Denatonium inhibits RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype by blocking p65 signaling pathway.

Background: Bone remodeling is a critical process that maintains skeletal integrity, orchestrated by the balanced activities of osteoclasts, which resorb bone, and osteoblasts, which form bone. Osteoclastogenesis, the formation of osteoclasts, is primarily driven by NFATc1, a process activated through c-Fos and NF-κB signaling pathways in response to receptor activator of nuclear factor κB ligand (RANKL). Dysregulation of RANKL signaling is a key contributor to pathological bone loss, as seen in conditions such as osteoporosis.

YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as gefitinib and osimertinib have primarily been used as first-line treatments for patients with EGFR-activating mutations in non-small cell lung cancer (NSCLC). Novel biomarkers are required to distinguish patients with lung cancer who are resistant to EGFR-TKIs. The aim of the study is to investigate the expression and functional role of YES1, one of the Src-family kinases, in EGFR-TKI-resistant NSCLC.

NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons.

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined.

Novel Inhibitor of Mixed-Lineage Kinase Domain-Like Protein: The Antifibrotic Effects of a Necroptosis Antagonist.

The pseudokinase mixed-lineage kinase domain-like protein plays a crucial role in programmed cell death via necroptosis. We developed a novel mixed-lineage kinase domain-like inhibitor, P28, which demonstrated potent necroptosis inhibition and antifibrotic effects. P28 treatment directly inhibited mixed-lineage kinase domain-like phosphorylation and oligomerization after necroptosis induction, inhibited immune cell death after necroptosis, and reduced the expression of adhesion molecules.

Multimodal Imaging Probe Development for Pancreatic β Cells: From Fluorescence to PET.

Pancreatic β cells are responsible for insulin secretion and are important for glucose regulation in a healthy body and diabetic disease patient without prelabeling of islets. While the conventional biomarkers for diabetes have been glucose and insulin concentrations in the blood, the direct determination of the pancreatic β cell mass would provide critical information for the disease status and progression. By combining fluorination and diversity-oriented fluorescence library strategy, we have developed a multimodal pancreatic β cell probe for both fluorescence and for PET (positron emission tomography).

Visualizing biofilm by targeting eDNA with long wavelength probe CDr15.

Detection of the biofilm of bacteria would be a counter strategy to detect hidden bacteria in their camouflage. Through unbiased screening of bacteria biofilm, we discovered a long wavelength probe CDr15 with extracellular DNA as the molecular target. CDr15 revealed a real-time geometric distribution of eDNA in a 3D bacterial colony.

Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate.

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging.

Development of a Universal Fluorescent Probe for Gram-Positive Bacteria.

The rapid and sensitive classification of bacteria is the first step of bacterial community research and the treatment of infection. Herein, a fluorescent probe BacGO is presented, which shows the best universal selectivity for Gram-positive bacteria among known probes with a minimum staining procedure for sample detection and enrichment of the live bacteria. BacGO could also be used to assess of the Gram status in the bacterial community from wastewater sludge.

Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target.

Activated macrophages have the potential to be ideal targets for imaging inflammation. However, probe selectivity over non-activated macrophages and probe delivery to target tissue have been challenging. Here, we report a small molecule probe specific for activated macrophages, called CDg16, and demonstrate its application to visualizing inflammatory atherosclerotic plaques in vivo.

CDy14: a novel biofilm probe targeting exopolysaccharide Psl.

Detection of biofilm bacteria would be an ideal method for the physicians to diagnose chronic bacterial infections directly, but there are few imaging probes available so far. Here, we report the development of a novel biofilm detecting fluorescent probe, CDy14, through an unbiased screening of a fluorescence library and elucidated its binding partner Psl, an exopolysaccharide of the biofilm.

A palette of background-free tame fluorescent probes for intracellular multi-color labelling in live cells.

A multi-color labelling technique for visualizing multiple intracellular apparatuses in their native environment using small fluorescent probes remains challenging. This approach requires both orthogonal and biocompatible coupling reactions in heterogeneous biological systems with minimum fluorescence background noise. Here, we present a palette of BODIPY probes containing azide and cyclooctyne moieties for copper-free click chemistry in living cells.

Effects of an applied voltage on direct interspecies electron transfer via conductive materials for methane production.

Direct interspecies electron transfer (DIET) between exoelectrogenic bacteria and methanogenic archaea via conductive materials is reported as an efficient method to produce methane in anaerobic organic waste digestion. A voltage can be applied to the conductive materials to accelerate the DIET between two groups of microorganisms to produce methane. To evaluate this hypothesis, two sets of anaerobic serum bottles with and without applied voltage were used with a pair of graphite rods as conductive materials to facilitate DIET.

Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes.

The identification of brown adipose deposits in adults has led to significant interest in targeting this metabolically active tissue for treatment of obesity and diabetes. Improved methods for the direct measurement of heat production as the signature function of brown adipocytes (BAs), particularly at the single cell level, would be of substantial benefit to these ongoing efforts. Here, we report the first application of a small molecule-type thermosensitive fluorescent dye, ERthermAC, to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes.

Specific Triazine Herbicides Induce Amyloid-β42 Production.

Proteolytic cleavage of the amyloid-β protein precursor (AβPP) by secretases leads to extracellular release of amyloid-β (Aβ) peptides. Increased production of Aβ42 over Aβ40 and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifying products of the 'human chemical exposome' (HCE) able to induce Aβ42 production may be a key to understanding some of the initiating causes of AD and to generate non-genetic, chemically-induced AD animal models.

Development of background-free tame fluorescent probes for intracellular live cell imaging.

Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky.

Enrichment of specific electro-active microorganisms and enhancement of methane production by adding granular activated carbon in anaerobic reactors.

Direct interspecies electron transfer (DIET) via conductive materials can provide significant benefits to anaerobic methane formation in terms of production amount and rate. Although granular activated carbon (GAC) demonstrated its applicability in facilitating DIET in methanogenesis, DIET in continuous flow anaerobic reactors has not been verified. Here, evidences of DIET via GAC were explored.

The development of a nucleus staining fluorescent probe for dynamic mitosis imaging in live cells.

A low-toxicity nucleus staining fluorescent probe, , was developed for real time mitosis imaging in live cells. was identified by unbiased high-throughput imaging-based screening of a new xanthone library (AX). Unlike the conventional Hoechst dye, the low toxicity of allows long term monitoring of cell division over more than one cell cycle.

Membrane distillation combined with an anaerobic moving bed biofilm reactor for treating municipal wastewater.

A fermentative strategy with an anaerobic moving bed biofilm reactor (AMBBR) was used for the treatment of domestic wastewater. The feasibility of using a membrane separation technique for post-treatment of anaerobic bio-effluent was evaluated with emphasis on employing a membrane distillation (MD). Three different hydrophobic 0.

Effects of volatile solid concentration and mixing ratio on hydrogen production by co-digesting molasses wastewater and sewage sludge.

Co-digesting molasses wastewater and sewage sludge was evaluated for hydrogen production by response surface methodology (RSM). Batch experiments in accordance with various dilution ratios (40- to 5-fold) and waste mixing composition ratios (100:0, 80:20, 60:40, 40:60, 20:80, and 0:100, on a volume basis) were conducted. Volatile solid (VS) concentration strongly affected the hydrogen production rate and yield compared with the waste mixing ratio.

Membrane fouling control using a rotary disk in a submerged anaerobic membrane sponge bioreactor.

Despite significant research efforts over the last few decades, membrane fouling in anaerobic membrane bioreactors (AnMBRs) remains an unsolved problem that increases the overall operational costs and obstructs the industrial applications. Herein, we developed a method for effectively controlling the membrane fouling in a sponge-submerged AnMBRs using an anaerobic rotary disk MBR (ARMBR). The disk rotation led the effective collision between the sponge and membrane surface; thus successfully enhanced the membrane permeability in the ARMBR.

Two-stage biogas production by co-digesting molasses wastewater and sewage sludge.

We evaluated the feasibility of co-digesting molasses wastewater and sewage sludge in a two-stage hydrogen- and methane-producing system. The highest energy was recovered at the 21-h hydraulic retention time (HRT) of the first hydrogenic reactor and at 56-h HRT of the secondary methanogenic reactor. Hence, the two-stage system recovered 1,822 kJ from 1 L of the mixed wastes (19.

Removal of pharmaceutical residue in municipal wastewater by DAF (dissolved air flotation)-MBR (membrane bioreactor) and ozone oxidation.

Growing attention is given to pharmaceutical residue in the water environment. It is known that pharmaceuticals are able to survive from a series of wastewater treatment processes. Concerns regarding pharmaceutical residues are attributed to the fact that they are being detected in water and sediment environment ubiquitously.

Characteristics of flux and gel layer on microfilter and non-woven fabric filter surface based on anoxic-aerobic MBRs.

Non-woven fabric filter- (NWFF) and microfilter-MBR modules were made using 100 μm polypropylene and 0.25 μm polyethylene materials, respectively. The performances and mechanisms of the two processes were investigated, including additional batch filtration tests to find the function of the dynamic gel layer on the membrane surface.

Effects of pH and carbon sources on biohydrogen production by co-culture of Clostridium butyricum and Rhodobacter sphaeroides.

To improve the hydrogen yield from biological fermentation of organic wastewater, a co-culture system of dark- and photo-fermentation bacteria was investigated. In a pureculture system of the dark-fermentation bacterium Clostridium butyricum, a pH of 6.25 was found to be optimal, resulting in a hydrogen production rate of 18.