physiological changes of lipid droplets during adipogenesis. A high throughput sequencing was used to examine the effects of metformin on the transcriptome of adipogenesis. Considering the inevitable errors among independent experiments, we performed integrated bioinformatics analysis to identify important genes involved in adipogenesis and reveal potential molecular mechanisms. During the process of adipogenesis, metformin visibly relieved the morphological and functional changes. In addition, metformin reverses the expression pattern of genes related to adipogenesis at the transcriptome level. Combining with integrated bioinformatics analyses to further identify the potential targeted genes regulated by metformin during adipogenesis. The present study identified novel changes in the transcriptome of metformin in the process of adipogenesis that might shed light on the underlying mechanism by which metformin impedes the progression of obesity.

Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice.

BACKGROUND & AIMS: Angiopoietin-like protein 8 (ANGPTL8) is a 198 amino-acid long, novel secreted protein that is mainly expressed in the liver and brown adipose tissues. At present, evidence supporting the involvement of ANGPTL8 in the regulation of glucose metabolism is inconclusive, along with its function in the liver. Previous studies mainly focused on the effect of ANGPTL8 on glucose metabolism in non-diabetic mice, and few relevant studies in diabetic mice exist. Therefore, this study aimed to investigate the role of ANGPTL8 on glucose homeostasis and elucidate the underlying mechanisms in diabetic mice. METHODS: db/db diabetic and high-fat diet/streptozotocin-induced diabetic mice were injected with adenovirus expressing ANGPTL8 through the tail vein. Blood glucose levels were measured and glucose, insulin, and pyruvate tolerance tests were performed. To explore the molecular mechanism by which ANGPTL8 regulates hepatic glucose metabolism and manipulate mouse ANGPTL8 expression levels both in vivo and in vitro based on adenoviral transduction, gain- and loss-of-function strategies were adopted. RESULTS: Adenovirus-mediated overexpression of ANGPTL8 decreased fasting blood glucose levels and improved glucose tolerance and insulin sensitivity in db/db and high-fat diet/streptozotocin-induced diabetic mice. ANGPTL8 knockdown yielded the opposite effects. ANGPTL8 was upregulated in the cAMP/Dex-induced hepatocyte gluconeogenesis model. Moreover, ANGPTL8 overexpression in primary hepatocytes and diabetic mouse livers inhibited the expression of gluconeogenesis-related genes, including PEPCK and G6PC, by activating the AKT signaling pathway and, thereby, reducing glucose production. Therefore, the results demonstrated that ANGPTL8 improved glucose metabolism via inhibition of hepatic gluconeogenesis in diabetic mice. CONCLUSIONS: Current findings highlight a critical role of hepatic ANGPTL8 in glucose homeostasis, suggesting that increased ANGPTL8 expression could be an underlying factor for the inhibition of hepatic gluconeogenesis, which could be targeted for the prevention and treatment of type 2 diabetes.