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A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors. Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE conjugated microtubule-associated protein 1 light chain3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mPFC: medial prefrontal cortex; P2A: 2A self-cleaving peptide; PPI: protein-protein interaction networks; PrL: prelimbic cortex; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; rtTA: reverse tetracycline-transactivator; SDS-PAGE: sodium dodecylsulfate-polyacrylamide gel electrophoresis; SHANK3: SH3 and multiple ankyrin repeat domains 3; SLC1A1/EAAC1: solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, systemXag), member 1; SNAP23: synaptosomal-associated protein 23; SNI:spared nerve injury; SQSTM1/p62: sequestosome 1; SYT3: synaptotagmin 3; TRE: tetracycline-responsive element; TRE3G: third-generation tetracycline-responsive element. [ABSTRACT FROM AUTHOR]

A new magnesium-based metal–organic framework with unprecedented short-chain secondary building units and ultra-micropore channels approaching the kinetic diameters of Xe is fabricated by decorating methyl groups on ligands. Due to the contracted pores, this MOF exhibits very high selectivity values for Xe/Kr, which ranks it among the top porous absorbents. [ABSTRACT FROM AUTHOR]

Many studies have shown that the brain can process subliminal numerals, i.e., participants can categorize a subliminal number into two categories: greater than 5 or less than 5. In the context of many studies on the unconscious integration of multiple subliminal stimuli, the issue of whether multiple subliminal numbers can be integrated is contentious. The same-different task is regarded as a perfect tool to explore unconscious integration. In the two experiments reported, we used a same-different task in which a pair of masked prime numbers was followed by a pair of target numbers, and participants were asked to decide whether the two target numbers were on the same (both smaller or larger than 5) or different sides (one smaller, the other larger than 5) of 5 in magnitude. The results indicated that the prime numbers could be categorized unconsciously, which was reflected by the category priming effect, and that the unconscious category relationship of the two prime numbers could affect the judgment on the category relationship of the two target numbers, as reflected by the response priming effect. The duration of the prime-to-target interstimulus interval (ISI) was also manipulated, showing a positive compatibility effect (PCE) of category priming and a negative compatibility effect (NCE) of response priming no matter whether the ISI was short (50 ms) or long (150 ms). The NCE, which occurred when the prime-to-target ISI was relatively short in this study, contradicted the conventional view but was consistent with previous results of unconscious integration based on an attention modulation mechanism. Importantly, this study provided evidence for the still-under-debate issue of numerical information integration. [ABSTRACT FROM AUTHOR]