Effectiveness of the Korean-Patient Placement Criteria for Alcohol Use Disorders: A Prospective Exploratory Study.

OBJECTIVE: Various patient placement criteria (PPC) have been developed to address alcohol use disorder (AUD), which has a high relapse rate and imposes substantial socioeconomic costs. Although research has shown PPC to be an effective tool, evidence supporting the Korean-PPC (K-PPC) is insufficient. This paper investigated whether treatment matching with the K-PPC was effective, based on variables related to AUD. METHODS: In total, 524 participants were evaluated using the 6 dimensions of the K-PPC and levels of care (LoC) were recommended based on the results. Participants whose treatment matched with the recommended LoC were classified into the matched group, and those whose treatment did not match were classified into the mismatched group. Subsequently, treatment was planned according to the determined LoC, and a total of 3 follow-up evaluations were conducted at 1 month, 3 months, and 6 months. RESULTS: There was no significant difference in the follow-up rate between the K-PPC matched group and the mismatched group. Of the variables measured by the 6 dimensions of the K-PPC, alcohol-related variables, depression, insight, and biomedical outcomes showed the most significant results (especially alcohol-related variables) from the baseline evaluation to the 6-month follow-up. In addition, the average adherence to the treatment program in the 6-month period was found to be higher in the matched group than in the mismatched group. CONCLUSION: The K-PPC could be effective for placing patients and providing treatment by matching patient characteristics. Enhancing treatment program retention can also have a positive effect on clinical outcomes.

Novel Inhibitor of Keap1-Nrf2 Protein-Protein Interaction Attenuates Osteoclastogenesis In Vitro and Prevents OVX-Induced Bone Loss In Vivo.

Keap1 interacts with Nrf2 by assisting in its ubiquitination and subsequent proteolysis. By preventing ROS accumulation during RANKL-induced osteoclastogenesis, Nrf2 activation can prevent the differentiation of osteoclasts. Additionally, inhibiting the Keap1-Nrf2 PPI can be an effective strategy for triggering Nrf2 to regulate oxidative stress. Structure-based virtual screening was performed to discover a potentially novel Keap1-Nrf2 PPI inhibitor wherein KCB-F06 was identified. The inhibitory effects of KCB-F06 on osteoclastogenesis were investigated in vitro through TRAP staining and bone resorption assays. An ovariectomy-induced osteoporosis mouse model was applied to evaluate KCB-F06's therapeutic effects in vivo. Lastly, the underlying mechanisms were explored using real-time PCR, Western blotting, and co-IP assays. KCB-F06 was discovered as a novel Keap1-Nrf2 PPI inhibitor. As a result, the expression of antioxidants (HO-1 and NQO1) was suppressed, hence reducing ROS accumulation during osteoclastogenesis. Subsequently, this caused the inactivation of RANKL-induced IKB/NF-kB signaling. This eventually led to the downregulation of osteoclast-specific proteins including NFATc1, which is an essential transcription factor for osteoclastogenesis. These results demonstrated that Nrf2 activation in osteoclasts is a valuable tool for osteoclastic bone loss management. In addition, KCB-F06 presents as an alternative candidate for treating osteoclast-related bone diseases and as a novel small molecule that can serve as a model for further Keap1-NRF2 PPI inhibitor development.

Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored intracellular calcium dynamics using calcium imaging techniques to measure spontaneous calcium oscillations in hPSC-CMs in the presence or absence of test compounds. For the cardiotoxicity test, hPSC-CMs were treated with various compounds, and calcium flux was measured to evaluate their effects on calcium dynamics. We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. Additionally, in the effectiveness test, hPSC-CMs were exposed to ATX-II, a sodium current inducer for mimicking long QT syndrome type 3, followed by exposure to test compounds. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics.

Discovery of TCP-(MP)-caffeic acid analogs as a new class of agents for treatment of osteoclastic bone loss.

Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1. Additionally, we elucidated a mechanism that 11a and its precursor that 11e directly bind to LSD1/CoREST complex through FAD to inhibit LSD1 demethylation activity and influence its downstream IκB/NF-κB signaling pathway, and thus regulate osteoclastic bone loss. These findings suggested 11a or 11e as potential novel candidates for treating osteoclastic bone loss, and a concept for further development of TCP-(MP)-Caffeic acid analogs for therapeutic use in osteoporosis clinics.

Influence of sleep stages on determining positional dependency in patients with obstructive sleep apnea.

Objective: Supine sleep position and rapid eye movement (REM) stage are widely known to aggravate the severity of obstructive sleep apnea (OSA). In general, position-dependent OSA is defined as an apnea-hypopnea index (AHI) at least twice as high in the supine position as in other sleep positions, but it can be misdiagnosed if a certain sleep stage, REM or NREM, is dominant in a specific sleep position. In this study, we investigated the influences of the sleep stages on positional dependency. Methods: The polysomnographic data from 111 OSA patients aged ≥ 18 years (AHI > five events/hour) who slept in both supine and non-supine positions (each ≥ 5% of the total sleep time) were retrospectively analyzed. The overall ratio of non-supine AHI/supine AHI (NS/S AHI ratio) during the entire sleep was compared between specific sleep stages, i.e., REM or NREM sleep. Additionally, the weighted NS/S AHI ratio reflecting the proportion of each sleep time was created and compared with the original NS/S AHI ratio. Results: The mean value of the NS/S AHI ratio did not differ between the entire sleep and the specific sleep stages. However, those ratios in the individual patients showed poor agreement of the NS/S AHI ratios between the entire sleep and the specific sleep stages. The weighted NS/S AHI ratio also demonstrated poor agreement with the original NS/S AHI ratio, mainly due to the discrepancy in mild to moderate OSA patients. Conclusion: The weighted NS/S AHI ratio might help assess precise positional dependency.

Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

PURPOSE: This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. METHODS: The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. RESULTS: The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. CONCLUSION: The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Improving the Electroluminescence Properties of New Chrysene Derivatives with High Color Purity for Deep-Blue OLEDs.

Two blue-emitting materials, 4-(12-([1,1':3',1″-terphenyl]-5'-yl)chrysen-6-yl)-N,N-diphenylaniline (TPA-C-TP) and 6-([1,1':3',1″-terphenyl]-5'-yl)-12-(4-(1,2,2-triphenylvinyl)phenyl)chrysene (TPE-C-TP), were prepared with the composition of a chrysene core moiety and terphenyl (TP), triphenyl amine (TPA), and tetraphenylethylene (TPE) moieties as side groups. The maximum photoluminescence (PL) emission wavelengths of TPA-C-TP and TPE-C-TP were 435 and 369 nm in the solution state and 444 and 471 nm in the film state. TPA-C-TP effectively prevented intermolecular packing through the introduction of TPA, a bulky aromatic amine group, and it showed an excellent photoluminescence quantum yield (PLQY) of 86% in the film state. TPE-C-TP exhibited aggregation-induced emission; the PLQY increased dramatically from 0.1% to 78% from the solution state to the film state. The two synthesized materials had excellent thermal stability, with a high decomposition temperature exceeding 460 °C. The two compounds were used as emitting layers in a non-doped device. The TPA-C-TP device achieved excellent electroluminescence (EL) performance, with Commission Internationale de L'Eclairage co-ordinates of (0.15, 0.07) and an external quantum efficiency of 4.13%, corresponding to an EL peak wavelength of 439 nm.

A Methodological Approach for Motor Selection in Dental Impression Material Dispensers Using Experimental and Image Analysis Techniques.

This study presents a methodology to prevent the overdesign of electric dispensers for dental impression materials by analyzing the necessary load and determining the appropriate pressurization speed and drive motor capacity. We derived an equation to calculate the required torque and rotational speed of the motor based on the extrusion load and the speed of the impression material. A specialized load measurement system was developed to measure the load necessary to extrude the impression material. Through experiments and image processing, we measured the radius of curvature of the trajectory of the impression material and correlated it with the pressurization speed. Techniques such as position coordinate plotting, curve fitting, and circle fitting were employed to determine the pressurization speed that aligns with the manufacturer's recommended curvature radius. These findings led to a substantial decrease in the necessary motor torque and rotational speed compared with the current standards. This research provides a systematic approach to sizing drive motors using extrusion load and pressurization speed, aiming to reduce overdesign, power consumption, and the weight and size of the motor and battery, thereby contributing to the development of more efficient and compact dental impression material dispensers.

Enhancement of Optical and Chemical Resistance Properties with a Novel Yellow Quinophthalone Derivative for Image Sensor Colorants.

A novel quinophthalone derivative, 4,5,6,7-tetrachloro-2-(2-(3-hydroxy-1-oxo-1H-cyclopenta[b]naphthalen-2-yl)quinolin-4-yl)isoindoline-1,3-dione (TCHCQ), was designed and synthesized as a yellow colorant additive for green color filters in image sensors. The characteristics of the new material were evaluated in terms of optical, thermal, and chemical properties under solution and color filter film conditions. TCHCQ exhibited a significantly enhanced molar extinction coefficient in solution, being 1.21 times higher than that of the commercially used yellow colorant Y138. It also demonstrated excellent thermal stability, with a decomposition temperature (Td) exceeding 450 °C. Utilizing the nano-pigmentation process, TCHCQ was used to prepare nano-sized particles with an excellent average size of 35 nm. This enabled the fabrication of a color filter film with outstanding properties. The optical properties of the produced film revealed outstanding yellow colorant transmittance of 0.97% at 435 nm and 91.2% at 530 nm. The color filter film exhibited similar optical and thermal stability to Y138, with an improved chemical stability, as evidenced by a ΔEab value of 0.52. The newly synthesized TCHCQ is considered a promising candidate for use as a yellow colorant additive in image sensor color filters, demonstrating superior optical, thermal, and chemical stability.

Enhancing OLED emitter efficiency through increased rigidity.

Three new blue materials, TPI-InCz, PAI-InCz, and CN-PAI-InCz, have been developed. In the film state, TPI-InCz and PAI-InCz exhibited emission peaks at 411 and 431 nm indicating deep blue emission. CN-PAI-InCz showed a peak emission at 452 nm, within the real blue region. When these three materials were used as the emissive layer to fabricate non-doped devices, CN-PAI-InCz showed the highest current efficiency of 2.91 cd A-1, power efficiency of 1.93 lm W-1, and external quantum efficiency of 3.31%. Among the synthesized materials, CN-PAI-InCz exhibited superior charge balance due to the introduction of CN groups, as confirmed by hole-only devices and electron-only devices. PAI-InCz demonstrated fast hole mobility with a value of 1.50 × 10-3 cm2 V-1 s-1, attributed to its planar and highly rigid structure. In the resulting devices, the Commission Internationale de l'Eclairage coordinates for TPI-InCz, PAI-InCz, and CN-PAI-InCz were (0.162, 0.048), (0.0161, 0.067), and (0.155, 0.099), all indicating emission in the blue region.

Understanding the Electron Beam Resilience of Two-Dimensional Conjugated Metal-Organic Frameworks.

Knowledge of the atomic structure of layer-stacked two-dimensional conjugated metal-organic frameworks (2D c-MOFs) is an essential prerequisite for establishing their structure-property correlation. For this, atomic resolution imaging is often the method of choice. In this paper, we gain a better understanding of the main properties contributing to the electron beam resilience and the achievable resolution in the high-resolution TEM images of 2D c-MOFs, which include chemical composition, density, and conductivity of the c-MOF structures. As a result, sub-angstrom resolution of 0.95 Å has been achieved for the most stable 2D c-MOF of the considered structures, Cu3(BHT) (BHT = benzenehexathiol), at an accelerating voltage of 80 kV in a spherical and chromatic aberration-corrected TEM. Complex damage mechanisms induced in Cu3(BHT) by the elastic interactions with the e-beam have been explained using detailed ab initio molecular dynamics calculations. Experimental and calculated knock-on damage thresholds are in good agreement.

Recent Progress on Quantum Dot Patterning Technologies for Commercialization of QD-LEDs: Current Status, Future Prospects, and Exploratory Approaches.

Colloidal quantum dots (QDs) are widely regarded as advanced emissive materials with significant potential for display applications owing to their excellent optical properties such as high color purity, near-unity photoluminescence quantum yield, and size-tunable emission color. Building upon these attractive attributes, QDs have successfully garnered attention in the display market as down-conversion luminophores and now venturing into the realm of self-emissive displays, exemplified by QD light-emitting diodes (QD-LEDs). However, despite these advancements, there remains a relatively limited body of research on QD patterning technologies, which are crucial prerequisites for the successful commercialization of QD-LEDs. Thus, in this review, an overview of the current status and prospects of QD patterning technologies to accelerate the commercialization of QD-LEDs is provided. Within this review, a comprehensive investigation of three prevailing patterning methods: optical lithography, transfer printing, and inkjet printing are conducted. Furthermore, several exploratory QD patterning techniques that offer distinct advantages are introduced. This study not only paves the way for successful commercialization but also extends the potential application of QD-LEDs into uncharted frontiers.

Predicting Receiver Characteristics without Sensors in an LC-LC Tuned Wireless Power Transfer System Using Machine Learning.

Improvement of wireless power transfer (WPT) systems is necessary to tackle issues of power transfer efficiency, high costs due to sensor and communication requirements between the transmitter (Tx) and receiver (Rx), and maintenance problems. Analytical techniques and hardware-based synchronization research for Rx-sensorless WPT may not always have been available or accurate. To address these limitations, researchers have recently employed machine learning (ML) to improve efficiency and accuracy. The objective of this work was to replace Tx-Rx communication with ML, utilizing Tx-side parameters to predict the load and coupling coefficients on an LC-LC tuned WPT system. Based on current and voltage features collected on the Tx-side for various load and coupling coefficient values, we developed two models for each load and coupling prediction. This study demonstrated that the extra trees regressor effectively predicted the characteristics of LC-LC tuned WPT systems, with coefficients of determination of 0.967 and 0.996 for load and coupling, respectively. Additionally, the mean absolute percentage errors were 0.11% and 0.017%.

Ultralow-Overpotential Acidic Oxygen Evolution Reaction Over Bismuth Telluride-Carbon Nanotube Heterostructure with Organic Framework.

The state-of-the-art iridium and ruthenium oxides-based materials are best known for high efficiency and stability in acidic oxygen evolution reaction (OER). However, the development of economically feasible catalysts for water-splitting technologies is challenging by the requirements of low overpotential, high stability, and resistance of catalysts to dissolution during the acidic oxygen evolution reaction . Herein, an organometallic core-shell heterostructure composed of a carbon nanotube core (CNT) and bismuth telluride (Bi2Te3) shell (denoted as nC-Bi2Te3) is designed and use it as a catalyst for the acidic OER. The proposed catalyst achieves an ultralow overpotential of 160 mV at 10 mA cm-2 (geometrical), thereby outperforming most of the state-of-the-art precious-metal-based catalysts. The low Tafel slope of 30 mV dec-1 and charge transfer resistance (RCT) of 1.5 Ω demonstrate its excellent electrocatalytic activity. The morphological and chemical compositions of nC-Bi2Te3 enable the generation of ─OH functional group in the Bi─Te sections formed via a ligand support, which enhances the absorption capacity of H+ ions and increases the intrinsic catalytic activity. The presented insights regarding the material composition-structure relationship can help expand the application scope of high-performance catalysts.

Cross-Referencing Self-Training Network for Sound Event Detection in Audio Mixtures.

Sound event detection is an important facet of audio tagging that aims to identify sounds of interest and define both the sound category and time boundaries for each sound event in a continuous recording. With advances in deep neural networks, there has been tremendous improvement in the performance of sound event detection systems, although at the expense of costly data collection and labeling efforts. In fact, current state-of-the-art methods employ supervised training methods that leverage large amounts of data samples and corresponding labels in order to facilitate identification of sound category and time stamps of events. As an alternative, the current study proposes a semi-supervised method for generating pseudo-labels from unsupervised data using a student-teacher scheme that balances self-training and cross-training. Additionally, this paper explores post-processing which extracts sound intervals from network prediction, for further improvement in sound event detection performance. The proposed approach is evaluated on sound event detection task for the DCASE2020 challenge. The results of these methods on both "validation" and "public evaluation" sets of DESED database show significant improvement compared to the state-of-the art systems in semi-supervised learning.

A High-Efficiency Deep Blue Emitter for OLEDs with a New Dual-Core Structure Incorporating ETL Characteristics.

In this study, we introduced the weak electron-accepting oxazole derivative 4,5-diphenyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazole (TPO) into both anthracene and pyrene moieties of a dual core structure. Ultimately, we developed 2-(4-(6-(anthracen-9-yl)pyren-1-yl)phenyl)-4,5-diphenyloxazole (AP-TPO) as the substitution on the second core, pyrene, and 4,5-diphenyl-2-(4-(10-(pyren-1-yl)anthracen-9-yl)phenyl)oxazole (TPO-AP) as the substitution on the first core, anthracene. Both materials exhibited maximum photoluminescence wavelengths at 433 and 443 nm in solution and emitted deep blue light with high photoluminescence quantum yields of 82% and 88%, respectively. When used as the emitting layer in non-doped devices, TPO-AP outperformed AP-TPO, achieving a current efficiency of 5.49 cd/A and an external quantum efficiency of 4.26% in electroluminescence. These materials introduce a new category of deep blue emitters in the organic light-emitting diodes field, combining characteristics related to the electron transport layer.

Reduced GSH Acts as a Metabolic Cue of OPDA Signaling in Coregulating Photosynthesis and Defense Activation under Stress.

12-oxo-phytodienoic acid (OPDA) is a primary precursor of jasmonates, able to trigger autonomous signaling cascades that activate and fine-tune plant defense responses, as well as growth and development. However, its mechanism of actions remains largely elusive. Here we describe a dual-function messenger of OPDA signaling, reduced glutathione (GSH), that cross-regulates photosynthesis machinery and stress protection/adaptation in concert, optimizing plant plasticity and survival potential. Under stress conditions, the rapid induction of OPDA production stimulates GSH accumulation in the chloroplasts, and in turn leads to protein S-glutathionylation in modulating the structure and function of redox-sensitive enzymes such as 2-cysteine (Cys) peroxiredoxin A (2CPA), a recycler in the water-water cycle. GSH exchanges thiol-disulfides with the resolving CysR175, while donating an electron (e-, H+) to the peroxidatic CysP53, of 2CPA, which revives its reductase activity and fosters peroxide detoxification in photosynthesis. The electron flow protects photosynthetic processes (decreased total non-photochemical quenching, NPQ(T)) and maintains its efficiency (increased photosystem II quantum yield, ΦII). On the other hand, GSH also prompts retrograde signaling from the chloroplasts to the nucleus in adjusting OPDA-responsive gene expressions such as Glutathione S-Transferase 6 (GST6) and GST8, and actuating defense responses against various ecological constraints such as salinity, excess oxidants and light, as well as mechanical wounding. We thus propose that OPDA regulates a unique metabolic switch that interfaces light and defense signaling, where it links cellular and environmental cues to a multitude of plant physiological, e.g., growth, development, recovery, and acclimation, processes.

Tailoring the Size and Shape of ZnO Nanoparticles for Enhanced Performance of OLED Device.

We synthesized zinc oxide nanoparticles (ZnO NPs) by meticulously controlling both temperature and reaction times, allowing us to fine-tune their crystalline properties, morphology, and particle dimensions. This analysis confirmed the existence of a mixture of rod and sphere shapes (ZnO-I), including rod-shaped NPs with an average size of 14.8 nm × 5.2 nm and spherical NPs with an average diameter of 5.27 nm. We subsequently incorporated these synthesized ZnO NPs into organic light-emitting diode (OLED) devices for red, green, and blue colors, utilizing them as the electron injection layer through a solution-based process. The green OLED device using ZnO-I exhibited a promising current efficiency of 4.02 cd/A and an external quantum efficiency of 1.47%.

RD29A and RD29B rearrange genetic and epigenetic markers in priming systemic defense responses against drought and salinity.

Drought has become the most important limiting factor to crop productions. Research thus far has been devoted to identifying drought-responsive genes (DRGs) via breeding and engineering approaches. Still, these efforts have not resulted in a solution to combat drought's effects because the ectopic expression of most DRGs causes adverse effects that reduce plant growth and yields. Lately, we discovered that two DRGs, Response to Desiccation (RD)29A and RD29B, induced by Paenibacillus polymyxa CR1, a plant growth-promoting rhizobacterium capable of priming drought tolerance and concurrently stimulating plant growth, play pivotal roles in defense responses against drought. In this study, we employ the ChlP and qRT-PCR analyses and further clarify that P. polymyxa CR1 reformats the chromatin/transcriptional memory of RD29s, positioned as upstream controllers that fine-tune the temporal dynamic of stress-regulating transcription factors (TFs) in elaborating induced systemic drought tolerance without growth penalties. Two genes coordinate the upregulation of NAC TFs, while feedback inhibiting CBF TFs, which regulate downstream DRG expressions. This supports that RD29s are unique, feasible transgene candidates for improving plants' survival capacity in both optimal and drought conditions. However, the mode of action of RD29A and RD29B are partly independent, exerting distinct roles in disparate ecological states. When subjected to increasing NaCl concentrations, the KO mutant of RD29A (rd29a) displayed enhanced tolerance compared to WT and rd29b plants, proposing that RD29B, but not RD29A, a key player in conferring WT-like tolerance to salinity stress; further studies will be needed to optimize/maximize their applications in engineering for-profit drought and/or broad-spectrum stress tolerant crops.

Synthesis and evaluation of 2-NMPA derivatives as potential agents for prevention of osteoporosis in vitro and in vivo.

Abnormal osteoclast differentiation causes various bone disorders such as osteoporosis. Targeting the formation and activation of osteoclasts has been recognized as an effective approach for preventing osteoporosis. Herein, we synthesized eleven 2-NMPA derivatives which are (2-(2-chlorophenoxy)-N-(4-alkoxy-2-morpholinophenyl) acetamides, and evaluated their suppression effects on osteoclastogenesis in vitro by using TRAP-staining assay. Among the synthesized eleven novel 2-NMPAs, 4-(2-(2-chlorophenoxy)acetamido)-3-morpholinophenyl trifluoromethanesulfonate (11b), 4-(2-(2-chlorophenoxy) acetamido)-3-morpholinophenyl-3-(N-(2-oxo-2-((2-(phenylthio) phenyl) amino) ethyl)methylsulfonamido)benzoate (11d), and 4-(2-(2-chlorophenoxy) acetamido)-3-morpholinophenyl 4-acetamidobenzenesulfonate (11h) displayed highly inhibitory bioactivity on the differentiation of primary osteoclasts. 11h was selected for further investigation of the inhibitory effects and potential mechanism involved in the suppression of osteoclastogenesis. In vitro analysis suggested that 11h inhibited osteoclastogenesis with an IC50 of 358.29 nM, decreased the formation of F-action belts and bone resorption, without interfering cell viability and osteoblast differentiation. Furthermore, the mRNA expressions of osteoclast-specific genes such as Acp5, Nfatc1, Dc-stamp, Atp6v0d2, Mmp9, and Ctsk significantly decreased following 11h treatment. RANKL-induced osteoclast-specific proteins analysis demonstrated that 11h suppressed osteoclast differentiation by downregulating of RANKL-mediated TRAF6 expression, followed by inactivation of PI3K/AKT and IκBα/NF-κB signaling pathways. Finally, 11h inhibited ovariectomy-induced bone loss in vivo. Therefore, the current work highlighted the therapeutic potential of 11h as an anti-osteoporosis lead compound.