An Exploration of Depression and Aggression Among Patients with Schizophrenia in China Rural Community.

Purpose: In schizophrenia, aggressive conduct is frequent. And depressed mood can also contribute to the occurrence of aggressive behaviors. The aim of this study was to investigate the risk factors for the occurrence of aggression in stable schizophrenia patients in rural China, mainly to investigate the role of depressed mood in the occurrence of aggression in schizophrenia patients. Patients and Methods: This is a cross-sectional study conducted in the townships surrounding Chaohu City, Anhui Province, China. Patients' depressive mood was evaluated using the PHQ-9 (The 9-item Patient Health Questionnaire). Patients' aggressiveness was evaluated using the Modified Overt Aggression Scale (MOAS). A score of ≥4 was used as a threshold and divided into aggressive and non-aggressive groups. Results: This study comprised a total of 821 schizophrenia patients. Among them, the prevalence of having aggressive behavior was 18.8%. After correcting for confounders, logistic regression analysis showed that low education level (OR=0.470, 95% CI 0.254-0.870; p=0.016), living with family (OR=0.383, 95% CI 0.174-0.845; p=0.017) depressed mood (OR=1.147, 95% CI 1.112-1.184; p<0.001) was significantly associated with the risk of aggressive behavior in patients with schizophrenia. Multivariate linear regression indicated that higher levels of aggression were linked with lower levels of education and higher depressive mood. Conclusion: This study suggests that aggression is more common in patients with stable schizophrenia, and lower levels of education and higher levels of depression are associated risk factors for its occurrence. Living alone may be helpful in reducing the likelihood of aggression.

Deciphering and overcoming Anti-PD-1 resistance in Melanoma: A comprehensive review of Mechanisms, biomarker Developments, and therapeutic strategies.

Worldwide, tens of thousands of people die from melanoma each year, making it the most frequently fatal form of cutaneous cancer. Immunotherapeutic advancements, particularly with anti-PD-1 medications, have significantly enhanced treatment outcomes over recent decades. With the broad application of anti-PD-1 therapies, insights into the mechanisms of resistance have evolved. Despite the development of combination treatments and early predictive biomarkers, a comprehensive synthesis of these advancements is absent in the current literature. This review underscores the prevailing knowledge of anti-PD-1 resistance mechanisms and underscores the critical role of robust predictive biomarkers in stratifying patients for targeted combinations of anti-PD-1 and other conventional or innovative therapeutic approaches. Additionally, we offer insights that may shape future melanoma treatment strategies.

Insomnia and aggression in stable schizophrenic patients: The mediating role of quality of life.

Aggression in schizophrenia patients is an issue of concern. Previous studies have shown that aggression in schizophrenia patients may be related to insomnia and quality of life to different extents. This study aimed to explore the potential mediating role of quality of life in the relationship between aggression and insomnia among schizophrenia patients. Demographic factors affecting aggression in schizophrenia patients were also explored. PATIENTS AND METHODS: A total of 781 stable patients aged 18-75 who met the ICD10 diagnosis of "schizophrenia" completed the completed questionnaire. Aggression was assessed using the Modified Overt Aggression Scale (MOAS), sleep was assessed using the Insomnia Severity Index Scale (ISI), and quality of life was assessed using the five Likert options. Descriptive statistics and correlation analysis examined the correlation between aggression and other variables. The mediating role of quality of life in the association between insomnia and aggression was examined by pathway analysis. RESULTS: A total of 781 patients participated in this study, and approximately 16 % of the schizophrenia patients were aggressive. According to the mediation analysis, the direct effect of insomnia on aggression was 0.147, and the mediating effect of quality of life on insomnia and aggression was 0.021. Specifically, for the four dimensions of the MOAS, the direct effects of insomnia on verbal aggression, aggression toward property, and aggression toward oneself were 0.028, 0.032, and 0.023, respectively, with mediating effects of 0.003, 0.007, and 0.006, respectively, and no mediating effect on physical aggression was found. CONCLUSION: This study showed that insomnia significantly influenced aggression in schizophrenia patients. Quality of life significantly mediated insomnia and aggression and played a vital role in moderating aggression. Therefore, we suggest that in the future, improving aggression in schizophrenia patients, while paying attention to the importance of sleep, could start with improving quality of life to address this problem from multiple perspectives.

The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA.

Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops. In all sirtuin-deficient human stem cell lines, we found that chromatin contacts are rewired to promote aberrant activation of the placenta-specific gene PAPPA, which controls the pro-senescence effects associated with sirtuin deficiency and serves as a potential aging biomarker. Based on our survey of the 3D chromatin architecture, we established connections between sirtuins and potential target genes, thereby informing the development of strategies for aging interventions.

Assessing and mitigating foodborne acetochlor exposure induced ileum toxicity in broiler chicks: The role of omega-3 polyunsaturated fatty acids supplementation and molecular pathways analysis.

Excessive acetochlor residues present ecological and food safety challenges. Here, broiler chicks were exposed to varied acetochlor doses to first assess its effects on the gut. Subsequent dietary supplementation with omega-3 was used to assess its anti-contamination effects. Pathologically, acetochlor induced notable ileal lesions including inflammation, barrier disruption, tight junction loss, and cellular anomalies. Mechanistically, acetochlor stimulated the TNFα/TNFR1 and TLR4/NF-κB/NLRP3 pathways, promoting RIPK1/RIPK3 complex formation, MLKL phosphorylation, NLRP3 inflammasome activation, Caspase-1 activation, and GSDMD shearing with inflammatory factor release. These mechanisms elucidate ileal cell death patterns essential for understanding chicken enteritis. Omega-3 supplementation showed promise in mitigating inflammation, though its precise counteractive role remains unclear. Our findings suggest early omega-3 intervention offered protective benefits against acetochlor's adverse intestinal effects, emphasizing its potential poultry health management role. Harnessing dietary interventions' therapeutic potential will be pivotal in ensuring sustainable poultry production and food safety despite persistent environmental contaminants.

Depression severity mediates stigma and quality of life in clinically stable people with schizophrenia in rural China.

BACKGROUND: Depressive symptoms associated with schizophrenia are closely related to stigma and quality of life(QOL). There is, however, no thorough research on the connection between the three. This study sought to investigate the possible factors influencing depressive symptoms in people with schizophrenia (PWS) in rural Chaohu, China, and to further explore the role of depression severity in stigma and lifestyle quality. METHODS: Eight hundred twenty-one schizophrenia patients accomplished the entire scale, including the 9-item Patient Health Questionnaire (PHQ-9), the Social Impact Scale (SIS), and the World Health Organization on Quality of Life Brief Scale(WHOQOL-BREF). A straightforward mediation model was employed to determine if the intensity of the depression could act as a mediator between stigma and QOL. RESULTS: Two hundred seventy-nine schizophrenia patients (34%) had depressive symptoms (PHQ ≥ 10), and 542 patients (66%) did not (PHQ < 10). Logistic regression showed that marital status, job status, physical exercise, standard of living, and stigma contributed to the depressed symptoms of schizophrenia. Depression severity partially mediated the effect between stigma and QOL, with a mediating effect of 48.3%. CONCLUSIONS: This study discovered a significant incidence of depressed symptoms associated with schizophrenia, with depression severity serving as a mediator variable connecting stigma and QOL and partially moderating the association.

SdH Oscillations from the Dirac Surface State in the Fermi-Arc Antiferromagnet NdBi.

The recent progress in CuMnAs and Mn3X (X = Sn, Ge, Pt) shows that antiferromagnets (AFMs) provide a promising platform for advanced spintronics device innovations. Most recently, a switchable Fermi-arc is discovered by the ARPES technique in antiferromagnet NdBi, but the knowledge about electron-transport property and the manipulability of the magnetic structure in NdBi is still vacant to date. In this study, SdH oscillations are successfully verified from the Dirac surface states (SSs) with 2-dimensionality and nonzero Berry phase. Particularly, it is observed that the spin-flop transition only appears when the external magnetical field is applied along [001] direction, and features obvious hysteresis for the first time in NdBi, which provides a powerful handle for adjusting the spin texture in NdBi. Crucially, the DFT shows the Dirac cone and the Fermi arc strongly depend on the high-order magnetic structure of NdBi and further reveals the orbital magnetic moment of Nd plays a crucial role in fostering the peculiar SSs, leading to unveil the mystery of the band-splitting effect and to manipulate the electronic transport, high-effectively, in the thin film works in NdBi. It is believed that this study provides important guidance for the development of new antiferromagnet-based spintronics devices based on cutting-edge rare-earth monopnictides.

Trichinella spiralis-Secreted Products Promote Collagen Capsule Formation through TGF-ß1/Smad3 Pathway.

Trichinella spiralis (T. spiralis) muscle larvae colonize in the host's skeletal muscle cells, which are surrounded by collagen capsules. The mechanism underlying muscle stage larva-induced collagen capsule formation remains unknown. To clarify the mechanism, a T. spiralis muscular-infected mouse model was established by a single lateral tail vein injection with 20,000 T. spiralis newborn larvae (NBL). The infected mice were treated with or without SB525334 (TGF-ß1 receptor type I inhibitor). Diaphragms were obtained post-infection, and the expression levels of the TGF-ß1/Smad3 pathway-related genes and collagen genes (type IV and VI) were observed during the process of collagen capsule formation. The changes in myoblasts under stimulation of the excretory-secretory (ES) products of NBL with or without SB525334 were further investigated. Results showed that the expression levels of type IV collagen gene, type VI collagen gene, Tgfb1, and Smad3 were significantly increased in infected mice muscle cells. The expression levels of all the above genes were enhanced by the products of NBL in myoblast cells. These changes were reversed by co-treatment with SB525334 in vivo and in vitro. In conclusion, the TGF-ß1/Smad3 pathway can be activated by T. spiralis infection in muscle cells. The activated TGF-ß1/Smad3 pathway can stimulate the secretion of collagens by myocytes and plays a promoting role in the process of collagen capsule formation. The research has the limitation that the protein identification of the products of NBL has yet to be performed. Therefore, the specific components in the T. spiralis ES products that induce collagen synthesis should be further investigated.

Suicidality and Its Association with Stigma in Clinically Stable Patients with Schizophrenia in Rural China.

Purpose: Patients with schizophrenia not only experience more stigma than those with other mental illnesses, but they also have a higher risk of committing suicide. There are, however, few research on the connection between rural individuals with clinically stable schizophrenia and suicidality when they feel stigmatized. Therefore, the purpose of this study was to look at the suicidality in clinically stable patients with schizophrenia in rural China, including the prevalence, clinical correlates, and its relationships with stigma. Patients and Methods: From September 2022 to October 2022, we conducted a multicenter, cross-sectional study in rural Chaohu, Anhui Province, China, and A total of 821 patients with schizophrenia completed the assessment. Three standardized questions were used to assess suicidality (including suicidal ideation, suicide plan, and suicide attempt), Patient Health Questionnaire with 9 items (PHQ-9) for determining depressive state, the first two items of the World Health Organization Quality of Life Questionnaire-Brief Version (QOL), which measures quality of life, the Social Impact Scale (SIS) to assess stigma, and some other important variables (eg employment, psychiatric medication, etc.) were measured using a homemade scale. Results: Of the 821 participants who completed the questionnaire, 19.2% of the patients were found to have suicidality, of which 19.2% (158/821) were suicidal ideation, 5.6% (46/821) were suicide plans and 4.5% (37/821) were suicide attempts. Binary logistic regression analysis showed that job status (OR=0.520, p=0.047), psychiatric medication (OR=2.353, p=0.020), number of hospitalizations (OR=1.047, p=0.042), quality of life (OR=0.829, p=0.027), PHQ-9 (OR=0.209, p<0.001) stigma (OR=1.060, p<0.001) and social isolation in stigma (OR=1.134, p=0.001) were associated independently with suicidality. Conclusion: Among clinically stable schizophrenia patients in rural China, suicidality is frequent and associated with stigma. Since stigma and some risk factors have a negative impact on suicidality, we should conduct routine screening and take suicide prevention measures to clinically stable schizophrenia patients in rural areas of China.

Storage strategy of outbound containers with uncertain weight by data-driven hybrid genetic simulated annealing algorithm.

It is necessary to ensure the ship's stability in container ship stowage and loading and unloading containers. This work aims to reduce the container dumping operation at the midway port and improve the efficiency of ship transportation. Firstly, the constraint problem of the traditional container ship stacking is introduced to realize the multi-condition mathematical model of the container ship, container, and wharf. Secondly, a Hybrid Genetic and Simulated Annealing Algorithm (HGSAA) model is proposed for the container stacking and loading stacking in the yard. The specific container space allocation and multi-yard crane adjustment scheme are studied. Finally, the effectiveness of the multi-condition container ship stowage model is verified by numerical experiments by changing the number of outbound containers, storage strategies, storage yards, and bridges. The experimental results show that the HGSAA mode converges to 106.1min at the 751st iteration. Of these, the non-loading and unloading time of yard bridge 1 is 3.43min. The number of operating boxes is 25. The non-loading and unloading time of yard bridge 2 is 3.2min, and the operating box volume is 25 boxes. The objective function of the genetic algorithm converges when it iterates to generation 903 and 107.9min. Among them, the non-loading and unloading time of yard bridge 1 is 4.1min. The non-loading and unloading time of yard bridge 2 is 3.1min. Therefore, the proposed HGSAA has a faster convergence speed than the genetic algorithm and can obtain relatively good results. The proposed container stacking strategy can effectively solve the specific container allocation and multi-yard crane scheduling problems. The finding provides a reference for optimizing container scheduling and improving shipping transportation efficiency.

Effect of Transition Metal Layer on Bending and Interfacial Properties of W/TiN/Ta-Laminated Composite.

The widespread applications of W in the fusion reactor are limited by its low-temperature brittleness, recrystallization brittleness, and irradiation-induced brittleness. Many toughening methods were used to improve the brittleness of W, such as adding second-phase particles, adding W fibers, preparing laminated composite, and so on. Among these, preparing laminated W-based composites has been proven to effectively improve both the low-temperature and high-temperature toughness of W. In this study, W/M/TiN/Ta-laminated composites with transition metal layer (M) were synthesized through the spark plasma sintering (SPS) at three different temperatures. The effects of nano-scale (Ni, Ti, and Cr) and micron-scale (Ni, Ti, and V) transition layers on the bending and interfacial properties of the W/M/TiN/Ta composite were studied via an electron probe micro-analyzer (EPMA) and transmission electron microscope (TEM). Compared with W/TiN/Ta, the flexural strength and strain of W/Ninm/TiN/Ta were increased by 25.6% and 17.6%, respectively. Ni, Ti, and V micron transition layers can improve the combination of the W-TiN interface and decrease the joining temperature. The micron V layer has the best strengthening effect. The flexural strength of W/V/TiN/Ta reached 1294 MPa, much higher than W/Ta's 1041 MPa.

Wildlife trade is likely the source of SARS-CoV-2.

Multiple transmissions from wildlife at a market in Wuhan probably led to SARS-CoV-2 emergence.

PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity.

Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves over-proliferation of cyst-lining epithelial cells and excessive cystic fluid secretion. While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate-activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF-06409577, an AMPK activator for diabetic nephropathy, in cellular, ex vivo and in vivo models of ADPKD. Our results demonstrated that PF-06409577 effectively down-regulated mammalian target of rapamycin pathway-mediated proliferation of cyst-lining epithelial cells and reduced cystic fibrosis transmembrane conductance regulator-regulated cystic fluid secretion. Overall, our data suggest that PF-06409577 holds therapeutic potential for ADPKD treatment.

Two Myricetin-Derived Flavonols from Morella rubra Leaves as Potent α-Glucosidase Inhibitors and Structure-Activity Relationship Study by Computational Chemistry.

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia, and oxidative stress is an important cause and therapeutic target of DM. Phytochemicals such as flavonols are important natural antioxidants that can be used for prevention and treatment of DM. In the present study, six flavonols were precisely prepared and structurally elucidated from Morella rubra leaves, which were screened based on antioxidant assays and α-glucosidase inhibitory activities of different plant tissues. Myricetin-3-O-(2″-O-galloyl)-α-L-rhamnoside (2) and myricetin-3-O-(4″-O-galloyl)-α-L-rhamnoside (3) showed excellent α-glucosidase inhibitory effects with IC50 values of 1.32 and 1.77 µM, respectively, which were hundredfold higher than those of positive control acarbose. Molecular docking simulation illustrated that the presence of galloyl group altered the binding orientation of flavonols, where it occupied the opening of the cavity pocket of α-glucosidase along with Pi-anion interaction with Glu304 and Pi-Pi stacked with His279. Pi-conjugations generated between galloyl moiety and key residues at the active site of α-glucosidase reinforced the flavonol-enzyme binding, which might explain the greatly increased activity of compounds 2 and 3. In addition, 26 flavonols were evaluated for systematic analysis of structure-activity relationship (SAR) between flavonols and α-glucosidase inhibitory activity. By using their pIC50 (-log IC50) values, three-dimensional quantitative SAR (3D-QSAR) models were developed via comparative molecular field analysis (CoMFA) and comparative similarity index analysis (CoMSIA), both of which were validated to possess high accuracy and predictive power as indicated by the reasonable cross-validated coefficient (q 2) and non-cross-validated coefficient (r 2) values. Through analyzing 3D contour maps of both CoMFA and CoMSIA models, QSAR results were in agreement with in vitro experimental data. Therefore, such results showed that the galloyl group in compounds 2 and 3 is crucial for interacting with key residues of α-glucosidase and the established 3D-QSAR models could provide valuable information for the prediction of flavonols with great antidiabetic potential.

The Influence of Psychological Capital and Social Capital on the Entrepreneurial Performance of the New Generation of Entrepreneurs.

To enable that the new generation of entrepreneurs can effectively use their own qualities and abilities to improve the level of entrepreneurial performance, and to successfully pass through the entrepreneurial period of the enterprise and achieve longer-term development, the new generation of entrepreneurs is taken as the research object, and firstly, the definition and interaction of psychological capital and entrepreneurial performance are pointed out. Secondly, the questionnaires are designed with reference to the relevant maturity scales, and the reliability, validity analysis, correlation analysis, and multiple linear regression analysis of the collected effective questionnaires are carried out through SPSS and AMOS software. Thirdly, on this basis, it verifies the influence of psychological capital of the new generation entrepreneurs on entrepreneurial performance and the moderating effect of entrepreneurial environment perception. The results show that there is a significant positive correlation between the dimensions of psychological capital and entrepreneurial performance. Gender, age, educational background, marital status, the establishment time of enterprises, and the number of employees all have a significant impact on the psychological capital of the new generation of entrepreneurs. Among them, the psychological capital of the new generation of entrepreneurs aged 31-35 is the best, followed by aged 26-30, 21-25, and the worst is 20 years old and below, which is logical. The correlation coefficient between psychological capital and entrepreneurial performance, social capital and entrepreneurial performance shows a significant positive correlation. The research on the relationship between psychological capital, social capital, and entrepreneurial performance of new generation entrepreneurs systematically explains why some enterprises created by the new generation of entrepreneurs can achieve rapid growth and deepen the research in related fields.

Claudin-12 Deficiency Inhibits Tumor Growth by Impairing Transendothelial Migration of Myeloid-Derived Suppressor Cells.

Migration of myeloid-derived suppressor cells (MDSC) out of the circulation, across vascular walls, and into tumor is crucial for their immunosuppressive activity. A deeper understanding of critical junctional molecules and the regulatory mechanisms that mediate the extravasation of MDSCs could identify approaches to overcome cancer immunosuppression. In this study, we used mice deficient in tight junction protein Claudin-12 (Cldn12) compared with wild-type mice and found that loss of host Cldn12 inhibited the growth of transplanted tumors, reduced intratumoral accumulation of MDSCs, increased antitumor immune responses, and decreased tumor vascular density. Further studies revealed that Cldn12 expression on the cell surface of both MDSCs and endothelial cells (EC) is required for MDSCs transit across tumor vascular ECs. Importantly, expression of Cldn12 in MDSCs was modulated by GM-CSF in an AKT-dependent manner. Therefore, our results indicate that Cldn12 could serve as a promising target for restoring the antitumor response by interfering with MDSCs transendothelial migration. SIGNIFICANCE: Claudin-12-mediated homotypic interactions are critical for migration of myeloid-derived suppressor cells across vascular walls into tumor tissue, providing a potential therapeutic approach to overcome cancer immunosuppression.

Exploration on Scientific Research Data-Targeted Intelligent Recommendation System Using Machine Learning Under the Background of Sustainable Development.

The purpose is to provide researchers with reliable Scientific Research Data (SRD) from the massive amounts of research data to establish a sustainable Scientific Research (SR) environment. Specifically, the present work proposes establishing an Intelligent Recommendation System (IRS) based on Machine Learning (ML) algorithm and SRD. Firstly, the IRS is established over ML technology. Then, based on user Psychology and Collaborative Filtering (CF) recommendation algorithm, a hybrid algorithm [namely, Content-Based Recommendation-Collaborative Filtering (CBR-CF)] is established to improve the utilization efficiency of SRD and Sustainable Development (SD) of SR. Consequently, the present work designs literature and SRD-targeted IRS using the hybrid recommendation under the background of SD. The proposed system's feasibility is analyzed through experiments. Additionally, the system performance is analyzed and verified from accuracy, diversity, coverage, novelty, and recommendation efficiency. The results show that the hybrid algorithm can make up for the shortcomings of a single algorithm and improve the recommendation efficiency. Experiments show that the accuracy of the proposed CBR-CF algorithm is the highest. In particular, the recommendation accuracy for the single-user system can reach 82-93%, and the recall of all recommended algorithms falls between 60 and 91%. The recall of the hybrid algorithm is higher than that of a single algorithm, and the highest recall is 91%. Meanwhile, the hybrid algorithm has comprehensive coverage, good applicability, and diversity. Therefore, SD-oriented SRD-targeted IRS is of great significance to improve the SRD utilization and the accuracy of IRS, and expand the achievement value of SR. The research content provides a reference for establishing a sustainable SR environment and improving SR efficiency.

Synthesis of Semiconducting 2H-Phase WTe2 Nanosheets with Large Positive Magnetoresistance.

Tungsten ditelluride (WTe2) is provoking immense interest because of its unique electronic properties, but studies about its semiconducting hexagonal (2H) phase are quite rare. Herein, we report the synthesis of semiconducting 2H WTe2 nanosheets with large positive magnetoresistance, for the first time, by a simple lithium-intercalation-assisted exfoliation strategy. Systematic characterizations including high-resolution transmission electron microscopy, X-ray diffraction, and Raman and X-ray photoelectron spectroscopies provide clear evidence to distinguish the structure of 2H WTe2 nanosheets from the orthorhombic (Td) phase bulk counterpart. The corresponding electronic phase transition from metal to semiconductor is also confirmed by density of states calculation, optical absorption, and electrical transport property measurements. Besides, the 2H WTe2 nanosheets exhibit large positive magnetoresistance with values of up to 29.5% (10 K) and 16.2% (300 K) at 9 T. Overall, these findings open up a promising avenue into the exploration of WTe2-based materials in the semiconductor field.

Effect of Hydrogen-Rich Water on Radiation-Induced Cognitive Dysfunction in Rats.

The goal of this work was to determine whether hydrogen-rich water (HRW) could attenuate radiation-induced cognitive dysfunction in rats and to explore the underlying mechanisms. Rats received 30 Gy whole-brain irradiation using a 6-MeV electron beam. Either purified water or HRW (0.8-0.9 ppm) was administrated at 10 min prior to irradiation, as well as a daily HRW treatment after irradiation for 30 consecutive days. The Morris water maze was used to test spatial memory in the rats. The concentration of glutathione (GSH), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG) and the super-oxidedismutase (SOD) activity in cerebral cortex, as well as brain-derived neurotrophic factor (BDNF) level in serum, were measured. Immunofluorescence staining was adopted to detect proliferating cells. The expression of BDNF-TrkB pathway-related genes and proteins were detected using qRT-PCR and Western blot. Models of cognitive dysfunction were successfully established using a 30 Gy dose of ionizing radiation. Compared to the radiation treated group, the radiation-HRW treated group showed significantly decreased escape latency (P < 0.05), but increased retention time, swimming distance of original platform quadrant (P < 0.05) and number of platform crossings (P < 0.05). Furthermore, the SOD, GSH (P < 0.05) and BDNF (P < 0.05) levels in the radiation-HRW treated group were higher compared to the radiation treated group. The MDA and 8-OHdG levels (P < 0.05) were decreased in the radiation-HRW treated group when compared to the radiation treated group. Additionally, treatment with HRW increased the number of BrdU+NeuN+ cells in the radiation treated group. The mRNA and protein levels of BDNF and TrkB (P < 0.05) in radiation-HRW treated group was higher than that in the radiation treated group. Collectively, our study indicates that HRW has a protective effect on radiation-induced cognitive dysfunction, and that the possible mechanisms mainly involve anti-oxidative and anti-inflammatory reactions, and its protection of newborn neurons by regulating the BDNF-TrkB signaling pathway.

Long residence time adenosine A1 receptor agonists produce sustained wash-resistant antilipolytic effect in rat adipocytes.

Elevated circulating free fatty acid (FFA) level is closely linked to the pathogenesis of insulin resistance and type 2 diabetes mellitus. Activation of the adenosine A1 receptor (A1R) inhibits lipolysis in adipocytes and hence reduces the concentration of FFA, which represents a potential target for the development of antilipolytic agents. We aimed to assess the binding affinity as well as target binding kinetics of A1R agonists and further delineate a possible relationship with their antilipolytic effect in adipocytes. Radioligand binding assays were performed to determine the affinity and kinetics of three representative A1R agonists, namely CPA, LUF6944 and LUF6941, on the rat A1R. Functional responses to these agonists were examined in both a recombinant cell system and physiologically relevant rat adipocytes. The three A1R agonists displayed similar affinity while divergent target binding kinetics on the rat A1R. Irrespective of equilibrium binding affinity, temporal analysis of receptor signaling demonstrated persistent functional responses for the long residence time agonist, despite removal of excess agonist, in both a recombinant cell system and in rat adipocytes. By contrast, such effect was less pronounced or even lost for agonists with medium or short receptor residence time, respectively. Our results indicate that ligand receptor binding kinetics rather than their affinity or potency play an essential role in regulating cellular responses. The long residence time A1R agonist produces a sustained wash-resistant antilipolytic effect in rat adipocytes and thus may represent a potential antilipolytic alternative for further investigation.