Assessment of wellbore integrity failure risk and hazardous zones in depleted reservoirs underground gas storage during the operation processes.

Depleted reservoirs are widely used for underground gas storage due to their advantages of low construction cost and easy development. Under the influence of complex geological conditions and frequent operations, the integrity of the wells in depleted reservoirs is prone to failure, which would potentially lead to gas leakage. In this study, by using a finite element-based computational fluid dynamics model, we have developed evaluation criteria for assessing the severity of the occurred wellbore integrity failure and the risk of the un-occurred wellbore integrity failures respectively to identify hazardous zones potentially prone to wellbore integrity failure. The study results indicate that the gas storage wellbore integrity failure is prone to occur inside the wellbore structure in the direction of the minimum ground stress near the lower boundary of the formation interlayer. The wellbore integrity failure hazardous zones are mainly concentrated at the formation interlayer boundaries. The practical guidelines and solutions derived from current research results can provide an accurate direction for monitoring and protecting work of wellbore integrity and avoid environment pollution problems caused by natural gas leakage.

Representation and control of pain and itch by distinct prefrontal neural ensembles.

Pain and itch are two closely related but essentially distinct sensations that elicit different behavioral responses. However, it remains mysterious how pain and itch information is encoded in the brain to produce differential perceptions. Here, we report that nociceptive and pruriceptive signals are separately represented and processed by distinct neural ensembles in the prelimbic (PL) subdivision of the medial prefrontal cortex (mPFC) in mice. Pain- and itch-responsive cortical neural ensembles were found to significantly differ in electrophysiological properties, input-output connectivity profiles, and activity patterns to nociceptive or pruriceptive stimuli. Moreover, these two groups of cortical neural ensembles oppositely modulate pain- or itch-related sensory and emotional behaviors through their preferential projections to specific downstream regions such as the mediodorsal thalamus (MD) and basolateral amygdala (BLA). These findings uncover separate representations of pain and itch by distinct prefrontal neural ensembles and provide a new framework for understanding somatosensory information processing in the brain.

Development of epitopephore-based rational hapten design strategy: A combination of theoretical evidence and experimental validation.

Antibody is the key biomolecule that governing the sensitivity and specificity of an immunoassay for chemical compound, also named hapten molecule. Obviously, predication of hapten effectiveness before chemical synthesis is beneficial to boost success, save cost and improve controllability. Here, we proposed and evaluated an epitopephore based rational hapten design (ERHD) to assist antibody production to chemical compound, combining theoretical evidence and then experimental validation by using dinitrocarbanilide (DNC) as a model analyte. Briefly, epitopephores of DNC were firstly generated by HipHop algorithm after features mapping. A homemade drug database also containing reported fragment haptens (HFR) and new designed full hapten (HFU) were constructed, and then was virtually screened by using generated epitopephore followed by structural analysis and visual inspection. The DNC haptens based on the selected hits were further identified by Density Functional Theory before total synthesis. To prove and clarify the usability of the ERHD, two retrieved HFU haptens, one non-retrieved HFU hapten and three non-retrieved HFR haptens were all selected to produce monoclonal antibodies (mAbs) for comparison purpose. A maximal 6000-fold increased affinity of mAb from retrieved HFU than HFR was observed, while, non-retrieved HFU failed to produce antibody to DNC. More importantly, mAbs from HFU haptens provided highly specificity to DNC, while, mAbs from HFR haptens could recognize 15 others analogues. We then constructed antibody structure and investigated molecular recognition of the mAbs to DNC, well supporting the rationality of the ERHD. Lastly, an icELISA was developed for DNC with an IC50 value as low as 0.19 ng mL-1 with high specificity, which has never achieved before.

An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice.

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Broad-specificity indirect competitive enzyme-linked immunosorbent assay for aristolochic acids: Computer-aided hapten design and molecular mechanism of antibody recognition.

Long-term dietary exposure of aristolochic acids (AAs)-contaminated food proved to be one of the main culprits of Endemic Nephropathy, renal failure; and urothelial cancer. The antibodies utilized in immunoassays for AAs suffer from low affinity and failure of recognition to the family of AAs. This study, we prepared a broad-specificity monoclonal antibody (mAb) 5H5 with highly and uniform affinity for AAs by help of computational chemistry fully exposing the AAs common structures of methoxy and hydroxyl groups. The mAb 5H5 exhibited half inhibitory concentrations of AAA, AAB, AAC, AAD were 0.03, 0.06, 0.05, 0.03 ng/mL. To explain the broad-specificity profile of mAb 5H5, molecular docking was performed. Results shown that multiple conformations of AAs can be flexibly oriented in the spacious cavity of single-chain variable fragment antibody (scFv) 5H5 and the specific hydron bonds were formed by ASN62 and GLY64 of scFV 5H5 to the nitro group of AAs which gave an explanation of the high cross-reactivity of mAb 5H5. The ELISA based on the broad-specificity mAb 5H5with detection limits of 0.04-0.11 µg/kg and 0.02-0.06 µg/kg for four AAs in flour and soil samples, respectively. The study provided a promising method for the family of AAs in environmental and food samples.

Minimum Distance Between Two Epitopes in Sandwich Immunoassays for Small Molecules.

The pursuit of the limit between dimensionalities is a scientific goal with high applicability. Sandwich immunoassay, usually based on two antibodies binding two epitopes, is one of the most popular mainstay tools in both academic and industrial fields. Herein, we determined and evaluated the minimum distance of two epitopes in sandwich immunoassays for small molecules. Briefly, nine model analytes comprising two hapten epitopes, that is, melamine (MEL) and p-nitroaniline (NIA), were designed by increasing the linear chain linkers brick by brick. Two groups of monoclonal antibodies (mAbs) were produced with different recognition properties toward MEL and NIA using 12 new haptens with different spacer arms. The results indicated that two epitopes of the analyte with a distance of only 2.4 Å could be simultaneously bound by two mAbs, which is the known limit of epitope distance in sandwich immunoassays thus far. We further found that an epitope distance of below 8.8 Å for the analyte generally induces noticeable steric hindrance of antibodies, preventing a sandwich immunoassay with high probability. These observations were investigated and evaluated by molecular docking, molecular dynamics, and surface plasmon resonance and using model and real analytes. Altogether, we determined the minimum distance of two epitopes and explored the molecular mechanism of the antibody-analyte-antibody ternary complex in sandwich immunoassays, providing a theoretical basis for hapten design, antibody discovery and development, and sandwich immunoassay establishment for small molecules.

Optimization of High Temperature-Resistant Modified Starch Polyamine Anti-Collapse Water-Based Drilling Fluid System for Deep Shale Reservoir.

During drilling in deep shale gas reservoirs, drilling fluid losses, hole wall collapses, and additional problems occur frequently due to the development of natural fractures in the shale formation, resulting in a high number of engineering accidents such as drilling fluid leaks, sticking, mud packings, and buried drilling tools. Moreover, the horizontal section of horizontal well is long (about 1500 m), and the problems of friction, rock carrying, and reservoir pollution are extremely prominent. The performance of drilling fluids directly affects drilling efficiency, the rate of engineering accidents, and the reservoir protection effect. In order to overcome the problems of high filtration in deep shale formations, collapse of borehole walls, sticking of pipes, mud inclusions, etc., optimization studies of water-based drilling fluid systems have been conducted with the primary purpose of controlling the rheology and water loss of drilling fluid. The experimental evaluation of the adsorption characteristics of "KCl + polyamine" anti-collapse inhibitor on the surface of clay particles and its influence on the morphology of bentonite was carried out, and the mechanism of inhibiting clay mineral hydration expansion was discussed. The idea of controlling the rheology and water loss of drilling fluid with high temperature resistant modified starch and strengthening the inhibition performance of drilling fluid with "KCl + polyamine" was put forward, and a high temperature-resistant modified starch polyamine anti-sloughing drilling fluid system with stable performance and strong plugging and strong inhibition was optimized. The temperature resistance of the optimized water-based drilling fluid system can reach 180 °C. Applied to on-site drilling of deep shale gas horizontal wells, it effectively reduces the rate of complex accidents such as sticking, mud bagging, and reaming that occur when resistance is encountered during shale formation drilling. The time for a single well to trip when encountering resistance decreases from 2-3 d in the early stages to 3-10 h. The re-use rate of the second spudded slurry is 100 percent, significantly reducing the rate of complex drilling accidents and saving drilling costs. It firmly supports the optimal and rapid construction of deep shale gas horizontal wells.

Surface Display of porcine circovirus type 2 antigen protein cap on the spores of bacillus subtilis 168: An effective mucosal vaccine candidate.

The oral mucosal vaccine has great potential in preventing a series of diseases caused by porcine circovirus type 2 (PCV2) infection. This study constructed a recombinant Bacillus subtilis RB with PCV2 Capsid protein (Cap) on its spore surface and cotB as a fusion partner. The immune properties of the recombinant strain were evaluated in a mouse model. IgA in intestinal contents and IgG in serum were detected by enzyme-linked immunosorbent assay (ELISA). The results demonstrated that recombinant spores could activate strong specific mucosal and humoral immune responses. In addition, spores showed good mucosal immune adjuvant function, promoting the proliferation of CD3+, CD4+ and CD8+ T cells and other immune cells. We also found that the relative expression of inflammatory cytokines such as IL-1ß, IL-6, IL-10, TNF-α and IFN in the small intestinal mucosa was significantly up-regulated under the stimulation of recombinant bacteriophage. These effects are important for the balance of Th1/Th2-like responses. In summary, our results suggest that recombinant B. subtilis RB as a feed additive provides a new strategy for the development of novel and safe PCV2 mucosal subunit vaccines.

Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways.

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC.

Significantly improved detection performances of immunoassay for ractopamine in urine based on highly urea-tolerant rabbit monoclonal antibody.

Highly sensitive and accurate screening of ractopamine (RAC) residue in animal urine is greatly needed to ensure food security. The detection performance of immunoassay for RAC was always seriously harmed by the antibody inactivation derived from urea. Here, we first discovered one rabbit monoclonal antibody (RmAb) to RAC with a high affinity of 0.007 ng mL-1 and a surprising urea tolerance of 3 M urea, which is beneficial for developing robustly developed immunoassay in urine without sample pretreatment. The limits of detection of developed indirect competitive enzyme-linked immunosorbent assay based on RmAb1 for RAC were 0.0042-0.014 µg L-1 with the coefficient of variation below 11.7% in swine, sheep, and cow urine, significantly improved 10-100-fold in sensitivity. Moreover, the urea-tolerant mechanism of RmAb1 showed that more non-polar amino acids, more hydrogen bond donors on the surface, and preponderant Pi interaction of antibody-RAC all contributed to the stability of the RmAb1 in a high concentration of urea.

'Three-To-One' multi-functional nanocomposite-based lateral flow immunoassay for label-free and dual-readout detection of pathogenic bacteria.

Sandwich lateral flow immunoassays (LFIAs) based on paired antibodies are the most frequently used platform for food-borne pathogen detection. Although label-free strategies are used in LFIAs to avoid the utilization of paired antibodies, challenges of probe design and detection reliability still remain. Here, we report a new label-free and dual-readout LFIA (LD-LFIA) mediated by a 'Three-To-One' multi-functional nanocomposite with a unique combination of magnetic-adhesion-color-nanozyme properties. The strengths of the new designed nanocomposite are: (i) the Fe3O4 magnetic core simplifies the separation processes; (ii) surface adherent polydopamine (PDA) films exhibit a strong adhesion to pathogenic bacteria and provide colorimetric detection signal; and (iii) the deposited platinum nanoparticles (Pt NPs) can function as nanozymes to generate an extra catalytic signal for constructing a dual-readout mode to improve the detection accuracy. The resulting Fe3O4@PDA@Pt nanocomposite-based LD-LFIA can detect highly pathogenic Escherichia coli O157:H7 with limits of detection of 102 and 10 CFU mL-1 for colorimetric and catalytic quantitative analyses, respectively. Systematic results also reveal that the proposed method exhibited high specificity and applicability for drinking water and chicken samples, serving as a promising tool for real bacterial sample testing. The multi-functional Fe3O4@PDA@Pt nanocomposite-based LD-LFIA can provide new ideas for designing new multi-functional probes for improving detection performance of conventional label-free LFIA and constructing more accurate and sensitive detection systems.

Study on anaerobic co-digestion of municipal sewage sludge and fruit and vegetable wastes: Methane production, microbial community and three-dimension fluorescence excitation-emission matrix analysis.

Constantly increased sewage sludge (SS) and fruit and vegetable wastes (FVW) are becoming the major organic solid wastes in human society. Thus, anaerobic digestion is employed as a low carbon energy strategy to reduce their environmental pollution risk. Anaerobic co-digestion system was developed based on the carbon to nitrogen ratio strategy. Results showed that the daily biogas production was higher in co-digester, and the volumetric biogas production rate (VBPR) significantly enhanced for 1.3 âˆ¼ 3 folds, and the highest VBPR was 2.04 L/L • day with optimal OLR of 2.083 Kg L-1 d-1. Analytic results indicated that co-digestion could improve the biodegradable of feedstocks, which transforming to more VFAs and biogas. Compared with mono SS digester, mixed substrates relieved ammonia nitrogen inhibition and enhanced the hydrolytic acidification and methanogenesis. Meanwhile, the excessive humification of organics was suppressed. This study supported the concepts of improving carbon recovery from SS and FVW.

Advances in Chicken IgY-Based Immunoassays for the Detection of Chemical and Biological Hazards in Food Samples.

As antibodies are the main biological binder for hazards in food samples, their performance directly determines the sensitivity, specificity, and reproducibility of the developed immunoassay. The overwhelmingly used mammalian-derived antibodies usually suffer from complicated preparation, high cost, frequent bleeding of animals, and sometimes low titer and affinity. Chicken yolk antibody (IgY) has recently attracted considerable attention in the bioanalytical field owing to its advantages in productivity, animal welfare, comparable affinity, and high specificity. However, a broad understanding of the application of IgY-based immunoassay for the detection of chemical and biological hazards in food samples remains limited. Here, we briefly summarized the diversity, structure, and production of IgY including polyclonal and monoclonal formats. Then, a comprehensive overview of the principles, designs, and applications of IgY-based immunoassays for these hazards was reviewed and discussed, including food-borne pathogens, food allergens, veterinary drugs, pesticides, toxins, endocrine disrupting chemicals, etc. Thus, the trend of IgY-based immunoassays is expected, and more IgY types, higher sensitivity, and diversification of recognition-to-signal manners are necessary in the future.

Hydrophobic Moiety of Capsaicinoids Haptens Enhancing Antibody Performance in Immunoassay: Evidence from Computational Chemistry and Molecular Recognition.

We previously found that the immune response to haptens is positively correlated with molecular hydrophobicity. The antibodies used in immunoassays for capsaicinoids (CPCs) in waste oil suffer from low affinity and loose recognition to structural analogues. To address this issue, four new haptens (hapten1-4), maximally exposing the hydrophobic alkane chain (noncommon moiety of CPCs), were designed and expected to produce antibodies with high affinity and accurate recognition to CPCs based upon our findings. The assumption was first evidenced by computational chemistry and animal immunization successively. Compared with four reported haptens (hapten5-8) that expose the hydrophilic vanillyl amide moiety (common structure of CPCs and other vanillin alkaloids), antisera from hapten1-4 showed an approximately 1000-fold increase in affinity and significantly improved recognition profiles for CPCs. The molecular recognition study showed that the high affinity of the antibody from new haptens mainly originated from hydrophobic forces. An indirect competitive enzyme-linked immunosorbent assay based on a monoclonal antibody from hapten1 was developed and exhibited limits of detection as low as 0.73-3.29 µg/kg for four CPCs in oils and with insignificant cross-reactivities for other eight vanillin alkaloids, which have been never achieved in previous reports.

Production of highly sensitive monoclonal antibody and development of lateral flow assays for phallotoxin detection in urine.

Phallotoxins, toxic cyclopeptides found in wild poisonous mushrooms, are predominant causes of fatal food poisoning. For the early and rapid diagnosis mushroom toxin poisoning, a highly sensitive and robust monoclonal antibody (mAb) against phallotoxins was produced for the first time. The half-maximum inhibition concentration (IC50) values of the mAb-based indirect competitive ELISAs for phallacidin (PCD) and phalloidin (PHD) detection were 0.31 ng mL-1 and 0.35 ng mL-1, respectively. In response to the demand for rapid screening of the type of poisoning and accurate determination of the severity of poisoning, colloidal gold nanoparticle (GNP) and time-resolved fluorescent nanosphere (TRFN) based lateral flow assays (LFA) were developed. The GNP-LFA has a visual cut-off value of 3.0 ng mL-1 for phallotoxins in human urine sample. The TRFN-LFA provides a quantitative readout signal with detection limit of 0.1 ng mL-1 in human urine sample. In this study, urine samples without pretreatment were used directly for the LFA strip tests, and both two LFAs were able to accomplish analysis within 10 min. The results demonstrated that LFAs based on the newly produced, highly sensitive, and robust mAb were able to be used for both rapid qualitative screening of the type of poisoning and accurate quantitative determination of the severity of poisoning after accidental ingestion by patients of toxic mushrooms.

Binding affinity-guided design of a highly sensitive noncompetitive immunoassay for small molecule detection.

Small molecules are immunochemically classified as hapten that lacking of at least two epitopes, usually using competitive format for establishing immunoassays. However, theoretically, noncompetitive immunoassay format is more sensitive and has a wider analytical range. In the present study, a novel hapten of halofuginone was synthesized and used to produce a monoclonal antibody (mAb). By analyzing the binding kinetics, we found that the affinity of analyte-enzyme to mAb was much greater than that of analyte, which could result in a low sensitivity of competitive assay format. Based on this, we established a novel noncompetitive immunoassay by using a replacement approach. The noncompetitive format has obvious advantages in sensitivity and analytical range, which promoted approximately 3.5- and 5-fold, respectively, compared to the competitive immunoassay. Ultimately, the newly designed noncompetitive immunoassay in this work will provide insights as well as alternative method to traditional small molecule competitive assays.

The potentially therapeutic targets of pediatric anaplastic ependymoma by transcriptome profiling.

Ependymoma (EPN) is a type of tumor that occurs in the central nervous system of children and adults. EPN produces resistance to chemotherapy, and there are no targeted drugs available as a proper cure. Therefore, the use of high-throughput sequencing technologies to elucidate pathogenic mechanisms is of prime importance to identify potential tumor target genes helpful for developing effective therapeutic approaches against EPN. With this objective, we used RNA-seq analysis to identify differentially expressed genes (DEGs) and pathways in 4 pairs of EPN tissues and adjacent tissues. In total, we found 5,445 differentially expressed genes. The synaptic vesicle cycle and extracellular matrix (ECM) receptor interaction pathways were highly enriched in the ependymoma group. Nine differentially expressed genes (SNAP25, GRM4, CELSR1, LAMA1, WNT5A, ROR2, CCND1, EPHB2, FOXJ1) were randomly verified by RT-qPCR, supporting the authenticity of our sequencing results. This study provides global gene information and some new potential biomarkers for the diagnosis and therapeutic targets of ependymoma.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a.

Acid-sensing ion channels (ASICs), the main H+ receptors in the central nervous system, sense extracellular pH fluctuations and mediate cation influx. ASIC1a, the major subunit responsible for acid-activated current, is widely expressed in brain neurons, where it plays pivotal roles in diverse functions including synaptic transmission and plasticity. However, the underlying molecular mechanisms for these functions remain mysterious. Using extracellular epitope tagging and a novel antibody recognizing the hASIC1a ectodomain, we examined the membrane targeting and dynamic trafficking of hASIC1a in cultured cortical neurons. Surface hASIC1a was distributed throughout somata and dendrites, clustered in spine heads, and co-localized with postsynaptic markers. By extracellular pHluorin tagging and fluorescence recovery after photobleaching, we detected movement of hASIC1a in synaptic spine heads. Single-particle tracking along with use of the anti-hASIC1a ectodomain antibody revealed long-distance migration and local movement of surface hASIC1a puncta on dendrites. Importantly, enhancing synaptic activity with brain-derived neurotrophic factor accelerated the trafficking and lateral mobility of hASIC1a. With this newly-developed toolbox, our data demonstrate the synaptic location and high dynamics of functionally-relevant hASIC1a on the surface of excitatory synapses, supporting its involvement in synaptic functions.

Restoration of Cingulate Long-Term Depression by Enhancing Non-apoptotic Caspase 3 Alleviates Peripheral Pain Hypersensitivity.

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. Whether Casp3-AMPAR interaction is involved in the maintenance of peripheral hypersensitivity after nerve injury remained unknown. Here, we show that nerve injury suppresses long-term depression (LTD) and downregulates Casp3 in the anterior cingulate cortex (ACC). Interfering with interactions between Casp3 and AMPAR subunits or reducing Casp3 activity in the ACC suppresses LTD induction and causes peripheral hypersensitivity. Overexpression of Casp3 restores LTD and reduces peripheral hypersensitivity after nerve injury. We reveal how Casp3 is involved in the maintenance of peripheral hypersensitivity. Our findings suggest that restoration of LTD via Casp3 provides a therapeutic strategy for neuropathic pain management.

WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death.

Mutations in the macroautophagy/autophagy gene WDR45 cause ß-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive wdr45 knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in several brain regions. Immunohistochemistry analysis showed loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in prefrontal cortex, recapitulating a hallmark of neurodegeneration. Quantitative proteomic analysis showed accumulation of endoplasmic reticulum (ER) proteins in KO mouse. At the cellular level, accumulation of ER proteins due to WDR45 deficiency resulted in increased ER stress and impaired ER quality control. The unfolded protein response (UPR) was elevated through ERN1/IRE1 or EIF2AK3/PERK pathway, and eventually led to neuronal apoptosis. Suppression of ER stress or activation of autophagy through MTOR inhibition alleviated cell death. Thus, the loss of WDR45 cripples macroautophagy machinery in neurons and leads to impairment in organelle autophagy, which provides a mechanistic understanding of cause of BPAN and a potential therapeutic strategy to treat this genetic disorder.Abbreviations: 7-ADD: 7-aminoactinomycin D; ASD: autistic spectrum disorder; ATF6: activating transcription factor 6; ATG: autophagy-related; BafA1: bafilomycin A1; BCAP31: B cell receptor associated protein 31; BPAN: ß-propeller protein-associated neurodegeneration; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CDIPT: CDP-diacylglycerol-inositol 3-phosphatidyltransferase (phosphatidylinositol synthase); DDIT3/CHOP: DNA-damage inducible transcript 3; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; GFP: green fluorescent protein; HIP: hippocampus; HSPA5/GRP78: heat shock protein family A (HSP70) member 5; KO: knockout; LAMP1: lysosomal-associated membrane 1; mEPSCs: miniature excitatory postsynaptic currents; MG132: N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal; MIB: mid-brain; MTOR: mechanistic target of rapamycin kinase; PCR: polymerase chain reaction; PFA: paraformaldehyde; PFC: prefrontal cortex; PRM: parallel reaction monitoring; RBFOX3/NEUN: RNA binding protein, fox-1 homolog [C. elegans] 3; RTN3: reticulon 3; SEC22B: SEC22 homolog B, vesicle trafficking protein; SEC61B: SEC61 translocon beta subunit; SEM: standard error of the mean; SNR: substantia nigra; SQSTM1/p62: sequestosome 1; TH: tyrosine hydroxylase; Tm: tunicamycin; TMT: tandem mass tag; TUDCA: tauroursodeoxycholic acid; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling; UPR: unfolded protein response; WDR45: WD repeat domain 45; WT: wild type; XBP1: X-box binding protein 1.