Curiosity evolves as information unfolds.

When people feel curious, they often seek information to resolve their curiosity. Reaching resolution, however, does not always occur in a single step but instead may follow the accumulation of information over time. Here, we investigated changes in curiosity over a dynamic information-gathering process and how these changes related to affective and cognitive states as well as behavior. Human participants performed an Evolving Line Drawing Task, during which they reported guesses about the drawings' identities and made choices about whether to keep watching. In Study 1, the timing of choices was predetermined and externally imposed, while in Study 2, participants had agency in the timing of guesses and choices. Using this dynamic paradigm, we found that even within a single information-gathering episode, curiosity evolved in concert with other emotional states and with confidence. In both studies, we showed that the relationship between curiosity and confidence depended on stimulus entropy (unique guesses across participants) and on guess accuracy. We demonstrated that curiosity is multifaceted and can be experienced as either positive or negative depending on the state of information gathering. Critically, even when given the choice to alleviate uncertainty immediately (i.e., view a spoiler), higher curiosity promoted continuing to engage in the information-gathering process. Collectively, we show that curiosity changes over information accumulation to drive engagement with external stimuli, rather than to shortcut the path to resolution, highlighting the value inherent in the process of discovery.

Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.

Hippocampal convergence during anticipatory midbrain activation promotes subsequent memory formation.

The hippocampus has been a focus of memory research since H.M's surgery abolished his ability to form new memories, yet its mechanistic role in memory remains debated. Here, we identify a candidate memory mechanism: an anticipatory hippocampal "convergence state", observed while awaiting valuable information, and which predicts subsequent learning. During fMRI, participants viewed trivia questions eliciting high or low curiosity, followed seconds later by its answer. We reasoned that encoding success requires a confluence of conditions, so that hippocampal states more conducive to memory formation should converge in state space. To operationalize convergence of neural states, we quantified the typicality of multivoxel patterns in the medial temporal lobes during anticipation and encoding of trivia answers. We found that the typicality of anticipatory hippocampal patterns increased during high curiosity. Crucially, anticipatory hippocampal pattern typicality increased with dopaminergic midbrain activation and uniquely accounted for the association between midbrain activation and subsequent recall. We propose that hippocampal convergence states may complete a cascade from motivation and midbrain activation to memory enhancement, and may be a general predictor of memory formation.

Effects of non-muscle myosin Ⅱ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury / 中华烧伤杂志

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.

Research progress of interleukin-1 and its receptor antagonist Anakinra in Kawasaki disease / 中华实用儿科临床杂志

Kawasaki disease (KD) is an acute vasculitis that often occurs in children under 5 years of age, leading to coronary artery aneurysms.It is the leading cause of acquired heart disease in children in many countries.Coronary artery stenosis, thrombosis, and even myocardial infarction may occur in the long-term course of KD, which seriously threaten the health of children.The etiology and pathogenesis of KD are complex, and it is recognized that KD is caused by the interaction of multiple factors like the heredity, immunity, inflammation, and environmental factors.Interleukin-1 plays an important role in the occurrence and progression of KD.This study mainly reviews the research progress of interleukin-1 and its receptor antagonist Anakinra in KD.

Dissociable influences of implicit temporal expectation on attentional performance and mind wandering.

Mind wandering at critical moments during a cognitive task degrades performance. At other moments, mind wandering could serve to conserve task-relevant resources, allowing a brief mental respite. Recent research has shown that, if target timing is predictable, mind wandering episodes coincide with moments of low target likelihood. Conversely, mind wandering can be avoided at moments when targets are expected. In the current study, we tested whether mind wandering can be guided by implicit temporal expectations when target timing is less predictable. In two experiments (Experiment 1: N = 37, Experiment 2: N = 61), participants performed a sustained attention task in which target events were preceded by a variable pre-target interval (foreperiod). As time passes over the foreperiod duration, implicit target expectation increases, given that it has not yet appeared. In Experiment 1, all foreperiod durations were equally probable (uniform distribution: 2-10 s). This resulted in faster responses when targets were preceded by long compared to short foreperiods (foreperiod-effect). In contrast, mind wandering, assessed by thought probes inserted following short or long foreperiods, did not follow this pattern. In Experiment 2, alterations in the foreperiod distribution (left or right-skewed) resulted in changes in the behavioral foreperiod-effect, but mind wandering was unaffected. Our findings indicate that implicit timing strongly affects behavioral response to target events, but has no bearing on the mind wandering. Contrastingly, mind wandering did correlate with performance deterioration due to fatigue (time-on-task), suggesting that the thought probe method was sufficiently sensitive to behaviorally relevant changes in mental state.

Interaction Between Lobetyolin and Bovine Serum Albumin by Steady-State Fluorescence and Molecular Docking / 中国实验方剂学杂志

Objective:The interaction between lobetyolin and bovine serumal bumin（bovine serum albumin，BSA）. Method:By the steady-state fluorescence analysis method，the molecular-docking，ultraviolet absorption spectrum and fluorescence quenching were used to calculate quenching constant and binding constant，the number of sites，the position，the force and the distance of lobetyolin-BSA system. In addition， the effect of metalionson quenching constant of the lobetyolin-BSA system was studied. Result:The quenching constant was 1.25×104 L·mol-1（37 ℃），the binding constant was 2.95×104 L·mol-1（37 ℃），and the number of sites was 1 and bound with site 1 in ⅡA of BSA， thermodynamic meters were ΔH=-19.374 kJ·mol-1，ΔS=23.1 J·mol-1·K-1， the interaction distance was 3.2 nm. Meta lions could accelerate the quenching. Conclusion:By the steady-state fluorescence technique，molecular-docking and ultraviolet absorption spectrum，the quenching mechanism of Lobetyolin-BSA is quiescent quenching，and the interactive force is electro static force. The Lobetyolin-BSA can be well combined. At the same time，it also shows that the molecular docking results are similar to the experimental results obtained by steady-state fluorescence analysis.

Longitudinal Changes in the Cerebral Cortex Functional Organization of Healthy Elderly.

Healthy aging is accompanied by disruptions in the functional modular organization of the human brain. Cross-sectional studies have shown age-related reductions in the functional segregation and distinctiveness of brain networks. However, less is known about the longitudinal changes in brain functional modular organization and their associations with aging-related cognitive decline. We examined age- and aging-related changes in functional architecture of the cerebral cortex using a dataset comprising a cross-sectional healthy young cohort of 57 individuals (mean ± SD age, 23.71 ± 3.61 years, 22 males) and a longitudinal healthy elderly cohort of 72 individuals (mean ± baseline age, 68.22 ± 5.80 years, 39 males) with 2-3 time points (18-24 months apart) of task-free fMRI data. We found both cross-sectional (elderly vs young) and longitudinal (in elderly) global decreases in network segregation (decreased local efficiency), integration (decreased global efficiency), and module distinctiveness (increased participation coefficient and decreased system segregation). At the modular level, whereas cross-sectional analyses revealed higher participation coefficient across all modules in the elderly compared with young participants, longitudinal analyses revealed focal longitudinal participation coefficient increases in three higher-order cognitive modules: control network, default mode network, and salience/ventral attention network. Cross-sectionally, elderly participants also showed worse attention performance with lower local efficiency and higher mean participation coefficient, and worse global cognitive performance with higher participation coefficient in the dorsal attention/control network. These findings suggest that healthy aging is associated with whole-brain connectome-wide changes in the functional modular organization of the brain, accompanied by loss of functional segregation, particularly in higher-order cognitive networks.SIGNIFICANCE STATEMENT Cross-sectional studies have demonstrated age-related reductions in the functional segregation and distinctiveness of brain networks. However, longitudinal aging-related changes in brain functional modular architecture and their links to cognitive decline remain relatively understudied. Using graph theoretical and community detection approaches to study task-free functional network changes in a cross-sectional young and longitudinal healthy elderly cohort, we showed that aging was associated with global declines in network segregation, integration, and module distinctiveness, and specific declines in distinctiveness of higher-order cognitive networks. Further, such functional network deterioration was associated with poorer cognitive performance cross-sectionally. Our findings suggest that healthy aging is associated with system-level changes in brain functional modular organization, accompanied by functional segregation loss particularly in higher-order networks specialized for cognition.

Reward supports flexible orienting of attention to category information and influences subsequent memory.

Preparatory control of attention facilitates the efficient processing and encoding of an expected stimulus. However, this can occur at the expense of increasing the processing cost of unexpected stimuli. Preparatory control can be influenced by motivational factors, such as the expectation of a reward. Interestingly, expectation of a high reward can increase target processing, as well as reduce the cost associated with reorienting. Using a semantic cueing paradigm, we examined the interaction of reward expectation and cue-validity on semantic judgment performance and subsequent memory. Preparatory attention was assessed with pupillometry. Valid category cueing was associated with better semantic judgment performance and better subsequent memory compared to invalidly cued items. Higher reward also resulted in a larger pre-target pupil diameter, which could be indicative of increased preparatory task engagement or arousal. Critically, higher reward also reduced reorienting cost in both semantic judgment and subsequent memory performance. Our findings suggest that reward expectation can facilitate the effective control of preparatory attention for semantic information, and can support optimal goal-directed behavior based on changing task demands.

Clinical observation of desmopressin in the treatment of 15 patients with DDAVP / 中华血液学杂志

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.

Comprehensive evaluation of quality of licorice (Glycyrrhiza uralensis) in different growing regions of Gansu Province based on multi-index components combined with chemometrics methods / 中草药

Objective: In this study, the wild and cultivated licorice of Gansu representative regions (Hexi, Longzhong and Longdong) were measured and analyzed by multi-index components combined with chemometrics methods, which will provide scientific basis for the evaluation of the quality of licorice and the suitable producing areas in Gansu Province. Methods: Seven main bioactive components (glycyrrhizin, liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, liquiritigenin and isoliquiritigenin) in 25 batches of licorice samples were simultaneously determined by HPLC-DAD to comprehensively evaluate the quality of licorice combined with factor analysis and cluster analysis. Results: Factor analysis showed that there was a strong correlation between the first common factor and glycyrrhizin, liquiritin and isoliquiritin; and between the second common factor and liquiritigenin, isoliquiritigenin. The variance contribution rate of two common factors was 84.28%, which reflected licorice quality overall. And cluster analysis showed that the quality of 3-year-old licorice (Glycyrrhizae Radix) cultivated in Hangjinqi of Inner Mongolia was the best, followed by that cultivated in Hexi and Longxi of Gansu Province. The quality of licorice in Longzhong of Gansu Province was worse. Conclusion: These results showed that it was more suitable to develop licorice planting in Longxi and Hexi area in Gansu Province. The overall evaluation of multi-index components and chemometrics has reference value for quality control of licorice and optimization its suitable planting areas.

Species distinction in scarless healing of myocardial injury and major influencing factors / 中华地方病学杂志

Heart failure is the leading cause of death in cardiovascular diseases.Despite effectiveness of current clinical treatment,it is not satisfactory in general,so more effective and optimal therapies are under seeking.All available evidences show that cardiac muscles have limited regenerative capacity in adult mammals,while some vertebrates,such as zebrafish and salamander,can completely recover through perfect regeneration following myocardial injury.In-depth investigation into underlying mechanism may facilitate the development of human heart's potential of scarless healing.In this review paper,we summarized recent progresses in distinct cardiac regenerative capacity and their main influencing factors of several model animals through comparative analysis.

Carrying the past to the future: Distinct brain networks underlie individual differences in human spatial working memory capacity.

Spatial working memory (SWM) relies on the interplay of anatomically separated and interconnected large-scale brain networks. EEG studies often observe load-associated sustained negative activity during SWM retention. Yet, whether and how such sustained negative activity in retention relates to network-specific functional activation/deactivation and relates to individual differences in SWM capacity remain to be elucidated. To cover these gaps, we recorded concurrent EEG-fMRI data in 70 healthy young adults during the Sternberg delayed-match-to-sample SWM task with three memory load levels. To a subset of participants (N = 28) that performed the task properly and had artefact-free fMRI and EEG data, we employed a novel temporo-spatial principal component analysis to derive load-dependent negative slow wave (NSW) from retention-related event-related potentials. The associations between NSW responses with SWM capacity were divergent in the higher (N = 14) and lower (N = 14) SWM capacity groups. Specifically, larger load-related increase in NSW amplitude was associated with greater SWM capacity for the higher capacity group but lower SWM capacity for the lower capacity group. Furthermore, for the higher capacity group, larger NSW amplitude was related to greater activation in bilateral parietal areas of the fronto-parietal network (FPN) and greater deactivation in medial frontal gyrus and posterior mid-cingulate cortex of the default mode network (DMN) during retention. In contrast, the lower capacity group did not show similar pattern. Instead, greater NSW was linked to higher deactivation in right posterior middle temporal gyrus. Our findings shed light on the possible differential EEG-informed neural network mechanism during memory maintenance underlying individual differences in SWM capacity.

Auditory stimulation of sleep slow oscillations modulates subsequent memory encoding through altered hippocampal function.

Study Objectives: Slow oscillations (SO) during sleep contribute to the consolidation of learned material. How the encoding of declarative memories during subsequent wakefulness might benefit from their enhancement during sleep is less clear. In this study, we investigated the impact of acoustically enhanced SO during a nap on subsequent encoding of declarative material. Methods: Thirty-seven healthy young adults were studied under two conditions: stimulation (STIM) and no stimulation (SHAM), in counter-balanced order following a night of sleep restriction (4 hr time-in-bed [TIB]). In the STIM condition, auditory tones were phase-locked to the SO up-state during a 90 min nap opportunity. In the SHAM condition, corresponding time points were marked but tones were not presented. Thirty minutes after awakening, participants encoded pictures while undergoing fMRI. Picture recognition was tested 60 min later. Results: Acoustic stimulation augmented SO across the group, but there was no group level benefit on memory. However, the magnitude of SO enhancement correlated with greater recollection. SO enhancement was also positively correlated with hippocampal activation at encoding. Although spindle activity increased, this did not correlate with memory benefit or shift in hippocampal signal. Conclusions: Acoustic stimulation during a nap can benefit encoding of declarative memories. Hippocampal activation positively correlated with SO augmentation.

Degradation of neural representations in higher visual cortex by sleep deprivation.

A night of total sleep deprivation (TSD) impairs selective attention and is accompanied by attenuated activation within ventral visual cortex (VVC). However, finer details of how TSD compromises selectivity of visual processing remain unclear. Drawing from prior work in cognitive aging, we predicted that TSD would result in dedifferentiation of neural responses for faces and houses within the VVC. Instead, we found preservation of category selectivity. This was observed both in voxels highly selective for each category, and also across multiple voxels evaluated using MVPA. Based on prior findings of impaired attentional modulation following TSD, we also predicted reduced biasing of neural representations towards the attended category when participants viewed ambiguous face/house images. When participants were well rested, attention to houses (or faces) caused activation patterns to more closely resemble those elicited by isolated house (face) images than face (house) images. During TSD, attention to faces enhanced neural similarity to both target (face) and distractor (house) representations, signifying reduced suppression of irrelevant information. Degraded sensory processing reflected in reduced VVC activation following TSD, thus appears to be a result of impaired top-down modulation of sensory representations instead of degraded selectivity of maximally category sensitive voxels, or the dedifferentiation of neural activation patterns.

Degradation of cortical representations during encoding following sleep deprivation.

A night of total sleep deprivation (TSD) reduces task-related activation of fronto-parietal and higher visual cortical areas. As this reduction in activation corresponds to impaired attention and perceptual processing, it might also be associated with poorer memory encoding. Related animal work has established that cortical columns stochastically enter a 'down' state in sleep deprivation, leading to predictions that neural representations are less stable and distinctive following TSD. To test these predictions participants incidentally encoded scene images while undergoing fMRI, either during rested wakefulness (RW) or after TSD. In scene-selective PPA, TSD reduced stability of neural representations across repetition. This was accompanied by poorer subsequent memory. Greater representational stability benefitted subsequent memory in RW but not TSD. Even for items subsequently recognized, representational distinctiveness was lower in TSD, suggesting that quality of encoding is degraded. Reduced representational stability and distinctiveness are two novel mechanisms by which TSD can contribute to poorer memory formation.

Effect of Necrostatin-1 on the inflammation in unilateral ureter obstruction mice / 临床与实验病理学杂志

Purpose To observe the effect of Necrostatin-1 (Nec-1),a necroptosis inhibitor,on the inflammation in unilateral ureter obstruction mice.Methods Male C57BL/6J mice were randomly divided into sham operation group,unilateral ureter obstruction operation group and UUO + Nec-1 treatment group,and the mice were sacrificed at 7th day after operated.Scr and BUN were measured.The pathological changes in the kidney were observed by HE staining.Immunohistochemistry and Western blot were used to detect the protein expression of necroptosis-related indicators RIP1,RIP3,MLKL and inflammatory cytokines TNF-α,IL-1β and MCP-1.Results Compared with sham operation group,the expression of RIP1,RIP3 and MLKL protein increased in the renal tissue of UUO mice,accompanied with increased expression of TNF-α,IL-1β and MCP-1.Nec-1 treatment significantly decreased above-mentioned protein expression in UUO mice,and also reduced renal interstitial inflammation and renal tubal injury according to HE staining.Scr and BUN levels suggested improved renal function.Conclusion Nec-1 could relieve the inflammatory reaction in renal tissue of the UUO mice by inhibiting necroptosis,which may be a new target for the treatment of secondary inflammation.

Establishment of allele-specific PCR for the detection of CYP3A5 and MDR-1 gene polymorphisms and its clinical application / 临床检验杂志

Objective To establish an allele-specific PCR method for the detection of cytochrome P-450 CYP3A5 (A6986G) and multiding resistance gene MDR-1 (C3435T) polymorphisms,and investigate the correlations of their polymorphisms with blood tacrolimus (Tac) concentration/dose (C/D) ratio in renal transplant recipients.Methods The allele-specific PCR primers were designed according to the polymorphism sites of CYP3A5 (A6986G) and MDR-1 (C3435T) genes.Then,their polymorphisms in the genomic DNA of peripheral blood samples from 72 renal transplant recipients were analyzed,and the results were validated by DNA sequencing.The blood Tac concentration was determined by the chemiluminescence microparticle immunoassay and the differences of concentration,dose and C/D ratio of blood Tac in renal transplant recipients with different genotypes were compared at 1 month after transplantation.Results The coincidence rate between the established allele-specific PCR and DNA sequencing was 100％.The frequencies of CYP3A5 * 1/* 1,* 1/* 3 and * 3/* 3 genotypes in 72 renal transplant recipients were 18.1％,31.9％ and 50.0％,respectively,and those of MDR-1 C/C,C/T and T/T genotypes were 27.8％,58.3％ and 13.9％,respectively.There were significant differences in blood Tac concentration (P =0.014) and Tac C/D ratio (P =0.019) between different CYP3A5 genotypes of renal transplant recipients.Further analysis found that the Tac C/D ratio of CYP3A5 * 3/* 3 genotype was significantly higher than that of CYP3A5 * 1/* 1 and * 1/* 3 genotypes (P ＜ 0.05).Conclusion The allele-specific PCR method for the detection of CYP3A5 and MDR-1 polymorphisms is successfully established and the polymorphism of CYP3A5 * 3 gene in renal transplant recipients is obviously correlated with the pharmacokinetics of Tac.