The lack of homology domain and leucine rich repeat protein phosphatase 2 ameliorates visual impairment in rats with diabetic retinopathy through regulation of the AKT-GSK-3ß-Nrf2 signal cascade.

Pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) is an emerging player in diverse disorders. Our previous findings have documented that reducing PHLPP2 levels in cultured retinal ganglion cells protects against cellular damage caused by high glucose, indicating a possible link between PHLPP2 and diabetic retinopathy (DR). The present work was dedicated to the investigation of PHLPP2 in DR through in vivo experiments with rat models induced by intraperitoneal injection of streptozotocin. Compared to normal rats, the retinas of rats with DR exhibited a notable increase in the level of PHLPP2. The reduction of PHLPP2 levels in the retina was achieved by the intravitreal administration of adeno-associated viruses expressing specific shRNA targeting PHLPP2. Decreasing the expression of PHLPP2 ameliorated visual function impairment and improved the pathological changes of retina in DR rats. Moreover, decreasing the expression of PHLPP2 repressed the apoptosis, oxidative stress and proinflammatory response in the retinas of rats with DR. Reduction of PHLPP2 levels led to an increase in the levels of phosphorylated AKT and glycogen synthase kinase-3ß (GSK-3ß). Decreasing the expression of PHLPP2 resulted in increased activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which was reversed by suppressing AKT. Notably, the protective effect of reducing PHLPP2 on DR was eliminated when Nrf2 was restrained. These observations show that the down-regulation of PHLPP2 has protective effects on DR by preserving the structure and function of the retina by regulating the AKT-GSK-3ß-Nrf2 signal cascade. Therefore, targeting PHLPP2 may hold promise in the treatment of DR.

The effect of childbirth trauma on willingness to donate milk in women following perinatal loss: The mediating role of resilience.

Limited studies have been conducted on Chinese women's willingness to donate milk following perinatal loss. In this study, we explore the relationship among childbirth trauma, willingness to donate milk, and resilience in women following perinatal loss, and the mediating effect of resilience between childbirth trauma and willingness to donate milk. A cross-sectional study was carried out throughout 4 months. We used convenience sampling methods and recruited 241 women following a perinatal loss from eight tertiary hospitals in Sichuan Province, China. Participants completed four questionnaires during a face-to-face individual interview: the general information questionnaire, the Willingness to Donate Milk Scale (WMDS), the City Birth Trauma Scale, and the Brief Resilience Scale. SPSS 20.0 was used to analyze the collected data. In our study, childbirth trauma was negatively correlated with the total and each dimension score of WMDS (p < 0.001). Resilience was positively correlated with the total and each dimension score of WMDS (p < 0.001). Resilience partially mediated the relationship between childbirth-related symptoms and willingness to donate milk (ß = -0.38, 95% confidence interval [CI]: -0.50 to -0.26), which accounted for 69.03% of the total effect. Resilience partially mediated the relationship between general symptoms and willingness to donate milk (ß = -0.31, 95% CI: -0.40 to -0.21), which accounted for 66.89% of the total effect. Resilience partially mediated the relationship between childbirth trauma and willingness to donate milk in women following perinatal loss. Our findings suggest that resilience can play a significant role in mediating the relationship between childbirth trauma and willingness to donate milk in women following perinatal loss. These results could help healthcare professionals design interventions for physical and mental recovery after perinatal loss.

Loss of pleckstrin homology domain and leucine-rich repeat protein phosphatase 2 has protective effects on high glucose-injured retinal ganglion cells via the effect on the Akt-GSK-3ß-Nrf2 pathway.

OBJECTIVE: Pleckstrin homology domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) is linked to various pathological states. However, whether PHLPP2 mediates diabetic retinopathy is unaddressed. This work explored the biological function of PHLPP2 in modulating high glucose (HG)-elicited damage of retinal ganglion cells (RGCs), an in vitro model for studying diabetic retinopathy. METHODS: Mouse RGCs were treated with HG to establish a cell model. PHLPP2 was silenced by transfecting specific shRNAs targeting PHLPP2. RT-qPCR, immunoblotting, CCK-8 assay, flow cytometry, TUNEL assay, and ELISA were carried out. RESULTS: Significant increases in PHLPP2 levels were observed in cultured RGCs exposed to HG. The severe damages evoked by HG to RGCs were remarkably weakened in PHLPP2-silenced RGCs, including improved cell survival, attenuated cell apoptosis, repressed oxidative stress, and prohibited proinflammatory response. The silencing of PHLPP2 strengthened the activation of Nrf2 in HG-treated RGCs via modulation of the Akt-GSK-3ß axis. Interruption of the Akt-GSK-3ß axis reversed PHLPP2-silencing-elicited Nrf2 activation. The protective effects of PHLPP2 silencing on HG-induced injury of RGCs were diminished by Nrf2 inhibition. CONCLUSIONS: The loss of PHLPP2 was beneficial for HG-injured RGCs through the effect on the Akt-GSK-3ß-Nrf2 pathway. This work suggests a possible role of PHLPP2 in diabetic retinopathy.

Sand supplementation favors tropical seagrass Thalassia hemprichii in eutrophic bay: implications for seagrass restoration and management.

BACKGROUND: Sediment is crucial for the unique marine angiosperm seagrass growth and successful restoration. Sediment modification induced by eutrophication also exacerbates seagrass decline and reduces plantation and transplantation survival rates. However, we lack information regarding the influence of sediment on seagrass photosynthesis and the metabolics, especially regarding the key secondary metabolic flavone. Meanwhile, sulfation of flavonoids in seagrass may mitigate sulfide intrusion, but limited evidence is available. RESULTS: We cultured the seagrass Thalassia hemprichii under controlled laboratory conditions in three sediment types by combining different ratios of in-situ eutrophic sediment and coarse beach sand. We examined the effects of beach sand mixed with natural eutrophic sediments on seagrass using photobiology, metabolomics and isotope labelling approaches. Seagrasses grown in eutrophic sediments mixed with beach sand exhibited significantly higher photosynthetic activity, with a larger relative maximum electron transport rate and minimum saturating irradiance. Simultaneously, considerably greater belowground amino acid and flavonoid concentrations were observed to counteract anoxic stress in eutrophic sediments without mixed beach sand. This led to more positive belowground stable sulfur isotope ratios in eutrophic sediments with a lower Eh. CONCLUSIONS: These results indicated that coarse beach sand indirectly enhanced photosynthesis in T. hemprichii by reducing sulfide intrusion with lower amino acid and flavonoid concentrations. This could explain why T. hemprichii often grows better on coarse sand substrates. Therefore, it is imperative to consider adding beach sand to sediments to improve the environmental conditions for seagrass and restore seagrass in eutrophic ecosystems.

Nutrient loading decreases blue carbon by mediating fungi activities within seagrass meadows.

Coastal pollution, including nutrient loading, can negatively impact seagrass health and cover and may consequently alter soil organic carbon (SOC) accumulation and preservation. Key to understanding how eutrophication impacts SOC cycling in seagrass ecosystems is how nutrient loading changes the sources of carbon being deposited and how these changes in resources, both nutrients and carbon availability, influence soil microbiota community and activity. Currently, the direction and magnitude of nutrient loading impacts on seagrass SOC dynamics are poorly understood at a meadow scale, limiting our ability to reveal the driving mechanisms of SOC remineralisation. The purpose of this study was to assess the response of surface SOC and soil microbiomes to nutrient loading within tropical seagrass meadows. To achieve this, we quantified both total SOC and recalcitrant soil organic carbon (RSOC) concentrations and sources, in addition to the composition of bacterial and fungal communities and soil extracellular enzyme activities. We found that nutrient loading elevated SOC and RSOC content, mainly facilitated by enhanced algal growth. There was no nutrient effect on the soil prokaryotic communities, however, saprotrophic fungi groups (i.e. Trapeliales, Sordaridales, Saccharomycetales and Polyporales) and fungal activities were elevated under high nutrient conditions, including extracellular enzyme activities linked to seagrass-based cellulose and lignin decomposition. This relative increase in RSOC transformation may decrease the relative contribution of seagrass carbon to RSOC pools. Additionally, significantly different fungal communities were observed between adjacent T. hemprichii and E. acoroides areas, which coincided with elevated RSOC-decomposing enzyme activity in T. hemprichii meadows, even though the mixed seagrass meadow received allochthonous SOC and RSOC from the same sources. These results suggest that nutrient loading stimulated fungal activity and community shifts specific to the local seagrass species, thereby causing fine-scale (within-meadow) variability in SOC cycling in response to nutrient loading. This study provides evidence that fungal composition and activity, mediated by human activities (e.g. nutrient loading), can be an important influence on seagrass blue carbon accumulation and remineralisation.

Effects of transcranial direct current stimulation with virtual reality on upper limb function in patients with ischemic stroke: a randomized controlled trial.

BACKGROUND: Non-invasive brain stimulation techniques have been shown in several studies to improve the motor recovery of the affected upper-limbs in stroke patients. This study aims to investigate whether or not cathodal transcranial direct current stimulation (c-tDCS), combined with virtual reality (VR), is superior to VR alone in reducing motor impairment and improving upper limb function and quality of life in stroke patients. METHODS: Forty patients who suffered ischemic stroke between 2 weeks to 12 months were recruited for this single-blind randomized control trial. The patients were randomly assigned either to an experimental group who receiving c-tDCS and VR, or a control group receiving sham stimulation and VR. The cathodal electrode was positioned over the primary motor cortex (M1) of the unaffected hemisphere. The treatment session consisted of 20 min of daily therapy, for 10 sessions over a 2-week period. The outcome measures were the Fugl-Meyer Upper Extremity (FM-UE), the Action Research Arm Test (ARAT) and the Barthel Index (BI). RESULTS: The two groups were comparable in demographic characteristic and motor impairment. After 2 weeks of intervention, both groups demonstrated significant improvement in FM-UE, ARAT and BI scores (P<0.05).The experiment group demonstrated more improvement in FM-UE than the control group (10.1 vs. 6.4, p = 0.003) and, ARAT (7.0 vs 3.6, p = 0.026) and BI (12.8 vs 8.5, p = 0.043). CONCLUSIONS: The findings from our study support that c-tDCS, along with VR, can facilitate a stronger beneficial effect on upper limb motor impairment, function and quality of life than VR alone in patients with ischemic stroke. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800019386) in November 8, 2018-Retrospectively registered.

Knockdown of FOXO6 inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells.

Oxidative stress and apoptosis in retinal pigment epithelium cells are involved in the pathogenesis of diabetic retinopathy (DR). Forkhead box class O 6 (FOXO6) is a member of the FOXO family that can regulate diabetes-induced oxidative stress. However, the role of FOXO6 in DR has not been clarified. The aim of the present study was to investigate the effects of FOXO6 on high glucose (HG)-induced oxidative stress and apoptosis in ARPE-19 cells. The results showed that FOXO6 was overexpressed in clinical vitreous samples from DR patients and in HG-induced ARPE-19 cells. Knockdown of FOXO6 by small interfeing RNA targeting FOXO6 (si-FOXO6) mitigated the HG-induced the production of reactive oxygen species and malondialdehyde, as well as the inhibition of superoxide dismutase activity. Knockdown of FOXO6 reduced the rate of cell apoptosis in HG-induced ARPE-19 cells. The increase in bax expression and decrease in bcl-2 expression caused by HG stimulation were reversed by si-FOXO6 transfection. Furthermore, knockdown of FOXO6 enhanced the activation of Akt/Nrf2 pathway in HG-stimulated ARPE-19 cells. Taken together, suppression of FOXO6 protects ARPE-19 cells from HG-induced oxidative stress and apoptosis, which is in part mediated by the activation of Akt/Nrf2 pathway.

[Effects of Gremlin on transdifferentiation and extracellular matrix synthesis in human lens epithelium cells].

OBJECTIVE: To explore the effects of Gremlin on transdifferentiation and extracellular matrix synthesis in cultured human lens epithelium cells (HLEC). METHODS: This is an experimental research. HLEC were incubated with different concentrations of Gremlin (0, 100, 200 and 400 µg/L) for 24 h. The morphological changes of HLEC were observed by inverted microscope. Real-time PCR and Western-Blot were used to evaluate the expression of α-smooth muscle actin (α-SMA) (as a landmark protein of epithelial mesenchymal transition), fibronectin (Fn) and collagen type 1 (COL-1) (as major components of extracellular matrix) after stimulation with different time (0, 12, 24, 48, 72 h) by 200 µg/L Gremlin. The same parameters were observed in Gremlin. siRNA transfected HLEC which treated with 1.0 µg/L TGF-ß2. α-SMA, Fn and COL-1 protein and mRNA expressions comparison with control group were analyzed using one-way and two-way ANOVA, while the difference between groups were compared using Turkey HSD and LSD-t test. RESULTS: The normal morphology of HLEC showed polygonal and anchorage-dependent. After the incubation of different concentrations of Gremlin for 24 h, morphological feature of HLEC were changed from monolayer and polygonal to multilayer and spindle fibroblast-like cells, and the intercellular space widened. The expression of α-SMA, Fn and COL-1 were increased with prolonging of Gremlin treatment time (α-SMA gene induction: 1.00 ± 0.00, 1.62 ± 0.57, 3.40 ± 0.83, 5.90 ± 0.49, 7.97 ± 0.91; F = 61.64, P < 0.05, q = 6.43, 13.13, 18.66, P < 0.05; Fn gene induction: 1.00 ± 0.00, 3.26 ± 0.23, 5.86 ± 0.90, 10.17 ± 2.16, 12.89 ± 1.63; F = 42.03, P < 0.05, q = 6.45, 12.18, 15.79, P < 0.05; COL-1 gene induction: 1.00 ± 0.00, 1.78 ± 0.88, 6.80 ± 0.44, 12.76 ± 2.46, 21.12 ± 3.66; F = 51.79, P < 0.05, q = 4.97, 10.08, 17.26, P < 0.05) (α-SMA protein expression: 0.13 ± 0.02, 0.26 ± 0.02, 0.29 ± 0.09, 0.47 ± 0.06, 0.68 ± 0.05; F = 45.14, q = 5.11, 10.67, 17.40, P < 0.05; Fn protein expression: 0.16 ± 0.04, 0.26 ± 0.07, 0.65 ± 0.03, 0.82 ± 0.04, 0.73 ± 0.02; F = 144.4, q = 20.09, 26.78, 23.12, P < 0.05; COL-1 protein expression: 0.11 ± 0.02, 0.23 ± 0.09, 0.41 ± 0.05, 0.61 ± 0.03, 0.74 ± 0.03; F = 75.47, q = 9.99, 16.60, 21.07, P < 0.05). Gremlin. siRNA transfection effectively suppressed TGF-ß2-induced expression of α-SMA, Fn, and COL-I (α-SMA gene induction: F = 81.89, P < 0.05, t = 3.234, 4.346, 10.35; t = 2.252, 7.272, 19.11, P < 0.05; Fn gene induction: F = 83.61, P < 0.05, t = 2.538, 8.202, 11.99; t = 6.316, 7.304, 14.80, P < 0.05; COL-1 gene induction: F = 73.64, P < 0.05, t = 3.385, 7.942, 11.64; t = 4.794, 9.006, 13.75, P < 0.05; Gremlin gene induction: F = 46.11, P < 0.05, t = 5.08, 7.24, 8.27; t = 6.27, 8.27, 12.14, P < 0.05) (α-SMA protein expression: F = 129.6, P < 0.05, t = 4.34, 4.85; 3.83, 4.34; 13.03, 14.82, P < 0.05; Fn protein expression: F = 26.18, P < 0.05, t = 5.68, 5.95; 3.10, 4.06; 4.19, 4.73, P < 0.05; COL-1 protein expression: F = 41.37, P < 0.05, t = 6.93, 5.51; 7.82, 6.93; 8.71, 7.64, P < 0.05; Gremlin protein expression: F = 59.52, P < 0.05, t = 2.24, 3.49; 5.74, 6.23; 6.98, 9.98, P < 0.05). CONCLUSIONS: Gremlin could induce HLEC to express α-SMA, Fn and COL-1 in a time-dependent manner and promote transdifferentiation and extracellular matrix synthesis. Specifically silencing the expression of Gremlin could effectively block the TGF-ß2-induced EMT and ECM synthesis in HLEC.

TGF-ß2 induces transdifferentiation and fibrosis in human lens epithelial cells via regulating gremlin and CTGF.

Transforming growth factor (TGF)-ß2, gremlin and connective tissue growth factor (CTGF) are known to play important roles in the induction of epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis. However, the complex functional relationship among gremlin, CTGF and TGF-ß2 in the induction of EMT and ECM synthesis in human lens epithelial cells (HLECs) has not been reported. In this study, we found that TGF-ß2, CTGF and gremlin can individually induce the expression of α-smooth muscle actin (α-SMA), fibronectin (Fn), collagen type I (COL-I), Smad2 and Smad3 in HLECs. Blockade of CTGF and gremlin effectively inhibited TGF-ß2-induced expression of α-SMA, Fn, COL-I, Smad2, and Smad3 in HLECs. Furthermore blockade of Smad2 and Smad3 effectively inhibited CTGF and gremlin induced expression of α-SMA, Fn, COL-I in HLECs. In conclusion, TGF-ß2, CTGF and gremlin are all involved in EMT and ECM synthesis via activation of Smad signaling pathway in HLECs. Specifically silencing CTGF and gremlin can effectively block the TGF-ß2-induced EMT, ECM synthesis due to failure in activation of Smad signaling pathway in HLECs.

Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

[Association between fragmented QRS complexes and imperfect ST-segment resolution in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention].

OBJECTIVE: To explore the relationship between fragmented QRS complexes (fQRS) and imperfect ST-segment resolution in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (p-PCI). METHODS: This study included 227 consecutive patients with STEMI who underwent p-PCI. They were divided into two groups: ECG with fQRS (n = 142) and without fQRS (n = 85). Baseline clinical characteristics,Gensini score, coronary angiography features and the rate of ST-segment resolution were compared between the two groups. RESULTS: (1) Patients with fQRS of ECG had higher cTnI, CK, CK-MB levels and Gensini score, prolonged QRS interval, lower rate of ST-segment resolution and left ventricular ejection fraction (LVEF) than in patients without fQRS (all P < 0.01 or P < 0.05). (2) Pearson correlation analysis showed that the rate of ST-segment resolution (r = -0.207, P = 0.002),Gensini score (r = 0.191, P = 0.004), LVEF(r = -0.188, P = 0.006), cTnI(r = 0.172, P = 0.010), and the TIMI grade post p-PCI (r = -0.148, P = 0.028) were significantly related with the presence of fQRS. (3) Multivariate logistic regression analysis demonstrated that presence of fQRS at pre-PCI (OR = 2.908, 95%CI:1.095-7.723, P = 0.032) , the number of leads with fQRS before PCI (OR = 1.582, 95%CI:1.250-2.002, P < 0.001), and increased QRS interval (OR = 0.955, 95%CI: 0.924-0.988, P = 0.008) were independent predictors of imperfect ST-segment resolution. CONCLUSIONS: fQRS is related to imperfect ST-segment resolution in STEMI patients undergoing p-PCI.fQRS may be a useful parameter to identify the patients with severe coronary lesion, larger areas of ischemic injury and myocardial infarction as well as severe left ventricular contracted dysfunction.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is used in anticoagulation therapies as a substitute for heparin, especially during cardiovascular procedures such as percutaneous coronary intervention. AIM: To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome (ACS). METHODS: In total, 165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study. From June 2020 to June 2022, elderly patients with ACS with complete data were selected and treated with interventional therapy. The study cohort was randomly divided into a study group (n = 80, administered bivalirudin) and a control group (n = 85, administered unfractionated heparin). Over a 6-mo follow-up period, differences in emergency processing times, including coronary intervention, cardiac function indicators, occurrence of cardiovascular events, and recurrence rates, were analyzed. RESULTS: Significant differences were observed between the study cohorts, with the observation group showing shorter emergency process times across all stages: Emergency classification; diagnostic testing; implementation of coronary intervention; and conclusion of emergency treatment (P < 0.05). Furthermore, the left ventricular ejection fraction in the observation group was significantly higher (P < 0.05), and the creatine kinase-MB and New York Heart Association scores were notably lower than those in the control group (P < 0.05). CONCLUSION: In elderly patients receiving interventional therapy for ACS, bivalirudin administration led to increased activated clotting time achievement rates, enhanced myocardial reperfusion, and reduced incidence of bleeding complications and adverse cardiac events.

Exploring the Association between Anxiety, Depression, and Gut Microbiota during Pregnancy: Findings from a Pregnancy Cohort Study in Shijiazhuang, Hebei Province, China.

Negative emotions and gut microbiota during pregnancy both bear significant public health implications. However, the relationship between them has not been fully elucidated. This study, utilizing data from a pregnancy cohort, employed metagenomic sequencing to elucidate the relationship between anxiety, depression, and gut microbiota's diversity, composition, species, and functional pathways. Data from 87 subjects, spanning 225 time points across early, mid, and late pregnancy, were analyzed. The results revealed that anxiety and depression significantly corresponded to lower alpha diversity (including the Shannon entropy and the Simpson index). Anxiety and depression scores, along with categorical distinctions of anxiety/non-anxiety and depression/non-depression, were found to account for 0.723%, 0.731%, 0.651%, and 0.810% of the variance in gut-microbiota composition (p = 0.001), respectively. Increased anxiety was significantly positively associated with the abundance of Oscillibacter sp. KLE 1745, Oscillibacter sp. PEA192, Oscillibacter sp. KLE 1728, Oscillospiraceae bacterium VE202 24, and Treponema socranskii. A similar association was significantly noted for Oscillibacter sp. KLE 1745 with elevated depression scores. While EC.3.5.3.1: arginase appeared to be higher in the anxious group than in the non-anxious group, vitamin B12-related enzymes appeared to be lower in the depression group than in the non-depression group. The changes were found to be not statistically significant after post-multiple comparison adjustment.

Hemodynamic activity is not parsimoniously tuned to index-of-difficulty in movement with dual requirements on speed-accuracy.

Background: Reaching movements are crucial for daily living and rehabilitation, for which Fitts' Law describes a speed-accuracy trade-off that movement time increases with task difficulty. This study aims to investigate whether cortical activation in motor-related areas is directly linked to task difficulty as defined by Fitts' Law. Understanding this relationship provides a physiological basis for parameter selection in therapeutic exercises. Methods: Sixteen healthy subjects performed 2D reaching movements using a rehabilitation robot, with their cortical responses detected using functional near-infrared spectroscopy (fNIRS). Task difficulty was manipulated by varying target size and distance, resulting in 3 levels of index-of-difficulty (ID). Kinematic signals were recorded alongside cortical activity to assess the relationship among movement time, task difficulty, and cortical activation. Results: Our results showed that movement time increased with ID by 0.2974s/bit across all subjects (conditional r2 = 0.6434, p < 0.0001), and all subjects showed individual trends conforming Fitts' Law (all p < 0.001). Neither activation in BA4 nor in BA6 showed a significant correlation with ID (p > 0.05), while both the target size and distance, as well as the interaction between them, showed a significant relationship with BA4 or BA6 activation (all p < 0.05). Conclusion: This study found that although kinematic measures supported Fitts' Law, cortical activity in motor-related areas during reaching movements did not correlate directly with task difficulty as defined by Fitts' Law. Additional factors such as muscle activation may call for different cortical control even when difficulty was identical.

Coronary microvascular dysfunction and myocardial area at risk assessed by cadmium zinc telluride single photon emission computed tomography after primary percutaneous coronary intervention in acute myocardial infarction patients.

Background: A high proportion of coronary microvascular dysfunction (CMD) has been observed in patients with acute myocardial infarction (AMI) who have received primary percutaneous coronary intervention (PCI), which may affect their prognosis. This study used cadmium zinc telluride (CZT) single photon emission computed tomography (SPECT) to evaluate the prevalence and characteristics of CMD and myocardial area at risk (AAR) in AMI patients who had undergone primary PCI. Methods: We conducted a single-center cross-sectional retrospective study at TEDA International Cardiovascular Hospital from September 2021 to June 2022. A total of 83 patients received primary PCI for AMI. Subsequently, a rest/stress dynamic and routine gated myocardial perfusion imaging (MPI) were performed 1 week after PCI. The CMD group was defined as having a residual stenosis of infarct-related artery (IRA) <50% and myocardial flow reserve (MFR) <2.0 in this corresponding territory, whereas MFR ≥2.0 of IRA pertained to the normal control group. Rest-AAR of infarction (%) and stress-AAR (%) were expressed by the percentage of measured rest-defect-size and stress-defect-size in the left ventricular area, respectively. Logistic regression analyses were performed to identify significant predictors of CMD. Results: A total of 53 patients with a mean age of 57.06±11.99 years were recruited, of whom 81.1% were ST-segment elevation myocardial infarction (STEMI). The proportion of patients with CMD was 79.2% (42/53). The time of pain to SPECT imaging was 7.50±1.27 days in the CMD group and 7.45±1.86 days among controls. CMD patients had a higher body mass index (BMI) than controls (26.48±3.26 vs. 24.36±2.73 kg/m2, P=0.053), and a higher proportion of STEMI, thrombolysis in myocardial infarction (TIMI) 0 grade of IRA prior PCI than controls (88.1% vs. 54.5%, P=0.011; 61.9% vs. 18.2%, P=0.004, respectively). No significant difference was identified in the rest-myocardial blood flow (MBF) of IRA between the 2 groups, whereas the stress-MBF and MFR of IRA, rest-AAR, and stress-AAR in the CMD group were remarkably lowered. Higher BMI [odds ratio (OR): 1.332, 95% confidence interval (CI): 1.008-1.760, P=0.044] and stress-AAR (OR: 1.994, 95% CI: 1.122-3.543, P=0.019) were used as independent predictors of CMD occurrence. Conclusions: The prevalence of CMD is high in AMI patients who received primary PCI. Each 1 kg/m2 increase in BMI was associated with a 1.3-fold increase in CMD risk. A 5% increase in stress-AAR was associated with a nearly 2-fold increase in CMD risk. Increased BMI and stress-AAR predicts decreased coronary reserve function.

Facile synthesis of ZnFe2O4 nanoparticles with tunable magnetic and sensing properties.

Nanoparticles (NPs) and colloidal nanocrystal clusters (CNCs) of ZnFe2O4 were synthesized by using a solvothermal method in a controlled manner through simply adjusting the solvents. When a glycerol/water mixture was used as the solvent, ZnFe2O4 NPs were obtained. However, using ethylene glycol solvent yielded well-dispersed ZnFe2O4 CNCs. X-ray diffraction (XRD) and transmission electron microscopy (TEM) data confirmed that the ZnFe2O4 NPs were a single crystalline phase with tunable sizes ranging from 12 to 20 nm, while the ZnFe2O4 CNCs of submicrometer size consisted of single-crystalline nanosheets. Magnetic measurement results showed that the ZnFe2O4 NPs were ferromagnetic with a very small hysteresis loop at room temperature. However, CNCs displayed a superparamagnetic behavior due to preferred orientations of the nanosheets. Electrochemical sensing properties showed that both the size of the NPs and the structure of the CNCs had a great influence on their electrochemical properties in the reduction of H2O2. Based on the experimental results, the formation mechanisms of both the ZnFe2O4 CNCs and NPs as well as their structure-property relationship were discussed.

Modification of carbon nanotube transparent conducting films for electrodes in organic light-emitting diodes.

Single-walled carbon nanotube (SWCNT) transparent conducting films (TCFs) were fabricated for the electrodes of organic light-emitting diodes (OLEDs); three types of film were studied. The as-prepared SWCNT TCFs displayed a relatively low sheet resistance of 82.6 Ω/sq at 80.7 T% with a relatively large surface roughness of 30 nm. The TCFs were top-coated with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to obtain PEDOT:PSS-coated TCFs. The PEDOT:PSS cover improved the conductivity and decreased the surface roughness to 12 nm at the cost of film transmittance. The SWCNT TCFs mixed with PEDOT:PSS (PM-TCFs) exhibited a high conductivity (70.6 Ω/sq at 81 T%) and a low surface roughness (3 nm) and were thus selected as the best TCFs for OLEDs. Blue flexible OLEDs with 4,4'-bis(2,2'-diphenylvinyl)-1,1'-biphenyl (Dpvbi) as the emitting layer were fabricated on TCFs with the same structures to evaluate the performances of the different types of SWCNT films for use in OLEDs. Of these three types of OLEDs, the PM-TCF devices exhibited the optimal performance with a maximum luminance of 2587 cd m(-2) and a current efficiency of 5.44 cd A(-1). This result was explored using field-emission scanning electron microscopy and atomic force microscopy to further study the mechanisms that are involved in applying SWCNT TCFs to OLEDs.

[Effects of transforming growth factor-ß2 on transdifferentiation, extracellular matrix synthesis and connective tissue growth factor expression of human lens epithelium cells].

OBJECTIVE: To explore the effects of transforming growth factor-ß2 (TGF-ß2) on the transdifferentiation, extracellular matrix synthesis and connective tissue growth factor (CTGF) expression in human lens epithelium cells (HLEC) in vitro. METHODS: HLEC were incubated with different concentrations of TGF-ß2 (0.0, 0.1, 1.0 and 10.0 µg/L) for 24 h in vitro. The morphological changes of HLEC were observed under inverted phase-contrast microscope. The expression of CTGF and α-smooth muscle actin (α-SMA, as a landmark protein of epithelial mesenchymal transition) in HLEC was measured by immunofluorescence method. Real-time PCR and Western blot were used to evaluate the expression of CTGF, α-SMA, fibronectin (Fn) and COL-I (as the major components of extracellular matrix) after stimulating by TGF-ß2. RESULTS: Normal HLEC presented polygonal shape and were anchorage-dependent. After incubated with different concentrations of TGF-ß2 for 24 h, the morphology of polygonal HLEC was changed into fibroblast-like shape and changed from monolayer and to multilayer cells, and the intercellular space became bigger. CTGF and α-SMA were expressed in the cytoplasm after induction of TGF-ß2. Expression of CTGF in HLEC was increased with increasing concentrations of TGF-ß2 (CTGF protein expression: 0.53 ± 0.03, 0.73 ± 0.01, 0.65 ± 0.03 in cells cultured with 0.1, 1.0 and 10 µg/L TGF-ß2, respectively; CTGF gene induction: 1.00 ± 0.00, 7.18 ± 0.41, 12.88 ± 0.45, 32.84 ± 1.61 in cells cultured with 0.0, 0.1, 1.0 and 10.0 µg/L TGF-ß2, respectively) (F = 77.55, P < 0.05; F = 379.0, P < 0.05). TGF-ß2 could induce HLEC transdifferentiation and accelerate. α-SMA expression was increased by TGF-ß2 dose-dependently (protein expression: 0.48 ± 0.01,0.78 ± 0.04, 0.69 ± 0.04; gene induction: 1.00 ± 0.00, 2.30 ± 0.22, 3.1 ± 0.21, 3.86 ± 0.10) (F = 62.73, P < 0.05; F = 80.22, P < 0.05). TGF-ß2 also promoted expression of Fn and COL-I in a dose-dependent manner (COL-I gene induction: 1.00 ± 0.00, 5.52 ± 0.96, 18.31 ± 1.2, 82.51 ± 1.45;COL-I protein expression: 0.78 ± 0.05, 1.15 ± 0.11, 2.16 ± 0.14; Fn gene induction: 1.00 ± 0.00, 2.36 ± 0.25, 3.27 ± 0.24, 4.25 ± 0.24; Fn protein expression: 0.64 ± 0.01,0.95 ± 0.02, 1.23 ± 0.14) (F = 1881.52, 105.30, P < 0.05; F = 64.44, 51.81, P < 0.05). CONCLUSION: TGF-ß2 induces the expression of CTGF by HLEC, promotes transdifferentiation of and extracellular matrix synthesis by HLEC.

Combined treatment with Prunella vulgaris and Radix bupleuri activated the Bax/Bcl-2 and Caspase-3 signal pathways in papillary thyroid carcinoma cells.

To explore the effect of Prunella vulgaris (PV) combined with Radix bupleuri (RB) on apoptosis of papillary thyroid carcinoma cells. Our study was divided into four groups: the control group, the PV group, the RB group, and the PV combined with the RB group. The viability of cells from different treatment groups was assessed by the CCK-8 assay. Cell migration and invasion were assessed by healing wounding and the transwell assay, respectively. Cell apoptosis rate and cell cycle arrest were detected by a flow cytometry assay. The protein expression of Bcl-2, Bax, Caspase-3, CyclinA1, CyclinB1, and CDK1 was detected using a western blot assay. Our results indicated that, compared with the control group, PV combined with RB group could significantly alter the cell morphology, inhibit cell migration and invasion, decrease the number of cells in the G0/G1 phase and increase the number of cells in the G2/M phase, and promote the cell apoptosis. Moreover, PV combined with RB treatment also obviously increased the expression of Bax/Bcl2 and caspase-3 proteins and decreased the expression of Cyclin A1, Cyclin B1, and CDK1 proteins. Overall, our results indicated that PV combined with RB could activate the Bax/Bcl-2 and Caspase-3 signal pathways to induce cell apoptosis in papillary thyroid carcinoma cells; this also provides a new way to treat thyroid cancer.

MicroRNA-142-5p promotes the proliferation and metastasis of nasopharyngeal carcinoma.

Growing pieces of evidence reported abnormal expression of microRNA in various cancer. Our research aimed to ascertain the miR-142-5p expression and its potential function in the growth and metastasis of human nasopharyngeal carcinoma (NPC). In human NPC tissues and cell lines, miR-142-5p expression was quantified via the real-time qPCR assay. Functionally, the potential effect of miR-142-5p in human CNE-1 and SUNE-1 cells through MTT assay, colony formation assay, Transwell assay, and cell cycle assay. In addition, the potential target gene of miR-142-5p was determined by the dual-luciferase reporter assay. MiR-142-5p expression was remarkably elevated in human NPC tissues, CNE-1 and SUNE-1 cells. MiR-142-5p overexpression obviously enhanced the ability of cell proliferative and colony formation, and prevented G1 phase arrest in CNE-1 and SUNE-1 cells. Further, the migration number of NPC cells was increased compared to NP69 cells. BTG3 was identified as the direct target gene of miR-142-5p. Inhibition of BTG3 expression could reverse the cell proliferation by miR-142-5p-induced. Overall, miR-142-5p could strengthen the NPC cell's proliferation and migration by directly targeting BTG3. Hence, miR-142-5p may provide a new strategy and program for future clinical treatment of NPC.