An Ascending Excitatory Circuit from the Dorsal Raphe for Sensory Modulation of Pain.

The dorsal raphe nucleus (DRN) is an important nucleus in pain regulation. However, the underlying neural pathway and the function of specific cell types remain unclear. Here, we report a previously unrecognized ascending facilitation pathway, the DRN to the mesoaccumbal dopamine (DA) circuit, for regulating pain. Chronic pain increased the activity of DRN glutamatergic, but not serotonergic, neurons projecting to the ventral tegmental area (VTA) (DRNGlu-VTA) in male mice. The optogenetic activation of DRNGlu-VTA circuit induced a pain-like response in naive male mice, and its inhibition produced an analgesic effect in male mice with neuropathic pain. Furthermore, we discovered that DRN ascending pathway regulated pain through strengthened excitatory transmission onto the VTA DA neurons projecting to the ventral part of nucleus accumbens medial shell (vNAcMed), thereby activated the mesoaccumbal DA neurons. Correspondingly, optogenetic manipulation of this three-node pathway bilaterally regulated pain behaviors. These findings identified a DRN ascending excitatory pathway that is crucial for pain sensory processing, which can potentially be exploited toward targeting pain disorders.

Nonreciprocal routing of microwave photons with broad bandwidth via magnon-cavity chiral coupling.

We propose a scheme for realizing nonreciprocal microwave photon routing with two cascaded magnon-cavity coupled systems, which work around the exceptional points of a parity-time (PT)-symmetric Hamiltonian. An almost perfect nonreciprocal transmission can be achieved with a broad bandwidth, where the transmission for a forward-propagating photon can be flexibly controlled with the backpropagating photon being isolated. The transmission or isolated direction can be reversed via simply controlling the magnetic field direction applied to the magnons. The isolation bandwidth is improved by almost three times in comparison with the device based on a single PT-symmetric system. Moreover, the effect of intrinsic cavity loss and added thermal noises is considered, confirming the experimental feasibility of the nonreciprocal device and potential applications in quantum information processing.

Development of an advanced separation and characterization platform for mRNA and lipid nanoparticles using multi-detector asymmetrical flow field-flow fractionation.

In recent years, the use of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA)-based therapies has gained substantial attention in the field of drug development. In such an application, multiple LNP attributes have to be carefully characterized to ensure product safety and quality, whereas accurate and efficient characterization of these complex mRNA-LNP formulations remains a challenging endeavor. Here, we present the development and application of an online separation and characterization platform designed for the isolation and in-depth analysis of mRNAs and mRNA-loaded LNPs. Our asymmetrical flow field-flow fractionation with a multi-detector (MD-AF4) method has demonstrated exceptional resolution between mRNA-LNPs and mRNAs, delivering excellent recoveries (over 70%) for both analytes and exceptional repeatability. Notably, this platform allows for comprehensive and multi-attribute LNP characterization, including online particle sizing, morphology characterization, and determination of encapsulation efficiency, all within a single injection. Furthermore, real-time online sizing by synchronizing multi-angle light scattering (MALS) and dynamic light scattering (DLS) presented higher resolution over traditional batch-mode DLS, particularly in differentiating heterogeneous samples with a low abundance of large-sized particles. Additionally, our method proves to be a valuable tool for monitoring LNP stability under varying stress conditions. Our work introduces a robust and versatile analytical platform using MD-AF4 that not only efficiently provides multi-attribute characterizations of mRNA-LNPs but also holds promise in advancing studies related to formulation screening, quality control, and stability assessment in the evolving field of nanoparticle delivery systems for mRNAs.

Exploring the phase change and structure of carbon using a deep learning interatomic potential.

Small-scale systems based on periodic boundary conditions often cannot accurately describe real-world situations, especially when conducting molecular dynamics simulations to study phase transitions, where it is very necessary to use large-scale systems. However, studying phase transitions in large-scale systems is an important and difficult task. Though ab initio molecular dynamics (AIMD), based on density functional theory (DFT), provides advantages in terms of accuracy, it is very difficult to study phase transitions in large-scale systems due to the considerable computational time required. In addition, although traditional empirical potentials are faster, their lower calculation accuracy makes it difficult to use them for phase transition studies. It is crucial to devise a method that has enabled a promising fusion of computational efficiency and precision to effectively investigate phase transitions in large-scale systems. In this work, the obtained machine learning potential function of carbon through deep neural networks not only demonstrates strong scalability but also effectively enables the study of the formation mechanisms of amorphous diamond and polycrystalline diamond using C60 crystals and graphene as precursors under high-pressure high-temperature conditions (HPHT). Furthermore, the structure search software (AIRSS) was used to generate numerous initial structures which were optimized using the machine learning potential, a process which led to finding new structural clusters of carbon. Interestingly, the predictive capabilities of the machine learning potential for symmetric and asymmetric carbon clusters aligned well with the Gaussian approximation potential (GAP), yet the former demonstrated higher computational efficiency, making it more suitable for carbon material research. The results of this work signify significant progress in the field of carbon transition study, opening up new possibilities for exploring and understanding carbon materials with improved computational efficacy.

The contributions of grandparents to preadolescent grandchildren's social skills in rural Malaysia.

This study aimed to generate localized knowledge by investigating the perceptions and experiences of preadolescent grandchildren and grandparents regarding grandparenting and intergenerational interactions and how these processes were related to the social skills of preadolescents from three ethnic groups in Malaysia. Using a concurrent quantitative-qualitative mixed method research design, Chinese, Malay, and Indian preadolescents (N = 465; ages 9-12 years old; M = 10.27 years; SD = 1.03) from rural areas in Malaysia completed a self-administered quantitative survey; furthermore, 25 grandparents participated in one-on-one interviews. Survey findings showed that preadolescent grandchildren who reported higher grandparental warmth and support had greater social skills, mediated by positive grandparent-grandchildren (GP-GC) relationships. The GP-GC relationship and preadolescent social skills association was stronger for skipped generation compared to three-generation households. Interview findings revealed that grandparents expressed unconditional love and autonomy support in their grandparenting roles by guiding and encouraging their preadolescent grandchildren to make decisions. The GP-GC interactions served as a dynamic force in promoting preadolescents' social skills. By employing a decolonized approach and drawing on the lived experiences of grandparents from three ethnic backgrounds in rural Malaysia, the study provided an understanding of grandparenting practices and their general implications across the three ethnic groups. The interview responses highlighted both commonalities and specificities in grandparenting practices and relationship dynamics shaped by religious, class, and sociocultural dimensions in rural Malaysia.

The role of cricoarytenoid joint ankylosis in bilateral vocal cord immobility.

OBJECTIVES: To stratify the severity of cricoarytenoid joint fixation (CAJF) by surgery and understand the role of it played in the bilateral vocal fold immobility (BVFI). The second objective emphasizes on the significance of the preoperative differential diagnosis from neurogenic immobility with medical history and endoscopic findings. METHODS: A retrospective review was conducted of 74 patients between 2005 and 2022. Careful medical history inquiry, and videolaryngoscopy are conducted to recruit the appropriate surgical candidates. All patients underwent arytenoid remobilization (AR) followed by vocal fold medialization with arytenoid adduction (AA) or lateralization with suture lateralization (SL). The severity of CAJF is graded during the operation or inferred based on the period from operation to recurrence. RESULT: A total of 18 patients, aged between 18 and 76 years, were analyzed. Among them, 14 cases were classified as the adducted type with ventilation problems, with three presenting with dyspnea, and 11 requiring artificial airways. Additionally, four patients presented with the abducted type, characterized by aphonia. Meanwhile, two additional cases were considered for comparison but were not included in this cohort of 18 subjects due to incorrect diagnosis and inappropriate management. Using AR procedure, the AA procedure offered three aphonia subjects a voiced sound without airway impairment and the SL procedure decannulated 100% (11/11) of the artificial airways and improved the airway patency in 100% (3/3) of the non-tracheostomized subjects despite the severity of CAJF. The severity of joint ankylosis was distributed as follows: In the aphonia group, there were three subjects with grade I, one subject with grade II, and 0 subjects with grade III. In the ventilation group, there was one subject with grade I, seven subjects with grade II, and six subjects with grade III. In contrast, the two cases used for comparison experienced recurrent dyspnea and failed decannulation because the AR procedure was not performed. The follow-up period was averaged in 58 and 14 months at least. CONCLUSION: From this experience, it is the accurate preoperative diagnosis instead of the severity of CAJF that determines the successful rate in airway patency and voiced phonation if the AR procedure is utilized. Careful medical history inquiry and videolaryngoscopic examination can correctly differentiate the mechanical from neurogenic origin without the help of EMG. Evidence of level: 4.

Development and Validation of a Nomogram for Evaluating the Incident Risk of Pain Catastrophizing Among Patients Who Have Severe Knee Osteoarthritis Awaiting Primary Total Knee Arthroplasty.

BACKGROUND: It is clinically important to anticipate the likelihood of pain catastrophizing in patients who undergo total knee arthroplasty (TKA). Persistent pain and diminished physical function following TKA are independently associated with preoperative pain catastrophizing. The purpose of this study was to develop and validate a nomogram model to predict pain catastrophizing in patients who have severe osteoarthritis undergoing primary TKA. METHODS: Data were collected from patients who have severe osteoarthritis undergoing primary TKA at four tertiary general hospitals in Changsha, China, from September to December 2023. The study cohort was randomly divided into a training group and a validation group in the proportion of 70 to 30%. Least absolute shrinkage and selection operator regression analysis was utilized to select the optimal predictive variables for the model. A nomogram model was created using independent risk factors that were identified through multivariate regression analysis. Their performance was assessed using the concordance index and calibration curves, and their clinical utility was analyzed using decision curve analysis. RESULTS: A total of 416 patients were included, 291 in the training group and 125 in the validation group. There were 115 (27.6%) who had pain catastrophizing. The predictors contained in the nomogram were pain intensity during activity, anxiety and depression, body mass index, social support, and household. The area under the curve of the nomogram was 0.976 (95% confidence interval = 0.96 to 0.99) for the training group and 0.917 (95% confidence interval = 0.88 to 0.96) for the validation group. The calibration curves confirmed the nomogram's accuracy, and decision curve analysis showed its strong predictive performance. CONCLUSIONS: The comprehensive nomogram generated in this study was a valid and easy-to-use tool for assessing the risk of pain catastrophizing in preoperative TKA patients, and helped healthcare professionals to screen the high-risk population.

Does Delivery Format Matter? A Pilot Study Comparing Telehealth Versus Face-to-Face Movement Interventions for Children With Autism Spectrum Disorder.

PURPOSE: Children with Autism Spectrum Disorder (ASD) have motor, social communication, and behavioral challenges. During the pandemic, children lost access to face-to-face (F2F) services and had to revert to telehealth (TH) options. We compared the efficacy, fidelity, acceptability, and feasibility of a general motor (GM) intervention using an F2F or telehealth (TH) format. METHODS: Fifteen children with ASD participated in an 8-week program involving gross motor games to promote motor and social communication skills. Differences across TH and F2F formats for motor and socially directed verbalization as well as stakeholder feedback on formats were collected. RESULTS: Gross motor and socially directed verbalization did not differ between the F2F and TH subgroups, and parents and trainers were satisfied with either format. However, TH interventions were longer, had more technological challenges, and required more parental effort. CONCLUSIONS: The findings of this study support the use of TH as a comparable and viable substitute for F2F interactions for children with ASD.

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.

Two types of peptides derived from the neurotoxin GsMTx4 inhibit a mechanosensitive potassium channel by modifying the mechanogate.

Atrial fibrillation is the most common sustained cardiac arrhythmia in humans. Current atrial fibrillation antiarrhythmic drugs have limited efficacy and carry the risk of ventricular proarrhythmia. GsMTx4, a mechanosensitive channel-selective inhibitor, has been shown to suppress arrhythmias through the inhibition of stretch-activated channels (SACs) in the heart. The cost of synthesizing this peptide is a major obstacle to clinical use. Here, we studied two types of short peptides derived from GsMTx4 for their effects on a stretch-activated big potassium channel (SAKcaC) from the heart. Type I, a 17-residue peptide (referred to as Pept 01), showed comparable efficacy, whereas type II (i.e., Pept 02), a 10-residue peptide, exerted even more potent inhibitory efficacy on SAKcaC compared with GsMTx4. We identified through mutagenesis important sequences required for peptide functions. In addition, molecular dynamics simulations revealed common structural features with a hydrophobic head followed by a positively charged protrusion that may be involved in peptide channel-lipid interactions. Furthermore, we suggest that these short peptides may inhibit SAKcaC through a specific modification to the mechanogate, as the inhibitory effects for both types of peptides were mostly abolished when tested with a mechano-insensitive channel variant (STREX-del) and a nonmechanosensitive big potassium (mouse Slo1) channel. These findings may offer an opportunity for the development of a new class of drugs in the treatment of cardiac arrhythmia generated by excitatory SACs in the heart.

Enhanced sensing of optomechanically induced nonlinearity by linewidth suppression and optical bistability in cavity-waveguide systems.

We study the enhanced sensing of optomechanically induced nonlinearity (OMIN) in a cavity-waveguide coupled system. The Hamiltonian of the system is anti-PT symmetric, with the two involved cavities being dissipatively coupled via the waveguide. The anti-PT symmetry may break down when a weak waveguide-mediated coherent coupling is introduced. However, we find a strong bistable response of the cavity intensity to the OMIN near the cavity resonance, benefiting from linewidth suppression caused by the vacuum induced coherence. The joint effect of optical bistability and the linewidth suppression is inaccessible by the anti-PT symmetric system involving only dissipative coupling. Due to that, the sensitivity measured by an enhancement factor is greatly enhanced by two orders of magnitude compared to that for the anti-PT symmetric model. Moreover, the enhancement factor shows resistance to a reasonably large cavity decay and robustness to fluctuations in the cavity-waveguide detuning. Based on the integrated optomechanical cavity-waveguide systems, the scheme can be used for sensing different physical quantities related to the single-photon coupling strength and has potential applications in high-precision measurements with systems involving Kerr-type nonlinearity.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

Improved genetically encoded near-infrared fluorescent calcium ion indicators for in vivo imaging.

Near-infrared (NIR) genetically encoded calcium ion (Ca2+) indicators (GECIs) can provide advantages over visible wavelength fluorescent GECIs in terms of reduced phototoxicity, minimal spectral cross talk with visible light excitable optogenetic tools and fluorescent probes, and decreased scattering and absorption in mammalian tissues. Our previously reported NIR GECI, NIR-GECO1, has these advantages but also has several disadvantages including lower brightness and limited fluorescence response compared to state-of-the-art visible wavelength GECIs, when used for imaging of neuronal activity. Here, we report 2 improved NIR GECI variants, designated NIR-GECO2 and NIR-GECO2G, derived from NIR-GECO1. We characterized the performance of the new NIR GECIs in cultured cells, acute mouse brain slices, and Caenorhabditis elegans and Xenopus laevis in vivo. Our results demonstrate that NIR-GECO2 and NIR-GECO2G provide substantial improvements over NIR-GECO1 for imaging of neuronal Ca2+ dynamics.

Structural, mechanical, electronic and optical properties of biphenylene hydrogenation: a first-principles study.

Biphenylene networks typically exhibit a metallic electronic nature, while hydrogenation can open the band gap changing it to a semiconductor. This property makes hydrogenated biphenylene a promising candidate for use in semiconductor optoelectronic materials and devices. In this work, three representative configurations of hydrogenated biphenylene, denoted by α, ß and γ, were investigated. The structural, mechanical, electronic, and optical properties of these hydrogenated biphenylene configurations were calculated by first-principles calculations. Band gaps with HSE correction were 4.69, 4.42 and 4.39 eV for α, ß, and γ configurations, respectively. Among these three configurations, ß presents the best electronic performance and special elastic properties (negative Poisson's ratio), while γ exhibits the best elastic properties. In addition, we comprehensively analyze the mechanical properties of these configurations and provide evidence that hydrogenated biphenylene possibly exhibits a negative-Poisson's-ratio along the zigzag and armchair directions when hydrogen atoms are added to biphenylene in certain ways. Furthermore, although the electronic properties of γ are weaker than those of ß, they are also excellent. In addition, the binding energies of ß and γ are relatively lower, which indicates that ß and γ are more stable. Our findings demonstrate that the hydrogenated biphenylene is a promising material with significant application potential in optoelectronic devices.

Corticotropin-releasing factor neurones in the paraventricular nucleus of the hypothalamus modulate isoflurane anaesthesia and its responses to acute stress in mice.

BACKGROUND: Corticotropin-releasing factor (CRF) neurones in the paraventricular nucleus (PVN) of the hypothalamus (PVNCRF neurones) can promote wakefulness and are activated under anaesthesia. However, whether these neurones contribute to anaesthetic effects is unknown. METHODS: With a combination of chemogenetic and molecular approaches, we examined the roles of PVNCRF neurones in isoflurane anaesthesia in mice and further explored the underlying cellular and molecular mechanisms. RESULTS: PVN neurones exhibited increased Fos expression during isoflurane anaesthesia (mean [standard deviation], 218 [69.3] vs 21.3 [7.3]; P<0.001), and ∼75% were PVNCRF neurones. Chemogenetic inhibition of PVNCRF neurones facilitated emergence from isoflurane anaesthesia (11.7 [1.1] vs 13.9 [1.2] min; P=0.001), whereas chemogenetic activation of these neurones delayed emergence from isoflurane anaesthesia (16.9 [1.2] vs 13.9 [1.3] min; P=0.002). Isoflurane exposure increased CRF protein expression in PVN (4.0 [0.1] vs 2.2 [0.3], respectively; P<0.001). Knockdown of CRF in PVNCRF neurones mimicked the effects of chemogenetic inhibition of PVNCRF neurones in facilitating emergence (9.6 [1.1] vs 13.0 [1.4] min; P=0.003) and also abolished the effects of chemogenetic activation of PVNCRF neurones on delaying emergence from isoflurane anaesthesia (10.3 [1.3] vs 16.0 [2.6] min; P<0.001). Acute, but not chronic, stress delayed emergence from isoflurane anaesthesia (15.5 [1.5] vs 13.0 [1.4] min; P=0.004). This effect was reversed by chemogenetic inhibition of PVNCRF neurones (11.7 [1.6] vs 14.7 [1.4] min; P=0.001) or knockdown of CRF in PVNCRF neurones (12.3 [1.5] vs 15.3 [1.6] min; P=0.002). CONCLUSIONS: CRF neurones in the PVN of the hypothalamus neurones modulate isoflurane anaesthesia and acute stress effects on anaesthesia through CRF signalling.

Telehealth Versus Face-to-Face Fine Motor and Social Communication Interventions for Children With Autism Spectrum Disorder: Efficacy, Fidelity, Acceptability, and Feasibility.

IMPORTANCE: The efficacy of telehealth (TH) interventions needs to be studied. OBJECTIVE: To compare the efficacy, fidelity, acceptability, and feasibility of face-to-face (F2F) versus TH seated play (SP) interventions among children with autism spectrum disorder (ASD). DESIGN: As part of a larger randomized controlled trial, children were assigned to the SP group and received TH and F2F interventions over 8 wk using a pretest-posttest study design. SETTING: A research lab or through videoconferencing. PARTICIPANTS: Fifteen children with ASD (ages 5-14 yr) were randomly assigned to the SP group and received the intervention F2F or through TH. INTERVENTION: Children received 16 SP intervention sessions (2 sessions per week for 8 wk). OUTCOMES AND MEASURES: Pretests and posttests included standardized fine motor assessments. Video coding compared socially directed verbalization during training sessions. Parents and trainers provided feedback on their experiences. RESULTS: Seven children received the intervention F2F, whereas 8 received TH intervention. Children in both subgroups showed similar training improvements in fine motor skills and socially directed verbalizations (ps > .01). Parents rated both interventions as acceptable and feasible; however, they reported longer preparation time and effort during TH interventions (ps < .01). Trainers reported greater parental involvement but more communication and technological issues during TH interventions. Fidelity checks indicated fewer reinforcements during TH versus F2F sessions. CONCLUSIONS AND RELEVANCE: TH intervention is feasible and effective in improving fine motor and social communication performance. Clinicians should reduce parental burden and overcome technological issues. What This Article Adds: This study confirmed the efficacy, fidelity, acceptability, and feasibility of delivering seated play, standard of care interventions for children with autism spectrum disorder via telehealth. However, clinicians should work on reducing parental burden and overcoming communication and technological issues related to telehealth.

Contralateral Projection of Anterior Cingulate Cortex Contributes to Mirror-Image Pain.

Long-term limb nerve injury often leads to mirror-image pain (MIP), an abnormal pain sensation in the limb contralateral to the injury. Although it is clear that MIP is mediated in part by central nociception processing, the underlying mechanisms remain poorly understood. The anterior cingulate cortex (ACC) is a key brain region that receives relayed peripheral nociceptive information from the contralateral limb. In this study, we induced MIP in male mice, in which a unilateral chronic constrictive injury of the sciatic nerve (CCI) induced a decreased nociceptive threshold in both hind limbs and an increased number of c-Fos-expressing neurons in the ACC both contralateral and ipsilateral to the injured limb. Using viral-mediated projection mapping, we observed that a portion of ACC neurons formed monosynaptic connections with contralateral ACC neurons. Furthermore, the number of cross-callosal projection ACC neurons that exhibited c-Fos signal was increased in MIP-expressing mice, suggesting enhanced transmission between ACC neurons of the two hemispheres. Moreover, selective inhibition of the cross-callosal projection ACC neurons contralateral to the injured limb normalized the nociceptive sensation of the uninjured limb without affecting the increased nociceptive sensation of the injured limb in CCI mice. In contrast, inhibition of the non-cross-callosal projection ACC neurons contralateral to the injury normalized the nociceptive sensation of the injured limb without affecting the MIP exhibited in the uninjured limb. These results reveal a circuit mechanism, namely, the cross-callosal projection of ACC between two hemispheres, that contributes to MIP and possibly other forms of contralateral migration of pain sensation.SIGNIFICANCE STATEMENT Mirror-image pain (MIP) refers to the increased pain sensitivity of the contralateral body part in patients with chronic pain. This pathology requires central processing, yet the mechanisms are less known. Here, we demonstrate that the cross-callosal projection neurons in the anterior cingulate cortex (ACC) contralateral to the injury contribute to MIP exhibited in the uninjured limb, but do not affect nociceptive sensation of the injured limb. In contrast, the non-cross-callosal projection neurons in the ACC contralateral to the injury contribute to nociceptive sensation of the injured limb, but do not affect MIP exhibited in the uninjured limb. Our study depicts a novel cross-callosal projection of ACC that contributes to MIP, providing a central mechanism for MIP in chronic pain state.

Nonreciprocal light transmission via optomechanical parametric interactions.

Nonreciprocal transmission of optical or microwave signals is indispensable in various applications involving sensitive measurements. In this paper, we study optomechanically induced directional amplification and isolation in a generic setup including two cavities and two mechanical oscillators by exclusively using blue-sideband drive tones. The input and output ports defined by the two cavity modes are coupled through coherent and dissipative paths mediated by the two mechanical resonators, respectively. By choosing appropriate transfer phases and strengths of the driving fields, either a directional amplifier or an isolator can be implemented at low thermal temperature, and both of them show bi-directional nonreciprocity working at two mirrored frequencies. The nonreciprocal device can potentially be demonstrated by opto- and electromechanical setups in both optical and microwave domains.

Nonequilibrium Self-Organization of Lipids into Hierarchically Ordered and Compositionally Graded Cylindrical Smectics.

When a dry mass of certain amphiphiles encounters water, a spectacular interfacial instability ensues: It gives rise to the formation of ensembles of fingerlike tubular protrusions called myelin figures─tens of micrometers wide and tens to hundreds of micrometers long─representing a novel class of nonequilibrium higher-order self-organization. Here, we report that when phase-separating mixtures of unsaturated lipid, cholesterol, and sphingomyelin are hydrated, the resulting myelins break symmetry and couple their compositional degrees of freedom with the extended myelinic morphology: They produce complementary, interlamellar radial gradients of concentrations of cholesterol (and sphingomyelin) and unsaturated lipid, which stands in stark contrast to interlamellar, lateral phase separation in equilibrated morphologies. Furthermore, the corresponding gradients of molecule-specific chemistries (i.e., cholesterol extraction by methyl-ß-cyclodextrin and GM1 binding by cholera toxin) produce unusual morphologies comprising compositionally graded vesicles and buckled tubes. We propose that kinetic differences in the information processing of hydration characteristics of individual molecules while expending energy dictate this novel behavior of lipid mixtures undergoing hydration.

Impact of Surface Polarity on Lipid Assembly under Spatial Confinement.

Molecular dynamics (MD) simulations in the MARTINI model are used to study the assembly of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) molecules under spatial confinement, such as during solvent evaporation from ultrasmall (femtoliter quantity) droplets. The impact of surface polarity on molecular assembly is discussed in detail. To the best of our knowledge, this work represents the first of its kind. Our results reveal that solvent evaporation gives rise to the formation of well-defined stacks of lipid bilayers in a smectic alignment. These smectic mesophases form on both polar and nonpolar surfaces but with a notable distinction. On polar surfaces, the director of the stack is oriented perpendicular to the support surface. By contrast, the stacks orient at an angle on the nonpolar surfaces. The packing of head groups on surfaces and lipid molecular mobility exhibits significant differences as surface polarity changes. The role of glycerol in the assembly and stability is also revealed. The insights revealed from the simulation have a significant impact on additive manufacturing, biomaterials, model membranes, and engineering protocells. For example, POPC assemblies via evaporation of ultrasmall droplets were produced and characterized. The trends compare well with the bilayer stack models. The surface polarity influences the local morphology and structures at the interfaces, which could be rationalized via the molecule-surface interactions observed from simulations.