Leveraging Electron Push-Pull Effect for Catalytic Polymerization and Degradation of a Cyclobutane Monomer System.

Ring-opening polymerization (ROP) offers a striking solution to solve problems encountered in step-growth condensation polymerization, including precise control over molecular weight, molecular weight distribution, and topology. This has inspired our interest in ROP of cycloalkanes with an ultimate goal to rethink polyolefins, which clearly poses a number of challenges. Practicality of ROP of cycloalkanes is actually limited by their low polymerizability and elusive mechanisms which arise from significantly varied ring size and non-polar C-C bonds in monomers. In this work, by using Lewis acid/Brønsted base/C(sp3)-H initiator system previously developed in our laboratory, we focus on cyclobutanes and explore the positional and electronic effects of substituents on the ring, namely electron push-pull effect, in promoting controlled polymerization to afford densely functionalized poly(cyclobutanes), as well as catalytic degradation of obtained polymers for upcycling. More importantly, experiments and DFT calculations unveil considerable population of Lewis-acid-induced thermostabilized 1,4-zwitterions, which distinguish cyclobutanes from cyclopropanes and others. All these findings would shed light on catalytic synthesis and degradation of saturated all-carbon main-chain polymers, as well as small molecule transformations of cyclobutanes.

Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Directional Pumpless Transport of Biomolecules through Self-Propelled Nanodroplets on Patterned Heterostructures.

The surface patterning in natural systems has exhibited appreciable functional advantages for life activities, which serve as inspiration for the design of artificial counterparts to achieve functions such as directional liquid transport at the nanoscale. Here, we propose a patterned two-dimensional (2D) in-plane heterostructure with a triangle-shaped hexagonal boron nitride (hBN) track embedded in graphene nanosheets, which can achieve unidirectional and self-propelled transport of nanodroplets carrying various biomolecules such as DNA, RNA, and peptides. Our extensive MD simulations show that the wettability gradient on the patterned heterostructure can drive the motion of nanodroplet with an instantaneous acceleration, which also permits long-distance transport (>100 nm) at the microsecond time scale. The different behaviors of various types of biomolecules have been further studied systematically within the transporting nanodroplets. These findings suggest that these specially designed, patterned heterostructures have the potential for spontaneous, directional transport of important biomolecules, which might be useful in biosensing, drug delivery, and biomedical nanodevices.

The Deinococcus protease PprI senses DNA damage by directly interacting with single-stranded DNA.

Bacteria have evolved various response systems to adapt to environmental stress. A protease-based derepression mechanism in response to DNA damage was characterized in Deinococcus, which is controlled by the specific cleavage of repressor DdrO by metallopeptidase PprI (also called IrrE). Despite the efforts to document the biochemical, physiological, and downstream regulation of PprI-DdrO, the upstream regulatory signal activating this system remains unclear. Here, we show that single-stranded DNA physically interacts with PprI protease, which enhances the PprI-DdrO interactions as well as the DdrO cleavage in a length-dependent manner both in vivo and in vitro. Structures of PprI, in its apo and complexed forms with single-stranded DNA, reveal two DNA-binding interfaces shaping the cleavage site. Moreover, we show that the dynamic monomer-dimer equilibrium of PprI is also important for its cleavage activity. Our data provide evidence that single-stranded DNA could serve as the signal for DNA damage sensing in the metalloprotease/repressor system in bacteria. These results also shed light on the survival and acquired drug resistance of certain bacteria under antimicrobial stress through a SOS-independent pathway.

Distinct antiviral activities of IFNφ1 and IFNφ4 in zebrafish.

Interferons (IFNs) are a group of secreted cytokines that play a crucial role in antiviral immunity. Type I IFNs display functional disparities. In teleosts, type I IFNs are categorized into two subgroups containing one or two pairs of disulfide bonds. However, their functional differences have not been fully elucidated. In this study, we comparatively characterized the antiviral activities of zebrafish IFNφ1 and IFNφ4 belonging to the group I type I IFNs. It was found that ifnφ1 and ifnφ4 were differentially modulated during viral infection. Although both IFNφ1 and IFNφ4 activated JAK-STAT signaling pathway via CRFB1/CRFB5 receptor complex, IFNφ4 was less potent in inducing phosphorylation of STAT1a, STAT1b and STAT2 and the expression of antiviral genes than IFNφ1, thereby conferring weaker antiviral resistance of target cells. Taken together, our results provide insights into the functional divergence of type I IFNs in lower vertebrates.

Sequential transcriptomic alterations in the cerebral cortex of mice after cerebral venous sinus thrombosis.

To investigate the expression alterations of specific genes that occur after venous stroke, we identified differentially expressed genes (DEGs) between sham and damaged cortical tissues at 2 and 7 days after induction of cerebral venous sinus thrombosis (CVST) model. The profiles of DEGs were analyzed using GO, KEGG, GSEA, and PPI, and the crucial gene was further verified by western blot and immunofluorescence. We found 969 and 883 DEGs at 2 and 7 days after CVST, respectively. A marked increase in biological-process categories, such as immune system process and inflammatory response, and a decrease in neuropeptide signaling pathway were observed both at 2 and 7 days post-CVST. The KEGG pathway was enriched to varying degrees on complement and coagulation cascades, cytokine-cytokine receptor interaction, and multiple immune-inflammatory signaling pathways at 2 and 7 days post-CVST, separately. Furthermore, GSEA highlights the potential roles of the NOD-like receptor signaling pathway and cytokine-cytokine receptor interaction in CVST. Importantly, numerous genes related to KEGG pathways above featured prominently in the PPI network analysis, with IL1b being one of the most conspicuous. These time-dependent alterations in gene profiles and enrichment pathways reveal the unique pathophysiological characteristics of CVST and indicate novel therapeutic targets for venous stroke. SIGNIFICANCE: Cerebral venous sinus thrombosis (CVST) is an underrated and potentially fatal cause of stroke with a reported mortality of 5-10% worldwide. Currently, in addition to anticoagulant and thrombolytic therapy, effective treatments targeting the injured brain parenchyma after CVST remain limited. Besides, accurate diagnostic markers are still sorely lacking. In the present study, we will detect the transcriptomic alterations of the cerebral cortex of mice post-CVST by RNA-sequencing, screen differentially expressed genes and abnormal pathways through bioinformatics methods, analyze the correlation of these signals and CVST pathology, and finally validate the key molecules through western blot and immunofluorescence assays. Collectively, the study aimed to offer a reference for the discovery of specific genes/pathway alterations in the damaged cortical tissues of CVST mice and further reveal the underlying pathogenesis, thereby providing evidence for the diagnosis and treatment of CVST.

Predicted superconductivity in one-dimensional A3Hf2B3-type electrides.

Inorganic electrides are considered potential superconductors due to the unique properties of their anionic electrons. However, most electrides require external high-pressure conditions to exhibit considerable superconducting transition temperatures (Tc). Therefore, searching for superconducting electrides under low or moderate external pressures is of significant research interest and importance. In this work, a series of A3Hf2B3-type compounds (A = Mg, Ca, Sr, Ba; B = Si, Ge, Sn, Pb) were constructed and systematically studied based on density functional theory calculations. According to the analysis of the electronic structures and phonon dispersion spectrums, stable one-dimensional electrides Ca3Hf2Ge3, Ca3Hf2Sn3, and Sr3Hf2Pb3, were screened out. Interestingly, the superconductivity of these electrides were predicted from electron phonon coupling calculations. It is highlighted that Sr3Hf2Pb3 showed the highest Tc, reaching 4.02 K, while the Tc values of Ca3Hf2Ge3 and Ca3Hf2Sn3 were 1.16 K and 1.04 K, respectively. Moreover, the Tc value of Ca3Hf2Ge3 can be increased to 1.96 K under 20 GPa due to the effect of phonon softening. This work enriches the types of superconducting electrides and has important guiding significance for the research on constructing electrides and related superconducting materials.

Characteristics and Potential Neural Substrates of Encoding and Retrieval During Memory Binding in Amnestic Mild Cognitive Impairment.

BACKGROUND: Whether encoding or retrieval failure contributes to memory binding deficit in amnestic mild cognitive impairment (aMCI) has not been elucidated. Also, the potential brain structural substrates of memory binding remained undiscovered. OBJECTIVE: To investigate the characteristics and brain atrophy pattern of encoding and retrieval performance during memory binding in aMCI. METHODS: Forty-three individuals with aMCI and 37 cognitively normal controls were recruited. The Memory Binding Test (MBT) was used to measure memory binding performance. The immediate and delayed memory binding indices were computed by using the free and cued paired recall scores. Partial correlation analysis was performed to map the relationship between regional gray matter volume and memory binding performance. RESULTS: The memory binding performance in the learning and retrieval phases was worse in the aMCI group than in the control group (F = 22.33 to 52.16, all p < 0.001). The immediate and delayed memory binding index in the aMCI group was lower than that in the control group (p < 0.05). The gray matter volume of the left inferior temporal gyrus was positively correlated with memory binding test scores (r = 0.49 to 0.61, p < 0.05) as well as the immediate (r = 0.39, p < 0.05) and delayed memory binding index (r = 0.42, p < 0.05) in the aMCI group. CONCLUSION: aMCI may be primarily characterized by a deficit in encoding phase during the controlled learning process. Volumetric losses in the left inferior temporal gyrus may contribute to encoding failure.

Co-pyrolysis of biomass and polyethylene: Insights into characteristics, kinetic and evolution paths of the reaction process.

Investigation on the distribution and mechanism of co-pyrolysis products is vital to the directional control and high-value utilization of agriculture solid wastes. Co-pyrolysis, devolatilization, kinetics characteristics, and evolution paths of corn stalk (CS) and low-density-polyethylene (LDPE) were investigated via thermogravimetric experiments. The co-pyrolysis behaviors could be separated into two stages: firstly, the degradation of CS (150- 400 °C); secondly, the degradation of CS (400- 550 °C). The devolatilization index (DI) increased with the addition of LDPE. Furthermore, a combination of devolatilization chemical analysis with product analysis to analyze the intrinsic mechanism during co-pyrolysis. The results indicated that the yield of alkanes and olefin in gas products increased with the addition of LDPE. Additionally, LDPE pyrolysis maybe abstract hydrogen from CS pyrolysis and evolved into hydrogen, methane, and ethylene. Further, the co-pyrolysis kinetic parameters were computed by using model-free isoconversion methods, which showed promotion of CS pyrolysis and the reduced activation energy. All the activation energy were declined, which indicated a "bidirectional positive effect" during co-pyrolysis. The mean activation energy of P-cellulose (P-CE), P-hemicellulose (P-HM), P-lignin (P-LG), and LDPE decreased by 23.49 %, 12.89 %, 15.36 %, and 27.82 %, respectively. This study further proves the hydrogen donor transfer pathway in the co-pyrolysis process of CS and LDPE, providing theoretical support for the resource utilization of agricultural solid waste.

Characteristics of Odor Identification and Hedonics and Their Association with Piriform Cortex-Based Resting-State Functional Connectivity in Amnestic Mild Cognitive Impairment.

BACKGROUND: Olfactory identification dysfunction (OID) might be an early sign of amnestic mild cognitive impairment (aMCI). However, odor hedonics, the ability to perceive odor pleasantness, is neglected. Also, the neural substrate of OID remains unclear. OBJECTIVE: To explore the characteristics of odor identification and hedonics in aMCI and examine the potential neural correlates of OID by analyzing olfactory functional connectivity (FC) patterns in MCI. METHODS: Forty-five controls and 83 aMCI patients were examined. The Chinese smell identification test was used to assess olfaction. Global cognition, memory, and social cognition were assessed. Resting-state functional networks associated with olfactory cortex seeds were compared between the cognitively normal (CN) and aMCI groups, as well as between aMCI subgroups by the degree of OID. RESULTS: Compared to controls, aMCI patients had a significant deficit in olfactory identification, mainly reflected in the identification of pleasant and neutral odors. aMCI patients also rated pleasant and neutral odors much lower than controls. A positive correlation between olfaction and social cognition was found in aMCI. The seed-based FC analysis found that aMCI patients had higher FC between the right orbitofrontal cortex and right frontal lobe/middle frontal gyrus than controls. Subgroup analysis showed that, compared to aMCI without OID, aMCI with severe OID had abnormal FC in the bilateral piriform region. CONCLUSION: Our results suggest that OID in aMCI primarily refers to the identification of pleasant and neutral odors. The FC alterations in bilateral orbitofrontal cortex and piriform cortices might contribute to the impairment in odor identification.

Structural basis of BAM-mediated outer membrane ß-barrel protein assembly.

The outer membrane structure is common in Gram-negative bacteria, mitochondria and chloroplasts, and contains outer membrane ß-barrel proteins (OMPs) that are essential interchange portals of materials1-3. All known OMPs share the antiparallel ß-strand topology4, implicating a common evolutionary origin and conserved folding mechanism. Models have been proposed for bacterial ß-barrel assembly machinery (BAM) to initiate OMP folding5,6; however, mechanisms by which BAM proceeds to complete OMP assembly remain unclear. Here we report intermediate structures of BAM assembling an OMP substrate, EspP, demonstrating sequential conformational dynamics of BAM during the late stages of OMP assembly, which is further supported by molecular dynamics simulations. Mutagenic in vitro and in vivo assembly assays reveal functional residues of BamA and EspP for barrel hybridization, closure and release. Our work provides novel insights into the common mechanism of OMP assembly.

De Novo Evolution of an Antibody-Mimicking Multivalent Aptamer via a DNA Framework.

Multivalent interactions can often endow ligands with more efficient binding performance toward target molecules. Generally speaking, a multivalent aptamer can be constructed via post-assembly based on chemical structural information of target molecules and pre-identified monovalent aptamers derived from traditional systematic evolution of ligands by exponential enrichment (SELEX) technology. However, many target molecules may not have known matched aptamer partners, thus a de novo evolution will be highly desired as an alternative strategy for directed selection of a high-avidity, multivalent aptamer. Here, inspired by the superiority of multivalent interactions between antibodies and antigens, a direct SELEX strategy with a preorganized DNA framework library for an "Antibody-mimicking multivalent aptamer" (Amap) selection to epithelial cell adhesion molecule (EpCAM), a model target protein is reported. The Amap presents a relatively good binding affinity through both aptamer moieties concurrently binding to EpCAM, which has been confirmed by affinity analysis and molecular modeling. Furthermore, dynamic interactions between Amap and EpCAM are directly visualized by magnetic tweezers at the single-molecule level. A nice binding affinity of Amap to EpCAM-positive cancer cells has also been verified, which hints that their Amap-SELEX strategy has the potential to be a new route for de novo evolution of multivalent aptamers.

Incongruent gray matter atrophy and functional connectivity of striatal subregions in behavioral variant frontotemporal dementia.

Previous studies on the striatum demonstrated that it is involved in the regulation of cognitive function and psychiatric symptoms in patients with behavioral variant frontotemporal dementia (bvFTD). Multiple lines of evidence have shown that striatal subregions have their own functions. However, the results of the existing studies on striatal subregions are inconsistent and unclear. In this study, we found that structural imaging analysis revealed that the bvFTD patients had smaller volumes of striatal subregions than the controls. We found that the degree of atrophy varied across the striatal subregions. Additionally, the right striatal subregions were significantly more atrophic than the left in bvFTD. Functional imaging analysis revealed that bvFTD patients exhibited different changed patterns of resting-state functional connectivity (RSFC) when striatal subregions were selected as regions of interest (ROI). The RSFC extending range on the right ROIs was more significant than on the left in the same subregion. Interestingly, the RSFC of the subregions extending to the insula were consistent. In addition, the left dorsolateral putamen may be involved in executive function regulation. This suggests that incongruence in striatal subregions may be critical to the bvFTD characteristics.

Comparative study on fuel characteristics and pyrolysis kinetics of corn residue-based hydrochar produced via microwave hydrothermal carbonization.

Corn residues are an important source of bioenergy. Due to their highly diverse lignocellulosic structures, the hydrochar produced from microwave-assisted carbonization of different corn residues may have distinct fuel properties and pyrolysis kinetics. This study comprehensively investigated the effect of processing temperature on the basic fuel properties of hydrochar and examined the pyrolysis behavior of hydrochar as a precursor through kinetic analysis. The results indicate that the fuel quality of corn straw hydrochar prepared by microwave-assisted hydrothermal carbonization at 230 °C was significantly improved over that of its feedstock, with a higher heating value of approximately 20.7 MJ/kg. Hydrochar prepared by microwave-assisted hydrothermal carbonization of corn cob at 230 °C presents noticeable environmental advantages because it contains the lowest ash and nitrogen contents (0.5% and 0.5%, respectively) and lower sulfur content (0.05%). Moreover, regarding the kinetic modeling, the Doyle and Coats-Redfern models, which are both first-order and single-step kinetic models, were identified as satisfactory in interpreting the key pyrolysis kinetic parameters. Additionally, the microwave-assisted hydrothermal process increased the apparent activation energy of hydrochar due to the increase in crystallinity and the increase in the number of CC and CO bonds.

The pattern of cortical thickness underlying disruptive behaviors in Alzheimer's disease.

Background: Disruptive behaviors, including agitation, disinhibition, irritability, and aberrant motor behaviors, are commonly observed in patients with Alzheimer's disease (AD). However, the neuroanatomical basis of these disruptive behaviors is not fully understood. Objective: To confirm the differences in cortical thickness and surface area between AD patients and healthy controls and to further investigate the features of cortical thickness and surface area associated with disruptive behaviors in patients with AD. Methods: One hundred seventy-four participants (125 AD patients and 49 healthy controls) were recruited from memory clinics at the Peking University Institute of Sixth Hospital. Disruptive behaviors, including agitation/aggression, disinhibition, irritability/lability, and aberrant motor activity subdomain scores, were evaluated using the Neuropsychiatry Inventory. Both whole-brain vertex-based and region-of-interest-based cortical thickness and surface area analyses were automatically conducted with the CIVET pipeline based on structural magnetic resonance images. Both group-based statistical comparisons and brain-behavior association analyses were performed using general linear models, with age, sex, and education level as covariables. Results: Compared with healthy controls, the AD patients exhibited widespread reduced cortical thickness, with the most significant thinning located in the medial and lateral temporal and parietal cortex, and smaller surface areas in the left fusiform and left inferior temporal gyrus. High total scores of disruptive behaviors were significantly associated with cortical thinning in several regions that are involved in sensorimotor processing, language, and expression functions. The total score of disruptive behaviors did not show significant associations with surface areas. Conclusion: We highlight that disruptive behaviors in patients with AD are selectively associated with cortical thickness abnormalities in sensory, motor, and language regions, which provides insights into neuroanatomical substrates underlying disruptive behaviors. These findings could lead to sensory, motor, and communication interventions for alleviating disruptive behaviors in patients with AD.

LncRNA HLA-F-AS1 Enhances the Migration, Invasion and Apoptosis of Glioblastoma Cells by Targeting lncRNA MEG3.

BACKGROUND: Previous studies revealed the oncogenic role of long non-coding RNA (lncRNA) HLA-F-AS1 in colon cancer and breast cancer, while its role in other cancers is unclear. We predicted the direct interaction between HLA-F-AS1 and MEG3, which is a tumor suppressor lncRNA. We then assessed the interaction between HLA-F-AS1 and MEG3 in glioblastoma (GBM). METHODS: The expression levels of HLA-F-AS1 and MEG3 in GBM and paired non-tumor tissues from 60 GBM patients were analyzed by RT-qPCR. Overexpression of HLA-F-AS1 and MEG3 was achieved in GBM cells to explore the interaction between them. The direct interaction between them was confirmed by RNA pull-down assay. The roles of HLA-F-AS1 and MEG3 in cell invasion, migration and apoptosis were explored by Transwell assays and cell apoptosis assay. RESULTS: HLA-F-AS1 was highly expressed, and MEG3 was downregulated in GBM. Overexpression of HLA-F-AS1 reduced the expression levels of MEG3 while overexpression of MEG3 did not alter the expression of HLA-F-AS1. HLA-F-AS1 increased cell migration and invasion, but decreased cell apoptosis. MEG3 played opposite roles and reduced the effects of HLA-F-AS1 on cell behaviors. CONCLUSION: HLA-F-AS1 may sponge MEG3 in GBM cells to promote cell invasion and migration, and to suppress cell apoptosis.

Long non-coding RNA as a potential biomarker for prognosis of glioma: A protocol for systematic review and meta-analysis.

BACKGROUND: The molecular mechanism of Glioma is still unclear, and there are few early diagnostic markers. Therefore, it is urgent to figure out effective preventive measures, active diagnostic methods and rapid treatment measures. In recent years, relevant studies have revealed that long non-coding RNA (lncRNA) is associated with the prognosis of Glioma. However, these results have not been supported by any evidence. Therefore, this study carried out a meta-analysis method to analyze the relationship between lncRNA and the prognosis of Glioma. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of lncRNAs in Glioma. METHODS: We performed a systematic search in electronic databases, including China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between lncRNA expression and prognostic significance and clinical features in glioma patients. Hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the prognosis value of lncRNA by Stata16.0 software. The online tool AnnoLnc was applied to screen the co-expressed gene related to each lncRNA, David was used for gene ontology (GO) analysis and enrichment analysis of the signal pathway, and through Starbase, the possible competitive endogenous RNA network of lncRNAs was constructed. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence-based medical evidence for lncRNA, so as to predict the prognosis of Glioma and bioinformatics analysis will provide ideas for the mechanism study on Glioma.

Memantine protects blood-brain barrier integrity and attenuates neurological deficits through inhibiting nitric oxide synthase ser1412 phosphorylation in intracerebral hemorrhage rats: involvement of peroxynitrite-related matrix metalloproteinase-9/NLRP3 inflammasome activation.

Memantine has demonstrated beneficial effects on several types of brain insults via therapeutic mechanisms mainly related to its activity as a receptor antagonist of N-methyl-d-aspartate. However, the influences of memantine on intracerebral hemorrhage (ICH) remain obscure. This research probed into the neurovascular protective mechanisms of memantine after ICH and its impacts on neuronal nitric oxide synthase (nNOS) ser1412 phosphorylation. ICH model was established by employing intrastriatal collagenase injection in rats. After modeling, rats were then allocated randomly into sham-operated (sham), vehicle-treated (ICH+V), and memantine-administrated (ICH+M) groups. Memantine (20 mg/kg/day) was intraperitoneally administered 30 min after ICH and thenceforth once daily. Rats were dedicated at 0.25, 6, 12, 24 h, 3 and 7 d post-ICH for measurement of corresponding indexes. Behavioral changes, brain edema, levels of nNOS ser1412 phosphorylation, peroxynitrite, matrix metalloproteinase (MMP)-9, NLRP3, IL-1ß and numbers of dying neurons, as well as the cellular localization of gelatinolytic activity, were detected among the groups. Memantine improved the neurologic deficits and mitigated brain water content, levels of MMP-9, NLRP3, IL-1ß and dying neurons. Additionally, treatment with memantine also reduced nNOS ser1412 phosphorylation and peroxynitrite formation compared with the ICH+V group at 24 h after ICH. In situ zymography simultaneously revealed that gelatinase activity was primarily colocalized with vessel walls and neurons. We concluded that memantine ameliorated blood-brain barrier disruption and neurologic dysfunction in an ICH rat model. The underlying mechanism might involve repression of nNOS ser1412 phosphorylation, as well as peroxynitrite-related MMP-9 and NLRP3 inflammasome activation.

Protein Structure Prediction Using Population-Based Algorithm Guided by Information Entropy.

Ab initio protein structure prediction is one of the most challenging problems in computational biology. Multistage algorithms are widely used in ab initio protein structure prediction. The different computational costs of a multistage algorithm for different proteins are important to be considered. In this study, a population-based algorithm guided by information entropy (PAIE), which includes exploration and exploitation stages, is proposed for protein structure prediction. In PAIE, an entropy-based stage switch strategy is designed to switch from the exploration stage to the exploitation stage. Torsion angle statistical information is also deduced from the first stage and employed to enhance the exploitation in the second stage. Results indicate that an improvement in the performance of protein structure prediction in a benchmark of 30 proteins and 17 other free modeling targets in CASP.

Decision-Making Under Ambiguity or Risk in Individuals With Alzheimer's Disease and Mild Cognitive Impairment.

BACKGROUND: Making advantageous decisions is essential in everyday life. Our objective was to assess how patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) make decisions under conditions of ambiguity or risk. In addition, the study also aimed to examine the relationship between decision-making competence and memory and executive function. METHODS: Patients with MCI (n = 36) and AD (n = 29) and healthy elderly controls (HC, n = 34) were recruited from the memory clinic. All subjects were administered a comprehensive neuropsychological battery test. We used the Iowa Gambling Task (IGT) to measure decision-making under ambiguity and the Game of Dice Task (GDT) to measure decision-making under risk. Pearson's correlation was used to examine the relationship between the performance of IGT and GDT with delayed recall and the Stroop test. RESULTS: In the GDT, MCI and AD patients presented similar performance but showed different patterns when compared with the HC group. The proportion of those making advantageous choices was lower in the AD group than in the HC group (p = 0.01), while the MCI and HC groups did not differ (p = 0.14). Meanwhile, concerning the ratio of accepting negative feedback, the AD (p < 0.01) group was significantly different from the HC patients, but the MCI (p = 0.06) and HC groups did not differ. In the IGT, MCI and AD patients selected randomly from advantageous and disadvantageous decks (p = 0.94 and p = 0.54), showing no significant change in performance over time. In contrast, the HC group made increasingly frequent advantageous selections over time (p = 0.04). Furthermore, the proportion of advantageous decision-makers for the GDT had a linear relationship with delayed recall of the Hopkins Verbal Learning Test and Stroop color words (p < 0.01 and p < 0.01, respectively). CONCLUSION: Our findings suggest that decision-making ability under ambiguity is compromised in MCI and AD, and the decision-making under risk is only impaired in AD. Reduced decision-making performance under risk is closely correlated with lower executive functions and memory.