Electron Localization in Rationally Designed Pt1Pd Single-Atom Alloy Catalyst Enables High-Performance Li-O2 Batteries.

Li-O2 batteries (LOBs) are considered as one of the most promising energy storage devices due to their ultrahigh theoretical energy density, yet they face the critical issues of sluggish cathode redox kinetics during the discharge and charge processes. Here we report a direct synthetic strategy to fabricate a single-atom alloy catalyst in which single-atom Pt is precisely dispersed in ultrathin Pd hexagonal nanoplates (Pt1Pd). The LOB with the Pt1Pd cathode demonstrates an ultralow overpotential of 0.69 V at 0.5 A g-1 and negligible activity loss over 600 h. Density functional theory calculations show that Pt1Pd can promote the activation of the O2/Li2O2 redox couple due to the electron localization caused by the single Pt atom, thereby lowering the energy barriers for the oxygen reduction and oxygen evolution reactions. Our strategy for designing single-atom alloy cathodic catalysts can address the sluggish oxygen redox kinetics in LOBs and other energy storage/conversion devices.

Surface reconstruction of pyrite-type transition metal sulfides during oxygen evolution reaction.

Reconstruction universally occurs over non-layered transition metal sulfides (TMSs) during oxygen evolution reaction (OER), leading to the formation of active species metal (oxy)hydroxide and thus significantly influences the OER performance. However, the reconstruction process and underlying mechanism quantitatively remain largely unexplored. Herein, we proposed an electrochemical reaction mechanism, namely sulfide oxidation reaction (SOR), to elucidate the reconstruction process of pyrite-type TMSs. Based on this mechanism, we evaluated the reconstruction capability of NiS2 doped with transition metals V, Cr, Mn, Fe, Co, Cu, Mo, Ru, Rh, and Ir within different doped systems. Two key descriptors were thus proposed to describe the reconstruction abilities of TMSs: USOR (the theoretical electric potential of SOR) and ΔU (the difference between the theoretical electric potential of SOR and OER), representing the initiation electric potential of reconstruction and the intrinsic reconstruction abilities of TMSs, respectively. Our finding shows that a lower USOR readily initiate reconstruction at a lower potential and a larger ΔU indicating a poorer reconstruction ability of the catalyst during OER. Furthermore, Fe-doped CoS2 was used to validate the rationality of our proposed descriptors, being consistent with the experiment findings. Our work provides a new perspective on understanding the reconstruction mechanism and quantifying the reconstruction of TMSs.

Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

Restoration of CPEB4 prevents muscle stem cell senescence during aging.

Age-associated impairments in adult stem cell functions correlate with a decline in somatic tissue regeneration capacity. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we provide a proteomic analysis of physiologically aged murine muscle stem cells (MuSCs), illustrating a pre-senescent proteomic signature. During aging, the mitochondrial proteome and activity are impaired in MuSCs. In addition, the inhibition of mitochondrial function results in cellular senescence. We identified an RNA-binding protein, CPEB4, downregulated in various aged tissues, which is required for MuSC functions. CPEB4 regulates the mitochondrial proteome and activity through mitochondrial translational control. MuSCs devoid of CPEB4 induced cellular senescence. Importantly, restoring CPEB4 expression rescued impaired mitochondrial metabolism, improved geriatric MuSC functions, and prevented cellular senescence in various human cell lines. Our findings provide the basis for the possibility that CPEB4 regulates mitochondrial metabolism to govern cellular senescence, with an implication of therapeutic intervention for age-related senescence.

ATAC-seq protocol for the profiling of chromatin accessibility of in situ fixed quiescent and activated muscle stem cells.

Chromatin accessibility is critical for cell identity. Conventional ATAC-seq can examine chromatin accessibility on freshly prepared muscle stem cells or satellite cells (SCs); however, isolating SCs in mice remains challenging. Here, we present a protocol to preserve the in vivo chromatin profile of SCs by applying paraformaldehyde (PFA) perfusion throughout the mouse before SC isolation. We describe steps for PFA perfusion and FACS sorting of SCs. We then detail library preparation for ATAC-seq. For complete details on the use and execution of this protocol, please refer to Dong et al.1.

A new kinematic dataset of lower limbs action for balance testing.

Balance is a common performance but nevertheless an essential part of performance analysis investigations in ski. Many skier pay attention to the training of balance ability in training. Inertial Measurement Unit, as a kind of Multiplex-type human motion capture system, is widely used because of its humanized human-computer interaction design, low energy consumption and more freedom provided by the environment. The purpose of this research is to use sensor to establish a kinematics dataset of balance test tasks extracted from skis to help quantify skier' balance ability. Perception Neuron Studio motion capture device is used in present. The dataset contains a total of 20 participants' data (half male) of the motion and sensor data, which is collected at a 100 Hz sampling frequency. To our knowledge, this dataset is the only one that uses a BOSU ball in the balance test. We hope that this dataset will contribute to multiple fields of cross-technology integration in physical training and functional testing, including big-data analysis, sports equipment design and sports biomechanical analysis.

Interfacially Engineered Nanoporous Cu/MnOx Hybrids for Highly Efficient Electrochemical Ammonia Synthesis via Nitrate Reduction.

Electrochemical reduction of nitrate to ammonia (NH3 ) not only offers a promising strategy for green NH3 synthesis, but also addresses the environmental issues and balances the perturbed nitrogen cycle. However, current electrocatalytic nitrate reduction processes are still inefficient due to the lack of effective electrocatalysts. Here 3D nanoporous Cu/MnOx hybrids are reported as efficient and durable electrocatalysts for nitrate reduction reaction, achieving the NH3 yield rates of 5.53 and 29.3 mg h-1 mgcat. -1 with 98.2% and 86.2% Faradic efficiency in 0.1 m Na2 SO4 solution with 10 and 100 mm KNO3 , respectively, which are higher than those obtained for most of the reported catalysts under similar conditions. Both the experimental results and density functional theory calculations reveal that the interface effect between Cu/MnOx interface could reduce the free energy of rate determining step and suppress the hydrogen evolution reaction, leading to the enhanced catalytic activity and selectivity. This work provides an approach to design advanced materials for NH3 production via electrochemical nitrate reduction.

Pramipexole inhibits astrocytic NLRP3 inflammasome activation via Drd3-dependent autophagy in a mouse model of Parkinson's disease.

Inflammation is one of the pathogenic processes in Parkinson's disease (PD). Dopamine receptor agonist pramipexole (PPX) is extensively used for PD treatment in clinics. A number of studies show that PPX exerts neuroprotection on dopaminergic (DA) neurons, but the molecular mechanisms underlying the protective effects of PPX on DA neurons are not fully elucidated. In the present study, we investigated whether PPX modulated PD-related neuroinflammation and underlying mechanisms. PD model was established in mice by bilateral striatum injection of lipopolyssaccharide (LPS). The mice were administered PPX (0.5 mg·kg-1·d-1, i.p.) 3 days before LPS injection, and for 3 or 21 days after surgery, respectively, for biochemical and histological analyses. We showed that PPX administration significantly alleviated the loss of DA neurons, and suppressed the astrocyte activation and levels of proinflammatory cytokine IL-1ß in the substantia nigra of LPS-injected mice. Furthermore, PPX administration significantly decreased the expression of NLRP3 inflammasome-associated proteins, i.e., cleaved forms of caspase-1, IL-1ß, and apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) in the striatum. These results were validated in LPS+ATP-stimulated primary mouse astrocytes in vitro. Remarkably, we showed that PPX (100-400 µM) dose-dependently enhanced the autophagy activity in the astrocytes evidenced by the elevations in LC3-II and BECN1 protein expression, as well as the increase of GFP-LC3 puncta formation. The opposite effects of PPX on astrocytic NLRP3 inflammasome and autophagy were eliminated by Drd3 depletion. Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 µM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.

CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1.

Metastasis is an important factor contributing to poor prognosis in patients with gastric cancer; yet, the molecular mechanism leading to this cell behavior is still not well understood. In this study, we explored the role of cysteine protease inhibitor SN (Cystatin SN, CST1) in promoting gastric cancer metastasis. We hypothesized that CST1 could regulate gastric cancer progression by regulating GPX4 and ferroptosis. Whole transcriptome sequencing suggested that the expression of CST1 was significantly increased in metastatic cancer, and high CST1 expression was correlated with a worse prognosis. Our data further confirmed that the overexpression of CST1 may significantly promote the migration and invasion of gastric cancer cells in vitro and enhance liver, lung, and peritoneal metastasis of gastric cancer in nude mice. Meanwhile, high expression of CST1 promoted the epithelial-mesenchymal transition (EMT) of gastric cancer cells. Mechanistically, a co-immunoprecipitation experiment combined with mass spectrometry analysis confirmed that CST1 could interact with GPX4, a key protein regulating ferroptosis. CST1 relieves GPX4 ubiquitination modification by recruiting OTUB1, improving GPX4 protein stability and reducing intracellular reactive oxygen species (ROS), thereby inhibiting ferroptosis and, in turn, promoting gastric cancer metastasis. Moreover, clinical data suggested that CST1 is significantly increased in peripheral blood and ascites of gastric cancer patients with metastasis; multivariate Cox regression model analysis showed that CST1 was an independent risk factor for the prognosis of gastric cancer patients. Overall, our results elucidated a critical pathway through which high CST1 expression protects gastric cancer cells from undergoing ferroptosis, thus promoting its progression and metastasis. CST1 may be used as a new oncological marker and potential therapeutic target for gastric cancer metastasis.

ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis.

The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.

Formaldehyde Decomposition from -20 °C to Room Temperature on a Mn-Mullite YMn2O5 Catalyst.

Large ambient temperature changes (-20->25 °C) bring great challenges to the purification of the indoor pollutant formaldehyde. Within such a large ambient temperature range, we herein report a manganese-based strategy, that is, a mullite catalyst (YMn2O5) + ozone, to efficiently remove the formaldehyde pollution. At -20 °C, the formaldehyde removal efficiency reaches 62% under the condition of 60,000 mL gcat-1 h-1. As the reaction temperature is increased to -5 °C, formaldehyde and ozone are completely converted into CO2, H2O, and O2, respectively. Such a remarkable performance was ascribed to the highly reactive oxygen species generated by ozone on the YMn2O5 surface based on the low temperature-programed desorption measurements. The in situ infrared spectra showed the intermediate product carboxyl group (-COOH) to be the key species. Based on the superior performance, we built a consumable-free air purifier equipped with mullite-coated ceramics. In the simulated indoor condition (25 °C and 30% relative humidity), the equipment can effectively decompose formaldehyde (150 m3 h-1) without producing secondary pollutants, rivaling a commercial removal efficiency. This work provides an air purification route based on the mullite catalyst + ozone to remove formaldehyde in an ambient temperature range (-20->25 °C).

BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson's disease.

Background: Neuroinflammation mediated by microglia plays a key role in the pathogenesis of Parkinson's disease (PD), and our previous studies showed this was significantly inhibited by enhanced autophagy. In the autophagy pathway, Bcl2-associated athanogene (BAG)3 is a prominent co-chaperone, and we have shown BAG3 can regulate autophagy to clear the PD pathogenic protein α-synuclein. However, the connection between BAG3 and microglia mediated neuroinflammation is not clear. Methods: In this study, we explored whether BAG3 regulated related neuroinflammation and its original mechanism in PD. An inflammatory model of PD was established by injecting adeno-associated virus (AAV)-BAG3 into the bilateral striatum of C57BL/6 male mice to induce overexpression of BAG3, followed by injection of lipopolysaccharide (LPS). The striatum was extracted at 3 days after injection of LPS for Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemical staining was performed at 21 days after injection. At the same time, LPS was used to induce activation of BV2 cells to verify the effect of BAG3 in vitro. Results: Overexpression of BAG3 reduced LPS-induced pyroptosis by reducing activation of caspase-1, the NOD-like receptor family, and the pyrin domain-containing 3 (NLRP3) inflammasome, and by release of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. The LPS-induced inflammatory environment inhibits autophagy, and overexpression of BAG3 can restore autophagy, which may be the mechanism by which BAG3 reduces neuronal inflammation in PD. Conclusions: Our results demonstrate BAG3 promotes autophagy and suppresses NLRP3 inflammasome formation in PD.

Global chromatin accessibility profiling analysis reveals a chronic activation state in aged muscle stem cells.

Regulation of chromatin accessibility is critical for cell fate decisions. Chromatin structure responds to extrinsic environments rapidly. The traditional adult stem cell isolation approach requires tissue dissociation, which triggers stem cell activation and leads to alterations in chromatin structure. To preserve the in vivo chromatin states, we utilized the PFA-perfusion-based isolation approach and characterized the DNA regulatory landscapes during muscle stem cell quiescence exit and aging. We showed that aged SCs display a chronically activated chromatin signature. Detailed analysis of the chromatin accessibility profiles identified key enhancer elements for SC quiescence. Constant activation of the enhancer elements promotes stemness and prevents SCs from differentiation, whereas genetic deletion causes cell-cycle arrest and leads to defects in activation. Our comprehensive characterization of the chromatin accessibility and transcriptomic landscapes in SC quiescence and aging broadens our understanding of these processes and identifies key distal regulatory elements for SC function.

Strong Electronic Metal-Support Interaction between Iridium Single Atoms and a WO3 Support Promotes Highly Efficient and Robust CO2 Cycloaddition.

The carbon dioxide (CO2 ) cycloaddition of epoxides to cyclic carbonates is of great industrial importance owing to the high economical values of its products. Single-atom catalysts (SACs) have great potential in CO2 cycloaddition by virtue of their high atom utilization efficiency and desired activity, but they generally suffer from poor reaction stability and catalytic activity arising from the weak interaction between the active centers and the supports. In this work, Ir single atoms stably anchored on the WO3 support (Ir1 -WO3 ) are developed with a strong electronic metal-support interaction (EMSI). Superior CO2 cycloaddition is realized in the Ir1 -WO3 catalyst via the EMSI effect: 100% conversion efficiency for the CO2 cycloaddition of styrene oxide to styrene carbonate after 15 h at 40 °C and excellent stability with no degradation even after ten reaction cycles for a total of more than 150 h. Density functional theory calculations reveal that the EMSI effect results in significant charge redistribution between the Ir single atoms and the WO3 support, and consequently lowers the energy barrier associated with epoxide ring opening. This work furnishes new insights into the catalytic mechanism of CO2 cycloaddition and would guide the design of stable SACs for efficient CO2 cycloaddition reactions.

Risk Factors and Timing of Additional Surgery after Noncurative ESD for Early Gastric Cancer.

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery. Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days, n = 11), delayed surgery (>30 days, n = 11) after ESD, and upfront surgery (n = 59) were compared. Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups. Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.

Mixed Catalyst SmMn2O5/Cu-SAPO34 for NH3-Selective Catalytic Oxidation.

Low-temperature selective catalytic oxidation (SCO) is crucial for removing the NH3 slip from the upstream of NH3-selective catalytic reduction (NH3-SCR). Herein, combining zeolite Cu-SAPO34 and the active oxidant mullite SmMn2O5, we developed mixed-phase catalysts SmMn2O5/Cu-SAPO34 by grinding powder mixtures to achieve a low-temperature activity and a reasonable N2 selectivity. The physicochemical properties of the catalysts were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) measurement, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The evaluation of NH3 oxidation activity showed that for 30 wt % SmMn2O5/Cu-SAPO34, 90% NH3 conversion was at a temperature of 215 °C in the presence of 500 ppm NH3 and 21% O2 balanced with N2. The in situ DRIFTS spectra reveal the internal SCR mechanism (i-SCR), i.e., NH3 oxidizing to NO x on mullite and NO x subsequently to proceed with SCR reactions, leading to higher conversion and selectivity over the mixed catalysts. This work provides a strategy to design the compound catalyst to achieve low-temperature NH3 oxidation via synergistic utilization of the advantages of each individual catalyst.

Reliability and Validity of an Inertial Measurement System to Quantify Lower Extremity Joint Angle in Functional Movements.

The purpose of this research was to determine if the commercially available Perception Neuron motion capture system was valid and reliable in clinically relevant lower limb functional tasks. Twenty healthy participants performed two sessions on different days: gait, squat, single-leg squat, side lunge, forward lunge, and counter-movement jump. Seven IMUs and an OptiTrack system were used to record the three-dimensional joint kinematics of the lower extremity. To evaluate the performance, the multiple correlation coefficient (CMC) and the root mean square error (RMSE) of the waveforms as well as the difference and intraclass correlation coefficient (ICC) of discrete parameters were calculated. In all tasks, the CMC revealed fair to excellent waveform similarity (0.47-0.99) and the RMSE was between 3.57° and 13.14°. The difference between discrete parameters was lower than 14.54°. The repeatability analysis of waveforms showed that the CMC was between 0.54 and 0.95 and the RMSE was less than 5° in the frontal and transverse planes. The ICC of all joint angles in the IMU was general to excellent (0.57-1). Our findings showed that the IMU system might be utilized to evaluate lower extremity 3D joint kinematics in functional motions.

Promotion of Low-Temperature Oxidation of Propane through Introduction of Ce into Mullite Oxide YMn2 O5.

A high-surface-area Ce doped mullite YMn2 O5 was developed via a facile hydrothermal approach, which exhibited higher catalytic activity with a long thermal stability towards propane oxidation in regards to pristine mullite YMn2 O5 . T90 (the temperature at 90 % conversion of reactant) of propane over the mixed oxides is ∼40 °C lower than that over pristine YMn2 O5 mullite (147 m2 /g). The complete oxidation temperature occurs at as low as 225 °C (1000 ppm C3 H8 and 10 % O2 balanced with N2 , WHSV=30,000 mL/g h). Notably, the mixed oxides maintain superior catalytic stability at 250 °C for 120 h without noticeable loss in the activity. Fundamentally, the remarkable performance stems from the abundant oxygen defects caused by the lattice mismatch between CeO2 and YMn2 O5 , which is conducive to the gas phase oxygen adsorption and activation, thereby enhancing the low temperature catalytic activity of the material. In addition, the CeO2 on the catalyst's surface acts as an oxygen reservoir and provides additional adsorption sites for propane to promote the oxidation reaction. In situ DRIFTS results indicates that the dissociation of acrylate could be the key step for propane oxidation since acrylate is more difficult to decompose and desorb than formate and acetate. These findings revealed the roles of ceria on mullite oxides for propane oxidation activity.

A Quantitative Assessment Grading Study of Balance Performance Based on Lower Limb Dataset.

Balance ability is one of the important factors in measuring human physical fitness and a common index for evaluating sports performance. Its quality directly affects the coordination ability of human movements and plays an important role in human productive activities. In the field of sports, balance ability is an important indicator of athletes' selection and training. How to objectively analyze balance performance becomes a problem for every non-professional sports enthusiast. Therefore, in this paper, we used a dataset of lower limb collected by inertial sensors to extract the feature parameters, then designed a RUS Boost classifier for unbalanced data whose basic classifier was SVM model to predict three classifications of balance degree, and, finally, evaluated the performance of the new classifier by comparing it with two basic classifiers (KNN, SVM). The result showed that the new classifier could be used to evaluate the balanced ability of lower limb, and performed higher than basic ones (RUS Boost: 72%; KNN: 60%; SVM: 44%). The results meant the established classification model could be used for and quantitative assessment of balance ability in initial screening and targeted training.

Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson's disease.

Depression is one of the strongest predictors of quality of life in patients with Parkinson's disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2-/- mice but not in DRD3-/- mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future.