Connectional-style-guided contextual representation learning for brain disease diagnosis.

Structural magnetic resonance imaging (sMRI) has shown great clinical value and has been widely used in deep learning (DL) based computer-aided brain disease diagnosis. Previous DL-based approaches focused on local shapes and textures in brain sMRI that may be significant only within a particular domain. The learned representations are likely to contain spurious information and have poor generalization ability in other diseases and datasets. To facilitate capturing meaningful and robust features, it is necessary to first comprehensively understand the intrinsic pattern of the brain that is not restricted within a single data/task domain. Considering that the brain is a complex connectome of interlinked neurons, the connectional properties in the brain have strong biological significance, which is shared across multiple domains and covers most pathological information. In this work, we propose a connectional style contextual representation learning model (CS-CRL) to capture the intrinsic pattern of the brain, used for multiple brain disease diagnosis. Specifically, it has a vision transformer (ViT) encoder and leverages mask reconstruction as the proxy task and Gram matrices to guide the representation of connectional information. It facilitates the capture of global context and the aggregation of features with biological plausibility. The results indicate that CS-CRL achieves superior accuracy in multiple brain disease diagnosis tasks across six datasets and three diseases and outperforms state-of-the-art models. Furthermore, we demonstrate that CS-CRL captures more brain-network-like properties, and better aggregates features, is easier to optimize, and is more robust to noise, which explains its superiority in theory.

Using a deep generation network reveals neuroanatomical specificity in hemispheres.

Asymmetry is an important property of brain organization, but its nature is still poorly understood. Capturing the neuroanatomical components specific to each hemisphere facilitates the understanding of the establishment of brain asymmetry. Since deep generative networks (DGNs) have powerful inference and recovery capabilities, we use one hemisphere to predict the opposite hemisphere by training the DGNs, which automatically fit the built-in dependencies between the left and right hemispheres. After training, the reconstructed images approximate the homologous components in the hemisphere. We use the difference between the actual and reconstructed hemispheres to measure hemisphere-specific components due to asymmetric expression of environmental and genetic factors. The results show that our model is biologically plausible and that our proposed metric of hemispheric specialization is reliable, representing a wide range of individual variation. Together, this work provides promising tools for exploring brain asymmetry and new insights into self-supervised DGNs for representing the brain.

A novel fluorescent aptasensor for sensitive and selective detection of environmental toxins fumonisin B1 based on enzyme-assisted dual recycling amplification and 2D δ-FeOOH-NH2 nanosheets.

Fumonisin (FB) is a pervasive hazardous substance in the environment, presenting significant threats to human health and ecological systems. Thus, the selective and sensitive detection of fumonisin B1 (FB1) is crucial due to its high toxicity and wide distribution in corn, oats, and related products. In this work, we developed a novel and versatile fluorescent aptasensor by combining enzyme-assisted dual recycling amplification with 2D δ-FeOOH-NH2 nanosheets for the determination of FB1. The established CRISPR/Cas12a system was activated by using activator DNA (aDNA), which was released via a T7 exonuclease-assisted recycling reaction. Additionally, the activated Cas12a protein was utilized for non-specifically cleavage of the FAM-labeled single-stranded DNA (ssDNA-FAM) anchored on δ-FeOOH-NH2 nanosheets. The pre-quenched fluorescence signal was restored due to the desorption of the cleaved ssDNA-FAM. Due to the utilization of this T7 exonuclease-Cas12a-δ-FeOOH-NH2 aptasensor for signal amplification, the detection range of FB1 was expanded from 1 pg/mL to 100 ng/mL, with a limit of detection (LOD) as low as 0.45 pg/mL. This study not only provides novel insights into the development of fluorescence biosensors based on 2D nanomaterials combined with CRISPR/Cas12a, but also exhibits remarkable applicability in detecting other significant targets.

The synergistic effect of metal ions and amino acids on the fermentation of ß-CGTase-producing statin DF257.

To meet the growing demand of ß-cyclodextrin (CD), innovative approaches are being developed to improve the production of ß-CD by ß-cyclodextrin glucose-transferase (CGTase). Considering the low production and efficacy of wild-type ß-CGTase-producing strains, to obtain the strains suitable for industrial production of ß-CGTase, the recombinant engineered bacteria strain DF257 is constructed by transfecting with the plasmid expressing His tagged ß-CGTase. The fermentation of ß-CGTase-expressing DF257 was optimized in the presence of different metal ions, amino acids, and incubated at a certain temperature and pH condition. The results showed that when Mg2+ and isoleucine were added into the culture medium at 0.5 mM and 0.5 g/L, respectively, the enzyme activity of ß-CGTase increased significantly after incubation at 37 °C with the initial pH of 7.5. In addition, the optimal temperature for ß-CGTase with the addition of Mg2+ and isoleucine was also determined. The T half of ß-CGTase under 50, 55, 60 and 65 °C was 9.5, 8.8, 6.2 and 1.2 h, respectively. Further investigation showed that ß-CGTase kept stable under the pH 6.0-10.0, and pH 7.5 was identified as the optimal pH condition of ß-CGTase. With the addition of Mg2+ and isoleucine, the kinetic properties of ß-CGTase in the cyclization reaction had a similar form with Michaelis equation under 50 °C and pH 7.5, and Vmax, Km, and Kcat was 3.74 mg/mL/min, 3.28 mg/mL, and 31.17/s, respectively. The possible underlying mechanism by which Mg2+ and isoleucine synergistically improved the thermostability of ß-CGTase was investigated by the surface hydrophobicity index analysis, Fourier transform infrared spectroscopy and differential scanning calorimetry (DSC) analysis. The results indicated that addition of Mg2+ and isoleucine maintained the spatial structure and enhanced the thermostability of ß-CGTase. These findings provided a theoretical basis for realizing the industrialization application of ß-CGTase in promoting the generation of ß-CD.

Neurovascular coupling dysfunction of visual network organization in Parkinson's disease.

Parkinson's disease (PD) has been showed perfusion and neural activity alterations in specific regions, such as the motor and visual networks; however, the clinical significance of coupling changes is still unknown. To identify how neurovascular coupling changes during the pathophysiology of PD, patients and healthy controls underwent multiparametric magnetic resonance imaging to measure neural activity organization of segregation and integration using amplitude of low-frequency fluctuation (ALFF) and functional connectivity strength (FCS), and measure vascular responses using cerebral blood flow (CBF). Neurovascular coupling was calculated as the global CBF-ALFF and CBF-FCS coupling and the regional CBF/ALFF and CBF/FCS ratio. Correlations and dynamic causal modeling was then used to evaluate relationships with disease-alterations to clinical variables and information flow. Neurovascular coupling was impaired in PD with decreased global CBF-ALFF and CBF-FCS coupling, as well as decreased CBF/ALFF in the parieto-occipital cortex (dorsal visual stream) and CBF/FCS in the temporo-occipital cortex (ventral visual stream); these decouplings were associated with motor and non-motor impairments. The distinctive patterns of neurovascular coupling alterations within the dorsal and ventral visual streams of the visual system could potentially provide additional understanding into the pathophysiological mechanisms of PD.

The combination of insulin and linezolid ameliorates Staphylococcus aureus pneumonia in individuals with diabetes via the TLR2/MAPKs/NLRP3 pathway.

Diabetes mellitus (DM) complicated with Staphylococcus aureus (S. aureus) infection lacks effective treatment strategies. In this study, we found that insulin combined with linezolid has potential to deal with the thorny problem. In vitro, our drug sensitivity assay, bacterial growth curve and hemolytic tests showed that a combination of insulin and linezolid exerted good antibacterial and anti-α-hemolysin activity, CCK8 experiment, glucose content and glycogen content determination showed that the combination of insulin and linezolid increased murine macrophage survival rate and reduced the extracellular glucose level of high glucose-treated MH-S cells and intracellular glycogen level, and Western blot showed that the combination inhibited TLR2/MAPKs/NLRP3-related inflammatory pathways in MH-S cells. The results of in vivo experiments showed that the combination therapy stabilized glucose level, remained body weight, ameliorated lung injury including improving pulmonary edema and decreasing lung wet/dry weight ratio, reduced the CFUs and inflammation in the lung tissue in a mouse model of diabetes with S. aureus pneumonia, and inhibited the expression of TLR2, MAPKs and NLRP3 inflammatory pathway. Overall, the combination of insulin and linezolid as autolytic inhibitor exhibited the effects of significant antibacterial and improving glucose level in vitro and in vivo, and also has an anti-inflammation activity via the TLR2/MAPKs/NLRP3 pathway, this paves the way for new treatments for diabetes mellitus complicated with S. aureus infection.

Multisectoral drivers of decarbonizing battery electric vehicles in China.

China has made great progress in the electrification of passenger cars, and the sales of battery electric vehicles (BEVs) have exceeded 10%. We applied a life-cycle assessment (LCA) method to estimate the carbon dioxide (CO2) emissions of the past (2015), present (2020), and future (2030) BEVs, incorporating China's carbon peaking and neutrality policies, which would substantially reduce emissions from the electricity, operation efficiency, metallurgy, and battery manufacturing industries. BEVs can reduce cradle-to-grave (C2G) CO2 emissions by ∼40% compared with internal combustion engine vehicles (ICEVs) on the national-average level in 2020, far more significant than the benefit in 2015. Improved BEV operating efficiency was the largest factor driving emission reductions from 2015 to 2020. Looking forward to 2030, China's BEVs equipped with nickel-cobalt-manganese (NCM) batteries can achieve a further 43% of CO2 emissions reductions, among which 51 g km-1 of reduction is from the well-to-wheels (WTW) stage majorly owing to the further cleaner electricity mix, while other vehicle-cycle benefits are mainly from the advancement of battery (12 g km-1) and related metal materials (5 g km-1). We highlight the importance of better material efficiency and synchronized decarbonization through the automotive industrial chain in promoting climate mitigation from transport activities.

Attention Modulates the Role of Speakers' Voice Identity and Linguistic Information in Spoken Word Processing: Evidence From Event-Related Potentials.

PURPOSE: The human voice usually contains two types of information: linguistic and identity information. However, whether and how linguistic information interacts with identity information remains controversial. This study aimed to explore the processing of identity and linguistic information during spoken word processing by considering the modulation of attention. METHOD: We conducted two event-related potentials (ERPs) experiments in the study. Different speakers (self, friend, and unfamiliar speakers) and emotional words (positive, negative, and neutral words) were used to manipulate the identity and linguistic information. With the manipulation, Experiment 1 explored the identity and linguistic information processing with a word decision task that requires participants' explicit attention to linguistic information. Experiment 2 further investigated the issue with a passive oddball paradigm that requires rare attention to either the identity or linguistic information. RESULTS: Experiment 1 revealed an interaction among speaker, word type, and hemisphere in N400 amplitudes but not in N100 and P200, which suggests that identity information interacted with linguistic information at the later stage of spoken word processing. The mismatch negativity results of Experiment 2 showed no significant interaction between speaker and word pair, which indicates that identity and linguistic information were processed independently. CONCLUSIONS: The identity information would interact with linguistic information during spoken word processing. However, the interaction was modulated by the task demands on attention involvement. We propose an attention-modulated explanation to explain the mechanism underlying identity and linguistic information processing. Implications of our findings are discussed in light of the integration and independence theories.

Distinct Neural Resource Involvements but Similar Hemispheric Lateralization Patterns in Pre-Attentive Processing of Speaker's Identity and Linguistic Information.

The speaker's identity (who the speaker is) and linguistic information (what the speaker is saying) are essential to daily communication. However, it is unclear whether and how listeners process the two types of information differently in speech perception. The present study adopted a passive oddball paradigm to compare the identity and linguistic information processing concerning neural resource involvements and hemispheric lateralization patterns. We used two female native Mandarin speakers' real and pseudo-Mandarin words to differentiate the identity from linguistic (phonological and lexical) information. The results showed that, in real words, the phonological-lexical variation elicited larger MMN amplitudes than the identity variation. In contrast, there were no significant MMN amplitude differences between the identity and phonological variation in pseudo words. Regardless of real or pseudo words, the identity and linguistic variation did not elicit MMN amplitudes differences between the left and right hemispheres. Taken together, findings from the present study indicated that the identity information recruited similar neural resources to the phonological information but different neural resources from the lexical information. However, the identity and linguistic information processing did not show a particular hemispheric lateralization pattern at an early pre-attentive speech perception stage. The findings revealed similarities and differences between linguistic and non-linguistic information processing, contributing to a better understanding of speech perception and spoken word recognition.

Potential role of ghrelin in the regulation of inflammation.

Several diseases are caused or progress due to inflammation. In the past few years, accumulating evidence suggests that ghrelin, a gastric hormone of 28-amino acid residue length, exerts protective effects against inflammation by modulating the related pathways. This review focuses on ghrelin's anti-inflammatory and potential therapeutic effects in neurological, cardiovascular, respiratory, hepatic, gastrointestinal, and kidney disorders. Ghrelin significantly alleviates excessive inflammation and reduces damage to different target organs mainly by reducing the secretion of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), and inhibiting the nuclear factor kappa-B (NF-κB) and NLRP3 inflammasome signaling pathways. Ghrelin also regulates inflammation and apoptosis through the p38 MAPK/c-Jun N-terminal kinase (JNK) signaling pathway; restores cerebral microvascular integrity, and attenuates vascular leakage. Ghrelin activates the phosphoInositide-3 kinase (PI3K)/protein kinase B (Akt) pathway and inhibits inflammatory responses in cardiovascular diseases and acute kidney injury. Some studies show that ghrelin exacerbates colonic and intestinal manifestations of colitis. Interestingly, some inflammatory states, such as non-alcoholic steatohepatitis, inflammatory bowel diseases, and chronic kidney disease, are often associated with high ghrelin levels. Thus, ghrelin may be a potential new therapeutic target for inflammation-related diseases.

Modular-level alterations of single-subject gray matter networks in schizophrenia.

Schizophrenia is often regarded as a psychiatric disorder caused by disrupted connections in the brain. Evidence suggests that the gray matter of schizophrenia patients is damaged in a modular pattern. Recently, abnormal topological organization was observed in the gray matter networks of patients with schizophrenia. However, the modular-level alteration of gray matter networks in schizophrenia remains unclear. In this study, single-subject gray matter networks were constructed for a total of 217 subjects (116 patients with schizophrenia and 101 controls). We analyzed the topological characteristics of the brain network and the strengths of connections between and within modules. Compared with the outcomes in the control group, the global efficiency and participation coefficient values of the single-subject gray matter networks in schizophrenic patients were significantly reduced. The nodal participation coefficient of the regions involving the frontoparietal attention network, default mode network and subcortical network were significantly decreased in subjects with schizophrenia. The intermodule connections between the frontoparietal attention network and visual network and between the default mode network and subcortical network, in the frontoparietal attention network were significantly reduced in the patient group. In the frontoparietal attention network, the intramodule nodal connection strength of the left orbital inferior frontal gyrus and right inferior parietal gyrus was significantly decreased in schizophrenia patients. Reduced intermodule nodal connection strength between the frontoparietal attention network and visual network was associated with the severity of schizophrenia symptoms. These findings suggest that abnormal intramodule and intermodule connections in the structural brain network may a biomarker of schizophrenia symptoms.

The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation.

Staphylococcus aureus (S. aureus) infection is difficult to fight, previous experimental reports have demonstrated thioridazine (TZ) and tetracycline (TC) is an inhibitor of S. aureus efflux pump NorA and autolysin Atl, respectively, here, by means of molecular docking and molecular dynamics simulation, we observed that thioridazine (TZ) and tetracycline (TC) blocked the binding of substrates to NorA and Atl, respectively, and reduced their activities, and our antibacterial susceptibility test and three-dimensional checkerboard method showed that the three-drug combination of antibiotic cloxacillin (CXN), TZ and TC had a synergistic anti-Staphylococcal activity in vitro, and α-Hemolysin tests and scanning electron microscopy showed that the three-drug combination and the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin relative to the number of membrane-derived vesicles produced by S. aureus. Whereas Western blot and pharmacological inhibition assays showed that the three-drug combination significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in macrophages induced with S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts in the viscera of a mouse peritonitis model of S. aureus infection, therapy reduced the primary inflammatory pathology and the bacteria-stimulated release of cytokines such as IL-1ß and TNF-α, and inhibited the expression of MAPK/NF-κB/NLRP3 proteins in peritoneal macrophages. Thus, the combination of efflux pump inhibitor, autolysis inhibitor and antibiotic, is a novel anti-Staphylococcal and anti-inflammatory strategy who owning good antibacterial activity and significant inhibiting staphylococcal α-hemolysin and inflammation.

Highly Emissive Metal-Organic Frameworks for Sensitive and Selective Detection of Nitrofuran and Quinolone Antibiotics.

The overuse of antibiotics makes its detection very significant for human health. New facile methods and high-performance sensory materials will be urgently needed for detection of antibiotics. Unfortunately, there are few reports on fluorescence enhancement of antibiotics detection. Herein, based on the modulability of the coordination mode, we proposed two MOFs with different coordination modes based on different metal ions: Zn-MOF (1) and Cd-MOF (2). The fluorescence of 1 and 2 can be efficiently and selectively quenched by nitrofuran antibiotics (nitrofurazone, NFZ and furazolidone, FZD) and chloramphenicol (CAP), respectively. Particularly, the matched energy levels between 2 and enrofloxacin (ENR) enables 2 with turn-on sensing for ENR. Moreover, apart from the sensitivity and selectivity, 1 and 2 also have strong recyclable ability, fast response time and anti-interference ability, which make them great potential sensory materials to detect antibiotics.

Disrupted Rich Club Organization of Hemispheric White Matter Networks in Bipolar Disorder.

Neuroimaging studies suggest disrupted connections of the brain white matter (WM) network in bipolar disorder (BD). A group of highly interconnected high-density structures, termed the 'rich club,' represents an important network for brain functioning. Recent works have revealed abnormal rich club organization in brain networks in BD. However, little is known regarding changes in the rich club organization of the hemispheric WM network in BD. Forty-nine BD patients and fifty-five age- and sex-matched normal controls (NCs) underwent diffusion tensor imaging (DTI). Graph theory approaches were applied to quantify group-specific rich club organization and nodal degree of hemispheric WM networks. We demonstrated that rich club organization of hemispheric WM networks in BD was disrupted, with disrupted feeder and local connections among hub and peripheral regions located in the default mode network (DMN) and the control execution network (CEN). In addition, BD patients showed abnormal asymmetry in the feeder and local connections, involving the hub and peripheral regions associated with emotion regulation and visuospatial functions. Moreover, the clinical symptoms of BD showed a significant correlation with the aberrant asymmetry in the regional degree of peripheral regions. These findings reveal that BD is closely associated with disrupted feeder and local connections but no alteration in rich-club connections in the rich club organization of hemispheric WM networks and provide novel insight into the changes of brain functions in BD.

Phosphodiesterase 4D Gene Modifies the Functional Network of Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is affected by several genetic variants. It has been demonstrated that genetic variants affect brain organization and function. In this study, using whole genome-wide association studies (GWAS), we analyzed the functional magnetic resonance imaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative dataset (ADNI) dataset and identified genetic variants associated with the topology of the functional brain network http://www.adni-info.org. We found three novel loci (rs2409627, rs9647533, and rs11955845) in an intron of the phosphodiesterase 4D (PDE4D) gene that contribute to abnormalities in the topological organization of the functional network. In particular, compared to the wild-type genotype, the subjects carrying the PDE4D variants had altered network properties, including a significantly reduced clustering coefficient, small-worldness, global and local efficiency, a significantly enhanced path length and a normalized path length. In addition, we found that all global brain network attributes were affected by PDE4D variants to different extents as the disease progressed. Additionally, brain regions with alterations in nodal efficiency due to the variations in PDE4D were predominant in the limbic lobe, temporal lobe and frontal lobes. PDE4D has a great effect on memory consolidation and cognition through long-term potentiation (LTP) effects and/or the promotion of inflammatory effects. PDE4D variants might be a main reasons underlyling for the abnormal topological properties and cognitive impairment. Furthermore, we speculated that PDE4D is a risk factor for neural degenerative diseases and provided important clues for the earlier detection and therapeutic intervention for AD.

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments.

Antibiotic resistance has become one of the world's most severe problems because of the overuse of antibiotics. Antibiotic-resistant bacteria are more difficult to kill and more expensive to treat. Researchers have been studied on antibiotic alternatives such as antimicrobial peptides and lipopeptides. A functional bacteria MB01 producing lipopeptides which can be used as bacteriostat was isolated from the Bohai Sea sediments, which had been identified as Bacillus licheniformis by the morphological, physiological, and biochemical identification and 16s rDNA sequence. The lipopeptides produced by MB01 were determined to be cyclic surfactin homologs by LC-ESI-MS structural identification after crude extraction and LH-20 chromatography. [M+H]+m/z 994, 1008, 1022, and 1036 were all the characteristic molecular weight of surfactin homologs. CID analysis revealed that the molecular structure of the lipopeptides was Rn-Glu1-Leu/Ile2-Leu3-Val4-Asp5-Leu6-Leu/Ile7. The lipopeptides showed well resistance to UV light and the change of pH and temperature.

Detoxification of Aflatoxin B1 by Zygosaccharomyces rouxii with Solid State Fermentation in Peanut Meal.

Aflatoxins are highly carcinogenic, teratogenetic, and morbigenous secondary metabolites of Aspergillus flavus and A. parasiticus that can contaminate multiple staple foods, such as peanut, maize, and tree nuts. In this study, Zygosaccharomyces rouxii was screened out and identified from fermented soy paste-one kind of traditional Chinese food-to detoxify aflatoxin B1 (AFB1) by aerobic solid state fermentation in peanut meal. The optimal degradation condition was chosen from single factor experiment, and the most effective detoxification rate was about 97%. As for liquid fermentation, we tested the binding ability of Z. rouxii, and the highest binding rate reached was 74.3% (nonviable cells of Z. rouxii) in phosphate-buffered saline (PBS). Moreover, the biotransformation of AFB1 through fermentation of Z. rouxii in peanut meal was further verified by liquid chromatography/mass spectrometry (LC/MS). According to TIC scan, after fermentation by Z. rouxii, the AFB1 in peanut meal was prominently degraded to the lowering peaks of AFB1. Additionally, m/s statistics demonstrated that AFB1 may be degraded to some new products whose structural properties may be different from AFB1, or the degradation products may be dissolved in the aqueous phase rather than the organic phase. As far as we know, this is the first report indicating that the safe strain of Z. rouxii has the ability to detoxify AFB1.

Identification of lipopeptides in Bacillus megaterium by two-step ultrafiltration and LC-ESI-MS/MS.

A two-step ultrafiltration and liquid chromatography-electronic spray ionization-tandem mass spectrometry (LC-ESI-MS/MS) were applied to investigate the nature of lipopeptides in the methanol extract harvested from marine Bacillus megaterium. The structure of lipopeptide homologs were characterized by using collision-induced dissociation mass spectrometry analysis. Collectively, two kinds of linear fengycin A and B with a double bond were characterized for the first time besides the popular cyclic fengycin A and B with the difference in the amino acid at position 6 of the peptide moiety. It is worth noting that two kinds of linear isoforms of surfactins and two kinds of cyclic isoforms of esperin with a smaller peptide ring formed by the fifth L-Asp and ß-hydroxy fatty acid were also separated and identified in addition to the all seven kinds of cyclic isoforms of surfactins. Only one analogue (bacillomycin D) of iturin family was identified in this research. To our best knowledge, this is the first report that more than 40 variants of lipopeptides from one strain of Bacillus were identified using our potent purification and identification methods.