Molecular Pathogenesis of Gastric Adenocarcinoma

The incidence and mortality of gastric cancer (GC) rank top five and top three, respectively, among cancers around the world. It is an intricate malignancy caused by the reciprocity of intrinsically genetic, environmental, and host-related elements. The silent property, advanced clinical characterization, and potential heterogeneity have made GC a thorny disease with a high death rate. The increasing knowledge of the abundant genetic abnormalities regarding GC will definitely elongate the patients’ survival. Scientists have been working hard to discover the myths beneath gastric tumorigenesis: novel biomarkers have been established, and cell transduction cascades have been well described. The study grouping GC into four molecular subtypes by The Cancer Genome Atlas (TCGA) broadens our horizon of GC etiologies. Knowledge regarding to the sophisticated networks in tumor microenvironment also bring new insights into the mechanisms assist GC development. In the future, people will strive for translating more research achievements into clinical utility. Successful translational medicine will lead to new methods for early GC diagnosis and precise medical strategies for individuals

C2G2: Controllable Co-speech Gesture Generation with Latent Diffusion Model

Co-speech gesture generation is crucial for automatic digital avatar animation. However, existing methods suffer from issues such as unstable training and temporal inconsistency, particularly in generating high-fidelity and comprehensive gestures. Additionally, these methods lack effective control over speaker identity and temporal editing of the generated gestures. Focusing on capturing temporal latent information and applying practical controlling, we propose a Controllable Co-speech Gesture Generation framework, named C2G2. Specifically, we propose a two-stage temporal dependency enhancement strategy motivated by latent diffusion models. We further introduce two key features to C2G2, namely a speaker-specific decoder to generate speaker-related real-length skeletons and a repainting strategy for flexible gesture generation/editing. Extensive experiments on benchmark gesture datasets verify the effectiveness of our proposed C2G2 compared with several state-of-the-art baselines. The link of the project demo page can be found at https://c2g2-gesture.github.io/c2_gestureComment: 12 pages, 6 figures, 7 table

A Metabonomic Approach to Analyze the Dexamethasone-Induced Cleft Palate in Mice

Mice models are an important way to understand the relation between the fetus with cleft palate and changes of maternal biofluid. This paper aims to develop a metabonomics approach to analyze dexamethasone-induced cleft palate in pregnant C57BL/6J mice and to study the relationship between the change of endogenous small molecular metabolites in maternal plasma and the incidence of cleft palate. To do so, pregnant mice were randomly divided into two groups. The one group was injected with dexamethasone. On E17.5th day, the incident rates of cleft palate from embryos in two groups were calculated. The 1H-NMR spectra from the metabolites in plasma in two groups was collected at same time. Then the data were analyzed using metabonomics methods (PCA and SIMCA). The results showed that the data from the two groups displayed distinctive characters, and the incidence of cleft palate were significantly different (P < .005). To conclude, this study demonstrates that the metabonomics approach is a powerful and effective method in detecting the abnormal metabolites from mother in the earlier period of embryos, and supports the idea that a change from dexamethasone induced in maternal metabolites plays an important role in the incidence of cleft palate

Mega-TTS 2: Zero-Shot Text-to-Speech with Arbitrary Length Speech Prompts

Zero-shot text-to-speech aims at synthesizing voices with unseen speech prompts. Previous large-scale multispeaker TTS models have successfully achieved this goal with an enrolled recording within 10 seconds. However, most of them are designed to utilize only short speech prompts. The limited information in short speech prompts significantly hinders the performance of fine-grained identity imitation. In this paper, we introduce Mega-TTS 2, a generic zero-shot multispeaker TTS model that is capable of synthesizing speech for unseen speakers with arbitrary-length prompts. Specifically, we 1) design a multi-reference timbre encoder to extract timbre information from multiple reference speeches; 2) and train a prosody language model with arbitrary-length speech prompts; With these designs, our model is suitable for prompts of different lengths, which extends the upper bound of speech quality for zero-shot text-to-speech. Besides arbitrary-length prompts, we introduce arbitrary-source prompts, which leverages the probabilities derived from multiple P-LLM outputs to produce expressive and controlled prosody. Furthermore, we propose a phoneme-level auto-regressive duration model to introduce in-context learning capabilities to duration modeling. Experiments demonstrate that our method could not only synthesize identity-preserving speech with a short prompt of an unseen speaker but also achieve improved performance with longer speech prompts. Audio samples can be found in https://mega-tts.github.io/mega2_demo/

Expanding Limit of Minimum Sampling Time Using Auxiliary Vectors for PMSM Drives with Single DC-Link Current Sensor

Phase current reconstruction (PCR) strategy can improve the fault tolerance of permanent magnet synchronous motor (PMSM) drives. The PCR precision is largely affected by the unmeasurable zones and time-sharing sampling errors. The upper limit (Tlimit) of PCR allowable range can reflect the requirement of different PCR methods for the minimum sampling time (Tmin). With a longer Tlimit, there is sufficient time for sampling, even if Tlimit is halved due to the symmetrical waveform. Therefore, the extension of Tlimit is the key to eliminate the unmeasurable zones and time-sharing sampling errors. In this paper, a method to increase Tlimit is proposed, which introduces the suitable auxiliary vectors (AVs) in different regions to extend the duration time of the sampling vectors. With the help of a longer Tlimit (12.5%Ts), its possible to eliminate all the unmeasurable zones and time-sharing sampling errors, relieve the pressure on the hardware of current loop, improve the sampling accuracy, and facilitate the reliable operation of the drive. Besides, the switching action times of IGBTs can be reduced by about one-third in the high modulation area. The proposed method is finally proved to accurately reconstruct the phase currents by the experimental results on the PMSM prototype

A Novel Systems Pharmacology Method to Investigate Molecular Mechanisms of Scutellaria barbata D. Don for Non-small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, cytotoxic chemotherapy, surgical resection, radiation, and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC is relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is imperative to identify or develop efficient lead compounds for the treatment of NSCLC. Here, we report that the herb Scutellaria barbata D. Don (SBD) can effectively treat NSCLC by anti-inflammatory, promoting apoptosis, cell cycle arrest, and angiogenesis. In this work, we analyze the molecular mechanism of SBD for NSCLC treatment by applying the systems pharmacology strategy. This method combines pharmacokinetics analysis with pharmacodynamics evaluation to screen out the active compounds, predict the targets and assess the networks and pathways. Results show that 33 compounds were identified with potential anti-cancer effects. Utilizing these active compounds as probes, we predicted that 145 NSCLC related targets mainly involved four aspects: apoptosis, inflammation, cell cycle, and angiogenesis. And in vitro experiments were managed to evaluate the reliability of some vital active compounds and targets. Overall, a complete overview of the integrated systems pharmacology method provides a precise probe to elucidate the molecular mechanisms of SBD for NSCLC. Moreover, baicalein from SBD effectively inhibited tumor growth in an LLC tumor-bearing mice models, demonstrating the anti-tumor effects of SBD. Our findings further provided experimental evidence for the application in the treatment of NSCLC

The international effort: building the bridge for Translational Medicine: Report of the 1st International Conference of Translational Medicine (ICTM)

Background: Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad. Findings: The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two-way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation. Conclusions: It was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two-fold: to accelerate the two-way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state-of-art translational research and salient aspects of the ensuing discussions

Identification of renal cyst cells of type I Nephronophthisis by single-nucleus RNA sequencing

Background: Nephronophthisis (NPH) is the most common genetic cause of end-stage renal disease (ESRD) in childhood, and NPHP1 is the major pathogenic gene. Cyst formation at the corticomedullary junction is a pathological feature of NPH, but the mechanism underlying cystogenesis is not well understood. The isolation and identification of cystic cell subpopulation could help to identify their origins and provide vital clues to the mechanisms underlying cystogenesis in NPH.Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed to produce an atlas of NPHP1 renal cells. Kidney samples were collected from WT (Nphp1+/+) mice and NPHP1 (Nphp1del2-20/del2-20) model mice.Results: A comprehensive atlas of the renal cellular landscape in NPHP1 was generated, consisting of 14 basic renal cell types as well as a subpopulation of DCT cells that was overrepresented in NPHP1 kidneys compared to WT kidneys. GO analysis revealed significant downregulation of genes associated with tubular development and kidney morphogenesis in this subpopulation. Furthermore, the reconstruction of differentiation trajectories of individual cells within this subpopulation confirmed that a specific group of cells in NPHP1 mice become arrested at an early stage of differentiation and proliferate to form cysts. We demonstrate that Niban1 is a specific molecular marker of cystic cells in both mice and human NPHP1.Conclusion: In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. These results offer fresh insights into the cellular and molecular basis of cystogenesis in NPH