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Emotion has a significant impact on how related experiences are organized into integrated memories. However, the neurobiological mechanisms of how emotion modulates memory integration for related information with different valences remain unclear. In this between-subject functional magnetic resonance imaging (fMRI) study, we investigated different emotional modulations of memory integration by manipulating the valence of stimuli used in an associative memory paradigm. Three groups of participants were tested: one group integrated emotional (i.e., negative) information with neutral information, one group integrated two emotional pieces of information, and one control group integrated two neutral pieces of information. Behaviorally, emotional information facilitated its integration with neutral information but interfered with the other emotional information. Neurally, the emotion-induced facilitation effect, occurring on memory integration of neutral and emotional information, was associated with increased trial-specific reactivation in the hippocampus during both encoding and retrieval. This facilitated integration was also supported by strengthened hippocampal connectivity with the amygdala, as well as a set of neocortical areas related to emotion regulation and the default mode network (DMN). In contrast, the emotion-induced interference effect, occurring on memory integration of two emotional pieces of information, was associated with impaired hippocampal trial-specific reactivation during retrieval that appeared to offset the facilitating effect of increased reactivation during encoding. Similar but relatively weak hippocampal connectivity was found underlying this interfered integration. Taken together, emotional information facilitates memory integration with neutral information, while disrupting the integration with other emotional information, through distinct dynamical processes of hippocampal trial-specific reactivation and connectivity.

Kidney renal clear cell carcinoma (KIRC) is the most common subtype of Renal cell carcinoma (RCC), with a high degree of immune infiltration. This study aimed to identify m6A-related biomarkers and downstream effectors in KIRC that may affect tumor immunity and to provide prognosis biomarkers of KIRC. In this study, the mRNA expression profiles and corresponding clinical data of KIRC patients were downloaded from public databases. The multigene signature was constructed using two transcription factors and an m6A-associated gene, and a TCGA cohort was constructed to stratify patients into two risk groups. Functional analysis showed that immune-related pathways were enriched and that immune status was different between the two risk groups, with IGF2BP3 and CENPA genes highly correlated with immune cell infiltration. In KIRC clinical patient samples, IGF2BP3 and CENPA expression was positively correlated with clinical staging, which was validated by immunohistochemistry. In conclusion, IGF2BP3 and its downstream CENPA signature can be used for prognostic prediction of KIRC.

A [4+1]/[3+3] domino sequential annulation reaction of o-aminotrifluoroacetophenone derivatives and β′-acetoxy allenoates enabled by DMAP has been reported. A variety of CF3-containing tetrahydropy...

A domino [2+4]/[2+3] sequential annulation reaction of MBH carbonates with N-unprotected indoles has been developed to provide various pyrroloquinoline derivatives in ≤94% yield and 20:1 dr. The reaction could be either mediated by stoichiometric PCy

Background The 2012 European Society of Intensive Care Medicine (ESICM) guidelines provided a clear definition of feeding intolerance (FI). The study aimed to investigate the association between FI based on the current ESICM definition and clinical outcome and to further explore the effect of the duration of FI on mortality. Methods Adult patients from 14 general intensive care units (ICUs) with an expected ICU stay ≥24 hours were prospectively studied. Based on FI duration in the first week of admission to the ICU, FI was categorized as 7-day persistent feeding tolerance (FT), delayed FT, delayed FI, and 7-day persistent FI. The primary outcomes were 28-day and 60-day all-cause mortality. Results Of 499 patients, the prevalence of 3-day and 7-day persistent FI was 39.2% (n = 196) and 25.4% (n = 106), respectively. The patients with 3-day FT had lower risk of 28-day and 60-day mortality rates and higher prevalence in ventilator weaning and vasoactive medication on the seventh day of ICU admission than those with 3-day FI. Three-day FI remained an independent predictor for 60-day mortality. In a subgroup analysis including 418 patients with 7-day survival, compared with those with 7-day persistent FT, the odds ratios of 60-day mortality were 1.67, 1.97, and 2.62 in the patients with delayed FT, delayed FI, and 7-day persistent FI, respectively. Conclusion FI was associated with increased mortality and longer duration of mechanical ventilation and vasoactive support. Prolonged or relapsing FI represented an incremental risk of adverse outcomes in critically ill patients.

A novel phosphine sequentially catalyzed domino 1, 6-addition/annulation process has been developed using p-quinone methides ( p-QMs) and α-substituted allenoates which generates a series of chroman and tetrahydroquinoline derivatives containing an ethynyl-substituted all-carbon quaternary center with up to 97% yield and 20:1 dr. value. In this reaction, allenoates act as C2 synthons.

Neutral events preceding emotional experiences are thought to be better remembered by tagging them as significant to simulate future event predictions. Yet, the neurobiological mechanisms how emotion transforms initially mundane events into strong memories remain unclear. By two behavioral and one fMRI studies with adapted sensory preconditioning paradigm, we show rapid neural reactivation and reorganization underlying emotion-tagged retroactive memory enhancement. Behaviorally, emotional tagging enhanced initial memory for neutral associations across the three studies. Neurally, emotional tagging potentiated reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. Moreover, it induced large-scale hippocampal-neocortical reorganization supporting such retroactive benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during online processing, and a shift from stimulus-relevant neocortex to transmodal prefrontal-parietal areas during offline post-tagging rest. Together, emotional tagging retroactively promotes associations between past neutral events through stimulating rapid reactivation of overlapping representations and reorganizing related memories into an integrated network.

A [4+1]/[3+3] domino sequential annulation reaction of

Background The socioeconomic status (SES) of a family can affect almost all aspects of a child’s life, including health and current and future achievement. The potential adverse effects of low SES on children’s emotional development are thought to result from proximal factors such as stress. The underlying neurobiological mechanisms, however, remain elusive. Methods The effect of SES on children’s integrative cortisol secretion and its modulations on emotion-related brain systems and connectivity were examined in children aged 6 to 12 years. In study 1, we investigated the relationship between SES and cortisol secretion in 239 children. In study 2, using resting-state and task-dependent functional magnetic resonance imaging in a subsample of 50 children, we investigated how SES affects children’s amygdala-prefrontal functional organization through cortisol secretion. Results Children from lower SES exhibited lower cortisol secretion, considering basal cortisol, nocturnal cortisol activity during sleep, and cortisol awakening response, which mediated higher amygdala nuclei intrinsic functional connectivity with the medial and dorsolateral prefrontal cortex (PFC). Critically, these children also exhibited higher task-evoked ventromedial PFC activity through higher intrinsic connectivity of the centromedial amygdala with the medial PFC. They also exhibited higher functional coupling of the centromedial amygdala with the dorsolateral PFC when processing negative emotions. Conclusions This study demonstrates that SES shapes children’s amygdala-prefrontal circuitry through stress-sensitive cortisol secretion, with the most prominent effect in the centromedial amygdala’s functional coordination with the ventromedial and dorsolateral PFC involved in processing negative emotions. Our findings provide important insight into the neurobiological etiology underlying how socioeconomic disparities shape children’s emotional development.

Collaboration in neuroscience is impeded by the difficulty of sharing primary data, results, and software across labs. Here we introduce Neuroscience Data Interface (NDI), a platform-independent standard that allows an analyst to use and create software that functions independently from the format of the raw data or the manner in which the data is organized into files. The interface is rooted in a simple vocabulary that describes common apparatus and storage devices used in neuroscience experiments. Results of analyses – and analyses of analyses – are stored as documents in a scalable, queryable database that stores the relationships and history among the experiment elements and documents. The interface allows the development of an application ecosystem where applications can focus on calculation rather than data format or organization. This tool can be used by individual labs to exchange and analyze data, and it can serve to curate neuroscience data for searchable archives.

Collaboration in neuroscience is impeded by the difficulty of sharing primary data, results, and software across labs. Here, we introduce Neuroscience Data Interface (NDI), a platform-independent standard that allows an analyst to use and create software that functions independently from the format of the raw data or the manner in which the data are organized into files. The interface is rooted in a simple vocabulary that describes common apparatus and storage devices used in neuroscience experiments. Results of analyses, and analyses of analyses, are stored as documents in a scalable, queryable database that stores the relationships and history among the experiment elements and documents. The interface allows the development of an application ecosystem where applications can focus on calculation rather than data format or organization. This tool can be used by individual labs to exchange and analyze data, and it can serve to curate neuroscience data for searchable archives.

An unprecedented [3+3]-annulation of p-quinamines and nitrile imines was developed, affording a series of 1,2,4-triazinone derivatives in moderate to excellent yields with excellent diastereoselectivity. This cycloaddition expands the scope of p-quinamines to the construction of six-membered nitrogen-containing heterocyclic compounds.

Background In 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients. Methods Adult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU. Results Among the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P

A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C3 synthons.

The first enantioselective sequential phosphine-catalyzed (SPC as abbreviation) mode for the formation of tetrahydroquinolines with an ethynyl-substituted all-carbon quaternary stereogenic center is reported. In this SPC process, a novel [4 + 2] annulation process was devised employing α-substituted allenoates as C2 synthons (α-β', 1,2-dipole) for the first time. 3-Ethynyl-substituted tetrahydroquinolines were readily prepared in good yields and high enantioselectivities.

Natural compounds have been confirmed as one of the most feasible solutions for hard-to-treat cancers such as hepatocellular carcinoma (HCC). Erianin, a natural bibenzyl compound from Dendrobium chrysotoxum, has been recently discovered with anticancer property in cancer cells. However, the roles and the molecular mechanisms of erianin in HCC remain unknown. The present study evaluates the effect of erianin on human HCC cells by inhibiting cell proliferation, inducing apoptotic-related cell death and hampering tumorigenicity. Furthermore, it was found that erianin could cause irreparable DNA damage, induce G2/M arrest and deregulate mitotic regulators. It was also observed that many cells with damaged DNA induced by erianin could overcome G2/M arrest and enter mitosis, leading to abnormal mitosis, and subsequently mitotic catastrophe and apoptotic-related cell death. The present study confirmed that erianin could be a potential antitumor agent for HCC clinical treatment.

Socioeconomic status (SES) disparities have profound impacts on child development and health, which are linked to negative emotions and alterations in the integrity of stress-sensitive hypothalamus-pituitary-adrenal (HPA)-axis system. However, its underlying psychophysiological mechanisms remain poorly understood. Here we investigate how family SES, in concert with parental anxiety, affects children's anxiety and their integrity of HPA-axis system in two studies involving a total of 1318 children and their parents. In Study 1 with a cohort of 1088 children and their parents, we found that low-SES children relative to high-SES ones experienced a higher level of anxiety mediated by increasing parental anxiety. In Study 2 with an independent cohort of 230 children and their parents, we found that low-SES children exhibited an increase in pre-bedtime basal cortisol but a decrease in cortisol awakening response (CAR). Structural equation modeling (SEM) further revealed that the association between low SES and children's reduced CAR was mediated by increased parental and child anxiety. Our findings suggest that low-SES children are more vulnerable to anxiety and altered HPA-axis integrity, most likely mediated through increased parental anxiety.

AGI grading during the 7-day ICU stay among survivors and nonsurvivors. (DOC 61 kb)

Characteristics of the patients with and without AGI. (DOC 54 kb)

In this paper, amphipathic poly(d,l-lactide-co-glycolide)-polyethylene glycol-poly(d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers were synthesized via bulk ring-opening polymerization with d,l-lactide (d,l-LA), glycolide (GA), and polyethylene glycol (PEG) as raw materials and tin(ii) bis(2-ethylhexanoate) (Sn(Oct)2) as catalyst. The synthesis and purification processes were free from organic solvent. The chemical structure of PLGA-PEG-PLGA was characterized by Fourier transform infrared spectroscopy, 1H NMR, gel permeation chromatography, differential scanning calorimetry, and thermo gravimetric analysis. The thermo-sensitivity of PLGA-PEG-PLGA aqueous solution was examined, and the results showed that the copolymers concentration, mass ratio of d,l-LA/GA, and molecular weight of PEG played important parts in controlling the sol–gel transition temperature. The sol–gel transition occurred at lower temperatures with higher copolymer concentrations and mass ratios of d,l-LA/GA. In contrast, the sol–gel transition temperature increased with higher molecular weights of PEG. In vitro drug release studies were carried out using ceftibuten as a model drug. The results indicated that PLGA-PEG-PLGA prepared with 30 wt-% PEG1500 and 70 wt-% PLGA (mass ratio of d,l-LA/GA = 2 : 1) was an effective system for achieving long-sustained controlled release. The drug release from the hydrogel showed a higher initial release followed by a slower pattern up to 120 h, and the mean retention time was ~50 h.