A phase separation-fortified bi-specific adaptor for conditional tumor killing.

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency, enabling sophisticated control of signal transduction. Leveraging the emerging concept of liquid-liquid phase separation (LLPS) and its ability to organize cell surface receptors into functional compartments, we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways, thus inducing the rapid, potent, and specific apoptosis of tumor cells. Despite their simplicity, these "triggers", named phase-separated Tumor Killers (hereafter referred to as psTK), are sufficient to yield interreceptor clustering of death receptors (represented by DR5) and tumor-associated receptors, with notable features: LLPS-mediated robust high-order organization, well-choreographed conditional activation, and broad-spectrum capacity to potently induce apoptosis in tumor cells.

Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis.

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats.

Long way up: rethink diseases in light of phase separation and phase transition.

Biomolecular condensation, driven by multivalency, serves as a fundamental mechanism within cells, facilitating the formation of distinct compartments, including membraneless organelles that play essential roles in various cellular processes. Perturbations in the delicate equilibrium of condensation, whether resulting in gain or loss of phase separation, have robustly been associated with cellular dysfunction and physiological disorders. As ongoing research endeavors wholeheartedly embrace this newly acknowledged principle, a transformative shift is occurring in our comprehension of disease.

Midgut membrane protein BmSUH facilitates Bombyx mori nucleopolyhedrovirus oral infection.

Baculoviruses are virulent pathogens that infect a wide range of insects. They initiate infections via specific interactions between the structural proteins on the envelopes of occlusion-derived virions (ODVs) and the midgut cell surface receptors in hosts. However, host factors that are hijacked by baculoviruses for efficient infection remain largely unknown.

Phase Separation-Based Biochemical Assays for Biomolecular Interactions.

A variety of protein functions are carried out by protein complexes. Identifying and understanding protein-protein interactions (PPIs) will shed light on the structural foundations of the complexity of life. Although multiple methods have been developed to detect protein-protein interactions (PPIs), few are suited for high-throughput analysis and many of them suffer from severe false-positive and/or false-negative results.

Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer's Disease Complicated With Osteoporosis.

Alzheimer's disease (AD) and osteoporosis (OP) are progressive degenerative diseases caused by multiple factors, placing a huge burden on the world. Much evidence indicates that OP is a common complication in AD patients. In addition, there is also evidence to show that patients with OP have a higher risk of AD than those without OP.

PI3K/AKT/Nrf2 signalling pathway is involved in the ameliorative effects of xanthohumol on amyloid β-induced oxidative damage and bone loss.

Objective: Xanthohumol (XAN), a natural isoflavone from Humulus lupulus L., possesses biological activities on relieving oxidative stress and osteoporosis (OP). This study aimed to evaluate the antioxidative and osteoprotective effect of XAN on Aβ-injured osteoblasts, and explore its underlying mechanism.

Compartmentalization-aided interaction screening reveals extensive high-order complexes within the SARS-CoV-2 proteome.

Bearing a relatively large single-stranded RNA genome in nature, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes sophisticated replication/transcription complexes (RTCs), mainly composed of a network of nonstructural proteins and nucleocapsid protein, to establish efficient infection. In this study, we develop an innovative interaction screening strategy based on phase separation in cellulo, namely compartmentalization of protein-protein interactions in cells (CoPIC). Utilizing CoPIC screening, we map the interaction network among RTC-related viral proteins.

Struggle for survival: new insights into NELF condensation for adaptive transcriptional reprogramming.

In this issue of Molecular Cell, Rawat et al. (2021) characterize novel stress-induced condensates of the negative elongation factor (NELF) as the nuclear counterparts of cytosolic stress granules. This provides a new perspective on transcription repression orchestrated by phase separation.

Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is a factor for viral-induced cytopathic effects via regulating oxidative phosphorylation and cellular ROS levels.

Bombyx mori nucleopolyhedrovirus (BmNPV) is highly pathogenic to Bombyx mori, silkworm, which causes serious cytopathic effects (CPEs) during infection. However, the role of viral protein in the virus-induced CPEs remains unclear. Here, we discovered that BmNPV infection induced severe CPEs including titer-dependent cell floating and changes in cellular surface morphology.

nucleopolyhedrovirus F-like protein Bm14 is a type I integral membrane protein that facilitates ODV attachment to the midgut epithelial cells.

Our previous study showed that the nucleopolyhedrovirus (BmNPV) F-like protein Bm14 is intrinsically related to the production of occlusion bodies, occlusion-derived virus (ODV) embedding and virulence in infected larvae. However, the exact mechanism by which Bm14 affects primary infection remains unknown. In this report, we characterized the detailed distribution and topology of Bm14 in occlusion bodies (OBs) and ODVs, and then further investigated the functional role of Bm14 in primary infection.

Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is a cofactor for GP64-Mediated efficient infection via forming a complex on the envelope of budded virus.

Our previous study showed that Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is involved in infectious BV production and its deletion reduces the production rate. However, the peculiar relationship between Bm14 and GP64, two major BV envelope proteins, is still unknown. Here, we demonstrated the predominant distribution of Bm14 in BVs rather than in ODVs.

Folic acid decorated metal-organic frameworks loaded with doxorubicin for tumor-targeted chemotherapy of osteosarcoma.

Effective cancer therapy usually requires the assistance of well-designed drug carriers. In order to increase the drug accumulation to tumor tissue as well as to reduce the side effects of drug carriers, the hybrid drug delivery system (DDS) was developed by integrating folic acid (FA) and a metal-organic framework (MOF). The anticancer drug doxorubicin (DOX) was preloaded into the MOF nanoparticles during the synthesis process of the MOF nanoparticles.

Bombyx mori nucleopolyhedrovirus protein Bm11 is involved in occlusion body production and occlusion-derived virus embedding.

Bombyx mori nucleopolyhedrovirus (BmNPV) orf11 (bm11) is a highly conserved gene with unknown function. It is homologous to AcMNPV orf19. In this study, a bm11 knockout virus was constructed and its role was investigated.

Bombyx mori nucleopolyhedrovirus F-like protein Bm14 affects the morphogenesis and production of occlusion bodies and the embedding of ODVs.

In group I nucleopolyhedrovirus such as Bombyx mori nucleopolyhedrovirus (BmNPV), the biological functions of F-like protein (Bm14) still remain elusive. Here, we found that the deletion of Bm14 reduced the production rate of infectious budded viruses in cell culture, delayed the lethal time of infected larvae by approximately 26 h, and produced less occlusion bodies (OBs). Scanning electron microscopy demonstrated that its disruption affected OB morphogenesis, forming irregular OBs with a pitted surface and irregular profiles.

A plasma-triggered gas switch.

This paper presents a low-jitter, low-trigger-threshold, high-dielectric-constant ceramic, plasma-triggered gas switch developed for pulsed power generators. We also discuss the principles behind the switch and the experiments and numerical calculations used. The electron emission and surface flashover in the trigger structure are used to create the initial plasma for switch breakdown.

Bombyx mori nucleopolyhedrovirus utilizes a clathrin and dynamin dependent endocytosis entry pathway into BmN cells.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a leading cause of silkworm mortality and economic loss to sericulture. The entry of BmNPV budded virus (BV) into host cells is a fundamental process required for the initiation of infection. However, our understanding of the mechanism of virus entry is limited and it is unclear whether BV enter BmN cells via clathrin-mediated endocytosis.

Bombyx mori nucleopolyhedrovirus orf133 and orf134 are involved in the embedding of occlusion-derived viruses into polyhedra.

Bombyx mori nucleopolyhedrovirus (BmNPV) orf133 (bm133) and orf134 (bm134), the orthologues of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac4 and ac5, are two adjacent genes with opposite transcriptional orientations and are highly conserved in all sequenced group I nucleopolyhedroviruses (NPVs). A double bm133-bm134 knockout bacmid was generated to enable the functional study of each gene independently or together. Compared with wild-type and double-repair viruses, deletion of both bm133 and bm134 did not affect budded virus (BV) production or viral DNA replication in transfected BmN cells.

Networks of protein-protein interactions among structural proteins of budded virus of Bombyx mori nucleopolyhedrovirus.

The structural proteins of baculovirus are well studied, but the interactions between them remain unclear. In order to reveal protein-protein interactions among viral structural proteins and their associated proteins of the budded virus of Bombyx mori nucleopolyhedrovirus (BmNPV), the yeast two hybrid (Y2H) system was used to evaluate the interactions of 27 viral genes products. Fifty-seven interactions were identified with 51 binary interactions and 6 self-associations.

Hydrothermal preparation of hierarchical ZIF-L nanostructures for enhanced CO capture.

A zeolitic imidazolate framework (ZIF-L) with hierarchical morphology was synthesized through hydrothermal method. The hierarchical product consists of ZIF-L leaves with length of several micrometers, width of 1 ∼ 2 μm and thickness of ∼300 nm cross connected symmetrically. It was found that the hydrothermal temperature is crucial for the formation of such hierarchical nanostructure.

Identification of a novel host protein SINAL10 interacting with GP64 and its role in Bombyx mori nucleopolyhedrovirus infection.

Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important pathogen of Bombyx mori, silkworm and causes severe losses in the silk industry. During the virus infectious cycle, budded virus (BVs) and occlusion-derived virus (ODVs) particles, which have identical genetic content but different phenotypes, are produced. The envelope glycoprotein GP64, specific in BVs, is involved in host cell receptor binding and is sufficient to mediate membrane fusion during the viral entry.