[Research Progress in the Role of the Ventral Tegmental Area-Medial Prefrontal Cortex Neural Circuit in the Regulation of Arousal].

There are mutual neural projections between the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC),which form a circuit.Recent studies have shown that this circuit is vital in regulating arousal from sleep and general anesthesia.This paper introduces the anatomical structures of VTA and mPFC and the roles of various neurons and projection pathways in the regulation of arousal,aiming to provide new ideas for further research on the mechanism of arousal from sleep and general anesthesia.

ß-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.

Serological positive markers of hepatitis B virus in femoral venous blood or umbilical cord blood should not be evidence of in-utero infection among neonates.

BACKGROUND: Maternal-infant transmission of hepatitis B virus(HBV) occurs even after passive-active immunization. Some scholars speculate that in-utero infection may be the main cause of immunoprophylaxis failure. However, there is a lack of evidence about the possible occurrence periods of perinatal transmission. METHODS: From 2008 to 2012, 428 pairs of HBsAg-positive mothers and neonates were enrolled and 385 infants aged 8-12 months were followed. HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, HBV-DNA) were performed on all subjects. RESULTS: Of mothers who were positive for HBsAg, HBeAg, HBV-DNA, 35.1 %, 94.3 %, 12.7 % of their neonates were positive for those indices, respectively. Neonates' mean titers of those indices were significantly lower than their mothers'. There were no significant differences in rates of positivity and mean titers of anti-HBe and anti-HBc between neonates and mothers. Most of the positive indices turned negative during the follow-up period. Immunoprophylaxis failed in seventeen infants: four infants had HBV-DNA > 6 log 10copies/mL both at birth and in follow-up; in six infants, mean viral load was 3.72 ± 0.17 log 10copies/mLat birth and 7.62 ± 0.14 log 10copies/mL at follow-up; seven infants were HBV-DNA negative at birth but were found to have > 6 log 10copies/mL during follow-up. Infants that were immunoprophylaxis failures were all born to HBeAg-positive mothers with HBV-DNA > 6 log 10copies/mL. CONCLUSIONS: The placental barrier can partly prevent maternal HBsAg, HBeAg, HBV-DNA from passing through to fetus. Performing HBsAg, HBeAg, HBV-DNA once at birth can neither diagnose nor exclude maternal-infant transmission. The diagnosis of infection period depends on the dynamic changes in viral load from birth through the follow-up period but whether the infection occurred in utero, at delivery or during the neonatal period could not be determined.

Molecular docking and MD simulation studies of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as novel inhibitors targeted to CDK2/4/6.

PURPOSE: Nowadays, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for treating metastatic breast cancer and have achieved inspiring curative effects. But some discoveries have indicated that CDK 4/6 are not the requisite factors in some cell types because CDK2 partly compensates for the inhibition of CDK4/6. Thus, it is urgent to design CDK2/4/6 inhibitors for significantly enhancing their potency. This study aims to explore the mechanism of the binding of CDK2/4/6 kinases and their inhibitors to design novel CDK2/4/6 inhibitors for significantly enhancing their potency in different kinds of cancers. MATERIALS AND METHODS: A series of 72 disparately functionalized 4-substituted N-phenylpyrimidin-2-amine derivatives exhibiting potent inhibitor activities against CDK2, CDK4 and CDK6 were collected to apply to this research. The total set of these derivatives was divided into a training set (54 compounds) and a test set (18 compounds). The derivatives were constructed through the sketch molecule module in SYBYL 6.9 software. A Powell gradient algorithm and Tripos force field were used to calculate the minimal structural energy and the minimized structure was used as the initial conformation for molecular docking. By the means of 3D-QSAR models, partial least squares (PLS) analysis, molecular dynamics (MD) simulations and binding free energy calculations, we can find the relationship between structure and biological activity. RESULTS: In this study, we used molecular docking, 3D-QSAR and molecular dynamics simulation methods to comprehensively analyze the interaction and structure-activity relationships of 72 new CDK2/4/6 inhibitors. We used detailed statistical data to reasonably verify the constructed 3D-QSAR models for three receptors (q2 of CDK2 = 0.714, R2pred = 0.764, q2 = 0.815; R2pred of CDK4 = 0.681, q2 = 0.757; R2pred of CDK6 = 0.674). MD simulations and decomposition energy analysis validated the reasonability of the docking results and identified polar interactions as crucial factors that influence the different bioactivities of the studied inhibitors of CDK2/4/6 receptors, especially the electrostatic interactions of Lys33/35/43 and Asp145/158/163. The nonpolar interaction with Ile10/12/19 was also critical for the differing potencies of the CDK2/4/6 inhibitors. We concluded that the following probably enhanced the bioactivity against CDK2/4/6 kinases: (1) electronegative groups at the N1-position and electropositive and moderate-sized groups at ring E; (2) electrogroups featured at R2; (3) carbon atoms at the X-position or ring C replaced by a benzene ring; and (4) an electrogroup as R4. CONCLUSION: Previous studies, to our knowledge, only utilized a single approach of 3D-QSAR and did not integrate this method with other sophisticated techniques such as molecular dynamics simulations to discover new potential inhibitors of CDK2, CDK4, or CDK6. So we applied the intergenerational technology, such as 3D-QSAR technology, molecular docking simulation techniques, molecular dynamics simulations and MMPBSA19/MMGBSA20-binding free energy calculations to statistically explore the correlations between the structure with biological activities. The constructed 3D-QSAR models of the three receptors were reasonable and confirmed by the excellent statistical data. We hope the results obtained from this work will provide some useful references for the development of novel CDK2/4/6 inhibitors.

The effect of different times of day for exercise on blood glucose fluctuations.

AIMS: This study aims to explore blood glucose variations before and after short-term intensive exercise in the morning or afternoon of a day and the trend of blood glucose fluctuations during exercise in patients with T2DM (type 2 diabetes, T2DM). METHODS: Blood glucose variations of Fouty during morning exercise 8:00-12:00 hours and twenty during afternoon exercise 14:30-18:30 hours). Patients with T2DM discharged from the hospital were analyzed retrospectively, with the baseline data checked through the medical record system before intervention. We were asked to perform seven times of treadmill aerobic exercise, which lasted for 30 minutes with incremental intensity for each time, for two weeks under the supervision of the Continuous Glucose Monitor (CGM) and the heart rate armband. The exercise intensity has been adjusted by the clinicians and specialist nurses from the Department of Diabetes Mellitus according to the blood glucose levels and heart rate curves during exercise; data including the height, weight, body mass index (BMI), waist-to-hip ratio, fasting blood glucose, glycosylated hemoglobin, in-exercise CGM-measured blood glucose value/min, and after-exercise fingertip blood glucose value of patients with T2DM were collected after the intensive exercise (2 weeks). SPSS 22.0 and GraphPad Prism 7 were adopted for statistical analysis using the T-test and ANOVA. RESULT: No difference was observed in the baseline data between the morning and afternoon exercise groups before intervention; compared to the morning exercise group, the fasting C-peptide value (2.15±0.97 vs. 1.53±0.46) in the afternoon exercise group was higher than that in the morning exercise group, with a superior (p=0.029) effect after two weeks of intervention, exhibiting a significant difference in the results. According to the results of repeated variance ANOVA analysis, the time for the appearance of significant improvement in blood glucose in the afternoon exercise group was 5 minutes earlier (11th minute vs 1 minute)than that in the morning exercise group (15th minute vs 1 min); significant differences were observed in both time (p=0.048 vs p<0.01) between the two groups on exercise days, as revealed by the results of bivariate ANOVA; in comparison to the morning exercise group (7.42±1.68), there was a significant difference (p=0.049)in the mean blood glucose between the two groups 25 min after patients with T2DM in the afternoon exercise group (6.25±1.53) started to exercise; in addition, a significant statistical difference (p=0.021) was revealed in the CGM-measured hourly the mean blood glucose on exercise days between the morning(8.18±1.88) and afternoon exercise (6.75±1.40)groups at 4:00 pm in week one and two w. CONCLUSIONS: Glycaemic improvement in the short-term intensive afternoon exercise group may be superior to that of the morning exercise group, which may be related to greater fasting C-peptide secretion and longer effective exercise duration. The time to exercise is a factor affecting blood glucose variations during exercise. However, significant variations in the level of blood glucose during exercise must be further observed through exercise intervention over a more extended period.

Nurses' and nursing students' knowledge and attitudes to pressure injury prevention: A meta-analysis based on APUP and PUKAT.

BACKGROUND: Morbidity and mortality among patients due to pressure injuries continue to rise. Nurses play a critical role in preventing pressure injuries. However, published results on nurses' knowledge and attitudes for pressure injury prevention are often contradictory. OBJECTIVES: To conduct a meta-analysis of nurses' and nursing students' knowledge and attitudes toward pressure injury prevention. DESIGN: A meta-analysis of cross-sectional studies. DATA SOURCES: Ten databases were queried for the meta-analysis. The search period was from the time of the databases' establishment to February 2023. REVIEW METHODS: This review followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The Agency for Healthcare Research and Quality (AHRQ) was used to assess the methodological quality of the included studies. Statistical analysis was conducted with the Stata 15.0 software, and the quantitative data of knowledge and attitude toward preventing PI in all studies were summarized. RESULTS: Thirteen studies from 9 countries were included. The meta-analysis showed that nurses and nursing students had low knowledge but positive attitudes toward pressure injury prevention. Subgroup analysis showed that the pooled proportion of both knowledge and attitudes was higher in Asia than in Europe. Nurses had higher knowledge than nursing students, however, the former had a more negative attitude than the latter. Sensitivity analyses were robust. Egger's test showed no significant publication bias. CONCLUSION: The knowledge of nurses and nursing students about pressure injury prevention is not promising and there is an urgent need for continuous learning. Attitudes are more positive but there is room for improvement. The relevant departments should strengthen nurses' and nursing students' knowledge of pressure injury prevention and further improve their attitudes toward pressure injury prevention.

Fortunella venosa (Champ. ex Benth.) C. C. Huang and F. hindsii (Champ. ex Benth.) Swingle as Independent Species: Evidence From Morphology and Molecular Systematics and Taxonomic Revision of Fortunella (Rutaceae).

Recently, the systematic status of Fortunella Swingle and its taxonomy has attracted much attention. Flora of China incorporates Fortunella into Citrus Linn. and treats all species of the traditional Fortunella as one species, namely Citrus japonica (Thunb.) Swingle. Furthermore, F. venosa (Champ. ex Benth.) C. C. Huang and F. hindsii (Champ. ex Benth.) Swingle are currently considered as synonyms of C. japonica. In this paper, morphological, palynological, and phylogenetic analyses were used to systematically explore the taxonomic status of traditional Fortunella. The key morphological features that differed among the Fortunella species were the leaf and the petiole hence could be key in its taxonomic classification of the species. Additionally, pollen morphological analysis based on the pollen size, germination grooves, polar, and equatorial axes also supported the separation of the species. The results of the phylogenetic analysis showed that each of the three species clustered separately, hence strongly supporting the conclusion of independent species. In addition, the phylogenetic analysis showed that the two genera clustered closely together hence our results support the incorporation of Fortunella into Citrus. Based on the above, this article has revised the classification of the traditional Fortunella and determined that this genus has three species, namely; F. venosa, F. hindsii, and F. japonica. F. venosa and F. hindsii are placed in the Citrus as separate species, and their species names still use the previous specific epithet. The revised scientific names of the new combinations of F. venosa and F. hindsii are as follows: Citrus venosa (Champ. ex Benth.) K. M. Liu, X. Z. Cai, and G. W. Hu, comb. nov. and Citrus hindsii (Champ. ex Benth.) K. M. Liu, G. W. Hu, and X. Z. Cai, comb. nov. F. venosa is the original species of Fortunella, F. venosa and F. hindsii are both listed as the second-class key protected wild plants in China. Therefore, the establishment of the taxonomic status of F. venosa and F. hindsii not only deepens our understanding, importance, and the complexity of the systematic classification of Fortunella, but is also significant for global biodiversity conservation, genetic resources for breeding purposes, and population genetics.

[Monthly changes in the benthic macro-invertebrate community structure in the habitats of Phragmites australis marsh in the Dongtan wetland of the Yangtze River estuary, China]. / é•¿æ±Ÿå£ä¸œæ»©æ¹¿åœ°èŠ¦è‹‡ç”Ÿå¢ƒå¤§åž‹åº•æ –æ— è„Šæ¤ŽåŠ¨ç‰©ç¾¤è½ç»“æž„çš„æœˆåŠ¨æ€.

Based on the data of the benthic macro-invertebrates community in the Phragmites australis marsh in the Dongtan Wetland of the Yangtze River estuary collected from May 2015 to April 2016, we evaluated the monthly variations in the species composition, biodiversity and community structure of the benthic macro-invertebrates. The results showed that the average height and degree of coverage for P. australis increased monthly from March to August, and then deceased from September. The density and aboveground biomass (dry mass, g) of P. australis peaked in July. A total of twenty species (including 2 species only identified to genus level and 2 species identified to family level) were found in the survey periods, including 11 Gastropoda, 5 Malacostraca, 2 Insecta and 2 Polychaeta. Three snail species (Assiminea latericea, Assiminea violacea and Cerithideopsis largillierti) dominated the benthic communities in terms of numerical abundance. The number of epifauna species was the most (11 species), followed by 5 burrowing species and 4 infauna species. There were significant monthly variations in the density and biomass of the macro-invertebrates. The density and biomass of benthic community reached the maximum in August. The Margalef's species richness index (D) and Shannon index (H) showed significant differences monthly, but Pielou's index (J) except in November. Three macro-zoobenthic assemblages were identified with the 42% similarity level. The non-Metric Multidimensional scaling plot indicates that the benthic community in May, October and November was distinct compared to that in the other months. The present study suggested the density of the benthic macro-invertebrates community in the P. australis marshes was somewhat correlated with water temperature, underground biomass and salinity. But those correlation were not significant (P>0.05). Because of the continuous impact of anthropogenic activities, the biodiversity of the benthic macro-invertebrate community has been decreasing for several years. More attention should be paid to the habitat value of the P. australis marshes in the future.

Up-regulation of NKG2A inhibitory receptor on circulating NK cells contributes to transfusion-induced immunodepression in patients with ß-thalassemia major.

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in ß-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent ß-thalassemia major patients were remarkably lower than those of ß-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with ß-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with ß-thalassemia major.

Genes underlying positive influence of prenatal environmental enrichment and negative influence of prenatal earthquake simulation and corrective influence of Chinese herbal medicine on rat offspring: Irf7 and Ninj2.

BACKGROUND: Prenatal environmental enrichment (EE) has been proven to positively affect but prenatal stress negatively influence the physiological and psychological processes in animals, whose trans-generational genetic mechanism remains unclearly defined. We aimed to investigate and find out key genes underlying the positive-negative effects derived from prenatal interventions. MATERIALS AND METHODS: Pregnant rats were randomized into EE group (EEG), earthquake simulation group (ESG), herbal group (HG) received herbal supplements in feed after earthquake simulation, and control group (CG). RESULTS: Light Box Defecation Test (LBDT) showed EEG offspring presented less fecal pellets than CG offspring, ESG's more than CG's, and HG's less than ESG (p's<0.05). Open-field Test (OFT) score of EEG was higher than CG offspring, of ESG's was lower than CG's, and HG's higher than ESG's. Irf7 and Ninj were screened, which were up-regulated in EEG, down-regulated in ESG (FC<0.5), and were neutralized in HG. Prenatal EE could positively promote the nervous system development, prenatal earthquake simulation could retard the nervous system development and Chinese herbal remedy (JKSQW) which could correct the retardation. CONCLUSION: The negative-positive prenatal effect could contribute to altered gene expression of Irf7 and Ninj2 which also could play a key role in the improving function of JKSQW for the kidneys.