T-cell exhaustion: A potential target biomarker of the tumour microenvironment affecting oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (EAC) is one of the most common malignant tumours, and the number of patients is increasing year by year. T-cell exhaustion (TEX) is an important risk factor for tumour immunosuppression and invasion, but its underlying mechanism in the pathogenesis of EAC is not clear. METHODS: Unsupervised clustering was performed to screen relevant genes based on Gene Set Variation Analysis scores of the three pathways of the HALLMARK gene set IL2/IFNG/TNFA. Multiple enrichment analyses and data combinations were used to depict the relationship between TEX-related risk models and CIBERSORTx immune infiltrating cells. In addition, to explore the impact of TEX on EAC therapeutic resistance, we assessed the impact of TEX risk models on the therapeutic sensitivity of various novel drugs using single-cell sequencing and searched for their potential therapeutic targets and cellular communication. RESULTS: Four risk clusters of EAC patients were identified by unsupervised clustering and searched for potential TEX-related genes. Based on this, LASSO regression and decision trees were used to construct risk prognostic models containing a total of three TEX-associated genes in EAC. The results showed that TEX risk scores were significantly associated with the survival prognosis of EAC patients in both the Cancer Genome Atlas dataset and the independent validation set of Gene Expression Omnibus. Immune infiltration and cell communication analyses identified mast cell resting as a protective factor in TEX, and pathway enrichment analyses showed that the TEX risk model was highly associated with multiple chemokines as well as inflammation-associated pathways. In addition, higher TEX risk scores were associated with a weak responsiveness to immunotherapy. CONCLUSION: We describe the immune infiltration, prognostic significance and potential possible mechanisms of TEX in the EAC patient population. This is a novel attempt to promote the development of novel therapeutic modalities and immunological target construction for oesophageal adenocarcinoma. It is expected to make a potential contribution to advancing the exploration of immunological mechanisms and the opening of target drugs in EAC.

Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors.

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL- and not BLA- and vHipp-NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL-NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

Predictable maternal separation confers adult stress resilience via the medial prefrontal cortex oxytocin signaling pathway in rats.

Early-life stress is normally thought of as a major risk for psychiatric disorders, but many researchers have revealed that adversity early in life may enhance stress resilience later in life. Few studies have been performed in rodents to address the possibility that exposure to early-life stress may enhance stress resilience, and the underlying neural mechanisms are far from being understood. Here, we established a "two-hit" stress model in rats by applying two different early-life stress paradigms: predictable and unpredictable maternal separation (MS). Predictable MS during the postnatal period promotes resilience to adult restraint stress, while unpredictable MS increases stress susceptibility. We demonstrate that structural and functional impairments occur in glutamatergic synapses in pyramidal neurons of the medial prefrontal cortex (mPFC) in rats with unpredictable MS but not in rats with predictable MS. Then, we used differentially expressed gene (DEG) analysis of RNA sequencing data from the adult male PFC to identify a hub gene that is responsible for stress resilience. Oxytocin, a peptide hormone, was the highest ranked differentially expressed gene of these altered genes. Predictable MS increases the expression of oxytocin in the mPFC compared to normal raised and unpredictable MS rats. Conditional knockout of the oxytocin receptor in the mPFC was sufficient to generate excitatory synaptic dysfunction and anxiety behavior in rats with predictable MS, whereas restoration of oxytocin receptor expression in the mPFC modified excitatory synaptic function and anxiety behavior in rats subjected to unpredictable MS. These findings were further supported by the demonstration that blocking oxytocinergic projections from the paraventricular nucleus of the hypothalamus (PVN) to the mPFC was sufficient to exacerbate anxiety behavior in rats exposed to predictable MS. Our findings provide direct evidence for the notion that predictable MS promotes stress resilience, while unpredictable MS increases stress susceptibility via mPFC oxytocin signaling in rats.

Reduced motor cortex GABABR function following chronic alcohol exposure.

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

Histamine H1 Receptor Contributes to Vestibular Compensation.

Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.

Suppression of microglial activation and monocyte infiltration ameliorates cerebellar hemorrhage induced-brain injury and ataxia.

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia.

[Analysis of adverse reactions of Xianling Gubao preparation based on real world SRS data].

From January 1, 2004 to July 21, 2016 a total of 2 796 cases of adverse drug reaction/adverse event(ADR/AE) after the use of Xianling Gubao Capsules/Tablets were reported by National Adverse Drug Reaction Monitoring Center. The following results were obtained by analyzing the reports of 2 796 cases of adverse drug reactions/adverse drug events after the use of Xianling Gubao Capsules/Tablets. A total of 75 patients, accounting for 2.68% of the total ADR/AE time, had severe ADR/AE events. Among them, 30 patients were aged 65 and above, accounting for 40.00% of the total number of severe ADR/AE patients. All the patients with ADR/AE were aged 45-64 years, which totaled 1 346 cases and took up 48.14% of the total patients with ADR/AE. All of ADR/AE cases and severe ADR/AE cases were orally given Xianling Gubao Capsules/Tablets. Females accounted for 52.50% and 76.00%, respectively, and the proportion of females was significantly higher than that of males. Among patients with a medical history of ADR/AE, severe ADR/AE was higher than the average, accounting for about 1.33%. The proportion of cases orally given 1-3 tablets of Xianling Gubao Capsules/Tablets in all ADR/AE cases and severe ADR/AE cases was 95.32% and 96.00%, which conformed to the usage in the package insert. All ADR/AE cases and severe ADR/AE cases orally given Xianling Gubao Capsules/Tablets twice daily occupied the highest proportions, or 77.00% and 61.00%, respectively. The proportion of severe ADR/AE cases orally given Xianling Gubao Capsules/Tablets was slightly higher than that of all ADR/AE cases in the medication frequency, which didn't conform to the usage in the package insert. All the symptoms of ADR/AE orally given Xianling Gubao Capsules showed many manifestations, and the top 10 symptoms were nausea, rash, itching, stomach dysfunction, vomiting, abdominal pain, dizziness, diarrhea, anaphylaxis, and reflux heartburn. The symptoms of severe ADR/AE after oral administration of Xianling Gubao Capsules were varied, and the top 10 symptoms were abnormal liver function, rash, suffocation, itching, dizziness, vomiting, anaphylaxis, abdominal pain, weakness, and convulsions. Abnormal liver function accounted for 44.12%. All of ADR/AE cases occurred within 2 days after oral administration of Xianling Gubao Capsules/Tablets, accounting for 54.26%. Severe ADR/AE occurred within 2 days after the use of Xianling Gubao Capsules/Tablets, accounting for 25.34%. The proportion of ADR/AE cases occurring within 15 days after oral administration of Xianling Gubao Capsules/Tablets increased again(57.33%). The overall trend contained two peaks.

Excitatory effect of norepinephrine on neurons in the inferior vestibular nucleus and the underlying receptor mechanism.

The central noradrenergic system, originating mainly from the locus coeruleus in the brainstem, plays an important role in many physiological functions, including arousal and attention, learning and memory, anxiety, and nociception. However, little is known about the roles of norepinephrine (NE) in somatic motor control. Therefore, using extracellular recordings on rat brainstem slices and quantitative real-time RT-PCR, we investigate the effect and mechanisms of NE on neuronal activity in the inferior vestibular nucleus (IVN), the largest nucleus in the vestibular nuclear complex, which holds an important position in integration of information signals controlling body posture. Here, we report that NE elicits an excitatory response on IVN neurons in a concentration-dependent manner. Activation of α1 - and ß2 -adrenergic receptors (ARs) induces an increase in firing rate of IVN neurons, whereas activation of α2 -ARs evokes a decrease in firing rate of IVN neurons. Therefore, the excitation induced by NE on IVN neurons is a summation of the excitatory components mediated by coactivation of α1 - and ß2 -ARs and the inhibitory component induced by α2 -ARs. Accordingly, α1 -, α2 -, and ß2 -AR mRNAs are expressed in the IVN. Although ß1 -AR mRNAs are also detected, they are not involved in the direct electrophysiological effect of NE on IVN neurons. All these results demonstrate that NE directly regulates the activity of IVN neurons via α1 -, α2 -, and ß2 -ARs and suggest that the central noradrenergic system may actively participate in IVN-mediated vestibular reflexes and postural control. © 2016 Wiley Periodicals, Inc.

[Common clinical medical combinations with Shenfu injection based on 25 704 electronic medical records].

Shenfu injection is a common clinical medicine. To explore the common clinical medical combinations with Shenfu injection the real world, 25 704 patients who used Shenfu injection were selected from the hospital information system (HIS) database established by Clinical and Basic Research Institute for Traditional Chinese Medicine of China Academy of Chinese Medical Sciences. The association rules were applied in a correlation analysis on common medical combinations with Shenfu injection in the patients. According to the findings, when Shenfu injection was combined with a single medicine in clinic, the ratio of using Omeprazole, Lidocaine or Furosemide were respectively 22.19%, 20.32%, 19.61%; when Shenfu injection was combined with two medicines, the top three medical combinations were respectively midazolam + omeprazole (11.01%), lidocaine + omeprazole (10.8%) and propofol + midazolam (10.76%); when Shenfu injection was combined with three medicines, the top three medical combinations were respectively propofol + fentany + midazolam (8.83%), remifentanil + propofol + midazolam (8.77% ) and propofol + midazolam + omeprazole (8.77%). According to the further analysis, the combination of Shenfu injection and Propofol + Fentany + Midazolam may reduce the incidence of hypotension and bradycardia during anesthesia, accelerate recovery after anesthesia and relieve the synergistic effect after anesthesia. The combination of Shenfu injection and furosemide may show the synergistic effect in treating the acute left ventricular failure by reducing the returned blood volume and increasing the myocardial contractile force and vitality. The combination of Shenfu injection and Omeprazole may play the synergistic effect in shortening the digestive tract ulcer healing time, reducing the ulcer recurrence and preventing hemorrhagic shock and stress ulcer caused by shock in treating ulcer hemorrhage.

Study on crease recovery property of warp-knitted jacquard spacer shoe upper material.

Shoe upper materials are often subjected to repeated creasing in use, which affects their shape retention and aesthetic. The crease recovery property of fabrics is an important property that affects its serviceability. Six variants of warp-knitted jacquard spacer fabrics with different jacquard layer structures were selected and the crease recovery angles on six orientation angles were tested for 30 cycles. The relationship between different orientation angles and crease recovery angles was studied and the comprehensive index for evaluating the crease recovery property of fabric was extracted by the grey relation analysis. The effect of the jacquard layer structure and the number of cycles on crease recovery property was analyzed with MATLAB. The results indicated that the crease recovery angles on different orientation angles were significantly different, and the comprehensive index could evaluate the crease recovery property more reasonably. The influence of the 3-needle underlap and the chain underlap on the crease recovery property was the most significant, and the influence of the 3-needle underlap was greater than that of the chain underlap. Base on solid structure, reducing the proportion of mesh structure or adding semi-transparent structure could improve the crease recovery property. The change rule of crease recovery angles with the number of cycles could be elucidated by the exponential function.

Multimodal integration for Barrett's esophagus.

The esophageal adenocarcinoma is facing a worldwide challenge: early prediction and risk assessment in clinical Barrett's esophagus (BE). In recent years, the growing interests have been witnessed in prediction and risk assessment in clinical BE. However, the resolution is limited, and the system is huge and expensive for the existing devices. Inspired by the principle of collaboration between human eye vision and brain cortex in data processing, here we propose multimodal learning framework to tackle tasks from various modalities, which can benefit from each other. To our findings, the experimental result indicates that low-level modality can directly affect high-level modality and form the final risk grading based on contribution, which maximizes the clinical performance of medical professionals based on our findings.

Azobenzene-based liposomes with nanomechanical action for cytosolic chemotherapeutic drug delivery.

The stimuli-responsive nano-carriers are at the forefront of research in nanotechnology and materials science. These advanced systems are designed to alter their physicochemical properties upon exposure to specific stimuli, enabling controllable and targeted delivery of therapeutic agents. Nevertheless, limited endosomal escape reduces the drug bioavailability in clinical use. We herein report azobenzene (Azo)-based liposomes, prepared by co-assembling the photoisomerizable cationic Azo lipids and helper lipids, which achieve controllable doxorubicin (Dox) release and enhanced cytosolic transport upon light irradiation. Azo lipids undergo reversible isomerization between cis-isomers and trans-isomer when received UV and visible (Vis) light irradiation, causing liposomal membrane permeability changes for controlled drug release. Moreover, the nanomechanical action created by the isomerization of Azo lipids promotes the endosomal escape of the liposomes. DSPC-Azo liposomes, with minimal Dox leakage, showed significant tumor cell killing upon irradiation. For in vivo study, we co-encapsulated the upconverting nanoparticles (UCNPs), which can convert the near-infrared (NIR) light into UV/Vis emissions, facilitating Azo units activation. UCNP/Dox-loaded DSPC-Azo liposomes inhibited tumor growth under NIR irradiation in a 4T1 tumor-bearing mouse model.

Adipose-Derived exosome from Diet-Induced-Obese mouse attenuates LPS-Induced acute lung injury by inhibiting inflammation and Apoptosis: In vivo and in silico insight.

BACKGROUND: Acute lung injury (ALI) is a severe clinical condition in the intensive care units, and obesity is a high risk of ALI. Paradoxically, obese ALI patients had better prognosis than non-obese patients, and the mechanism remains largely unknown. METHODS: Mouse models of ALI and diet-induced-obesity (DIO) were used to investigate the effect of exosomes derived from adipose tissue. The adipose-derived exosomes (ADEs) were isolated by ultracentrifugation, and the role of exosomal miRNAs in the ALI was studied. RESULTS: Compared with ADEs of control mice (C-Exo), ADEs of DIO mice (D-Exo) increased survival rate and mitigated pulmonary lesions of ALI mice. GO and KEGG analyses showed that the target genes of 40 differentially expressed miRNAs between D-Exo and C-Exo were mainly involved with inflammation, apoptosis and cell cycle. Furthermore, the D-Exo treatment significantly decreased Ly6G+ cell infiltration, down-regulated levels of pro-inflammatory cytokines (IL-6, IL-12, TNF-α, MCP-1) and chemokines (IL-8 and MIP-2), reduced pulmonary apoptosis and arrest at G0G1 phase (P < 0.01). And the protective effects of D-Exo were better than those of C-Exo (P < 0.05). Compared with the C-Exo mice, the levels of miR-16-5p and miR-335-3p in the D-Exo mice were significantly up-regulated (P < 0.05), and the expressions of IKBKB and TNFSF10, respective target of miR-16-5p and miR-335-3p by bioinformatic analysis, were significantly down-regulated in the D-Exo mice (P < 0.05). CONCLUSIONS: Exosomes derived from adipose tissue of DIO mice are potent to attenuate LPS-induced ALI, which could be contributed by exosome-carried miRNAs. Our data shed light on the interaction between obesity and ALI.

Site-recognition boosted the sensing performance of terbium-based organic frameworks for UO22+ detection.

A unique fluorescent sensing probe for UO22+ detection was fabricated with terbium-based metal organic frameworks via introducing specific recognition sites (denoted as Tb-TDPAT). The newly formed Tb-TDPAT presented remarkable detection sensitivity and selectivity towards UO22+, surpassing the need for complex post-modification methods.

A Ligand-Directed Spatial Regulation to Structural and Functional Tunability in Aggregation-Induced Emission Luminogen-Functionalized Organic-Inorganic Nanoassemblies.

Aggregation-induced emission luminogen (AIEgen)-functionalized organic-inorganic hybrid nanoparticles (OINPs) are an emerging category of multifunctional nanomaterials with vast potential applications. The spatial arrangement and positioning of AIEgens and inorganic compounds in AIEgen-functionalized OINPs determine the structures, properties, and functionalities of the self-assembled nanomaterials. In this work, a facile and general emulsion self-assembly tactic for synthesizing well-defined AIEgen-functionalized OINPs is proposed by coassembling alkane chain-functionalized inorganic nanoparticles with hydrophobic organic AIEgens. As a proof of concept, the self-assembly and structural evolution of plasmonic-fluorescent hybrid nanoparticles (PFNPs) from concentric circle to core shell and then to Janus structures is demonstrated by using alkane chain-modified AuNPs and AIEgens as building blocks. The spatial position of AuNPs in the signal nanocomposite is controlled by varying the alkane ligand length and density on the AuNP surface. The mechanism behind the formation of various PFNP nanostructures is also elucidated through experiments and theoretical simulation. The obtained PFNPs with diverse structures exhibit spatially tunable optical and photothermal properties for advanced applications in multicolor and multimode immunolabeling and photothermal sterilization. This work presents an innovative synthetic approach of constructing AIEgen-functionalized OINPs with diverse structures, compositions, and functionalities, thereby championing the progressive development of these OINPs.

CGMega: explainable graph neural network framework with attention mechanisms for cancer gene module dissection.

Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

Association of selenium intake with bone mineral density and osteoporosis: the national health and nutrition examination survey.

Background: Osteoporosis (OP) is a systemic metabolic skeletal disorder characterized by a decrease in bone mineral density (BMD) and an increase in the risk of fracture. The level of selenium (Se) in serum is associated with BMD. However, the relationship between dietary and total selenium intake and parameters such as osteoporosis and BMD is unclear. By conducting National Health and Nutritional Examination Surveys (NHANES), in this study, we assessed the association of Se intake with BMD and the risk of OP among general middle-aged and elderly people. Methods: The data were collected from three cycles of NHANES [2009-2010, 2013-2014, and 2017-2020]. Information on the dietary and supplementary Se intake was obtained from 24-h dietary recall interviews. Additionally, dual-energy X-ray absorptiometry (DXA) was performed to measure BMD, which was later transformed into T-scores; OP was diagnosed when the T-score was ≤ -2.5. We constructed a logistic regression model for the association between selenium intake and the risk of OP based on the estimated odds ratios (ORs) and the 95% confidence intervals (CIs). We also constructed a multivariable linear regression model to analyze the relationship between selenium intake and BMD. Results: In this study, 3,250 individuals (average age: 60.01 ± 10.09 years; 51.88% females) participated. The incidence of OP was 9.35% (3.30% for males and 17.75% for females). In the logistic regression model adjusted for every interested covariate, a higher quartile of dietary Se intake (OR for quartile 4 vs. quartile 1: 0.63; 95% CI: 0.41-0.96; P for trend = 0.027) was related to a lower risk of OP relative to the lowest quartile. The total selenium intake also exhibited a consistent trend (OR for quartile 4 vs. quartile 1: 0.67; 95% CI: 0.44-1.01; P for trend = 0.049). The results of the adjusted multivariate linear regression model showed that the participants with the highest quartile of dietary Se intake (Q4) had higher BMD in the total femur (ß = 0.069, P = 0.001; P for trend = 0.001), femoral neck (ß = 0.064, P = 0.001; P for trend = 0.001), and total spine (ß = 0.030, P = 0.136; P for trend = 0.064) compared to those in quintile 1 (Q1). A similar trend of associations was observed for the total selenium intake with BMD, which was more prominent among females, as determined by the subgroup analysis. Conclusion: In this study, the dietary intake and total intake of selenium were positively associated with BMD, whereas they were negatively associated with the risk of OP among adults in the US. Further studies are required to verify our results and elucidate the associated biological mechanism.

Large off-diagonal magnetoelectricity in a triangular Co2+-based collinear antiferromagnet.

Magnetic toroidicity is an uncommon type of magnetic structure in solid-state materials. Here, we experimentally demonstrate that collinear spins in a material with R-3 lattice symmetry can host a significant magnetic toroidicity, even parallel to the ordered spins. Taking advantage of a single crystal sample of CoTe6O13 with an R-3 space group and a Co2+ triangular sublattice, temperature-dependent magnetic, thermodynamic, and neutron diffraction results reveal A-type antiferromagnetic order below 19.5 K, with magnetic point group -3' and k = (0,0,0). Our symmetry analysis suggests that the missing mirror symmetry in the lattice could lead to the local spin canting for a toroidal moment along the c axis. Experimentally, we observe a large off-diagonal magnetoelectric coefficient of 41.2 ps/m that evidences the magnetic toroidicity. In addition, the paramagnetic state exhibits a large effective moment per Co2+, indicating that the magnetic moment in CoTe6O13 has a significant orbital contribution. CoTe6O13 embodies an excellent opportunity for the study of next-generation functional magnetoelectric materials.

Breakdown of the scaling relation of anomalous Hall effect in Kondo lattice ferromagnet USbTe.

The interaction between strong correlation and Berry curvature is an open territory of in the field of quantum materials. Here we report large anomalous Hall conductivity in a Kondo lattice ferromagnet USbTe which is dominated by intrinsic Berry curvature at low temperatures. However, the Berry curvature induced anomalous Hall effect does not follow the scaling relation derived from Fermi liquid theory. The onset of the Berry curvature contribution coincides with the Kondo coherent temperature. Combined with ARPES measurement and DMFT calculations, this strongly indicates that Berry curvature is hosted by the flat bands induced by Kondo hybridization at the Fermi level. Our results demonstrate that the Kondo coherence of the flat bands has a dramatic influence on the low temperature physical properties associated with the Berry curvature, calling for new theories of scaling relations of anomalous Hall effect to account for the interaction between strong correlation and Berry curvature.