HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.

Heat shock protein 90β (Hsp90β, encoded by Hsp90ab1 gene) is the most abundant proteins in the cells and contributes to variety of biological processes including metabolism, cell growth and neural functions. However, genetic evidences showing Hsp90β in vivo functions using tissue specific knockout mice are still lacking. Here, we showed that Hsp90β exerted paralogue-specific role in osteoclastogenesis.

Tripartite Dynamic Zero-Sum Quantum Games.

The Nash equilibrium plays a crucial role in game theory. Most of results are based on classical resources. Our goal in this paper is to explore multipartite zero-sum game with quantum settings.

Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3.

Proton and Li-Ion Permeation through Graphene with Eight-Atom-Ring Defects.

Defect-free graphene is impermeable to gases and liquids but highly permeable to thermal protons. Atomic-scale defects such as vacancies, grain boundaries, and Stone-Wales defects are predicted to enhance graphene's proton permeability and may even allow small ions through, whereas larger species such as gas molecules should remain blocked. These expectations have so far remained untested in experiment.

Dual targeting of SREBP2 and ERRα by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss.

Osteoporosis develops because of impaired bone formation and/or excessive bone resorption. Several pharmacological treatment of osteoporosis has been developed; however, new treatments are still necessary. Cholesterol and estrogen receptor-related receptor alpha (ERRα) promote osteoclasts formation, survival, and cellular fusion and thus become high risk factors of osteoporosis.

Inhibition of HSP90β Improves Lipid Disorders by Promoting Mature SREBPs Degradation via the Ubiquitin-proteasome System.

Heat shock protein 9 (HSP90) are a family of the most highly expressed cellular proteins and attractive drug targets against cancer, neurodegeneration diseases, etc. HSP90 proteins have also been suggested to be linked to lipid metabolism. However, the specific function of HSP90 paralogs, as well as the underlying molecular cascades remains largely unknown.

Retained foreign objects in casts in children.

Cast immobilization is a noninvasive and effective option in the treatment of fractures in children. However, its use can be associated with complications, such as pressure sores, skin infections, thermal injuries, and joint stiffness. In clinical practice, retained foreign objects in casts are not uncommon.

Phellodendrine chloride suppresses proliferation of KRAS mutated pancreatic cancer cells through inhibition of nutrients uptake via macropinocytosis.

Despite the massive efforts to develop the treatment of pancreatic cancers, no effective application exhibits satisfactory clinical outcome. Macropinocytosis plays a critical role for continuous proliferation of pancreatic ductal adenocarcinoma (PDAC). In this study, we generated a screening method and identified phellodendrine chloride (PC) as a potential macropinocytosis inhibitor.

Enhancement of protein stability by an additional disulfide bond designed in human neuroglobin.

Human neuroglobin (Ngb) forms an intramolecular disulfide bond between Cys46 and Cys55, with a third Cys120 near the protein surface, which is a promising protein model for heme protein design. In order to protect the free Cys120 and to enhance the protein stability, we herein developed a strategy by designing an additional disulfide bond between Cys120 and Cys15 A15C mutation. The design was supported by molecular modeling, and the formation of Cys15-Cys120 disulfide bond was confirmed experimentally by ESI-MS analysis.

Formation of Cys-heme cross-link in K42C myoglobin under reductive conditions with molecular oxygen.

The structure and function of heme proteins are regulated by diverse post-translational modifications including heme-protein cross-links, with the underlying mechanisms not well understood. In this study, we introduced a Cys (K42C) close to the heme 4-vinyl group in sperm whale myoglobin (Mb) and solved its X-ray crystal structure. Interestingly, we found that K42C Mb can partially form a Cys-heme cross-link (termed K42C Mb-X) under dithiothreitol-induced reductive conditions in presence of O, as suggested by guanidine hydrochloride-induced unfolding and heme extraction studies.

DL-mandelic acid intercalated Zn-Al layered double hydroxide: A novel antimicrobial layered material.

DL-mandelic acid (MA) has been intercalated into Zn-Al layered double hydroxide (LDH) by an anion-exchange reaction. After intercalation of MA anions, the basal spacing of the LDH increased from 0.75 to 1.

Effectiveness of rapid rail transit system in Beijing.

The effectiveness of rapid rail transit system is analyzed using tools of complex network for the first time. We evaluated the effectiveness of the system in Beijing quantitatively from different perspectives, including descriptive statistics analysis, bridging property, centrality property, ability of connecting different part of the system and ability of disease spreading. The results showed that the public transport of Beijing does benefit from the rapid rail transit lines, and the benefit of different regions from RRTS is gradually decreased from the north to the south.

Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown.

Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD) and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD.

Artocarpin Induces Apoptosis in Human Cutaneous Squamous Cell Carcinoma HSC-1 Cells and Its Cytotoxic Activity Is Dependent on Protein-Nutrient Concentration.

Artocarpin, a natural prenylated flavonoid, has been shown to have various biological properties. However, its effects on human cutaneous squamous cell carcinoma (SCC) have not been previously investigated. We set out to determine whether artocarpin has cytotoxic effects on SCC cells and whether its pharmacological activity is dependent on protein-nutrient concentration.

The hypothetical protein Ycf46 is involved in regulation of CO2 utilization in the cyanobacterium Synechocystis sp. PCC 6803.

The Ycf46 mutant of Synechocystis showed growth inhibition under low dissolved CO 2 conditions, suggesting a role for the Ycf46 protein in the process of photosynthetic CO 2 uptake and utilization. Hypothetical chloroplast open reading frame Ycf46 proteins are highly conserved in all cyanobacterial lineages and most algal chloroplast genomes, but their exact function is still unknown. In the cyanobacterium Synechocystis sp.

Inactivation of Ca(2+)/H(+) exchanger in Synechocystis sp. strain PCC 6803 promotes cyanobacterial calcification by upregulating CO(2)-concentrating mechanisms.

Cyanobacteria are important players in the global carbon cycle, accounting for approximately 25% of global CO2 fixation. Their CO2-concentrating mechanisms (CCMs) are thought to play a key role in cyanobacterial calcification, but the mechanisms are not completely understood. In Synechocystis sp.

N,N'-Bis(2-quinolylcarbon-yl)hydrazine.

The title compound, C(20)H(14)N(4)O(2), crystallizes in the ortho-rhom-bic system with a crystallographic twofold axis through the N-N bond. The mol-ecule is non-planar and the dihedral angle between two amide groups is 74.9 (2)°.