Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

BACKGROUND: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. METHODS: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. RESULTS: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. CONCLUSION: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

A Single Central Pattern Generator for the Control of a Locomotor Rolling Wave in Mollusc Aplysia.

Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.

Neural valuation of rewards and punishments in posttraumatic stress disorder: a computational approach.

Posttraumatic stress disorder (PTSD) is associated with changes in fear learning and decision-making, suggesting involvement of the brain's valuation system. Here we investigate the neural mechanisms of subjective valuation of rewards and punishments in combat veterans. In a functional MRI study, male combat veterans with a wide range of posttrauma symptoms (N = 48, Clinician Administered PTSD Scale, CAPS-IV) made a series of choices between sure and uncertain monetary gains and losses. Activity in the ventromedial prefrontal cortex (vmPFC) during valuation of uncertain options was associated with PTSD symptoms, an effect which was consistent for gains and losses, and specifically driven by numbing symptoms. In an exploratory analysis, computational modeling of choice behavior was used to estimate the subjective value of each option. The neural encoding of subjective value varied as a function of symptoms. Most notably, veterans with PTSD exhibited enhanced representations of the saliency of gains and losses in the neural valuation system, especially in ventral striatum. These results suggest a link between the valuation system and the development and maintenance of PTSD, and demonstrate the significance of studying reward and punishment processing within subject.

Electrochemical process of early-stage corrosion detection based on N-doped carbon dots with superior Fe3+ responsiveness.

Iron corrosion is a subject of great technological importance and extensive public concern. However, the highly efficient detection of iron corrosion at early stage is still a challenging task. Herein, bright fluorescent carbon dots (CDs) with superior response to Fe3+ were prepared by simple solvothermal process based on citric acid and ammonia. The obtained CDs are able to rapidly, sensitively and selectively respond to Fe3+. The quantitative analysis showed that the CDs exhibited a linear response to Fe3+ in the range of 10 to 300 µM, with a detection limit of 0.9 µM. And the fluorescence quenching of CDs was obvious enough to be detected by the naked eyes. Such promising responsiveness of CDs offers a great opportunity for real-time and visual detection of Fe3+ during electrochemical corrosion process. In addition, due to the excellent stability and solubility of CDs, patterned papers and hydrogels have been fabricated utilizing cellulose and PVA as matrices. The as-prepared biocompatible, environmental-friendly and disposable CDs based fluorescent materials were successfully used for detecting the degree of iron corrosion. This could provide a simple and visual strategy for monitoring the safety of structural metal materials.

Specific immunity proteomic profile of the skin mucus of Antarctic fish Chionodraco hamatus and Notothenia coriiceps.

The white-blooded Antarctic icefish is the only known vertebrate lacking oxygen-transporting haemoglobins. Fish skin mucus, as the first line of defence against pathogens, can reflect fish welfare. In this study, we analysed the skin mucus proteome profiles of the two Antarctic fish species, the white-blooded Antarctic icefish, Chionodraco hamatus, and the red-blooded Antarctic fish, Notothenia coriiceps, unfolding the different proteins by liquid chromatography coupled with tandem mass spectrometry isobaric tags for relative and absolute quantitation (iTRAQ) technology. Of the 4444 totally identified proteins, 227 differentially expressed proteins (DEPs) were found in the comparison between C. hamatus and N. coriiceps, of which 121 were upregulated and 106 were downregulated in the icefish. In the Kyoto Encyclopedia of Genes and Genomes pathway annotation, we found two pathways "Legionellosis" and "Complement and coagulation cascades" were significantly enriched, among of which innate immune candidate proteins such as C3, CASP1, ASC, F3 and C9 were significantly upregulated, suggesting their important roles in C. hamatus immune system. Additionally, the DEP protein-protein interaction network analysis and "Response to stress" GO category provided candidate biomarkers for deep understanding of the distinct immune response of the two Antarctic fish underlying the cold adaptation.

The Reward System and Post-Traumatic Stress Disorder: Does Trauma Affect the Way We Interact With Positive Stimuli?

Post-traumatic stress disorder (PTSD) is a highly prevalent disorder and a highly debilitating condition. Although anhedonia is an important construct of the disorder, the relationship between PTSD and reward functioning is still under-researched. To date, the majority of research on PTSD has focused on fear: fear learning, maintenance, and extinction. Here we review the relevant literature-including clinical observations, self-report data, neuroimaging research, and animal studies-in order to examine the potential effects of post-traumatic stress disorder on the reward system. Our current lack of sufficient insight into how trauma affects the reward system is one possible hindrance to clinical progress. The current review highlights the need for further investigation into the complex relationship between exposure to trauma and the reward system to further our understandings of the ethology of PTSD.

Learning about the Ellsberg Paradox reduces, but does not abolish, ambiguity aversion.

Ambiguity aversion-the tendency to avoid options whose outcome probabilities are unknown-is a ubiquitous phenomenon. While in some cases ambiguity aversion is an adaptive strategy, in many situations it leads to suboptimal decisions, as illustrated by the famous Ellsberg Paradox. Behavioral interventions for reducing ambiguity aversion should therefore be of substantial practical value. Here we test a simple intervention, aimed at reducing ambiguity aversion in an experimental design, where aversion to ambiguity leads to reduced earnings. Participants made a series of choices between a reference lottery with a 50% chance of winning $5, and another lottery, which offered more money, but whose outcome probability was either lower than 50% (risky lottery) or not fully known (ambiguous lottery). Similar to previous studies, participants exhibited both risk and ambiguity aversion in their choices. They then went through one of three interventions. Two groups of participants learned about the Ellsberg Paradox and their own suboptimal choices, either by actively calculating the objective winning probability of the ambiguous lotteries, or by observing these calculations. A control group learned about base-rate neglect, which was irrelevant to the task. Following the intervention, participants again made a series of choices under risk and ambiguity. Participants who learned about the Ellsberg Paradox were more tolerant of ambiguity, yet ambiguity aversion was not completely abolished. At the same time, these participants also exhibited reduced aversion to risk, suggesting inappropriate generalization of learning to an irrelevant decision domain. Our results highlight the challenge for behavioral interventions: generating a strong, yet specific, behavioral change.

Cellulose-based fluorescent sensor for visual and versatile detection of amines and anions.

It is practical and challenging to construct ultrasensitive and multi-responsive sensors for visual and real-time monitoring of the environment. Herein, a cellulose-based multi-responsive fluorescent sensor (Phen-MDI-CA) is fabricated, and realizes a visual and ultrasensitive detection of not only various amines but also three anions based on the change of the fluorescence and/or visible colors. Once exposure to various amines in both the solution and vapor state, the Phen-MDI-CA solution and test paper exhibit different fluorescence colors, which can be used to distinguish triethylamine, ethylenediamine, methylamine, aniline, hydrazine and pyrrolidine from other amines. Moreover, via combining the Phen-MDI-CA with the Phen-MDI-CA/malachite green ratiometric system, phosphate (PO43-), carbonate (CO32-) and borate (B4O72-) can be visually and accurately recognized depending on the change of the visible and fluorescence colors. In fluorescent mode, the LOD for B4O72-, PO43- and CO32- ions is as low as 0.18 nmol, 0.69 nmol and 0.86 nmol, respectively. Significantly, the Phen-MDI-CA can readily make a qualitative and quantitative detection of B4O72-, PO43- and CO32- anions in the mixture of anions. The state-of-the-art responsive behavior of Phen-MDI-CA originates from the amplification effect of cellulose polymer chain and the differentiated interactions between the sensor and analytes.

3D Hollow Quasi-Graphite Capsules/Polyaniline Hybrid with a High Performance for Room-Temperature Ammonia Gas Sensors.

Designing sensing materials with novel morphologies and compositions is eminently challenging to achieve high-performance gas sensor devices. Herein, an in situ oxidative polymerization approach is developed to construct three-dimensional (3D) hollow quasi-graphite capsules/polyaniline (GCs/PANI) hierarchical hybrids by decorating protonated PANI on the surface of GCs; as a result, an immensely active and sensitive material was developed for sensing ammonia gas at room temperature. Moreover, the GCs possessed a capsule-like hollow/open structure with partially graphitized walls, and PANI nanospheres were uniformly decorated on the GC surfaces. Furthermore, the inflexible and rigid 3D ordered chemistry of these materials provides the resulting hybrids with a large interfacial surface area, which not only allows for rapid adsorption and charge transfer but also provides the necessary structural stability. The 3D hollow GCs/PANI hybrids exhibit excellent performance; the GCs/PANI-3 hybrid is highly sensitive (with a response value of 1.30) toward 10 ppm NH3 gas and has short response and recovery times of 34 and 42 s, respectively. The GCs/PANI-3 hybrid also demonstrates a good selectivity, repeatability, and long-term stability, which are attributed to the substantial synergistic effect of the GCs and PANI. The design of such a unique 3D ordered framework provides a promising pathway to achieve room-temperature gas sensors for commercial applications.

The dorsomedial prefrontal cortex computes task-invariant relative subjective value for self and other.

Few studies have addressed the neural computations underlying decisions made for others despite the importance of this ubiquitous behavior. Using participant-specific behavioral modeling with univariate and multivariate fMRI approaches, we investigated the neural correlates of decision-making for self and other in two independent tasks, including intertemporal and risky choice. Modeling subjective valuation indicated that participants distinguished between themselves and others with dissimilar preferences. Activity in the dorsomedial prefrontal cortex (dmPFC) and ventromedial prefrontal cortex (vmPFC) was consistently modulated by relative subjective value. Multi-voxel pattern analysis indicated that activity in the dmPFC uniquely encoded relative subjective value and generalized across self and other and across both tasks. Furthermore, agent cross-decoding accuracy between self and other in the dmPFC was related to self-reported social attitudes. These findings indicate that the dmPFC emerges as a medial prefrontal node that utilizes a task-invariant mechanism for computing relative subjective value for self and other.

Sunlight-Driven Wearable and Robust Antibacterial Coatings with Water-Soluble Cellulose-Based Photosensitizers.

Herein, a simple, effective, and general strategy is demonstrated to obtain a water-soluble and nontoxic cellulose-based photosensitizer (CPS) with enhanced photodynamic antibacterial activity through introducing protoporphyrin IX (PpIX) and quaternary ammonium salt (QAS) groups onto the cellulose backbone. The synergistic effect of the anchoring and diluting effect of the cellulose backbone and the electrostatic repulsion between QAS groups effectively inhibit the π-π stacking of PpIX groups, thus the as-prepared CPS exhibits markedly enhanced reactive oxygen species (ROS) yield. Meanwhile, the positively charged QAS groups endow the CPS with water-solubility and a strong attractive force to bacteria. As a result, the CPS can rapidly and efficiently kill drug-resistant bacteria strains, including E. coli and S. aureus, with a low light dose (2.4 J cm-2 ) and low concentration of PpIX groups (0.35 × 10-6 m). Benefiting from the excellent processability and formability, the CPS is readily applied as a sunlight-driven wearable and robust antibacterial coating by a spray coating and later crosslinking procedure.

Amine-responsive cellulose-based ratiometric fluorescent materials for real-time and visual detection of shrimp and crab freshness.

Herein, we design and prepare cellulose-based ratiometric fluorescent materials with superior amine-response, which offers the real-time and visual detection of seafood freshness. Through utilizing the reactive hydroxyl groups along cellulose chains, we covalently immobilize the fluorescein isothiocyanate (FITC) as indicator and protoporphyrin IX (PpIX) as internal reference onto cellulose acetate (CA), respectively. Subsequently, a series of dual-emission solid fluorescent materials are achieved by simply blending green emitting CA-FITC with red-emitting CA-PpIX with varying ratios. They exhibit a sensitive, color-responsive, rapid and linear response to ammonia in a wide range of 5.0 ppm to 2.5 × 104 ppm. Benefiting from the excellent solubility and processibility of cellulose derivatives, the as-prepared materials are readily processed into different material forms, including printing ink, coating, flexible film, and nanofibrous membrane. The electrospun nanofibrous membrane is successfully employed as a low-cost, high-contrasting, quick-responsive fluorescent trademark for visual monitoring the freshness of shrimp and crab.

Visual and Precise Detection of pH Values under Extreme Acidic and Strong Basic Environments by Cellulose-Based Superior Sensor.

Precise determination of pH values with an instrument-free mode is challenging and practical in industry processes, life science, and environmental monitoring. Here, taking advantage of the intramolecular charge transfer process, we construct a cellulose-based superior pH sensor, Phen-MDI-CA, which contains a highly sensitive, pH-responsive, and extended conjugation structure by combining phenanthroline moiety as a chromophore with urea group as a bridge. The resultant Phen-MDI-CA can precisely and visually determine pH values under extreme acidic and strong basic environments, depending on the different colors. In visible light mode, Phen-MDI-CA can readily discriminate the pH values of 14.0, 13.0, 12.0, and 11.0 and distinguish pH 2.0 from 1.0 by the naked eye. In fluorescent mode, Phen-MDI-CA can recognize more accurate pH values of pH 11.6-13.2 at a 0.2-0.4 pH interval by the high-contrasting color change. After addition of pH-irresponsive dyes as the reference, the corresponding ratiometric systems exhibit different colors at a 0.2-0.4 pH interval during the pH values of 11.0-14.0 and 1.0-2.0. Benefiting from the excellent formability, the Phen-MDI-CA was readily fabricated into pH test strips by coating method. To our knowledge, this is the first study to monitor extreme acidity and strong basicity in such precise pH values with an instrument-free mode.

Multifunctional Cellulose Ester Containing Hindered Phenol Groups with Free-Radical-Scavenging and UV-Resistant Activities.

Excessive radicals and UV irradiation can trigger oxidative and physiological stresses, which cause tissue aging, human disease, food spoilage, and material degradation. In this study, a multifunctional cellulose ester containing hindered phenol groups, cellulose 3,5-di- tert-butyl-4-hydroxybenzoate (CBH), with free-radical-scavenging and UV-resistant activities was synthesized and used as a functional material. The obtained CBHs can effectively scavenge reactive nitrogen free radicals and hydroxyl free radicals in both solid and solution states. Moreover, CBHs have no cytotoxicity, and, on the contrary, they promote the proliferation of human epidermal keratinocytes. Benefiting from excellent solubility, processability, and formability, CBHs have been readily processed into flexible films, transparent coatings, and nanoribbons membranes. The highly transparent and flexible CBH film completely absorbs the light of 200-300 nm range and partially absorbs the light of 300-400 nm range, indicating a UV-shielding capability. After the CBHs were loaded on an ordinary facial mask by electrospinning or added into a hand cream, the resultant facial mask and hand cream exhibited outstanding free-radical-scavenging properties. In addition, CBHs can also be used to fabricate functional sprays with antioxidative and UV-shielding activities. Accordingly, the obtained CBHs have a huge potential in cosmetics, personal care products, biopharmaceuticals, papermaking, and art protection because of their excellent antioxidation, nontoxicity, UV resistance, formability, and odorless properties.

ExoCET: exonuclease in vitro assembly combined with RecET recombination for highly efficient direct DNA cloning from complex genomes.

The exponentially increasing volumes of DNA sequence data highlight the need for new DNA cloning methods to explore the new information. Here, we describe 'ExoCET' (Exonuclease Combined with RecET recombination) to directly clone any chosen region from bacterial and mammalian genomes with nucleotide precision into operational plasmids. ExoCET combines in vitro exonuclease and annealing with the remarkable capacity of full length RecET homologous recombination (HR) to retrieve specified regions from genomic DNA preparations. Using T4 polymerase (T4pol) as the in vitro exonuclease for ExoCET, we directly cloned large regions (>50 kb) from bacterial and mammalian genomes, including DNA isolated from blood. Employing RecET HR or Cas9 cleavage in vitro, the directly cloned region can be chosen with nucleotide precision to position, for example, a gene into an expression vector without the need for further subcloning. In addition to its utility for bioprospecting in bacterial genomes, ExoCET presents straightforward access to mammalian genomes for various applications such as region-specific DNA sequencing that retains haplotype phasing, the rapid construction of optimal, haplotypic, isogenic targeting constructs or a new way to genotype that presents advantages over Southern blotting or polymerase chain reaction. The direct cloning capacities of ExoCET present new freedoms in recombinant DNA technology.

Cellulose-Based Sensor Containing Phenanthroline for the Highly Selective and Rapid Detection of Fe2+ Ions with Naked Eye and Fluorescent Dual Modes.

Iron ions play a vital role in many biological processes, and their concentrations are responsible for human health. Therefore, it is essential to detect the concentration of iron ions by a rapid, accurate, highly selective, and practical method. Herein, we have synthesized a cellulose-based fluorescent sensor (Phen-MDI-CA) for the highly selective and rapid detection of Fe2+ ions via chemically bonding 1,10-phenanthroline-5-amine (Phen) onto cellulose acetate (CA) using 4,4'-methylene diphenyl diisocyanate (MDI) as a cross-linker. Benefiting from the anchoring and diluting effect of a cellulose skeleton, the resultant Phen-MDI-CA displays excellent fluorescence properties in both solution and solid state. More interestingly, a cellulose-based polymer chain significantly improves the sensitivity of phenanthroline to Fe2+ ions. Upon meeting Fe2+ ions, a red, insoluble, and nonfluorescent Fe-(Phen-MDI-CA) complex appears immediately; thus, Phen-MDI-CA can work as a multimode chromogenic sensor for the highly selective, sensitive, and rapid detection of Fe2+ ions. In the instrument-free visual mode, the detection limit for Fe2+ ions is 50 ppb, and in fluorescence mode, the detection limit is 2.6 ppb. To our knowledge, this is the first time that such a low detection limit for Fe2+ ions in aqueous media has been observed by the naked eye. In addition, Phen-MDI-CA has good solubility and processability in common organic solvents, which facilitates its use in different material forms, e.g., printing ink, coating, and film. Therefore, the Fe2+-responsive and chromogenic Phen-MDI-CA exhibits a huge potential in the detection and extraction of Fe2+ ions.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function.SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition.

A clarifying method that improves imaging of Aplysia ganglia.

Improvements in the imaging of neural circuits are essential for studies of network function in both invertebrates and vertebrates. Therefore, CLARITY, a new imaging enhancement technique developed for mouse brains has attracted broad interest from researchers working on other species. We studied the potential of a modified version of CLARITY to enhance the imaging of ganglia in an invertebrate Aplysia. For example, we have modified the hydrogel solution and designed a small container for the Aplysia ganglia. The ganglia were first processed for immunohistochemistry, and then for CLARITY. We examined the compatibility of these techniques and the extent to which the imaging of fluorescence improved using confocal microscopy. We found that CLARITY did indeed enhance the imaging of CP2 immunopositive neurons in Aplysia ganglia. For example, it improved visualization of small, weak immunoreactive neurons deep in the ganglia. Our modifications of CLARITY make this new method suitable for future use in Aplysia experiments. Furthermore, our techniques are likely to facilitate imaging in other invertebrate ganglia.

RecET direct cloning and Redαß recombineering of biosynthetic gene clusters, large operons or single genes for heterologous expression.

Full-length RecE and RecT from Rac prophage mediate highly efficient linear-linear homologous recombination that can be used to clone large DNA regions directly from genomic DNA into expression vectors, bypassing library construction and screening. Homologous recombination mediated by Redαß from lambda phage has been widely used for recombinant DNA engineering. Here we present a protocol for direct cloning and engineering of biosynthetic gene clusters, large operons or single genes from genomic DNA using one Escherichia coli host that harbors both RecET and Redαß systems. The pipeline uses standardized cassettes for horizontal gene transfer options, as well as vectors with different replication origins configured to minimize recombineering background through the use of selectively replicating templates or CcdB counterselection. These optimized reagents and protocols facilitate fast acquisition of transgenes from genomic DNA preparations, which are ready for heterologous expression within 1 week.