π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Enhanced fractional-order total variation regularization-based velocity field reconstruction for CUP-VISAR diagnostic system.

The fusion of a velocity interferometer system for any reflector with compressed ultrafast photography systems in recent literature can achieve two-dimensional spatiotemporal diagnosis of shock wave velocities. Addressing the limitations posed by 7 × 7 coded aperture sampling, this study introduces an enhanced three-dimensional reconstruction algorithm grounded in fractional-order total variation regularization (E-3DFOTV). Simulated reconstructions and analysis were conducted on 80 frames of 350 × 800 fringes.

Proteomic and ubiquitinome analysis reveal that microgravity affects glucose metabolism of mouse hearts by remodeling non-degradative ubiquitination.

Long-term exposure to a microgravity environment leads to structural and functional changes in hearts of astronauts. Although several studies have reported mechanisms of cardiac damage under microgravity conditions, comprehensive research on changes at the protein level in these hearts is still lacking. In this study, proteomic analysis of microgravity-exposed hearts identified 156 differentially expressed proteins, and ubiquitinomic analysis of these hearts identified 169 proteins with differential ubiquitination modifications.

Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade.

Tardigrades are captivating organisms known for their resilience in extreme environments, including ultra-high-dose radiation, but the underlying mechanisms of this resilience remain largely unknown. Using genome, transcriptome, and proteome analysis of , we explored the molecular basis contributing to radiotolerance in this organism. A putatively horizontally transferred gene, DOPA dioxygenase 1 (), responds to radiation and confers radiotolerance by synthesizing betalains-a type of plant pigment with free radical-scavenging properties.

Nedl1 knockout impaired the learning and memory of mice.

Background: Protein ubiquitination is a common post-translational modification involved in protein degradation and various life processes in cells. NEDL1 is a ubiquitin ligase that is highly expressed primarily in the brain. However, the functions of NEDL1 in social approach/novelty preference, anxiety, learning and memory remain poorly understood.

Spatiotemporal Analysis of Mesenchymal Stem Cells Fate Determination by Inflammatory Niche Following Soft Tissue Injury at a Single-Cell Level.

Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma-induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells.

Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.

The phosphoinositide 3-kinase (PI3K)-Akt axis is one of the most frequently activated pathways and is demonstrated as a therapeutic target in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC). Targeting the PI3K-Akt pathway has been a challenging undertaking through the decades. Here we unveiled an essential role of E3 ligase SMAD ubiquitylation regulatory factor 1 (Smurf1)-mediated phosphoinositide-dependent protein kinase 1 (PDK1) neddylation in PI3K-Akt signaling and tumorigenesis.

LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis.

Chronic infections, including Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), can induce host immune exhaustion. However, the key checkpoint molecules involved in this process and the underlying regulatory mechanisms remain largely undefined, which impede the application of checkpoint-based immunotherapy in infectious diseases. Here, through adopting time-of-flight mass cytometry and transcriptional profiling to systematically analyze natural killer (NK) cell surface receptors, we identify leukocyte immunoglobulin like receptor B1 (LILRB1) as a critical checkpoint receptor that defines a TB-associated cell subset (LILRB1 NK cells) and drives NK cell exhaustion in TB.

Deubiquitylase OTUD3 regulates integrated stress response to suppress progression and sorafenib resistance of liver cancer.

The integrated stress response (ISR) is activated in response to intrinsic and extrinsic stimuli, playing a role in tumor progression and drug resistance. The regulatory role and mechanism of ISR in liver cancer, however, remain largely unexplored. Here, we demonstrate that OTU domain-containing protein 3 (OTUD3) is a deubiquitylase of eukaryotic initiation factor 2α (eIF2α), antagonizing ISR and suppressing liver cancer.

A protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions.

Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, the DUB-substrate interactions (DSIs) remain insufficiently investigated.

TRIM25 predominately associates with anti-viral stress granules.

Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role in the antiviral process, owing to their potent translational repressive effects and ability to trigger signal transduction; however, it is poorly understood how these antiviral SGs differ from SGs induced by other environmental stressors. Here we identify that TRIM25, a known driver of the ubiquitination-dependent antiviral innate immune response, is a potent and critical marker of the antiviral SGs.

OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition.

Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 () is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance.

TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux.

Infectious diseases, such as (Mtb)-caused tuberculosis (TB), remain a global threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a promising strategy for infection treatment through targeting host immunity. However, the limited understanding of the function and regulatory mechanism of host factors involved in immune defense against infections has impeded HDT development.

Whole-transcriptome defines novel glucose metabolic subtypes in colorectal cancer.

Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized.

CRISPR screening identifies the deubiquitylase ATXN3 as a PD-L1-positive regulator for tumor immune evasion.

Regulation of tumoral PD-L1 expression is critical to advancing our understanding of tumor immune evasion and the improvement of existing antitumor immunotherapies. Herein, we describe a CRISPR-based screening platform and identified ATXN3 as a positive regulator for PD-L1 transcription. TCGA database analysis revealed a positive correlation between ATXN3 and CD274 in more than 80% of human cancers.

SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis.

Macroautophagy/autophagy is a homeostatic process in response to multiple signaling, such as the lysosome-dependent recycling process of cellular components. Starvation-induced MTOR inactivation and PPP3/calcineurin activation were shown to promote the nuclear translocation of TFEB. However, the mechanisms via which signals from endomembrane damage are transmitted to activate PPP3/calcineurin and orchestrate autophagic responses remain unknown.

The ubiquitin-specific protease 5 mediated deubiquitination of LSH links metabolic regulation of ferroptosis to hepatocellular carcinoma progression.

Epigenetic regulators and posttranslational modifications of proteins play important roles in various kinds of cancer cell death, including ferroptosis, a non-apoptotic form of cell death. However, the interplay of chromatin modifiers and deubiquitinase (DUB) in ferroptosis remains unclear. Here, we found that ubiquitin-specific protease 5 (USP5) is regarded as a bona fide DUB of lymphoid-specific helicase (LSH), a DNA methylation repressor, in hepatocellular carcinoma (HCC).

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future.