A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

A temperature-regulated circuit for feeding behavior.

Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.

High conductivity and stability of polystyrene/MXene composites with orientation-3D network binary structure.

Recently, two-dimensional transition metal carbide/nitride (MXene) and its composites with polymers have attracted great interest from researchers due to their potential applications in flexible electronics, electromagnetic shielding, catalysis, and energy storage. However, the easy oxidation of MXene and the low efficiency of traditional composites preparation methods have brought great challenges to the practical application of polymer/MXene composites. Here, we prepared polystyrene/Mxene (PS/MXene) composites with a 3D conductive network structure through particle construction strategy. Because of the compact and ordered structure, the conductivity of the material reached 3846.15 S/m when the filler content was only 1.81 vol%, and it can retain 53.4% of the initial value after 180 days. Furthermore, based on the 3D network, we orientated the MXene nanosheets in the matrix to form the MXene orientated 3D network binary structure. This unique structure design further increased the utilization rate of MXene and made the material conductivity reach to 4471.13 S/m, with the percolation threshold as low as 0.175 vol%. We believe that this research can provide a feasible way for the practical application of MXene composite materials.

Disrupted Anti-correlation Between the Default and Dorsal Attention Networks During Hyperthermia Exposure: An fMRI Study.

Environmental hyperthermia is a common risk factor for occupational safety in many situations due to decreased vigilance performances. Previously, we have reported that decreased resting-state functional connectivity within the default mode network (DMN) and decreased activations in dorsal attention network (DAN) such as dorsolateral prefrontal cortex (DLPFC) were correlated with selective attention deficits during hyperthermia. However, whether the inherent functionally organized anti-correlation between the DMN and DAN would contribute to the behavioral deficits remains unclear. In this study, we collected the resting-state fMRI data of 25 participants during two simulated thermal conditions: normothermic condition (25°C for 1 h) and hyperthermic condition (50°C for 1 h). Using group independent component analysis (ICA), we investigated the functional connectivity within the DMN and DAN, as well as the anti-correlations between both networks. Paired comparisons revealed that decreased intranetwork functional connectivity in the medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) in the DMN contributed to executive control performance during hyperthermia using multivariate linear regression analysis. Paired comparison on the DAN showed that increased one in the posterior part of the middle and inferior temporal gyrus nearby the temporal-parietal junction area contributed to preserved alerting performance. Lastly but most importantly, we found that decreased correlation between mPFC in the DMN and intraparietal sulcus (IPS) area in the DAN contributed to the executive control deficit, suggesting a weaker intrinsic anti-correlation between DMN and DAN during hyperthermia. These findings indicated that a functional reorganized architecture of DMN and DAN might provide a potential neural basis of the selective deficits for different cognitive-demand attention tasks in high-temperature environments.

Resting-state brain activity predicts selective attention deficits during hyperthermia exposure.

Purpose: Environmental hyperthermia exerts detrimental effect on attention performance that might increase the probability of accidents for high risk occupation. Previously, we reported aberrant activations and selective attention deficits under task performing during hyperthermia. However, whether resting-state baseline during hyperthermia would contribute to the reported selective attention deficits remains unclear.Materials and methods: Here, we investigated the resting-state activity within two attention subsystems named dorsal attention network (DAN) and ventral attention network (VAN) using the conjoint analysis of functional connectivity (FC) and regional cerebral blood flow (CBF). Blood oxygenation level dependent (BOLD) and 3 D arterial spin labeling data were obtained from 25 healthy male participants under two simulated thermal conditions: normothermic (25 °C for 1 h) and hyperthermic condition (50 °C for 1 h).Results: Paired comparisons on the FC and CBF showed decreased activity in the bilateral frontal eye field (FEF) and intraparietal sulcus (IPS) in the DAN but increased activity in the ventral frontal cortex (VFC) in the VAN. The CBF-FC correlation analysis further confirmed decreased CBF-FC coupling in the bilateral FEF in the DAN and increased coupling in the VFC in the VAN. Additionally, the left IPS and FEF in the DAN showed altered CBF per unit functional connectivity in the CBF/FC ratio analysis. Multiple regression analysis revealed that the selectively altered performances were predicted by alterations of the multiple metrics within the DAN and VAN.Conclusions: These findings suggested that altered resting-state brain activity within the attention networks might provide potential neural basis of the selective deficits for different cognitive-demand attention tasks under hyperthermia.

Ultrafast freestanding microfiber humidity sensor based on three-dimensional graphene network cladding.

An all-fiber humidity sensor is proposed and fabricated by depositing three-dimensional graphene network (3DGN) around the surface of a freestanding microfiber (MF). The high specific surface area and porosity of 3DGN enhances its interaction with water molecules, allowing high performance of the humidity sensor. The sensor can operate in a wide relative humidity (RH) range of 11.6%RH-90.9%RH with a high sensitivity of -2.841 dB/%RH in the RH range (80.3%RH - 90.9%RH). The response and recovery times of this type of microfiber sensor are measured respectively to be 57 ms and 55 ms, which are one order magnitude faster than those of other fiber RH sensors activated by two-dimensional materials coating. Such an all-fiber RH sensor with high sensitivity and fast response property possesses great potential of application in widespread fields, such as biology, chemical processing and food processing.

Atypical Response Properties of the Auditory Cortex of Awake MECP2-Overexpressing Mice.

Methyl-CpG binding protein 2 (MECP2) is a gene associated with DNA methylation and has been found to be important for maintaining brain function. In humans, overexpression of MECP2 can cause a severe developmental disorder known as MECP2 duplication syndrome. However, it is still unclear whether MECP2 overexpression also causes auditory abnormalities, which are common in people with autism. MECP2-TG is a mouse model of MECP2 duplication syndrome and has been widely used for research on social difficulty and other autism-like disorders. In this study, we used a combination of multiple electrophysiological techniques to document the response properties of the auditory cortex of awake MECP2-TG mice. Our results showed that while the auditory brainstem responses are similar, cortical activity patterns including local field potentials (LFPs), multiunit activity (MUA), and single-neuron responses differ between MECP2-TG and wild-type (WT) mice. At the single-neuron level, the spike waveform of fast-spiking (FS) neurons from MECP2-TG mice is different from that of WT mice, as reflected by reduced peak/trough ratios in the transgenic mice. Both regular-spiking (RS) and FS neurons exhibited atypical response properties in MECP2-TG mice compared with WT mice, such as prolonged latency and an elevated intensity threshold; furthermore, regarding the response strength to different stimuli, MECP2-TG mice exhibited stronger responses to noise than to pure tone, while this pattern was not observed in WT mice. Our findings suggest that MECP2 overexpression can cause the auditory cortex to have atypical response properties, an implication that could be helpful for further understanding the nature of auditory deficits in autism.

Anterior Auditory Field Is Needed for Sound Categorization in Fear Conditioning Task of Adult Rat.

Both primary auditory cortex (A1) and anterior auditory field (AAF) are core regions of auditory cortex of many mammalians. While the function of A1 has been well documented, the role of AAF in sound related behavioral remain largely unclear. Here in adult rats, sound cued fear conditioning paradigm, surgical ablation, and chemogenetic manipulations were used to examine the role of AAF in fear related sound context recognition. Precise surgical ablation of AAF cannot block sound cued freezing behavior but the fear conditioning became non-selective to acoustic cue. Reversible inhibition of AAF using chemogenetic activation at either training or testing phase can both lead to strong yet non-selective sound cued freezing behavior. These simple yet clear results suggested that in sound cued fear conditioning, sound cue and detailed content in the cue (e.g., frequency) are processed through distinct neural circuits and AAF is a critical part in the cortex dependent pathway. In addition, AAF is needed and playing a gating role for precise recognition of sound content in fear conditioning task through inhibiting fear to harmless cues.

Excitatory effects of the primary auditory cortex on the sound-evoked responses in the ipsilateral anterior auditory field in rat.

In the neocortex, interaction and cooperation between different areas are important for information processing, which also applies to different areas within one sensory modality. In the temporal cortex of rodents and cats, both the primary auditory cortex (A1) and the anterior auditory field (AAF) have tonotopicity but with a mirrored frequency gradient. However, whether and how A1 modulates the responses in AAF is largely unknown. Here, we functionally identified the locations of A1 and AAF in rats and used an optogenetic approach to manipulate the activity of A1 in vivo. We found that activation of A1 axon terminals in AAF did not change AAF responses, but activating A1 neuronal cell bodies could increase the sound-evoked responses in AAF, as well as decrease the intensity threshold and broaden the frequency bandwidth, while suppressing A1 could cause the opposite effects. Our results suggested that A1 could modulate the general excitability of AAF through indirect pathways, which provides a potential relationship between these two parallel auditory ascending pathways.

Preparation and Enantioseparation of Biselector Chiral Stationary Phases Based on Amylose and Chitin Derivatives.

Amylose derivatives chiral stationary phases (CSPs), some of which are commercially available, are well known for their powerful enantioseparation performance. However, due to the dissolution or swelling properties of amylose derivatives, this type of CSPs prepared by coating method exhibit poor solvent tolerance and stability. In order to overcome the defect as well as maintain the chiral recognition capability of amylose tris(3,5-dimethylphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) with good stability and good chiral recognition capability was blended with the amylose derivative at different ratios, and the resulting blends were further coated onto 3-aminopropyl silica gel to obtain three biselector CSPs. Meanwhile, the corresponding individual selector CSPs were also prepared, respectively, for the sake of comparison with biselector CSPs. The chiral recognition capacity and solvent tolerance of five CSPs were systematically investigated. In addition, the influence of composition and interaction of amylose tris(3,5-dimethylphenylcarbamate) and chitin bis(3-chloro-4-methylphenylcarbamate) in the biselector CSPs on the chiral recognition and the elute orders of enantiomers was also discussed in detail.

Enantioseparation characteristics of tadalafil and its intermediate on chitin derived chiral stationary phases.

Due to the low solubility and swelling properties of chitin bis(arylcarbamate) in most organic solvents, the chiral stationary phases (CSPs) prepared from chitin derivatives can be analyzed with a wide range of solvents. In order to develop new CSPs of chitin derivatives with halogen groups, chitin was derivatized with three different phenyl isocyanates to obtain chitin bis(4-trifluoromethoxyphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) and chitin bis(4-chloro-3-trifluoromethylphenylcarbamate). Then, the three chitin derivatives were coated on macroporous 3-aminopropyl-functionalized silica gel to obtain three CSPs 1-3 respectively. These CSPs showed good enantioseparation capabilities towards tadalafil and its intermediate. Therefore, these CSPs are potentially applied for the enantioseparation and determination of tadalafil and its intermediate. It was also found that the retention times of some enantiomers were prolonged in the presence of their diastereoisomers or structural analogues and as a result, the resolution was improved to some extent. Hence, in the enantioseparation of a compound with two chiral centers, the resolution is hopefully improved by adding a diastereoisomer or a structural analogue.

Enantioseparation characteristics of biselector chiral stationary phases based on derivatives of cellulose and amylose.

Cellulose tris(4-methylphenylcarbamate) (CMPC) and cellulose tris(4-chlorophenylcarbamate) (CCPC) are well known for their powerful chiral recognition capability, and the chiral columns prepared from these two polymers have been commercialized. However, the chiral stationary phases (CSPs) can be only used in the mobile phases containing no more than 20% ethanol (referring to CMPC) or cannot be used in ethanol-containing mobile phases (referring to CCPC). In order to overcome the defect and to study the enantioseparation characteristics of biselector CSPs, CMPC, cellulose tris(phenylcarbamate) (CPC) and CCPC were, respectively, mixed with amylose tris(3,5-dimethylphenylcarbamte) (ADMPC) at a ratio of 1:1 (mol/mol) of glucose unit, and three new CSPs were prepared by coating the resulting blends on 3-aminopropyl silica gel. For the purpose of enantioseparation comparison, the corresponding single selector CSPs were also prepared with the individual derivatives of cellulose and amylose. The enantioseparation evaluation indicated that the biselector CSPs still bear excellent enantioseparation capability. The interaction between two polymers in each blend was investigated by using circular dichroism (CD) spectroscopy. Owing to the interaction, the durability of the biselector CSP derived from CMPC and ADMPC was significantly improved. The CSP could be analyzed with a mobile phase of 100% ethanol. And the biselector CSP derived from CCPC and ADMPC could safely work in a normal phase containing 30% ethanol. Therefore, the workable ranges of the mobile phases were broadened. The elution order on the biselector CSPs was generally dominated by the one on the corresponding single selector CSPs that provided a higher resolution. In addition, the suprastructure variation caused by the interaction between the individual polymers might also affect the enantioseparation of the biselector CSPs. The trends of the retention factors and the resolutions of partially racemic mixtures were discussed.

PS microspheres coated by AuNPs via thermodynamic driving heterocoagulation and their high catalytic activity.

A unique method of fabricating PS/AuNPs composite particles in ex situ mode is proposed on the basis of thermodynamically driving mechanism. It is facile and versatile as it eliminates the need for surface functionalizations and modifications of both PS microspheres and AuNPs. The PS/AuNPs composite particles take on a raspberry-like morphology with controllable coverage according to some thermodynamic factors, which have been extensively characterized by scanning electron microscopy, transmission electron microscopy, and thermogravimetric analysis. More importantly, the PS/AuNPs composite particles hold higher catalytic efficiency and better repeatability than the previously reported results, which are confirmed in two oxidation-reduction reactions of 2-nitroaniline/NaBH(4) and rhodamine B/NaBH(4).

Colloid thermodynamic effect as the universal driving force for fabricating various functional composite particles.

The design and fabrication of functional nanocomposites is an active area of research because composite particles have significantly improved physical and chemical properties over those of their single-component counterparts. Traditionally, chemical pretreatments of the components were used to enhance their physicochemical or chemical interactions. Here, we propose a novel approach to taking advantage of the beauty of thermodynamics. A series of functional materials, including graphene nanosheets, carbon nanotubes, noble metals, magnetic materials, conducting polymers, attapulgite, and etc. were incorporated with polystyrene particles by a thermodynamic driving force. This unique approach is facile and versatile and shows the considerable significance of developments in both scientific methodology and particle engineering.

Facile and controlled fabrication of functional gold nanoparticle-coated polystyrene composite particle.

Gold nanoparticles-coated polystyrene (AuNPs-coated PS) composite particles with raspberry-like morphology are successfully prepared with the aid of a unique thermodynamically driving effect. It is of considerable interest that the AuNPs generate and self-assemble with raw, ordinary PS microspheres that preexist in the oxidation-reduction systems. The synthesized AuNPs-coated PS composite particles have been extensively characterized using scanning electron microscope, transmission electron microscope, and UV-Vis-NIR spectroscopy. The results indicate that the morphology of the resultant composite particles is governed by simply changing the amount and type of reductants and the concentration of PS microspheres. The AuNPs-coated PS composite particles also exhibit the good surface-enhanced Raman scattering and catalytic performances.

Efficient coating of polystyrene microspheres with graphene nanosheets.

Herein, we propose a facile and efficient method to obtain the polystyrene/graphene nanosheets (PS/GNSs) nanocomposite particles. As far as we know, it is the first example that GNSs are attached onto the surface of PS microspheres, with such smooth morphology, and without relying on any surface pretreatments of substrate microspheres.

A facile strategy for synthesis of multilayer and conductive organo-silica/polystyrene/polyaniline composite particles.

By means of a facilely designed strategy, we successfully fabricated the multilayer and conductive organo-silica/polystyrene/polyaniline (organo-silica/PS/PANi) composite particles. First, organo-silica/PS core/shell composite particles were synthesized by seeded emulsion polymerization and the vinyl groups located on the surface of organo-silica nanoparticles were used to induce in situ polymerization of styrene. The influence of the route of the addition of styrene on the morphology of organo-silica/PS composite particles was investigated. Then, the coating of organo-silica/PS composite particles with PANi was achieved by virtue of the "Swelling-Diffusion-Interfacial-Polymerization Method" (SDIPM). The whole preparation process was monitored by transmission electron microscope, scanning electron microscope, Fourier transform infrared, Raman spectroscopy, dynamic light scattering, and thermogravimetry. As a result, the multilayer and conductive organo-silica/PS/PANi nanocomposites possessed of a uniform size and well-defined morphology, and furthermore, their structure could be well controlled by simply changing the weight ratio of aniline/PS.

A facile strategy for controlling the self-assembly of nanocomposite particles based on colloidal steric stabilization theory.

A heterocoagulation strategy based on colloidal steric stabilization theory has been developed, through which polystyrene (PS) and silica (SiO(2)) particles without any surface modification or functionalization self-assembled rapidly via solution to afford nanocomposite particles with raspberry-like morphology. The formation mechanism is fully studied on the basis of a thermodynamic analysis. The soluble stabilizer and the solvent quality are the main determining factors, which have a significant influence on this self-assembly process and the silica coverage of resultant composites. The relative size of PS to SiO(2) candidates also has the effect of control on the extent of self-assembly. Furthermore, this strategy can be applied to fabricate a broad range of composite materials, including PS/TiO(2), PS/AgI, as well as PS/PS composites.