In response to stressors, individuals adopt different behavioral styles, which are essential for survival and form the basis of differential susceptibility to stress-related disorders. ...Corticotropin-releasing factor (CRF) and the medial prefrontal cortex (mPFC) have predominantly been studied in behavioral response to stress, while the role of mPFC CRF neurons is poorly understood. Using morphology, electrophysiology, and calcium imaging approaches, we characterized mPFC CRF neurons as a unique subtype of GABAergic inhibitory interneurons that were directly engaged in the tail suspension challenge. Genetic ablation or chemogenetic inhibition of dorsal mPFC (dmPFC) CRF neurons increased immobility under the tail-suspension and forced-swimming challenges and induced social avoidance behavior, whereas activation had the opposite effect on the same measures. Furthermore, increasing CRF neuronal activity promoted durable resilience to repeated social defeat stress. These results uncover a critical role of mPFC CRF interneurons in bidirectionally controlling motivated behavioral style selection under stress.
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•Prefrontal CRF GABAergic interneurons are recruited during behavioral challenges•Manipulation of CRF neurons motivates selection of behavioral styles under challenges•Activation of CRF neurons promotes persistent stress-resistant behaviors
Chen et al. identify a population of mPFC CRF neurons that form monosynaptic GABAergic inhibitory connections with pyramidal cells and play a key role in controlling behavioral style selection in the face of various stressful challenges.
Designing electrocatalysts with high-performance for both reduction and oxidation reactions faces severe challenges. Here, the uniform and ultrasmall (~3.4 nm) high-entropy alloys (HEAs) Pt
Ni
Fe
Co
...Cu
nanoparticles are synthesized by a simple low-temperature oil phase strategy at atmospheric pressure. The Pt
Ni
Fe
Co
Cu
/C catalyst exhibits excellent electrocatalytic performance for hydrogen evolution reaction (HER) and methanol oxidation reaction (MOR). The catalyst shows ultrasmall overpotential of 11 mV at the current density of 10 mA cm
, excellent activity (10.96 A mg
at -0.07 V vs. reversible hydrogen electrode) and stability in the alkaline medium. Furthermore, it is also the efficient catalyst (15.04 A mg
) ever reported for MOR in alkaline solution. Periodic DFT calculations confirm the multi-active sites for both HER and MOR on the HEA surface as the key factor for both proton and intermediate transformation. Meanwhile, the construction of HEA surfaces supplies the fast site-to-site electron transfer for both reduction and oxidation processes.
Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) ...in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up- and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.
Aim
To examine the impact of both individual and cumulative social determinants of health (SDoH) on the likelihood of developing periodontitis, while also exploring any gender disparities in this ...relationship.
Materials and Methods
Data of self‐reported SDoH domains and sub‐items based on Healthy People 2030 were obtained from the U.S. National Health and Nutrition Examination Surveys between 1999 and 2014. Logistic regression models, weighted by survey responses, were used to examine the relationship between SDoH (including eight sub‐items and the cumulative number of unfavourable SDoH) and periodontitis. The results were further analysed by gender.
Results
A total of 18,075 participants (8867 males and 9208 females) were included in the main analysis, of which 5814 (32.2%) had periodontitis. The study found that certain unfavourable SDoH were individually associated with higher odds of periodontitis, and the cumulative number of unfavourable SDoH was positively linked to the odds of developing periodontitis. Furthermore, males exposed to more unfavourable SDoH appeared to be more susceptible to developing periodontitis than females.
Conclusions
The findings suggest that unfavourable SDoH, especially when they accumulate, are associated with an increased odds of periodontitis and contribute to gender disparities within the U.S. population.
Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressive-like behaviors are not well understood. Here, we show ...that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4-type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIα neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHb-projecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by long-term exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.
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•Activation of LHb-projecting vLGN/IGL neurons inhibits neuronal activity in the LHb•M4-type mRGCs directly innervate the vLGN/IGL-LHb pathway•Activation of the retina-vLGN/IGL-LHb pathway decreases depressive-like behaviors•Light therapy ameliorates depressive symptoms via the retina-vLGN/IGL-LHb pathway
Huang et al. identified a visual circuit related to the LHb that regulates depressive-like behaviors. They demonstrate that activation of the disynaptic retina-vLGN/IGL-LHb pathway underlies the antidepressive effects of light therapy.
Electrocatalytic nitrogen reduction reaction (NRR) has been an important area for many scientists. However, high voltage requirements, low NH3 yield, and poor stability remain the biggest challenges ...for NRR. Here, novel high‐entropy alloys RuFeCoNiCu nanoparticles with small size (≈16 nm) and uniformity, prepared in oil phase at atmospheric pressure and low temperature (≤250 °C) are reported for the first time and are applied to NRR. According to the experiments, there is a high NH3 yield at a low overpotential. It has a surprising NH3 yield of 57.1 µg h–1 mgcat−1 (11.4 µg h–1 cm–2) at 0.05 V versus RHE in 0.1 m KOH, and the corresponding Faradaic efficiency reaches 38.5%, which is the electrocatalyst with the highest NH3 yield at the voltage of 0.05 V versus RHE reported so far. Similarly, the material also exhibits excellent electrochemical properties in other electrolytes such as 0.1 m Li2SO4, 0.1 m Na2SO4, and 0.1 m HCl electrolytes. Besides, after the 100 h test, only slightly diminished in activity. Theoretical calculation shows that Fe surrounded by alloy metals is the best site for N2 adsorption and activation. Co‐Cu and Ni‐Ru couples show an excellent capacity to surface hydrogenation at a low overpotential.
RuFeCoNiCu high‐entropy alloy nanoparticles are synthesized at low temperature (≤250 °C) and atmospheric pressure for the first time and used for boosting nitrogen reduction reaction. Density functional theory shows that the synergetic roles between alloy elements have been identified as a key reason for observed performance offered by high‐entropy alloy at low overpotential.
Programmed death ligand 1 (PD-L1) is a typical immune checkpoint protein, whose up-regulation on the membrane of different tumor cells inhibits the immune response of T cells and leads to the escape ...of tumor cells. In this work, we designed a facile and highly specific surface plasmon resonance (SPR) biosensor to detect PD-L1 in human plasma based on magnetite nanorods containing ordered mesocages (MNOM) and silver nanoclusters (AgNCs). Magneto-optical nanocomplex MNOM@AgNCs with superior magneto-optical properties and high signal-to-noise ratio were fabricated to improve the detection sensitivity owing to the high specific surface area of MNOM and excellent localized SPR of AgNCs. The PD-L1 Antibody on the surface of gold chip and the PD-L1 aptamer on MNOM@AgNCs could realize dual selective recognition of PD-L1, providing the specificity of the sensor and reducing non-specific binding. The SPR sensor showed a good linear range of PD-L1 from 10 ng/mL to 300 ng/mL with the detection limit of 3.29 ng/mL. The practical performance of this immunosensing platform had been successfully verified by clinical samples which included healthy donors and cancer patients. Based on the analysis, the developed immunosensor provided a new strategy for point-of-care detection of PD-L1 and could be used as clinical companion diagnosis of PD-1/PD-L1 inhibitor therapy.
•Magneto-optical nanocomplex was fabricated from silver nanoclusters and magnetite nanorods containing ordered mesocages.•Ultra-sensitive and quantitative detection of PD-L1 was achieved by excellent LSPR and magnetic properties.•The superior practical performance was verified by real samples collected from healthy donors and cancer patients.
The tree shrew (Tupaia belangeri chinensis) is the closest living relative of primates. Yet, little is known about the anatomical distribution of tyrosine hydroxylase (TH)‐immunoreactive (ir) ...structures in the hypothalamus of the tree shrew. Here, we provide the first detailed description of the distribution of TH‐ir neurons in the hypothalamus of tree shrews via immunohistochemical techniques. TH‐ir neurons were widely distributed throughout the hypothalamus of tree shrew. The majority of hypothalamic TH‐ir neurons were found in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON), as was also observed in the human hypothalamus. In contrast, rare TH‐ir neurons were localized in the PVN and SON of rats. Vasopressin (AVP) colocalized with TH‐ir neurons in the PVN and SON in a large number of neurons, but oxytocin and corticotropin‐releasing hormone did not colocalize with TH. In addition, colocalization of TH with AVP was also observed in the other hypothalamic regions. Moreover, TH‐ir neurons in the PVN and SON of tree shrews expressed other dopaminergic markers (aromatic l‐amino acid decarboxylase and vesicular monoamine transporter, Type 2), further supporting that TH‐ir neurons in the PVN and SON were catecholaminergic. These findings provide a detailed description of TH‐ir neurons in the hypothalamus of tree shrews and demonstrate species differences in the distribution of this enzyme, providing a neurobiological basis for the participation of TH‐ir neurons in the regulation of various hypothalamic functions.
The anatomical characteristics of tyrosine hydroxylase‐immunoreactive (TH‐ir) neurons in the tree shrew hypothalamus were analyzed using single and double‐labeled immunostaining techniques. TH‐ir neurons were abundantly distributed in paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON) and were exclusively colocalized with neuropeptide vasopressin. Moreover, TH‐ir neurons also expressed other dopaminergic markers (aromatic l‐amino acid decarboxylase and vesicular monoamine transporter, Type 2), further supporting that TH‐ir neurons in the PVN and SON were catecholaminergic.
The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene ...manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa+ but not PDGFRa–PDGFRb+ perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.
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•More than 70 new Dre driver lines are provided as a resource for intersectional genetics•PDGFRa+PDGFRb+ or PDGFRa+ perivascular cells contribute to de novo adipocytes•“Exclusion” dual recombinase enables gene deletion in white but not brown adipocytes•Sequential dual recombinase enables gene deletion in lymphatic endothelial cells
The combinatory use of Dre and Cre recombinase-mediated intersectional genetics significantly enhances the precision of in vivo lineage tracing and gene targeting. Han et al. developed more than 70 new intersectional drivers to target diverse cell lineages. Highlighting their application, Han et al. used these new tools to study perivascular progenitors of adipocytes and performed gene knockout in white adipocytes (WAs) and lymphatic endothelial cells (LECs).
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