Aromatic Ethers Induced Electronic Structure Reconstruction on Encapsulated Nickel Catalysts for High-Performance Catalytic Hydrogenation.

Carbon-encapsulated metal (CEM) catalysts effectively address supported metal catalyst instability by protecting the active metal with a shell. However, mass transfer limitations lead to reduced activity for catalytic hydrogenation reaction over most CEM catalysts. Herein, we introduce a dopant strategy aimed at incorporating nickel metal within graphene-like shells (GLS) featuring oxygen-containing functional groups (OFGs). The core of this strategy involves precise control of GLS modification and the demonstrated pivotal influence of aromatic ether linkages (═C-O-C) in GLS for significant enhancement of catalytic performance. The introduction of ═C-O-C into GLS with stability was beneficial to improve the work function of the catalyst and promoted electron transmission from Ni metal core to GLS, further elevating the catalytic activity, based on the Mott-Schottky effect. In addition, the experimental characterization and density functional theory (DFT) calculations showcased that the ═C-O-C reconstructed the electronic state of GLS, imparting it highly specific for the adsorption of hydrogen and para-chloronitrobenzene (p-CNB) to obtain para-chloroaniline (p-CAN) with high selectivity. This work manifested a feasible direction for the precise modulation and design of the OFGs in CEM catalysts to achieve highly efficient catalytic hydrogenation.

Tenascin-C modulates alveolarization in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by retarded alveolarization. Tenascin-C (TN-C), an extracellular matrix glycoprotein and soluble molecule, is involved in tissue morphogenesis. In the present study, we demonstrated that the level of TN-C in lung tissues was greater in a mouse model of BPD induced by 85% oxygen. TN-C deficiency, however, impaired alveolarization in the hyperoxia-induced BPD model. In contrast, a functional TN-C blocking antibody ameliorated alveolar dysplasia in BPD-like mice. Mechanistically, hyperoxia increased the soluble TN-C (sTN-C) released from respiratory epithelial cells. On one hand, low-dose sTN-C promoted lung epithelial cell proliferation and migration, which was mediated by ICAM-1. On the other hand, high-dose sTN-C hindered the proliferation and migration of epithelial cells. Overall, this study revealed that TN-C plays a dual role in lung alveolarization and that TN-C may be a target in BPD therapy.

Iron-Based Catalysts with Oxygen Vacancies Obtained by Facile Pyrolysis for Selective Hydrogenation of Nitrobenzene.

The development of preparation strategies for iron-based catalysts with prominent catalytic activity, stability, and cost effectiveness is greatly significant for the field of catalytic hydrogenation but still remains challenging. Herein, a method for the preparation of iron-based catalysts by the simple pyrolysis of organometallic coordination polymers is described. The catalyst Fe@C-2 with sufficient oxygen vacancies obtained in specific coordination environment exhibited superior nitro hydrogenation performance, acid resistance, and reaction stability. Through solvent effect experiments, toxicity experiments, TPSR, and DFT calculations, it was determined that the superior activity of the catalyst was derived from the contribution of sufficient oxygen vacancies to hydrogen activation and the good adsorption ability of FeO on substrate molecules.

Magnetic resonance-guided focused ultrasound for essential tremor: a prospective, single center, single-arm study.

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

Resting-state functional magnetic resonance imaging study comparing tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease.

PURPOSE: The symptom-specific intrinsic neural mechanisms underlying Parkinson's disease (PD) subtypes (tremor dominant [TD] and postural instability gait difficulty [PIGD]) remain unclarified. We examined spontaneous brain activity patterns in TD and PIGD. MATERIAL AND METHODS: We included 49 patients with PD (21 with TD/28 with PIGD) and 32 healthy controls (HCs) in this study. We conducted analysis of variance and post-hoc analyses of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of the three groups, with age, sex, and gray matter volume as covariates, and a relationship analysis of the ALFF and ReHo values with clinical variables. RESULTS: In comparison with HCs, PIGD PD patients had increased ALFF values in the right middle occipital gyrus and left superior occipital gyrus and decreased values primarily in the bilateral inferior frontal gyrus (triangular part). TD PD patients had lower ALFF values in the right inferior frontal gyrus (triangular part) and left insula. In comparison to TD PD patients, PIGD PD patients had higher ALFF values in the left middle occipital gyrus and left superior occipital gyrus. In contrast to HCs, TD PD patients demonstrated a reduction of ReHo values in the left middle temporal gyrus, and PIGD patients showed a decrease of ReHo values in the left inferior temporal gyrus. CONCLUSION: ALFF values increased in the occipital gyrus of the PIGD PD patients, thus providing evidence of a compensatory mechanism of altered motor function in comparison with the TD PD patients.

Iodine-Catalyzed Borylation of Benzylic Alcohols.

Direct borylation of benzylic alcohols has been achieved via an iodine-catalyzed process. This transition-metal-free borylation transformation is compatible with various functional groups and provides a practical and convenient method to access important and useful benzylic boronate esters from widely available benzylic alcohols. Preliminary mechanistic investigations indicated that benzylic iodide and radicals are involved as the key intermediates in this borylation reaction.

Inhibition of hippocampal cyclin-dependent kinase 5 activity ameliorates learning and memory dysfunction in a mouse model of bronchopulmonary dysplasia.

AIMS: Oxygen therapy plays a vital role in the development of bronchopulmonary dysplasia (BPD), which is the independent risk factor for neurodevelopment deficits in premature infants. However, the effect of hippocampal cyclin-dependent kinase 5 (CDK5) on BPD-associated neurodevelopment deficits is not fully understood. METHODS: Mice were placed in a hyperoxia chamber from postnatal Day 1 to Day 7. Hematoxylin and eosin staining was used to evaluate the lung histomorphological characteristics. Learning and memory functions of mice were detected by Morris water maze. TUNEL staining was applied to measure the number of apoptotic cells. The expression of CDK5, apoptosis-related protein, and neuroplasticity-related proteins were analyzed by Western blot. Golgi staining was used to assess the structure of dendritic spines. RESULTS: Hyperoxia-induced BPD mice showed a long-term learning and memory dysfunction, more severe neuronal apoptosis, and a decline of synaptic plasticity. Inhibition of CDK5 overactivation ameliorated cognitive deficits, neuronal apoptosis, and synaptic plasticity disorders in BPD mice. CONCLUSIONS: This study first found a vital role of CDK5 in BPD-associated neurodevelopmental disorders. Inhibition of CDK5 overexpression could effectively improve cognitive dysfunctions in BPD mice, which indicated that hippocampal CDK5 may be a new target for prevention and treatment in learning and memory dysfunction of BPD.

The epidemic of thyroid cancer in China: Current trends and future prediction.

Background: Thyroid cancer (TC) is one of the most common cancers in China. The aim of this study was to identify the potential age, period, and cohort effect under the long-term trends in TC incidence and mortality, making projections up to 2030. Methods: Incidence and mortality data on TC were obtained from the Global Burden of Disease Study 2019. The population predictions were obtained from the United Nations World Population Prospects 2019. An age-period-cohort model was used for the analysis. Results: From 1990 to 2019, the net drift (the overall annual percentage change of TC over time adjusted for age groups) of the TC incidence was 5.01% (95% confidence interval [CI]: 4.72%, 5.29%) for men and 1.48% (95% CI: 1.14%, 1.82%) for women. The net drift of TC mortality was 1.64% (95% CI: 1.38%, 1.91%) for men and -2.51% (95% CI: -2.77%, -2.26%) for women. Regarding the incidence of TC, both the period and the cohort relative risks (RRs) in men and women showed an overall increasing trend. As to the mortality rate of TC, both the period and cohort RRs in women showed a monotonic declining trend. The period RRs for men decreased after 2015, but the cohort RRs revealed a fluctuating upward pattern. From 2019 to 2030, the TC incidence was projected to rise by 32.4% in men and 13.1% in women, the mortality declining by 13.0% in men and 17.3% in women. The elderly was projected to have an increasing proportion of TC occurrence and deaths. Conclusions: Over the past 30 years, the incidence rate of TC in China has continually increased, and this trend was projected to continue. Although male mortality has increased in the past, it is expected to decline in the future. The proportion of older people among TC occurrence and death was projected to gradually increase, and the difficulties elderly with TC lrequire more attention.

Comparison of Motor Scores between OFF and ON States in Tremor-Dominant Parkinson's Disease after MRgFUS Treatment.

Objective: To compare the motor function improvements in ON and OFF states in tremor-dominant Parkinson's disease (TDPD) patients within one year of follow-up after ablation of the unilateral ventral intermediate nucleus of the thalamus (Vim) by magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS). Methods: A total of nine consecutive patients confirmed with TDPD who underwent unilateral Vim ablation by MRgFUS between April 2019 and September 2019 were included. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRSIII) and Clinical Rating Scale for Tremor (CRST) were performed in the ON and OFF stages to distinguish the surgical effects from drug therapy effects. The adverse events and adjustment of drug doses were also recorded. Results: The preoperative MDS-UPDRSIII score in OFF and ON states was 55.0 (48.0, 65.5) and 26.0 (17.0, 27.0), while the CRST score was 46.0 (39.5, 53.5) and 20.0 (13.0, 23.5), respectively; the Levodopa equivalent dose was 600 (456, 600) mg/d. At 1 year after operation, the total MDS-UPDRSIII score and CRST score were 40.0 (30.0, 60.5) and 16.0 (10.0, 29.5) in the OFF state, and 21.0 (17.5, 27.0) and 2.0 (1.5, 7.0) in the ON state, respectively. Compared with the preoperative levels, follow-up at the two-time points (three months and one year after operation) showed the total MDS-UPDRSIII score, as well as MDS-UPDRSIII tremor, bradykinesia, and rigidity scores of contralateral limbs all significantly improved in OFF state. However, in the ON state, only the total MDS-UPDRSIII score and tremor score of contralateral limbs significantly improved. The total CRST score and the CRST (A + B) score of contralateral limbs significantly improved at three months and one year after the operation compared with before the operation in both ON and OFF states. The Levodopa equivalent dose at one and three months were not significantly different from the preoperative dose (p > 0.05). No serious adverse responses were observed. Conclusion: Treating TDPD with unilateral Vim ablation by MRgFUS could improve the symptoms of limb tremor and the other core symptoms, such as bradykinesia and rigidity, as well as some non-motor symptoms and the symptoms of ipsilateral limbs.

Water quality profits by the submerged macrophyte community consisting of multi-functional species-rich groups.

The re-establishment of submerged macrophytes facilitates the formation of a clear-water state in shallow eutrophic lakes. But most restorations of submerged macrophytes are often unstable and cannot maintain a stable clear-water state, probably because the species and functional diversity have not been fully taken into account. In this study, we try to explore submerged macrophyte communities and water quality changes under different submerged macrophyte combinations through mesocosm experiments. We hypothesized that communities with high species and functional diversity would be more conducive to improving water quality. The results showed that the mean community biomass of single-species and 8-species were higher than 5-species. And the stability and mean relative growth rate of the 8-species community were higher than the 5-species community. With the same configuration of three functional groups, the 8-species community was more stable and had better water quality than the 5-species community. The path analysis revealed that different functional groups of submerged macrophytes play different roles. The erect and canopy-producing submerged macrophytes were conducive to reducing total suspended solids (TSS) concentrations in the water column during community construction. In contrast, bottom-dwelling submerged macrophytes were conducive to reducing total nitrogen, total phosphorus, and TSS concentrations during the stage of disturbances. Our results also suggested that canopy-producing groups may have a competitive advantage for light over bottom-dwelling species. Based on the above results and biodiversity insurance hypothesis, we conclude that the community consisting of multi-functional species-rich groups is conducive to building stable submerged macrophyte communities and obtaining a stable clear-water state. Our findings will improve water quality management and pollution control for eutrophic shallow lakes.

A Multi-Scale Simulation Study of Irradiation Swelling of Silicon Carbide.

Silicon carbide (SiC) is a promising structural and cladding material for accident tolerant fuel cladding of nuclear reactor due to its excellent properties. However, when exposed to severe environments (e.g., during neutron irradiation), lattice defects are created in amounts significantly greater than normal concentrations. Then, a series of radiation damage behaviors (e.g., radiation swelling) appear. Accurate understanding of radiation damage of nuclear materials is the key to the design of new fuel cladding materials. Multi-scale computational simulations are often required to understand the physical mechanism of radiation damage. In this work, the effect of neutron irradiation on the volume swelling of cubic-SiC film with 0.3 mm was studied by using the combination of molecular dynamics (MD) and rate theory (RT). It was found that for C-vacancy (CV), C-interstitial (CI), Si-vacancy (SiV), Si-interstitial (SiI), and Si-antisite (SiC), the volume of supercell increases linearly with the increase of concentration of these defects, while the volume of supercell decreases linearly with the increase of defect concentration for C-antisite (CSi). Furthermore, according to the neutron spectrum of a certain reactor, one RT model was constructed to simulate the evolution of point defect under neutron irradiation. Then, the relationship between the volume swelling and the dose of neutrons can be obtained through the results of MD and RT. It was found that swelling typically increases logarithmically with radiation dose and saturates at relatively low doses, and that the critical dose for abrupt transition of volume is consistent with the available experimental data, which indicates that the rate theory model can effectively describe the radiation damage evolution process of SiC. This work not only presents a systematic study on the relationship between various point defect and excess volume, but also gives a good example of multi-scale modelling through coupling the results of binary collision, MD and RT methods, etc., regardless of the multi-scale modelling only focus on the evolution of primary point defects.

Objective quantification of the severity of postural tremor based on kinematic parameters: A multi-sensory fusion study.

BACKGROUND: Current clinical assessments of essential tremor (ET) are primarily based on expert consultation combined with reviewing patient complaints, physician expertise, and diagnostic experience. Thus, traditional evaluation methods often lead to biased diagnostic results. There is a clinical demand for a method that can objectively quantify the severity of the patient's disease. METHODS: This study aims to develop an artificial intelligence-aided diagnosis method based on multi-sensory fusion wearables. The experiment relies on a rigorous clinical trial paradigm to collect multi-modal fusion of signals from 98 ET patients. At the same time, three clinicians scored independently, and the consensus score obtained was used as the ground truth for the machine learning models. RESULTS: Sixty kinematic parameters were extracted from the signals recorded by the nine-axis inertial measurement unit (IMU). The results showed that most of the features obtained by IMU could effectively characterize the severity of the tremors. The accuracy of the optimal model for three tasks classifying five severity levels was 97.71%, 97.54%, and 97.72%, respectively. CONCLUSIONS: This paper reports the first attempt to combine multiple feature selection and machine learning algorithms for fine-grained automatic quantification of postural tremor in ET patients. The promising results showed the potential of the proposed approach to quantify the severity of ET objectively.

Enhanced Thermal Transport Properties of Graphene/SiC Heterostructures on Nuclear Reactor Cladding Material: A Molecular Dynamics Insight.

Owing to the excellent thermal properties of graphene, silicon carbide (SiC) combined with graphene is expected to obtain more outstanding thermal performance and structural stability at high temperatures. Herein, the thermal conductivity of graphene/SiC heterostructures (GS-Hs) with different structures and atomic orientations was calculated through non-equilibrium molecular dynamics (NEMD) simulations. The temperature dependence and size effect on the thermal transport properties of GS-Hs were systematically investigated and discussed. The continuous addition of graphene layers did not always have a positive effect. The thermal transport performance of GS-Hs approached the intrinsic thermal conductivity of SiC when the interaction gradually decreased with the distance between SiC and graphene. Studies on temperature and size dependence show opposite trends. The enhancement effect of graphene was limited at small distances. The thermal conductivity of GS-Hs had a negative correlation with temperature and increased with the system size. Meanwhile, the thermal conductivity of GS-Hs was predicted to be 156.25 (W·m-1·K-1) at the macroscopic scale via extrapolation. The model established in this paper is also applicable to other material simulation processes, as long as the corresponding parameters and potential functions are available. This study will provide inspiration for the optimized design and preparation of highly efficient cladding materials in nuclear reactors.

The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common challenge in preterm neonates. Retardation of alveolar development characterizes the pulmonary pathology in BPD. In the present study, we explored the roles of the CD146-HIF-1α axis in BPD. We demonstrated that the levels of reactive oxygen species (ROS) and soluble CD146 (sCD1146) were increased in the peripheral blood of preterm neonates with BPD. In alveolar epithelial cells, hyperoxia promoted the expression of HIF-1α and CD146, which reinforced each other. In a mouse model of BPD, by exposing pups to 65% hyperoxia, HIF-1α and CD146 were increased in the pulmonary tissues. Mechanistically, CD146 hindered the migration of alveolar epithelial cells; in contrast, movement was significantly enhanced in CD146-knockout alveolar epithelial cells. As expected, CD146-knockout ameliorated alveolarization and improved BPD disease severity. Taken together, our findings imply that the CD146-HIF-1α axis contributes to alveolarization and that CD146 may be a novel candidate in BPD therapy.

Unreactive C-N Bond Activation of Anilines via Photoinduced Aerobic Borylation.

Unreactive C-N bond activation of anilines was achieved by photoinduced aerobic borylation. A diverse range of tertiary and secondary anilines were converted to aryl boronate esters in moderate to good yields with wide functional group tolerance under simple and ambient photochemical conditions. This transformation achieved the direct and facile C-N bond activation of unreactive anilines, providing a convenient and practical route transforming widely available anilines into useful aryl boronate esters.

Relationship between multimorbidity, disease cluster and all-cause mortality among older adults: a retrospective cohort analysis.

BACKGROUND: Previous studies have evaluated the association of multimorbidity with higher mortality, but epidemiologic data on the association between the disease clusters and all-cause mortality risk are rare. We aimed to examine the relationship between multimorbidity (number/ cluster) and all-cause mortality in Chinese older adults. METHODS: We conducted a population-based study of 50,100 Chinese participants. Multiple logistic regression analysis was used to estimate the impact of long-term conditions (LTCs) on all-cause mortality. RESULTS: The prevalence of multimorbidity was 31.35% and all-cause mortality was 8.01% (50,100 participants). In adjusted models, the odds ratios (ORs) and 95% confidence intervals (CIs) of all-cause mortality risk for those with 1, 2, and ≥ 3 LTCs compared with those with no LTCs was 1.45 (1.32-1.59), 1.72 (1.55-1.90), and 2.15 (1.85-2.50), respectively (Ptrend < 0.001). In the LTCs ≥2 category, the cluster of chronic diseases that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher among the ≥75 age group with an increasing number of LTCs. However, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those < 75 years. CONCLUSIONS: The risk of all-cause mortality is increased with the number of multimorbidity among Chinese older adults, particularly disease clusters.

Association of body mass index and waist circumference with high blood pressure in older adults.

BACKGROUND: The relationship between obesity and prevalent high blood pressure in older adults has predominantly been estimated using categorical measures of body mass index (BMI) and waist circumference (WC), masking the shape of the dose-response relationship. We aimed to examine the precise relationship of BMI, WC with high blood pressure and to assess the appropriate level of BMI and WC for high blood pressure. METHODS: We examined data for 126,123 individuals in Xinzheng city aged ≥60 years from a population based study from January to December 2019. Logistic regression and restricted cubic spline models were applied to assess the relationship and the appropriate level of BMI and WC for high blood pressure. An additive interaction analysis was used to test synergistic effects between a higher BMI and WC for high blood pressure. RESULTS: The full-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of an increase of 1 kg/m2 in BMI and 1 cm in WC for high blood pressure were 1.084 (1.080-1.087) and 1.026(1.024-1.027), respectively. Multivariable adjusted restricted cubic spline analyses showed the nonlinear relationships of BMI and WC with high blood pressure in both men and women (all P < 0.001). The risk of high blood pressure increased steeply with increasing BMI from ≥25 kg/m2 and WC ≥ 88 cm or 86 cm for males and females, respectively. And we observed a significant additive interaction between a higher BMI and WC such that the prevalence of high blood pressure was significantly enhanced. CONCLUSION: These findings suggest increased high blood pressure prevalence in the older adults with increased BMI and WC. BMI ≤ 25 kg/m2 and WC ≤ 88 cm or 86 cm for males and females may be the best suggestion with regard to primary prevention of high blood pressure in older adults.

Association of changes in waist circumference with cardiovascular disease and all-cause mortality among the elderly Chinese population: a retrospective cohort study.

BACKGROUND: To examine the association of baseline waist circumference (WC) and changes in WC with cardiovascular disease (CVD) and all-cause mortality among elderly people. METHODS: A total of 30,041 eligible participants were included from a retrospective cohort in China. The same questionnaire, anthropometric and laboratory measurements were performed at baseline (2010) and the first follow-up (2013). The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC. We collected the occurrence of CVD and all-cause death from the first follow-up to December 31, 2018. Restricted cubic splines and Cox proportional-hazards regression models were used to evaluate the relationship between baseline WC/ changes in WC and mortality. RESULTS: The dose-response relationships between baseline WC and CVD mortality were U- or J-shaped. In low WC group, compared with stable group, the fully adjusted hazard ratio (aHR) for CVD mortality was 1.60 (95% CI: 1.24-2.06) in WC gain group among men. In normal WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.86, 95% CI: 1.36-2.56; women: aHR = 1.83, 95% CI: 1.29-2.58). In moderate-high WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.76, 95% CI: 1.08-2.88; women: aHR = 1.46, 95% CI: 1.04-2.05) and risk decreased with WC loss (men: aHR = 0.54, 95% CI: 0.30-0.98; women: aHR = 0.59, 95% CI: 0.37-0.96). CONCLUSIONS: For the elderly population, WC gain may increase CVD mortality risk regardless of baseline WC, whereas WC reduction could decrease the risk only in the moderate-high WC group.

A novel method for automatic pharmacological evaluation of sucrose preference change in depression mice.

Sucrose preference test (SPT) is a most frequently applied method for measuring anhedonia, a core symptom of depression, in rodents. However, the method of SPT still remains problematic mainly due to the primitive, irregular, and inaccurate various types of home-made equipment in laboratories, causing imprecise, inconsistent, and variable results. To overcome this issue, we devised a novel method for automatic detection of anhedonia in mice using an electronic apparatus with its program for automated detecting the behavior of drinking of mice instead of manual weighing the water bottles. In this system, the liquid surface of the bottles was monitored electronically by infrared monitoring elements which were assembled beside the plane of the water surface and the information of times and duration of each drinking was collected to the principal machine. A corresponding computer program was written and installed in a computer connected to the principal machine for outputting and analyzing the data. This new method, based on the automated system, was sensitive, reliable, and adaptable for evaluation of stress- or drug-induced anhedonia, as well as taste preference and effects of addictive drugs. Extensive application of this automated apparatus for SPT would greatly improve and standardize the behavioral assessment method of anhedonia, being instrumental in novel antidepressant screening and depression researching.

Neuronal Nitric Oxide Synthase in Nucleus Accumbens Specifically Mediates Susceptibility to Social Defeat Stress through Cyclin-Dependent Kinase 5.

Stress-induced depression is common worldwide. NAc, a "reward" center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5.SIGNIFICANCE STATEMENT Stress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.